http://ueg.sagepub.

com October 2014 : Volume 2 : Supplement 1

ISSN 2050-6406 (Print) : ISSN 2050-6414 (Online)

An international forum for clinical practice

and research in gastroenterology

nd
22 United European
UEG gratefully acknowledges the support
Gastroenterology Week
of this years Premium Partners: Vienna 2014

October 2014 : Volume 2 : Supplement 1

Abstract Issue
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22nd UEG Week 2014

Vienna, Austria, October 1822, 2014

Accepted abstracts available online at:

www.ueg.eu/education/library
http://ueg.sagepub.com

Disclaimer: United European Gastroenterology (UEG) is not responsible for errors or omissions in the
abstracts. This abstract book was nalized on August 7, 2014, any changes received after this date have not
been incorporated. Changes to presenters received after August 7 have been included in the online version of the
programme and can be obtained at: www.ueg.eu/education/library.

Disclosure policy: UEG is committed to ensuring scientic rigour and objectivity in all of its educational
activities. These include all aspects of the educational programme at UEG Week including those that are
directly and jointly sponsored activities.

All presenters, whether invited Faculty or abstract presenters, are required to disclose to those organising and
attending meetings any relevant nancial or other relationship that may lead to a potential bias. UEG reserves
the right to review the information disclosed for potential conicts of interest. Please note that the sole
responsibility for the content of each presentation lies with the presenting author.

The UEG Scientic Committee requires all presenters to disclose any advisory or consultancy roles in the
Biomedical Industry during the past two years. These and any other potential conicts of interest should be
disclosed verbally during introductory comments to the presentation. Invited speakers and oral abstract pre-
senters are requested to disclose potential conicts of interest on a PowerPoint slide to be shown immediately at
the beginning of the presentation. Poster presenters are requested to disclose potential conicts of interest at the
bottom of their poster.

Conicts of interest may exist through a nancial relationship or when the individual has the opportunity to
inuence the content of a presentation, and can involve grants, honoraria, shares, paid positions on advisory
boards, etc. Conicts of interest are frequent and expected, and do not preclude an individual from making a
presentation providing the conict is disclosed. If there is any doubt about the relevance of a potential conict
of interest UEG requires all presenters to err on the safe side and to disclose it.
Editor
Jan Tack, University of Leuven, Belgium

Associate Editors
Tim Greten, NIH, USA
Arthur Kaser, University of Cambridge, UK
Oliver Pech, St John of God Hospital, Regensburg, Germany

Editorial Board
Alberto Arezzo, University of Turin, Italy
David Armstrong, McMaster University, Canada
Michael Bourke, Westmead Hospital, Australia
Guido Costamagna, Catholic University of the Sacred Heart, Italy
Carlo Di Lorenzo, Childrens Hospital of Colombus, USA
Wouter De Jonge, Academic Medical Center, The Netherlands
Doug Drossman, University of North Carolina at Chapel Hill, USA
Mohamad Eloubeidi, American University of Beirut School of Medicine, Lebanon
Johanna C Escher, Erasmus MC, The Netherlands
Ronnie Fass, The Neuro-Enteric Clinical Research Group, USA
Richard Hunt, McMaster University, Canada
Michael P Jones, Macquarie University, Australia
John Kellow, The University of Sydney, Australia
Markus Lerch, University Medicine Greifswald, Germany
Lars Lundell, Karolinska Institute, Sweden
Hendrik Manner, HSK Wiesbaden, Germany
Helmut Neumann, University of Erlangen-Nuremberg, Germany
Qin Ouyang, West China Hospital, China
Stefan Schreiber, UKSH Campus Kiel, Germany
Vincenzo Stanghellini, University of Bologna, Italy
Jaap Stoker, Academic Medical Centre, The Netherlands
Hidekazu Suzuki, Keio University School of Medicine, Japan
Michael Vieth, University of Bayreuth, Germany
Michael Wallace, Mayo Clinic, USA
Heiner Wedemeyer, Hannover Medical School, Germany
Frank Zerbib, CHU Bordeaux, France
Aims and scope
Launched in 2013, United European Gastroenterology Journal is the official Journal of United European Gastroenterology (UEG), a professional non-
profit organisation combining all the leading European societies concerned with digestive disease. UEGs member societies represent over 22,000
specialists working across medicine, surgery, paediatrics, GI oncology and endoscopy, which makes UEG a unique platform for collaboration and
the exchange of knowledge.
United European Gastroenterology Journal provides an international forum for research in gastroenterology, publishing original articles which
describe basic research, translational and clinical studies of interest to gastroenterologists and researchers in related fields. Articles from across
all fields of gastroenterology are be welcomed by the Editor-in-Chief, including luminal, liver and pancreatic diseases, gastrointestinal surgery,
gastrointestinal oncology, paediatric gastroenterology and nutrition as well as endoscopy.
Published article types include original research, reviews, guidelines papers and news items. The journal is a member of the Committee on
Publication Ethics (COPE).

2014 annual subscription rates

United European Gastroenterology Journal ISSN: 2050-6406 (print) 2050-6414 (online) is published in February, April, June, August, October and
December by SAGE Publications (London, Thousand Oaks, CA, New Delhi, Singapore and Washington DC).
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! UEG 2014
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Printed on acid-free paper by Page Bros., Norwich, UK.
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United European Gastroenterology Journal

2(5S) v
! Author(s) 2014
Letter of Thanks for UEG Week 2014 Reviewers Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/2050640614548983
ueg.sagepub.com

Dear Colleagues,

On behalf of the UEG Scientic Committee, I would like to take this opportunity to thank you most sincerely for
your contribution as an abstract reviewer for the original programme of UEG Week Vienna 2014.

The abstract reviewing process has been again very important this year with a number of innovations intro-
duced to improve especially the poster abstract presentations. I know just how much time and eort reviewing
abstracts takes, but without your expertise we would not have the quality that I believe we have achieved in the
free paper and poster sessions, and the UEG Week would not be the top international digestive diseases meeting
that it has become today. Thank you!

I am delighted to announce that we received a total of 3,339 abstracts for UEG Week Vienna 2014, excluding
late breakers and video cases. 2,127 of these were accepted, giving an acceptance rate of 63.7%. 406 abstracts will
be delivered as oral presentations and 1,721 as posters. I am even more pleased to tell you that standards have
again reached a very high level and we can expect to be exposed to most interesting research and great
presentations.

This high volume and high standard conrm that UEG Week is the most important forum at which to present
your best research. Additionally, we have received 57 video cases which were formally evaluated by the Scientic
Committee for presentation in Vienna. The quality of reviewing this year was excellent but if you have any further
(positive or negative) comments, please do let us know!

Finally, but most importantly, many thanks to all investigators both within and outside Europe who have
submitted their research to the meeting, and who are clearly contributing to making UEG Week Vienna 2014 such
a great success!

Magnus Simren
Chair, UEG Scientific Committee, Vienna 2014
 United European Gastroenterology Journal
2(5S) viiviii
! Author(s) 2014
Thanks to Partners, Sponsors and Exhibitors Reprints and permissions:
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DOI: 10.1177/2050640614548988
ueg.sagepub.com

United European Gastroenterology (UEG) gratefully acknowledges

the support of the following companies other exhibitors:

This list reects the status as per 17 August 2014.

Premium Partners
AbbVie Inc.
FUJIFILM Europe GmbH
OLYMPUS EUROPA SE
Shire International GmbH
Takeda Pharmaceuticals International GmbH
Major Partners
Almirall, S.A.
Covidien
Merck & Co., Inc.
Norgine Limited
PENTAX Europe GmbH
General Sponsors and Exhibitors

8th Paris Hepatitis Conference Chongqing Jinshan Science & Technology (Group)
Abbott Products Operations AG Co., Ltd. / OMOM Capsule
ACTIAL FARMACEUTICA Lda CONMED Europe
Alfa Wassermann S.p.A. Cook Medical
ALTON (Shanghai) Medical Instruments Co., Ltd DDW Digestive Disease Week
ANEMGI onlus Associazione per la Diagnoplex SA
NeUroGastroenterologia e la Motilita` Dr. Falk Pharma GmbH
Gastrointestinale EAES European Association for Endoscopic Surgery
Anrei Medical (Hangzhou) Co., Ltd. EAGEN European Association for
Apollo Endosurgery, Inc. Gastroenterology, Endoscopy and Nutrition
APTALIS PHARMA SAS EASL European Association for the Study of the
ARC Medical Design Ltd Liver
AstraZeneca EB Neuro S.p.A.
BALTON Sp. z o.o. ECCO European Crohns and Colitis Organisation
Bedfont Scientic Ltd ECOSTER SYSTEMS
BIOCODEX EDS European Digestive Surgery
Biohit Oyj EFISDS International Society of Digestive Surgery
Boehringer Ingelheim Pharma GmbH & Co. KG (European Federation)
Boston Scientic International S.A. EFSUMB European Federation of Societies for
BOWA-electronic GmbH & Co. KG Ultrasound in Medicine and Biology
Bracco Diagnostics Inc. EGYPT GASTRO HEP
BUHLMANN Laboratories AG EHSG European Helicobacter Study Group
CALPRO AS ELLA-CS, s.r.o.
CapsoVision Inc. Elsevier Ltd.
CBC (Europe) GmbH EMcision International Inc.
Celltrion Healthcare Co., Ltd. EMED SP. Z O. O. SP. K.
viii United European Gastroenterology Journal 2(5S)

ENDALIS SARL Life Partners Europe

Endo Live Roma 2014 M.I. Tech Co., Ltd
EndoAid Ltd. Mauna Kea Technologies
EndoChoice GmbH Mayoly Spindler
EndoClot Plus Inc. Mederi Therapeutics Inc.
ENDO-Flex GmbH Medical Innovations Group
Endoscopic Ultrasound Editorial Oce c/o Spring Medical Measurement Systems B.V.
Media Publishing Co. Medi-Globe GmbH
Endoscopy/ESGE MEDIGUS LTD
EPC European Pancreatic Club MEDITHEQUE Bookshop
Era Endoscopy S.r.l. Medivators BV
ERBE Elektromedizin GmbH medwork GmbH
ESCP European Society of Coloproctology Micro-Tech (Nanjing) Co., Ltd.
ESDO European Society of Digestive Oncology MOBILWAVE Tecnologias de Informacao
ESGAR European Society of Gastrointestinal and MTW-Endoskopie W. Haag KG
Abdominal Radiology NDS Surgical Imaging BV
ESGE European Society of Gastrointestinal NIKKISO Europe GmbH
Endoscopy NISO BIOMED srl
ESNM European Society of Neurogastroenterology NPS Pharma International Ltd.
and Motility Omega Medical Imaging
ESPCG European Society for Primary Care Origin Sciences Limited
Gastroenterology Orion Diagnostica Oy
ESPGHAN European Society for Paediatric Otsuka Pharmaceutical Europe Ltd.
Gastroenterology, Hepatology and Nutrition Ovesco Endoscopy AG
Eurodigest PAULDRACH medical GmbH
European Board of Gastroenterology & Hepatology Peter Pugbeil GmbH
Eurospital S.p.A. PRO.MED.CS Praha a.s.
Exact Sciences RB
FENDO Medizintechnik e.K. Robarts Clinical Trials
Ferring International Center S.A. Rome Foundation
Finemedix Co., Ltd. Ruhof Corporation
Fischer ANalysen Instrumente GmbH S&G Biotech Inc.
Fractyl Laboratories Inc. SAGE Publications
GE Healthcare Sandhill Scientic, Inc.
Gebr. Martin GmbH & Co. KG KLS Martin Group Shenyang Shenda Endoscope Co., Ltd.
Genetic Analysis AS Soluscope SAS
G-FLEX Europe Sprl SonoScape Co., Ltd.
GI Supply Sony Professional Solutions Europe
GID Germany GmbH Spatz FGIA, Inc.
Hangzhou AGS MedTech Co., Ltd. STEELCO S.p.A.
Holy Stone Biotech Co., Ltd. Sucampo AG
HUGER Endoscopy Instruments Co; Ltd SUMITOMO BAKELITE Co., Ltd.
Immundiagnostik AG SuperSonic Imagine
INFAI GmbH Taewoong Medical Co., Ltd.
Institut Allergosan, Pharmazeutische Produkte The Standard Co., Ltd
Forschungs- u. vertriebs GmbH Thermo Fisher Scientic Phadia GmbH
IntroMedic Co., Ltd Tillotts Pharma AG
Ipsen Pharma US Endoscopy
ISDE International Society for Diseases of the WEO World Endoscopy Organization
Esophagus WGO World Gastroenterology Organisation
Karl Storz GmbH & Co. KG Wiley
Kellogg Wilson Instruments (SHA) Co., Ltd
KIBION AB Wisepress Medical Bookshop
La Lettre de lHepato-Gastroenterologue Ziehm Imaging GmbH
Laboratories Casen Fleet
Contents
Letter of Thanks . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v
Thanks to Partners, Sponsors and Exhibitors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii

UEG Week 2014 Oral Presentations

Monday, October 20, 2014
Opening Plenary Session Hall A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A1
Failed ERCP: What options do we have? Hall E . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A2
Altered intestinal microbiota composition in IBS: Does it affect clinical practice? Hall G/H . . . . . . . . . A3
Conventional therapy for IBD: Room for improvement Hall I/K . . . . . . . . . . . . . . . . . . . . . . . . . . . . A3
Advances in ERCP Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A5
Cellular crosstalk in pancreatic cancer Hall O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A7
Clinico-pathological features of GI cancer Lounge 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A9
Small bowel imaging and endoscopic interventions Lounge 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A10
New thoughts on functional dyspepsia Hall B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A12
Clinical challenges in hepatitis C virus therapy Hall F1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A12
New imaging techniques in colonoscopy Hall F2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A15
Late breaking digestive oncology abstracts Hall I/K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A17
New imaging tools for IBD Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A19
Imaging in pancreatic cancer: Still a challenge Hall O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A21
Clinical and molecular factors in oesophago-gastric cancer outcomes Lounge 5 . . . . . . . . . . . . . . . . . A22
Obesity and the gut Lounge 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A24
Hot topics from Latin America Hall F1 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A26
New diagnostic modalities in upper GI endoscopy Hall G/H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A26
Late breaking clinical trials in digestive diseases Hall I/K. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A28
IBD: New therapeutics for specific targets Hall L/M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A30
Immunopathogenesis of pancreatitis and hepatitis Hall R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A31
Progress in gastric and duodenal endotherapy Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A33
Changing landscape of H. pylori infection Hall O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A35
Minimally invasive interventions in the pancreas Lounge 5. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A36
Cirrhosis and non-invasive diagnosis of fibrosis Lounge 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A38

Tuesday, October 21, 2014

Therapy update: GORD Hall D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A40
Update on the management of acute pancreatitis Hall B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A40
Colorectal cancer screening: The future Hall C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A40
 x

Challenges in coeliac disease and gluten-related disorders Hall F1. . . . . . . . . . . . . . . . . . . . . . . . . . . A41

Management of complicated Crohns disease Hall F2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A41
Optimising lesion detection in colonoscopy Hall G/H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A42
Old and new biomarkers in IBD Hall I/K. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A44
Implications of molecular pathogenesis on endoscopic therapy for Barretts oesophagus Hall L/M . . . A47
Risk factors and management of upper GI bleeding Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A48
Gastric cancer: New insights into pathogenesis and management Lounge 5 . . . . . . . . . . . . . . . . . . . . A51
Hot topics in cholestatic and pancreatic diseases Lounge 6. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A53
Inflammation and cell death in GI disorders Hall R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A56
Towards better understanding of IBD pathogenesis Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A58
Novel endoscopic interventions in the oesophagus Hall O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A60
Upper GI motility diseases: Mechanisms, diagnostics and new treatment options Lounge 5. . . . . . . . . A61
Peptic ulcer disease: Risk factors and treatment Lounge 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A63
New drugs in IBD Hall C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A65
IBD: Dysplasia and cancer Hall I/K. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A68
Normal and abnormal cross-talk at the mucosal border:
Relevance for GI function and dysfunction Hall L/M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A70
Update on capsule endoscopy Hall N. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A71
From risk stratification to ablation in Barretts oesophagus Hall O. . . . . . . . . . . . . . . . . . . . . . . . . . A73
Challenges in the treatment of pancreatic and biliary tract cancer Lounge 5 . . . . . . . . . . . . . . . . . . . A74
Colorectal cancer: Novel mechanisms, novel targets Lounge 6 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A76
Video Case Session Hall A . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A78
How to manage IBD in 2014 Hall D . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A80
Novel approaches for the treatment of liver metastases Hall B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A82
Evidence-based treatment of achalasia Hall C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A83
Endoscopic management of early colorectal neoplasia Hall G/H . . . . . . . . . . . . . . . . . . . . . . . . . . . . A83
Safety in endoscopy Hall I/K. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A84
Novel insights into the immunopathogenesis of colitis Hall R. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A86
IBD: Epidemiology and disease outcomes Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A88
Cystic pancreatic lesions: A clinical dilemma Hall O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A90
Visceral sensitivity: Clinical and translational science aspects Lounge 5 . . . . . . . . . . . . . . . . . . . . . . . A92
Liver steatosis: The road from inflammation to fibrosis Lounge 6. . . . . . . . . . . . . . . . . . . . . . . . . . . A93

Wednesday, October 22, 2014

Best use of immunosuppressants in IBD Hall E. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A95
Challenges in GORD Hall B . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A96
Advances in diagnosis and management of liver nodules Hall C . . . . . . . . . . . . . . . . . . . . . . . . . . . . A97
xi

New frontiers in Barretts oesophagus Hall F2 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A98

Novel approaches to rectal cancer Hall G/H . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A98
Colorectal cancer screening: Strategies and outcomes Hall I/K . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A99
Genetic information in upper GI cancer: Already clinically relevant? Hall L/M . . . . . . . . . . . . . . . . A102
Diagnosis and treatment of constipation and faecal incontinence Hall R . . . . . . . . . . . . . . . . . . . . . A102
Update on endoscopic resection of early colorectal neoplasia Hall N. . . . . . . . . . . . . . . . . . . . . . . . A105
Pathophysiology and management of pain and fibrosis in chronic pancreatitis Hall O . . . . . . . . . . . A108
Hot topics in small intestinal diseases Lounge 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A111
Advanced colonoscopic imaging Hall C . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A114
Endoscopy meets pathology: Early neoplasia in the upper GI tract Hall I/K . . . . . . . . . . . . . . . . . . A114
Therapeutic drug monitoring in IBD Hall R . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A115
Improving safety of ERCP Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A117
Shedding new light on microbiota in IBD Hall O . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A118
Clinical perspectives on gastric malignant tumours Lounge 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A120
Targeting new pathways in IBD Hall L/M . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A121
Symptoms in patients with functional gastrointestinal disorders Hall R . . . . . . . . . . . . . . . . . . . . . . A124
Innovations in biliary stenting Hall N . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A126
Eosinophilic oesophagitis and other immune mediated upper GI diseases Hall O . . . . . . . . . . . . . . . A127
Viral hepatitis, cytokines and liver regeneration Lounge 5 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A129

UEG Week 2014 Poster Presentations

Monday, October 20, 2014
POSTER PLUS VIDEO I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A132
LIVER & BILIARY I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A134
PANCREAS I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A154
ENDOSCOPY AND IMAGING I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . A162
SURGERY I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A196
IBD I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A199
PAEDIATRIC: LOWER GI Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A227
OTHER LOWER GI DISORDERS I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . A231
NERVE GUT AND MOTILITY I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . A248
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS I Poster Exhibition Hall XL . . . A251
H. PYLORI I Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A272
SMALL INTESTINAL I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A277
NUTRITION I Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A281
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE I Poster
Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A288
 xii

Tuesday, October 21, 2014

POSTER PLUS VIDEO II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A291
LIVER & BILIARY II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A293
PAEDIATRIC: LIVER, BILIARY AND PANCREAS Poster Exhibition Hall XL . . . . . . . . . . . . A312
PANCREAS II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A313
ENDOSCOPY AND IMAGING II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . A321
SURGERY II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A355
IBD II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A358
OTHER LOWER GI DISORDERS II Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . A386
NERVE GUT AND MOTILITY II Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . A404
IMMUNOLOGY AND MICROBIOLOGY Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . A407
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS II Poster Exhibition Hall XL . . A409
H. PYLORI II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A428
SMALL INTESTINAL II Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A432
NUTRITION II Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A436
PAEDIATRIC: UPPER GI Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A439
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE II
Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A444

Wednesday, October 22, 2014

POSTER PLUS VIDEO III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A446
LIVER & BILIARY III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A448
PANCREAS III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A467
ENDOSCOPY AND IMAGING III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . A475
SURGERY III Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A510
IBD III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A513
OTHER LOWER GI DISORDERS III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . A540
NERVE GUT AND MOTILITY III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . A562
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS III Poster Exhibition Hall XL . A566
H. PYLORI III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A585
SMALL INTESTINAL III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A590
NUTRITION III Poster Exhibition Hall XL . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A598
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE III
Poster Exhibition Hall XL. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A601

Author Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . A606

UEG Week 2014 Oral Presentations
MONDAY, OCTOBER 20, 2014 8:0010:30
OPENING PLENARY SESSION HALL A_____________________
OP001 HELICOBATER PYLORI ALTERS STEM CELL HOMEOSTASIS
BY DIRECT COLONIZATION OF THE GASTRIC GLANDS
M. Sigal1,2,*, M.R. Amieva2,3
1
Gastroenterology and Hepatology, Charite University Medicine, Berlin, Germany,
2
Microbiology and Immunology, Stanford University, 3Pediatrics, Infectious
Diseases, Stanford School of Medicine, Stanford, United States
Contact E-mail Address: msigal@stanford.edu
INTRODUCTION: Helicobater pylori (Hp) is a bacterial pathogen that colonizes
the human stomach, and is the main risk factor for gastro-duodenal ulcers and
gastric cancer. Hp are found in close proximity to the surface of the stomach
epithelium either as a free-swimming population in the gastric mucus or adhered
to epithelial cells. The attached bacteria are known to alter cell signalling and
behavior though different virulence factors.
AIMS & METHODS: While the effects of attachment have been studied exten-
sively in vitro, we aimed to study the localization and pathological relevance of
the direct interaction of bacteria with the gastric epithelum, and in particular
with gastric stem cells, in vivo. We utilized a murine model of Hp infection using a
mouse adapted Hp strain PMSS1. We developed a novel technique to visualize
Hp in mouse stomachs using 3D confocal microscopy. In addition, full thickness
stomach surgical specimens were used to visualize bacteria in human stomachs.
Lgr5eGFP mice were used to study the interaction of Hp with stem cells.
Lgr5eGFPCreER RosadtTomato compound heterozygous mice were used for
lineage tracing experiments.
RESULTS: We discovered that Hp colonize the epithelial surface deep in the
gastric glands where they grow as distinct microcolonies associated with the
epithelial junctions. In addition, using EdU or mitosis labeling, we find that
the gland-associated H. pylori directly colonize the surface of progenitor cells.
In addition to the data obtained in our murine model, we document gland-
associated Hp microcolonies deep in the human gastric glands in association
with the epithelial junctions and with dividing precursor cells. We hypothesized
that direct colonization of precursor/stem cells may drive pathological responses.
Using quantitative microscopy we mapped the distribution of bacteria in the
glands of the antrum vs the corpus. We found that the location of bacteria in
the glands correlates with hyperplastic and metaplastic lesions. Using Lgr5eGFP
mice, we observerd a direct interaction of Hp with gastric Lgr5 expressing stem
cells. Infection induced an expansion of the stem cell number. In addition, lineage
tracing experiments revelaed a significantly higher number of cells being gener-
ated from Lgr5 expressing stem cell in infected animals compared to uninfected
controls. The acclerated tracing tightly correlated with the bacteria in the gastric
glands.
CONCLUSION: Taken together our data reveals that bacteria directly interact
with progenitor and stem cells in the stomach, induce hyper-proliferation and
alter the stem cell homeostasis of the colonized glands.
Disclosure of Interest: None declared
OP002 RANDOMIZED COMPARISON OF SURVEILLANCE
INTERVALS AFTER COLONOSCOPIC REMOVAL OF
ADENOMATOUS POLYPS: THE JAPAN POLYP STUDY
T. Matsuda1,*, T. Fujii2, Y. Sano3, S.-E. Kudo4, Y. Oda5, K. Kaneko6,
K. Hotta7, T. Shimoda1, Y. Saito1, N. Kobayashi8, K. Konishi9, H. Ikematsu6,
H. Iishi10, K. Kobayashi11, Y. Yamaguchi7, K. Hasuda12, T. Shinohara13,
H. Ishikawa14, Y. Murakami15, H. Taniguchi1, S. Yoshida16 on behalf of the
Japan Polyp Study Workgroup
1
National Cancer Center Hospital, Tokyo, 2TF Clinic, Tokyo, 3Sano Hospital,
Kobe, 4Showa University Northern Yokohama Hospital, Yokohama, 5Oda GI
Endoscopy and Gastroenterology Clinic, Kumamoto, 6National Cancer Center
Hospital East, Kashiwa, 7Shizuoka Cancer Center, Mishima, 8Tochigi Cancer
Center, Tochigi, 9Showa University School of Medicine, Tokyo, 10Osaka Medical
Center for Cancer and Cardiovascular Diseases, Osaka, 11Kitasato University East
Hospital, Sagamihara, 12Hattori GI Endoscopy and Gastroenterology Clinic,
Kumamoto, 13Saku Central Hospital, Saku, 14Kyoto Prefectural University of
Medicine, Kyoto, 15Toho University School of Medicine, Tokyo, 16Aomori
Prefectural Central Hospital, Aomori, Japan
Contact E-mail Address: tamatsud@ncc.go.jp
INTRODUCTION: The National Polyp Study (NPS) Workgroup recommended
an interval of at least 3 years between colonoscopic removal of all adenomatous
polyps and the follow-up examination in 1993. However, the study was con-
ducted prior to the recent studies documenting the importance of nonpolypoid
colorectal neoplasms (NP-CRNs).
AIMS & METHODS: The aim of this study was to assess whether follow-up
colonoscopy using high-definition colonoscope at 3 years as well as at both 1 and
3 years would detect important lesions including NP-CRNs. The Japan Polyp
Study (JPS), a multicenter randomized control trial conducted at 11 participating
centers was initiated in 2003. Patients were eligible if they have had two complete
United European Gastroenterology Journal
2(5S) A1A131
! Author(s) 2014
Reprints and permissions:
sagepub.co.uk/journalsPermissions.nav
DOI: 10.1177/2050640614548974
ueg.sagepub.com
RESULTS: 3926 patients mean age 57.3 years (40-69), 2440 (62%) males with no
history of FAP, HNPCC, IBD or personal history of polypectomy with unknown
histology, no history of colectomy, participated in this study. Of these, 2166
patients who had 1st-CS and 2nd-CS, with removal of all adenomatous polyps
were randomly assigned into two groups (1087 to two-exam and 1079 to one-
exam group). The results of the non-inferiority test were significant (p0.017 in
per-protocol, p0.001 in intention-to-treat). In per-protocol analysis (701 in two-
exam vs 763 in one-exam group), the IL incidences of two groups were similar
(1.7% vs 2.1%). Among all ILs, there were 6 LGD 10mm, 5 HGD and 1
invasive cancer in two-exam group, 9 LGD 10mm and 8 HGD in one-exam
group, respectively. Morphologically, NP-CRNs were dominant (62%, 18/29)
and most of them were classified into laterally spreading tumor non-granular
(LST-NG) type; (83%, 15/18). According to the univariate analysis, the number
of adenomas ( 5) [RR:2.84 (1.37-5.91)] and family history of colorectal cancer
[RR:2.39 (1.07-5.35)] were considered as significant risk factors of ILs.
CONCLUSION: Even if NP-CRNs are considered, an interval of at least 3 years
between endoscopic removal of adenomatous polyps and follow-up examination
is feasible. Two complete colonoscopies before randomization provided us a
lower incidence of ILs compared with NPS data (3.3%). Further investigation
will be necessary to evaluate whether the detection of NP-CRNs, especially LST-
NG type determines a change in the prevention of colorectal cancer.
Disclosure of Interest: T. Matsuda Financial support for research from: Grant
from the Japanese Ministry of Health, Labor and Welfare, T. Fujii: None
declared, Y. Sano: None declared, S.-E. Kudo: None declared, Y. Oda: None
declared, K. Kaneko: None declared, K. Hotta: None declared, T. Shimoda:
None declared, Y. Saito: None declared, N. Kobayashi: None declared, K.
Konishi: None declared, H. Ikematsu: None declared, H. Iishi: None declared,
K. Kobayashi: None declared, Y. Yamaguchi: None declared, K. Hasuda: None
declared, T. Shinohara: None declared, H. Ishikawa: None declared, Y.
Murakami: None declared, H. Taniguchi: None declared, S. Yoshida: None
declared
OP003 LYMPHOTOXIN PROMOTES ACINAR CELL
REPROGRAMMING AND ACCELERATES PRE-NEOPLASTIC
CONVERSION IN KRAS INDUCED PANCREATIC TUMORIGENESIS
G.M. Seleznik1,*, T. Reding1, S. Sonda1, M. Heikenwaelder2, R. Graf1
1
Swiss HPB Center, University Hospital Zurich, Zurich, Switzerland, 2Institute of
Virology, Technische Universitat MunchenHelmholtz Zentrum Munchen,
Munich, Germany
Contact E-mail Address: gittamaria.seleznik@usz.ch
INTRODUCTION: Pancreatic inflammation is a well-known risk factor for
pancreatic ductal adenocarcinoma (PDAC) development in humans. PDAC
initiation is linked to activating mutations in KRAS oncogene. An early event
in the malignant transformation is acinar cell transdifferentiation, the formation
of acinar-to-ductal metaplasia (ADM), which can give rise to pancreatic intrae-
pithelial neoplasia (PanIN), the most common PDAC precursor. Importantly,
ADM formation is also observed during pancreatitis both in humans and
rodents. Despite the crucial role played by ADM in the pathophysiology of
the pancreas, the regulatory mechanisms governing the dynamics of this trans-
differentiation are not completely defined.
AIMS & METHODS: The aim of this study is to explore the inflammatory
mechanisms promoting ADM regression and PanIN development. Therefore,
we established a new genetic model (LTKP) by intercrossing the commonly
used p48/Cre;Kras/G12D (KP) model for pancreatic tumorigenesis, to a novel
transgenic mouse developing spontaneous pancreatitis, due to pancreas specific
Lymphotoxin (LT) overexpression. Immunohistochemistry and RT-PCR were
used to obtain an inflammatory signature. In-vitro experiments were performed
to investigate the direct role of LT in ADM development.
RESULTS: Lymphotoxin overexpression in mice harbouring a constitutively
active form of Kras mutation in the pancreas (LTKP) dramatically accelerates
the development of premalignant PanIN lesions compared to KP animals.
Already after 6 weeks increased cell proliferation, extensive ADM and PanIN
development was observed in LTKP mice. This coincides with a significant upre-
gulation of inflammatory genes and increased ratio of active (GTP-bound) Kras.
These molecular and phenotypic changes are only observed around 16 weeks in
Kras animals. In-vitro, acinar cells isolated from LTKP mice formed significantly
faster ADMs than KP cells. In contrast to wild type acinar cells, cells overex-
pressing Lymphotoxin, without the presence of Kras mutation could also spon-
taneously transdifferentiate.
colonoscopies (1st-CS and 2nd-CS: interval; 1 year) with removal of all neoplas-
tic lesions. Following this they were randomly assigned to have follow-up colo-
noscopy at 1 and 3 years (two-exam group) or at 3 years only (one-exam group).
Index lesions (ILs) were defined as any low-grade dysplasia (LGD) 10mm,
high-grade dysplasia (HGD) or invasive cancer. Moreover, the risk ratios
(RRs) of ILs were estimated in association with age, gender, family history
and endoscopic findings before randomization.
CONCLUSION: Our data point towards the involvement of LTR-signalling in
the initiation of pancreatic cancer. Lymphotoxin is a critical component of spon-
taneous and pancreatitis-accelerated PDAC precursor formation, by (1) inducing
inflammatory environment and by (2) regulating acinar cell transdifferentiation,
leading to accelerated pre-malignant PanIN lesion development.
Disclosure of Interest: None declared
A2
OP004 A RANDOMIZED CLINICAL TRIAL OF OBSERVATIONAL
VERSUS ANTIBIOTIC TREATMENT FOR A FIRST EPISODE OF
UNCOMPLICATED ACUTE DIVERTICULITIS
L. Daniels1,*, C. Unlu1, N de Korte2, S. van Dieren3, H.B. Stockmann4,
B.C. Vrouenraets5, E.C. Consten6, J.A. van der Hoeven7, Q.A. Eijsbouts2,
IF. Faneyte8, M.G. Dijkgraaf3, M.A. Boermeester1 on behalf of Collaborators of
the DIABOLO Trial
1
Surgery, Academic Medical Center - University of Amsterdam, Amsterdam,
2
Surgery, Spaarne Hospital, Hoofddorp, 3Clinical Research Unit, Academic
Medical Center - University of Amsterdam, Amsterdam, 4Surgery, Kennemer
Gasthuis Hospital, Haarlem, 5Surgery, Sint Lucas Andreas Hospital, Amsterdam,
6
Surgery, Meander Medical Center, Amersfoort, 7Surgery, Albert Schweitzer
Hospital, Dordrecht, 8Surgery, Ziekenhuisgroep Twente Hospital, Almelo/
Hengelo, Netherlands
Contact E-mail Address: l.daniels@amc.uva.nl
INTRODUCTION: Do antibiotics improve the course and/or outcome of a first
episode of uncomplicated acute diverticulitis? To date, most guidelines advise the
use of antibiotics1-3. One previous randomized trial4 has been performed but
included about 40% recurrent diverticulitis, and did not change clinical practice.
Whether or not antibiotics are used varies between countries and disciplines5-7.
Importantly, use of antibiotics can lead to adverse effects and its overuse results
in escalating antimicrobial resistance8.
AIMS & METHODS: We conducted a multicenter, randomized, controlled,
pragmatic, noninferiority trial (DIABOLO trial, NCT01111253) of an observa-
tional versus an antibiotic treatment strategy in patients with a CT-proven diag-
nosis of a first episode of acute, left-sided, uncomplicated (Hinchey 1A or 1B)
diverticulitis. The primary endpoint was the time-to-recovery at 6 months as
assessed by a patient diary. Main secondary endpoints were readmission rate,
occurrence of complicated, recurrent and ongoing diverticulitis, need for sigmoid
resection and other (non-)surgical interventions, adverse events and mortality.
An intention-to-treat analysis was done.
RESULTS: In 22 centers, 528 diverticulitis patients were analyzed after rando-
mization to an observational or antibiotic treatment strategy. In the observa-
tional arm 13% was treated on outpatient basis, and 95% did not receive
antibiotics during the study period. At 6 months follow-up recovery occurred
in 234 (89.3%) patients assigned to observation and in 248 (93.2%) patients
assigned to antibiotics (P0.183). Median time-to-recovery was comparable
among observational and antibiotic treatment strategies (14 days [IQR, 6 to
35] vs. 12 days [IQR, 7 to 30]; P0.291 by the Log-Rank test), with a hazard
ratio for recovery of 0.910 (upper limit one-sided 95 % CI, 1.059; P0.151). We
found no significant differences between both treatment strategies for main sec-
ondary endpoints.
CONCLUSION: Observational treatment of uncomplicated acute diverticulitis,
even without primary admission, does not result in an increase in time-to-recov-
ery and readmission rate, nor in higher rates of complicated, recurrent or
ongoing diverticulitis or sigmoid resection. Observational treatment is without
short-term or long-term repercussions, which indicates that antibiotic treatment
can safely be omitted in uncomplicated diverticulitis.
REFERENCES
1. Feingold et al. Dis Colon Rectum 2014.
2. Agresta et al. Surg Endosc 2012.
3. Sartelli et al. World J Emerg Surg 2011.
4. Chabok et al. Br J Surg 2012.
5. Van de Linde et al. Ned Tijdschr Heelk 1996.
6. De Korte et al. Colorectal Dis 2011.
7. Munikrishnan et al. Dis Colon Rectum 2006.
8. World Health Organization. http://whqlibdoc.who.int/publications/2012/
9789241503181_eng.pdf?ua1 2012
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 11:0012:30
FAILED ERCP: WHAT OPTIONS DO WE HAVE? HALL E_____________________
OP005 SENIOR DISCUSSION REDUCES MORTALITY FOLLOWING
PERCUTANEOUS TRANSHEPATIC CHOLANGIOGRAPHY: A 12-
MONTH PROSPECTIVE AUDIT
D. Subramaniam1,*, M. James2 on behalf of Department of Interventional
Radiology, Nottingham University Hospitals, NHS Trust, Nottingham,
United Kingdom
1
Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom,
2
Department of Gastroenterology, Nottingham University Hospitals NHS Trust,
Nottingham, United Kingdom
Contact E-mail Address: martin.james@nuh.nhs.uk
INTRODUCTION: Percutaneous transhepatic cholangiography (PTC) achieves
effective biliary drainage in proximal biliary obstruction and failed ERCP but
carries significant morbidity and mortality. The 2009 British Society of
Interventional Radiology Audit Report recommends that post-PTC in-hospital
mortality should be under 19.8%.
AIMS & METHODS: The aim of this project was to identify potential causes of
high post-PTC mortality at our tertiary centre and evaluate the impact of PTC on
quality of life. All patients undergoing PTC were prospectively audited in 3
consecutive four-month cycles. Quality of life pre- and 30 days post-PTC was
assessed objectively based on ECOG performance status and subjectively using a
United European Gastroenterology Journal 2(5S)
visual analog scale (VAS). The Trust electronic database and patient case notes
were reviewed for indication, type of intervention, post-PTC complications and
mortality. Senior (consultant) level discussion between physician/surgeon and
radiologist was incorporated into PTC guidelines at the start of the second
cycle and made a mandatory requirement before electronic requesting for PTC
in the third cycle.
RESULTS: 23 patients underwent 32 procedures in the first audit cycle. Total
mortality was 30.4% with an in-hospital mortality of 21.7%. 52% of patients had
single-stage stenting while 35% underwent a two-stage procedure of internal-
external drainage followed by stenting at a later date. 78% of procedures were
discussed at senior (consultant) level and the majority of these were performed as
single-stage interventions. In the second cycle 27 patients underwent 40 proce-
dures. 55% were single-stage stents while 33% were two-stage procedures. Senior
level discussion took place for 80% of procedures. Total mortality remained high
at 29.6% but in-hospital mortality decreased slightly to 18.5%. The third cycle
comprised 20 patients undergoing 30 procedures, of which 45% were single-stage
and 35% were two-stage. Following new electronic requesting protocols senior
level discussion increased to 97%. There was a dramatic decrease in total (and in-
hospital) mortality to 5%. We also found a significant improvement in subjective
quality of life at 30 days post-PTC with similar rates of improvement across all 3
cycles (see table).
Senior Total In-hospital VAS VAS
discussion Mortality mortality pre-PTC post-PTC
(%) (%) (%) (%) (%)
Cycle 1 78 30.4 21.7 27.5 75
(Oct 12 - Jan 13)
Cycle 2 80 29.6 18.5 20 60
(Feb 13 - May 13)
Cycle 3 97 5 5 25 70
(Jun 13 - Sept 13)
CONCLUSION: Appropriate senior level discussion before PTC improves
patient selection and significantly decreases 30-day mortality. However, it did
not decrease the number of two-stage interventional procedures performed in
favour of single-stage stenting. Percutaneous biliary intervention also signifi-
cantly improves quality of life at 30 days in appropriately selected patients and
has an important role in palliation of symptoms in patients with malignant
biliary obstruction.
REFERENCES
1. Uberoi et al. BSIR first biliary drainage and stent audit report. 2009.
2. Sut M, Kennedy R, McNamee J, et al. Long-term results of percutaneous
transhepatic cholangiographic drainage for palliation of malignant biliary
obstruction. J Palliat Med 2010; 13: 1311-1313.
Disclosure of Interest: None declared
OP006 CONTRIBUTION OF EARLY NEEDLE-KNIFE
INFUNDIBULOTOMY IN DIFFICULT ERCP: A PROSPECTIVE
STUDY
R. Alhameedi1, A. Di Fiore1, M. Antonietti1, P. Michel1, P. Ducrotte1,
S. Lecleire1,*
1
Gastroenterology, University Hospital of Rouen, Rouen, France
INTRODUCTION: Difficult commun bile duct (CBD) cannulation remains a
frequent problem in ERCP (approximately 10-15 % depending on the study).
There are several techniques for difficult cannulation of the CBD, including
precut and infudibulotomy procedures. However, the complication rate in
these patient groups seems to be higher than for patients who underwent con-
ventional sphincterotomy.
AIMS & METHODS: The aim of our study was to prospectively assess whether
repetitive attempts of CBD cannulation or infundibulotomy are primarily
involved in the post-ERCP complications and to evaluate the effectiveness of
early infudibulotomy in difficult ERCP.
All the patients who underwent ERCP between 01/01/13 and 06/10/2013 were
included in our prospective study. Patients were divided into 3 groups based on
the timing of CBD cannulation before infundibulotomy (5 5 min, between 5 and
15 min and 15 min). The increase in rate of CBD cannulation with infundibu-
lotomy, the correlation between post ERCP complications and timing of infudi-
bulotomy have been analyzed.
RESULTS: One hundred and thirteen patients were analyzed, 43 patients with a
tumor CBD obstrcution and 70 patients with gallstones. In 80 patients, the
cannulation was obtained by conventional procedure (70.8%). In 30 patients,
infundibulotomy was performed with total success of cannulation in 108 (95.6
%). In 5 patients the cannulation was not possible (3 patients without attempted
infundibulotomy). ERCP complications included 13 cases of post-ERCP pan-
creatitis (PEP), 8 of them for whom the infundibulotomy was done after more
than 15 min of CBD cannulation attempts. In 84.6 % of the patients with a post-
ERCP pancreatitis, the cannulation time lasted more than 15 min. In the 22
patients with a cannulation that lasted more than 15 minutes, 11 PEP occurred
(50 %). There was a significant correlation between the occurrence of PEP and
CBD cannulation 4 15 min (p50.001). There was no case of perforation or
relevant bleeding. Mortality was 0%. We did not observe PEP in patients with an
early infundibulotomy (5 15 min).
United European Gastroenterology Journal 2(5S)
Correlation between PEP and the timing of CBD cannulation
Table to abstract OP006
Cannulation ERCP without ERCP with infundiblotomy
time infundibulotomy (5 patients) (8 patients)
1 to 5 min 20% (1/ 5) 0 Mansfield Magnetic Resonance Centre, University of Nottingham, Nottingham,
5 to 15 min 20 % (1/ 5) 0 Diabetes and Nutritional Sciences, Kings College, London, United Kingdom
4 15 min 60% (3/5) 100% (8/8)
CONCLUSION: Early infundibulotomy is an efficient procedure that increases
the percentage of ERCP success rate from 71% to 96%. PEP occurrence is
correlated to the duration of the CBD cannulation (50% in case of pancreatitis
lasting 15 min). Early infundibulotomy could avoid PEP if used early before 15
min of cannulation.
Disclosure of Interest: R. Alhameedi: no conflict, A. Di Fiore: no conflict, M.
Antonietti: no conflict, P. Michel: no conflict, P. Ducrotte: no conflict, S.
Lecleire: no conflict
MONDAY, OCTOBER 20, 2014 11:0012:30
ALTERED INTESTINAL MICROBIOTA COMPOSITION IN IBS: DOES IT AFFECT CLINICAL
PRACTICE? HALL G/H_____________________
OP007 A MULTI-CENTER, RANDOMIZED, CONTROLLED, SINGLE-
BLIND, COMPARATIVE TRIAL: LOW-FODMAP DIET VERSUS
TRADITIONAL DIETARY ADVICE IN IBS
L. Bohn1,2,*, S. Storsrud1,2, T. LiIjebo3, L. Collin4, H. Tornblom1,2, M. Simren1,2
1
Internal Medicine and Clinical Nutrition, Medicine, 2Centre for Person-Centered
Care (GPCC), Sahlgrenska Academy, Goteborg, 3Department of Nutrition,
Karolinska University hospital, 4Department of Gastroenterology, Sabbatsbergs
hospital, Stockholm, Sweden
Contact E-mail Address: lena.bohn@gu.se
INTRODUCTION: Irritable bowel syndrome (IBS) is characterized by abdom-
inal pain or discomfort in combination with disturbed bowel habit. A diet with
reduced content of fermentable short chain carbohydrates ((Fermentable Oligo-,
Di-, Monosaccharides And Polyols) FODMAP) have been reported as effective
in the treatment of IBS (Halmos et al Gastroenterology 2014), but proof of its
superiority compared to traditional dietary advice in IBS has not yet been
established.
AIMS & METHODS: The aim of the study was to compare the effects on IBS
symptoms of a low-FODMAP diet and traditional dietary advice in patients with
IBS. This study was performed at three Swedish hospitals and recruited adult
patients diagnosed with IBS (Rome III criteria). Symptom intensity was assessed
by use of the IBS Severity Scoring System (IBS-SSS) at randomization (day 0)
and at the end of the four-week treatment period (day 29). An IBS-SSS score of
at least 175 was needed for inclusion. Randomization (1:1) was done with the
patient blinded to the identity of the dietary advice. The instructions were given
in both oral and written form. A low-FODMAP diet implies specific restrictions
of fermentable short chain carbohydrates. Traditional IBSs diet imply small,
frequent meals, to peel and divide foods into pieces, chew thoroughly, boil
food, reduce fatty and spicy foods, legumes, onions, coffee and alcohol.
Carbonated beverages and sweeteners that end with ol should be avoided.
Fiber intake evenly distributed over the day. For the analysis, the patients
were divided into moderate (IBS-SSS 175-300) or severe (IBS-SSS 4300) symp-
tom intensity by use of baseline data. A responder to diet treatment was defined
as a reduction in IBS-SSS by at least 50 comparing day 0 with day 29.
RESULTS: Eighty-two patients completed the screening period. Eight patients
were excluded due to IBS-SSS less than 175 and 9 patients did not finish the
intervention period. A total of 65 patients (54 women; median age 43 years (range
19-68)) completed the full study (32 low-FODMAP, 33 traditional diet). At the
end of the study 18 patients (56%) in the low-FODMAP group were responders
to treatment and 17 (52%) were responders to the traditional IBS diet (p.70).
Equal response was also seen comparing patients with moderate (p.62) and
severe (p.90) IBS. According to IBS-SSS the low-FODMAP diet reduced the
symptom score from 337 (287-382) (median (25th-75th percentile)) to 231 (154-
350) (p.001), and the traditional diet reduced the symptom score from 312 (250-
346) to 240 (171-296) (p5.001). The reduction in IBS-SSS was similar comparing
the two groups (p.64) and also when comparing the individual items of the IBS-
SSS score; abdominal pain severity (p.81) and frequency (p.39), dissatisfac-
tion with bowel habits (p.47) and how symptoms interfered with life in general
(p.69). There was a trend for a larger reduction in abdominal distension in the
traditional diet group (p.08).
CONCLUSION: Dietary advice is efficient in reducing the gastrointestinal symp-
toms of IBS without any difference noted when comparing a low-FODMAP diet
with traditional IBS dietary advice. Further investigations need to be done in
order to find predictors of response to specific dietary regimens.
Disclosure of Interest: None declared
A3
OP008 FASTING COLONIC VOLUME AND BREATH HYDROGEN
INCREASE AFTER THE ADDITION OF A FODMAP TO THE
USUAL DIET OF HEALTHY VOLUNTEERS: THE USE OF MRI TO
MEASURE PHYSIOLOGICAL CHANGES IN THE GI TRACT
G. Major1,*, A. Teale1, S. Pritchard2, L. Marciani1, K. Whelan3, P. Gowland2,
R.Spiller1 on behalf of The University of Nottingham GI MRI Group
1
NIHR Nottingham Digestive Diseases Biomedical Research Unit, 2Sir Peter
3
Contact E-mail Address: giles.major@nottingham.ac.uk
INTRODUCTION: Indigestible fermentable carbohydrates, grouped as
FODMAPs, have been proposed to induce gastrointestinal symptoms. Some,
such as oligofructose (OF), are prebiotics and modify the microbiota. The meta-
bolic activity of the microbiota affected transit time in a mouse model1. This
study hypothesized that dietary supplementation with OF would shorten whole
gut transit time (WGTT) and improve the capacity of the microbiota to meta-
bolise a FODMAP challenge.
AIMS & METHODS: The study was an open-label case series. 16 healthy volun-
teers underwent fasting MRI to assess colonic volume2 and the position of 5
transit markers ingested 24 hours earlier from which WGTT could be calculated3.
Breath hydrogen (H2) and methane (CH4) were also measured. Subjects then
consumed an inulin challenge drink (ICD): 500ml water containing 40g inulin.
Inulin is fermented in the colon and known to increase H2 and colonic volume4.
After ICD subjects could sip water and were given a low FODMAP lunch but no
other food was allowed. 8 hours post-ICD MRI was repeated. Breath measure-
ments were repeated 4 and 8 hours post-ICD. Subjects then supplemented their
usual diet with OF (gift from BENEO, Germany), 5g twice daily, for a week.
Fasting and post-ICD measurements were then repeated. Dietary questionnaires
were completed for the weeks preceding MRIs to assess dietary fructan intake.
RESULTS: Median [IQR] given unless stated as mean [95% C.I.]. Baseline fast-
ing colonic volume (510ml [400-710]) and WGTT (34h [10 45]) were similar to
previous studies of healthy volunteers. The most notable finding was that after
consuming OF for a week there was a mean increase in fasting colonic volume of
94ml [12 177, p0.03]. Fasting H2 (33ppm [987]) increased by mean 39ppm [6
71, p0.02]. No acceleration of WGTT was demonstrated: rather, transit times
increased by 19h [-9 42] but this increase did not reach significance (p0.09,
Wilcoxon). Colonic volumes post-ICD were similar across weeks (mean 726ml
[667-785]). The change from baseline was significant in week 1 but not week 2 due
to the difference in fasting volumes. There was no difference between weeks 1 and
2 in H2 at 4 or 8 hours after ICD. CH4 did not change. Dietary fructan intake was
similar in both weeks (mean 58g/ day).
CONCLUSION: OF increased fasting colonic volumes by 18%. H2 also rose.
This may reflect increased bacterial mass with increased capacity for fermenta-
tion. The suggestion that OF slows WGTT is surprising and warrants further
investigation. MRI can complement research on the microbiota to describe its
impact on gut physiology.
REFERENCES
1. Kashyap et al. Gastroenterology 2013; 144: 967-977.
2. Pritchard et al. Neurogastroenterol Motil 2014; 26: 124-130.
3. Chaddock et al. Neurogastroenterol Motil 2014; 26: 205-214.
4. Murray et al. Am J Gastroenterol 2014; 109: 110-119.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 11:0012:30
CONVENTIONAL THERAPY FOR IBD: ROOM FOR IMPROVEMENT HALL
I/K_____________________
OP009 ST10, A NOVEL ORAL FERRIC IRON, IS AN EFFECTIVE AND
WELL-TOLERATED TREATMENT FOR IRON DEFICIENCY
ANAEMIA IN IBD PATIENTS WHO FAIL TO RESPOND OR
TOLERATE ORAL FERROUS PREPARATIONS: RESULTS FROM
THE PHASE 3 STUDY PROGRAM
C. Gasche1, Z. Tulassay2, T. Ahmad3, A. Stallmach4,*, J. Howell5 on behalf of
The, AEGIS Study Group: ST10 in the treatment of iron deficiency anaemia in
IBD.
1
Medical University of Vienna, Vienna, Austria, 2Semmelweis University,
Budapest, Hungary, 3Royal Devon and Exeter Hospital, Exeter, United Kingdom,
4
Friedrich Schiller University Jena, Jena, Germany, 5Shield Therapeutics Ltd.,
Newcastle Upon Tyne, United Kingdom
Contact E-mail Address: christoph.gasche@meduniwien.ac.at
INTRODUCTION: Iron deficiency anemia (IDA) is common in inflammatory
bowel disease (IBD). Traditional oral ferrous (Fe2) salts, are often poorly tol-
erated and may lead to worsening of IBD symptoms. Ferric (Fe3) iron salts are
well tolerated and have less redox potential compared to ferrous salts, but are
poorly absorbed due to insoluble oxide formation in the gut. ST10 is a novel Fe3
iron that has been chelated with maltol. The chemistry of this product keeps it in
an absorbable state through a range of pH, but readily donates the Fe to a
stronger ligand i.e. the Fe transporter protein. The aim of this study was to
demonstrate the efficacy of oral ST10 over placebo in the treatment of IDA in
subjects with mild-to moderate IBD who have failed to respond, or been intol-
erant to, oral ferrous salts. The primary endpoint was change in hemoglobin (Hb)
from baseline to Week 12.
AIMS & METHODS: This was a double-blind randomised controlled trial of
120 IBD subjects with IDA (Hb 9.5 - 12.0g/dL female, 9.5-13.0g/dL male; and
ferritin 530mg/L). Subjects were randomised to receive oral 30mg ST10 twice a
day for 12 weeks or identical placebo. At the study end all available subjects were
enrolled in a 52 week open label study. In addition to routine safety monitoring
subjects completed Simple Clinical Colitis Activity Index (SCCAI), Crohns
A4
Disease Activity Index (CDAI) and IBD Questionnaires (IBDQ) at baseline and
regular intervals.
RESULTS: 128 subjects were randomised. Baseline Hb, age and gender were
comparable in both groups. The pre-specified analysis plan included the first 120
subjects randomised (60 ST10, 60 Placebo; 67 CD, 53 UC). 101 (87% ST10, 82%
Placebo) completed at least 12 weeks treatment. Mean Hb improved by 2.3g/dL
from 10.9 to 13.2g/dL in the ST10 group and remained at 11.1g/dL in the
Placebo group (p50.0001, ANCOVA). There was no significant worsening in
disease activity scores (SCCAI, CDAI and IBDQ) after 12 weeks of treatment
with ST10 (Table). Adverse events (AEs) were recorded in 58% of ST10 and 72%
of placebo subjects. Gastrointestinal (GI) AEs were observed in 38% and 40%,
respectively. In the ST10 group the most common AEs were abdominal pain
(10%), diarrhoea (7%), constipation (6%) and nasopharyngitis (4%). Study
medication was discontinued due to related AEs in 5 ST10 and 4 Placebo sub-
jects; these were mostly GI related.
ST10 Placebo
Week 0 Week 12 Week 0 Week 12
SCCAI 1.8 2.2 1.5 2.1
CDAI 85 63 105 113
IBDQ 176 180 171 176
CONCLUSION: At 12 weeks of treatment ST10 gave a statistically significant,
and clinically relevant rise in Hb of 2.3g/dL in patients with mild-to-moderate
IDA and IBD who were previously unresponsive or intolerant to oral iron. Over
the study period ST10 was well-tolerated (87% completing 12 weeks of treat-
ment) and did not exacerbate Crohns disease or ulcerative colitis symptoms.
ST10 may provide an alternative to IV iron in IBD patients with IDA who fail
to respond, or who are intolerant of existing oral ferrous therapies.
Disclosure of Interest: C. Gasche: None declared, Z. Tulassay: None declared, T.
Ahmad: None declared, A. Stallmach: None declared, J. Howell Other:
Employee
OP010 PRE-TREATMENT DIFFERENTIAL MICRORNA EXPRESSION
PROFILE IN ULCERATIVE COLITIS PATIENTS ACCORDING TO
THEIR RESPONSE TO CORTICOSTEROIDS
J. Naves1,*, J. Mane2, V Loren2, M. Manosa1, I. Moret3, A. Garcia-
Jaraquemada2, G. Bastida3, B. Beltran3, E. Cabre2, E. Dome`nech2
1
GASTROENTEROLOGY DEPARTMENT, 2HOSPITAL UNIVERSITARI
GERMANS TRIAS I PUJOL, BADALONA, 3HOSPITAL UNIVERSITARI
LA FE DE VALENCIA, VALENCIA, Spain
Contact E-mail Address: navesjuan@gmail.com
INTRODUCTION: Corticosteroids (CS) remain the first-line treatment for mod-
erate-to-severe active ulcerative colitis (UC). However, up to 40% of patients do
not have an adequate response, an event that to date, cannot be predicted yet.
microRNA (miRNA) are small non-coding RNA fragments that modulate gene
expression at posttranscriptional level, thus playing a critical role in many bio-
logical processes. Little is known about the influence of miRNA in the response
to CS in UC.
AIMS & METHODS: To compare the miRNA profile in rectal mucosa of
patients with active UC responding and non-responding to CS.
Methods: Rectal biopsies were obtained from consecutive UC patients before
starting CS therapy for a moderate-to-severe flare. Patients were grouped accord-
ing to clinical response (non-responder moderate or severe activity according to
Montreals classification at day 7 or need for rescue therapy before day 7; respon-
der Less than moderate activity without need for rescue therapy at day 7).
miRNA were identified by means of a sequencing method (TruSeq SmallRNA
kit from Illumina) on those fresh-frozen rectal biopsies that reached a RNA
Integrity Number (RIN) 8. Comparison of miRNA profile between groups
was carried out on the miRanalyzer D.E. tool through DESeq package. Those
miRNA with a fold change  1.5 and adjusted p-value 0.05 were further
studied. Potential targets of selected miRNA were checked in Target Human
Scan database (www.targetscan.org), and their impact on biological activity was
searched in GeneCodis database (http://genecodis.cnb.csic.es). scarce.
RESULTS: 15 out of 24 tissue samples (8 responders and 7 non-responders)
reached a RIN value 8 allowing miRNA sequencing. We found more than
1,300 known miRNA and about 70 new miRNA. Responders to CS had an
up-regulated expression of has-miR-5701 and has-miR-625-3p, and down-
regulated expression of has-miR-1246 and has-miR-1291 as compared to non-
responders. Bioanalysis using miRNA targets database showed up to 2,000
potential targets for the aforementioned miRNA, most of them involved in
MAPK signalling pathways, cytoskeleton organization pathway, and cell differ-
entiation endocytosis and autophagy mechanisms.
CONCLUSION: Patients with active UC not responding to CS show a differ-
ential mucosal miRNA expression profile before starting therapy. These findings
suggest that regulation of gene expression by miRNA might play a role in the
response to treatment in UC patients.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP011 RAC1 POLYMORPHISMS AND THIOPURINE EFFICACY IN
CHILDREN WITH INFLAMMATORY BOWEL DISEASE
R. Lev Tzion1,*, O. Ledder1, P. Renbaum2, R. Mevorach3, N. Algur4, R. Segel2,
A. Karban5,6, E. Koifman7, E. Efrati5,8, A. Muise9,10, D. Turner1
1
Pediatric Gastroenterology, 2Medical Genetics Institute, 3Clinical
Gastroenterology Laboratory, 4Clinical Biochemistry Laboratory, Shaare Zedek
Medical Center, Jerusalem, 5Rappaport Institute for Research in the Medical
Sciences, Technion-Israel Institute of Technology, 6Department of
Gastroenterology, Rambam Health Care Campus, 7Department of
Gastroenterology, 8Clinical Pharmacology Institute, Rambam Health Care
Campus, Haifa, Israel, 9Program in Cell Biology, University of Toronto, 10Division
of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics,
Hospital for Sick Children, Toronto, Canada
Contact E-mail Address: raffilv@szmc.org.il
INTRODUCTION: Thiopurines are effective in approximately one third of
inflammatory bowel disease (IBD) patients; predictors of response may assist
in selecting the most appropriate patients for this intervention. RAC1 is a
GTPase that, when activated, initiates a cascade whose effects include suppres-
sion of T-cell apoptosis. The thiopurine metabolite 6-Thio-GTP binds to and
suppresses Rac-1, thereby increasing apoptosis. A genetic association has been
demonstrated between two RAC1 single nucleotide polymorphisms (SNPs) and
ulcerative colitis (UC) (rs10951982 and rs4720672). A different SNP (rs34932801)
was recently found to be associated with poorer response to thiopurines in adult
Crohns disease (CD) patients. We aimed to determine whether these SNPs in the
RAC1 gene are associated with response to thiopurines in children with IBD.
AIMS & METHODS: 59 children with IBD were enrolled to this 1-year pro-
spective cohort study at the time of commencing thiopurines (mean age 12.7 
4.1 years, 37 (63%) males, median disease duration 4.5 (IQR 0.7-17.4) months, 47
(80 %) CD and 9 (15 %) UC). Response to treatment was assessed on standar-
dized forms at 4 and 12 months thereafter. Patients receiving concomitant anti-
TNF or tacrolimus were excluded. Children were genotyped for the RAC1 SNPs
rs10951982 and rs4720672 using Real-time PCR TaqMan assays, and for
rs34932801by direct sequencing. The primary outcome was steroid-free remission
at 12 months without the need for treatment escalation.
RESULTS: Genotyping results are displayed in the table below:
SNP Wild Type (WT) n (%) Heterozygous n (%) Homozygous n (%)
rs10951982 41 (69) 15 (25) 3 (5)
rs4720672 45 (76) 12 (20) 2 (3)
rs34932801 45 (90) 5 (10) 0
There was no association between genotype and disease type. Baseline PGA was
similar for all genotypes except for rs4720672 homozygotes, who had a lower
baseline PGA than WT (p 0.003). At 12 months, 16/41 (39%) WT and 8/15
(53%) heterozygotes for rs10951982 were in remission (p0.38), while 18/45
(40%) WT and 7/12 (58%) heterozygotes for rs4720672 were in remission
(p0.33); 22/45 (49%) WT and 2/5 (40%) heterozygotes for rs34932801 were
in remission (p1.0). All 3 homozygotes for the former 2 SNPs were in remission.
CONCLUSION: These three Rac1 SNPs of RAC1 were not found to be asso-
ciated with 1-year response to thiopurines in a prospective study of pediatric
IBD.
Disclosure of Interest: None declared
OP012 DIFFERENT PROFILE OF EFFICACY OF THIOPURINES IN
ULCERATIVE COLITIS AND CROHNS DISEASE
A. Testa1,*, A. Rispo1, M. Rea1, G.D. De Palma1, M. Diaferia1, D. Musto1,
F. Sasso1, N. Caporaso1, F. Castiglione1
1
Clinical Medicine and Surgery, University "Federico II" of Naples, Naples, Italy
INTRODUCTION: Azathioprine (AZT) and 6-mercaptopurine (6-MP) are
effective drugs in treating ulcerative colitis (UC) and Crohns disease (CD) as
they can induce/maintain clinical remission (CR) and mucosal healing (MH) in
steroid-dependent patients. Nevertheless, even if trials and meta-analyses have
confirmed the efficacy of thiopurines in UC and CD, studies directly investigat-
ing a possible different profile of efficacy in UC in comparison with CD are
AIMS & METHODS: To explore the rate of CR and MH in UC patients treated
by thiopurines compared to that of subjects with CD. From September 2011 to
April 2014 we performed an observational longitudinal study evaluating steroid-
free CR and MH in all UC and CD patients who would complete 2 years of
maintenance treatment with thiopurines (AZT 2-2.5 mg/kg/day; 6-MP 1-1.5 mg/
kg/day). Patients characteristics were classified according to the ECCO guide-
lines. CR and MH were assessed before starting treatment and 2 years later by
Mayo score for UC (CR Mayo score 52; MH Mayo sub-score 51); CR and
MH were assessed at same time-points by Crohns disease activity index
(CRCDAI5 150) and Simplified Endoscopic Score for Crohns Disease
(MHSES-CD 52) for CD. Statistical analysis was performed using chi-
square, MannWhitney U test and odd ratio (OR) where appropriate. To test
the concordance between CR and MH in UC and CD, the Cohens k measure
was applied. Regarding the differences in outcomes for CR and MH we esti-
mated that a total sample size of 120 patients would allow detection of a 20%
difference between the 2 groups. A p value lower than 0.05 was considered
significant.
RESULTS: The study included 70 patients with UC (AZT/6-MP60/10; M/
F37/33; mean age39 years; E10, E224, E346; mean baseline Mayo
score8.5) and 70 subjects with CD (AZT/6-MP62/8; M/F 39/31; mean
age33 years; L134, L226, L310; B154, B210, B36; mean baseline
United European Gastroenterology Journal 2(5S)
CDAI290) treated with thiopurines for 2 years. At the end of the study, steroid-
free CR was recorded in 43 patients with UC and 37 with CD (61% vs 53%;
p0.3). MH was obtained in 38 patients with UC and 17 with CD (54% vs 25%;
p50.01; O.R.4.5). The concordance between CR and MH was higher in UC
patients than in subjects with CD (k0.71 in UC; k0.41 in CD).
CONCLUSION: Thiopurines are equally effective in maintaining steroid-free
clinical remission in both UC and CD even if with a better profile of efficacy
in UC in terms of mucosal healing. Our data confirm the higher concordance
between clinical and endoscopic findings in UC compared to that observed in CD
patients.
Disclosure of Interest: None declared
OP013 RANDOMIZED CONTROLLED TRIAL COMPARING THE
EFFICACY OF MEASALAMINE AND ORAL STEROIDS IN
PATIENTS WITH MODERATELY ACTIVE ULCERATIVE COLITIS
A. Raj1,*, Y.R. Reddy1, S.K. Sinha1, C. Vaishnavi1, K.K. Prasad1,
M.L. Thakur1, P.K. Siddappa1, K. Singh1, R. Kochhar1
1
Gastroenterology, Postgraduate Institute of Medical Education and
Research(PGIMER), Chandigarh, India
Contact E-mail Address: dr_kochhar@hotmail.com
INTRODUCTION: The treatment of active ulcerative colitis (UC) has been
aimed at the alleviation of symptoms. However, mounting evidence suggests
mucosal healing better marker of long-term outcomes.
AIMS & METHODS: To compare the efficacy of oral mesalamine with that of
oral prednisolone in patients with moderately active ulcerative colitis (UC).
In this open label randomized controlled study between June 2012 and December
2013 consecutive patients of moderately active UC were randomly assigned to
two treatment groups. One group (ASA) received mesalamine tablets 800mg, two
tablets TID (total dosage-4.8gm/day) and the other group (CS) received predni-
solone in tapering doses (40mg OD for 1 week, then 30mg for next 1 week and
then 20mg for next 4 weeks). All patients were followed for 6 weeks. Mayo score,
sigmoidoscopy with biopsy, and fecal calprotectin (FC) were determined at the
baseline and at the end of treatment. Mucosal healing was defined as decrease in
sigmoidoscopy subscore to 1. Clinical response was defined as a decrease of 3
points from the baseline Mayo score. Clinical remission was defined as achieve-
ment of Mayo score 2. Data was recorded in excel sheet and statistical analysis
was done using SPSS v17.0
RESULTS: Twenty nine patients received mesalamine and 25 patients received
steroids. Mucosal healing was achieved in 19 (65.5%) of the patients in ASA
group and 17 (68%) of the patients in CS group (p0.847). There was significant
improvement in Mayo score from 8.51.2 to 3.51.7 in ASA group as well as
from 8.11.6 to 3.11.8 in CS group (p0.001). Clinical response was achieved
in 26 (89.7%) patients in ASA group and 23 (92%) patients in the CS group.
Clinical remission was achieved in 8 (27.6%) patients in ASA group and 12
(48%) patients in the CS group. There was no statistically significant difference
between ASA and CS groups with regard to treatment response or remission.
Total histopathology score in CS group decreased from 11.92.4 to 8.13
(p0.001), but at the end of treatment total score in both ASA and CS groups
was not significantly different from each other (9.73.4 vs 8.13; p0.088).
There was improvement in FC levels in both the groups (132136.6 mg/g stool
to 75.977.1 mg/g stool in ASA group and 165.7116.4 mg/g stool to 115.683.1
mg/g stool in CS group) although the difference between paired samples could not
reach a significant level (p0.057 and p0.136 respectively). In subgroup analy-
sis, we observed a significant (p0.007) improvement in FC level from
163.7133.2 mg/g stool to 89.986.6 mg/g stool on follow up at 6 weeks in
patients who achieved mucosal healing as compared to those who did not
(p0.783). There was significant improvement in erythrocyte sedimentation
rate in ASA group; from 28.413.5 to 20.711.8 (p0.002) as well as in CS
group; from 33.518.8 to 21.313.7 (p0.003).
CONCLUSION: Prednisolone and mesalamine are equally effective in inducing
mucosal healing and clinical response in moderately severe UC. Both the drugs
were associated with significant improvement in endoscopic as well as clinical
activity of the disease. Mucosal healing was positively correlated with fall in FC
levels.
Disclosure of Interest: None declared
OP014 CORTICOSTEROID DOSING IN PEDIATRIC ACUTE SEVERE
ULCERATIVE COLITIS: A MULTICENTER PROPENSITY SCORE
STUDY
S. Choshen1, H. Finnamore2, M. Auth2, T. Bdolah3, E. Shteyer3, D. Mack4,
J. Hyams5, N. Leleiko6, A.M. Griffiths7, D. Turner1,*
1
Shaare Zedek Medical Center, Jerusalem, Israel, Jerusalem, Israel, 2University of
Liverpool, Liverpool, United Kingdom, 3Hadassah Medical Center, Jerusalem,
Israel, 4CHEO, Ottawa, Canada, 5Connecticut Childrens Medical Center,
Hartford, 6Brown University, Providence, United States, 7HSC, Toronto, Canada
Contact E-mail Address: turnerd@szmc.org.il
INTRODUCTION: Data to support dosing of intravenous corticosteroids
(IVCS) in pediatric acute severe ulcerative colitis (ASC) are lacking and extra-
polated from adult literature. We aimed to explore the optimal dosing of IVCS
using a robust statistical method called propensity score analysis on the largest
pediatric cohort of ASC to date.
AIMS & METHODS: 283 children treated with IVCS for ASC were included
from the OSCI studies (n227) and another 55 newly reviewed patients from
Jerusalem and Liverpool, which uses high IVCS doses as part of local practice.
As children were treated according to physician discretion, a simple comparison
of the dosing may lead to confounding-by-indication bias. This was addressed by
the propensity score method, which is the conditional probability of receiving the
A5
treatment given many pre-treatment observed covariates. By using the probabil-
ity that a subject would have been treated with low dose (1.25mg/kg/day
methylprednisolone-equivalent, max 50mg) vs. high-dose IVCS (41.25mg/kg/d
or 450mg/d) we individually matched children from both groups, thus creating a
quasi-randomized trial (matching according to the nearest value of the logit of
the propensity score within the determined caliper size in a blinded fashion to all
outcomes). Secondary analyses utilized a high cutoff value (42mg/kg/d or
480mg/d).
RESULTS: Of the total cohort, 208 were matched (104 in each of the high and
low dose groups). The mean age was 12.14 years, median disease duration 2
(IQR 0-13.8) months, 47% males and mean PUCAI at admission 7112 points,
implying severe disease. The two groups were similar in important pre-treatment
basic variables alluding to successful matching. Median IVCS dose was 0.84
(IQR 0.7-1.02; min 0.5) mg/kg/d in the low dose group and 1.57 (1.03-1.99;
max 30.3) mg/kg/d in the high dose group. There were no significant differences
in clinically relevant outcomes between the high and the low-dose groups (i.e.
need for salvage therapy by discharge (35% vs 32%, respectively; P0.77) and
time to salvage therapy, rate of children achieving PUCAI535 points by day 5
(41% vs. 43% P0.92) and mean day-5 albumin (P0.36), CRP (P0.26), plate-
lets (P0.72) and hemoglobin (P0.32)). The low-dose group had significantly
lower mean admission-days by 3.8 days (P0.02) and mean day-5 ESR (lower by
9mm; P0.04). In the secondary analysis, 84 children were matched in the high-
dose cutoff. Among the measured outcomes, the only different outcome was the
mean admission days, which was higher by 3.67 (P0.04) in the high dose group.
CONCLUSION: Our data suggest that IVCS doses up to 1.25mg/kg/d (max
50mg/d) are at least as effective as higher doses in ASC. These results should
be considered for inclusion in clinical guidelines.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 11:0012:30
ADVANCES IN ERCP HALL N_____________________
OP015 BILIARY DYSPLASIA SCREENING IN PSC - THE VALUE OF
BRUSH CYTOLOGY AND ERCP SCORING
S. Boyd1,*, A. Tenca2, K. Jokelainen2, L. Krogerus3, J. Arola1, M. Farkkila2
1
Department of Pathology, 2Clinic of Gastroenterology, Helsinki University and
Helsinki University Central Hospital, Helsinki, 3Department of Pathology,
Helsinki University and Helsinki University Central Hospital Jorvi, Espoo, Finland
Contact E-mail Address: sonja.boyd@hus.fi
INTRODUCTION: Primary sclerosing cholangitis (PSC) is a chronic cholestatic
biliary disease associated with inflammatory bowel disease (IBD). The risk for
malignancies, especially cholangiocarcinoma (CCA) is elevated among PSC
patients. Biliary intraepithelial neoplasia (BilIN) is the precursor of CCA.
AIMS & METHODS: We performed brush cytology (BC) for 261 consecutive
patients referred for their first endoscopic retrograde cholangiography (ERCP)
due to suspicion of PSC between 1st of January 2006 and 31th of October 2011.
Macroscopic biliary duct changes (i.e. strictures and dilations) were graded
according to the modified Amsterdam score (Ponsioen 2010). BC was graded
as benign (normal or benign atypia), suspicious (cytologic dysplasia) or malig-
nant. End points were follow up for at least two years, liver transplantation or
development of CCA.
RESULTS: BC was classified as benign (93.1%), suspicious (6.1%) or malignant
(0.8%). All patients with nonadvanced PSC based on ERC-scoring had benign
BC, with the exception of one without known end-point. During the follow up
time for at least two years (mean 4.8 years) most patients (n249, 95.4%)
reached the end point (follow up for 2 years without evidence of CCA, no biliary
neoplasia in the explanted liver, BilIN, or CCA). Seven patients were diagnosed
with CCA, five of them within 5 months after diagnosis of PSC. Eight out of nine
patients with liver transplantation had BilIN. Two patients were diagnosed with
gallbladder carcinoma. Most patients (n232, 93.2%) who reached end-point
were classified as having benign disease course. Majority of patients with BilIN
or CCA were male (n11, 73.3%), and the first BC was suspicious or malignant
in eight (53.3%) of them.
CONCLUSION: In unselected patient population coming for the first time for
diagnostic ERCP for PSC 7% had already a suspicion of malignancy or biliary
malignancy in brush cytology. Advanced PSC and male sex were associated with
biliary neoplasia.
REFERENCES
Validation of a cholangiographic prognostic model in primary sclerosing
cholangitis.
Ponsioen et al. Endoscopy 2010: 742-747.
Disclosure of Interest: None declared
OP016 COMPARATIVE ANALYSIS OF ERCP, IDUS, EUS AND CT IN
PREDICTING MALIGNANT BILE DUCT STRICTURES RESULTS
OF A TERTIARY REFERRAL CENTER WITH 234 PATIENTS
H.S. Heinzow1,*, S. Kammerer2, D. Domagk1, T. Meister3
1
Department of Medicine B, 2Department of Radiology, UNIVERSITY OF
MUENSTER, Muenster, 3Department of Medicine II, Helios Albert-Schweitzer-
Klinik Northeim, Northeim, Germany
Contact E-mail Address: hauke.heinzow@ukmuenster.de
INTRODUCTION: There are no definite guidelines for the management and
diagnostics of biliary strictures of indeterminate etiology so far. Various endo-
scopic and radiographic imaging modalities such as endoscopic retrograde cho-
langio-pancreatography (ERCP), intraductal ultrasound (IDUS),
endosonography (EUS) and computed tomography (CT) are available and com-
pete with each other.
A6
AIMS & METHODS: We aimed to evaluate the diagnostic yield of IDUS, EUS
and CT in a large patient cohort of 234 scheduled for ERCP with IDUS, CT and
EUS due to indeterminate strictures or filling defects of the common bile duct.
Sensitivity, specificity and accuracy rates of the diagnostic procedures were cal-
culated relating to the definite diagnoses proved by histopathology or long-term
follow-up in those patients who did not undergo surgery. For each of the diag-
nostic measures, sensitivity, specificity and accuracy rates were calculated. In all
cases, gold standard was the histopathologic staging of specimens or long-term
follow-up of at least 12 months.
RESULTS: Comparison of the different diagnostic tools for detecting bile duct
malignancy resulted in accuracy rates of 91% (ERCP/IDUS), 59% (ETP), 92%
(IDUSETP), 74% (EUS) and 73% (CT), respectively. In the subgroup analysis
accuracy rates (%, ERCPIDUS/ETP/IDUSETP; EUS; CT) for each tumor
entity were as follows: cholangiocellular carcinoma: 92/74/92/70/79; pancreatic
carcinoma: 90/68/90/81/76; ampullary carcinoma: 88/90/90/76/76. The detection
rate of malignancy by ERCP/IDUS was superior to ETP (91 vs. 59% p50.0001),
EUS (91 vs. 74% p50.0001) and CT (91 vs. 73%p50.0001), EUS was compar-
able to CT (74 vs. 73%, p0.649). When analyzing accuracy rates with regard to
localization of the bile duct stenosis the accuracy rate of EUS for proximal vs.
distal stenosis was significantly higher for distal stenosis (79 vs. 57%, p50.0001).
CONCLUSION: ERCP/IDUS is superior to EUS and CT in accurate diagnos-
tics of bile duct strictures of uncertain etiology. However, multimodal diagnostics
due to even better accuracy rates is recommended.
Disclosure of Interest: None declared
OP017 SMART ATLAS FOR SUPPORTING THE INTERPRETATION OF
PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY (PCLE) OF
BILIARY STRICTURES: FIRST CLASSIFICATION RESULTS OF A
COMPUTER-AIDED DIAGNOSIS SOFTWARE BASED ON IMAGE
RECOGNITION
M. Kohandani Tafreshi1,*, M. Giovannini2, V. Joshi3, C. Lightdale4,
A. Meining5, N. Ayache1, B. Andre6
1
INRIA, Sophia Antipolis, 2Institut Paoli Calmettes, Marseille, France, 3Ochsner
Clinic Foundation, New Orleans, 4Columbia University Medical Center, New York,
United States, 5Klinikum rechts der Isar, Munchen, Germany, 6Mauna Kea
Technologies, Paris, France
Contact E-mail Address: marzieh.kohandani-tafreshi@inria.fr
INTRODUCTION: pCLE enables microscopic imaging of biliary strictures,
in vivo and in real time, during an ERCP procedure. Results of a multicentric
study (Meining et al., GIE 2011) have shown that pCLE allows endoscopists to
differentiate benign from malignant strictures in real time with high sensitivity
and NPV. A computer-aided diagnosis software called Smart Atlas has been
developed to assist endoscopists with the interpretation of pCLE sequences.
This study aims at evaluating the performance of this software for the differen-
tiation of benign and malignant strictures.
AIMS & METHODS: Several high quality pCLE sequences were retrospectively
collected from pCLE procedures performed in multiple clinical centers. These
sequences, along with their annotated final diagnosis, were used to train a clas-
sification software that uses a content-based image retrieval algorithm to predict
the diagnosis of a query video based on the diagnoses of the most visually similar
atlas videos. For all cases, final diagnosis was based on histology, positive tissue
sampling, or one year follow-up. All evaluations were performed using leave-one-
patient-out cross-validation to avoid bias. To evaluate binary classification, a
receiver operating curve was generated, allowing optimization of the trade-of
between false positives and negatives.
RESULTS: Among the 60 pCLE sequences collected from 30 patients, 14 were
representative of healthy bile duct, 10 of inflammatory strictures and 36 of
malignant strictures. The resulting receiver operating curve shows two points
of interest: the first (reps. second) point has a high sensitivity of 88.9% (reps.
high specificity of 91.7%), an acceptable specificity of 70.8% (reps. acceptable
sensitivity of 69.4%), an accuracy of 81.7% (resp. 78.3%), a PPV of 82.1% (resp.
92.6%) and a NPV of 81.0% (resp. 66.7%). In comparison, Meining et al.
reported that, for in vivo pCLE diagnosis of malignant stricture, endoscopists
achieve overall sensitivity, specificity, accuracy, PPV and NPV of 98%, 67%,
81%, 71% and 97%, respectively.
CONCLUSION: These first results demonstrate that benign and malignant stric-
tures can be automatically discriminated by the Smart Atlas software using only
the image content of pCLE sequences of high quality, with an accuracy compar-
able to that achieved in real-time by endoscopists. The software is also able to
achieve high specificity and PPV to help reduce false positives caused by inflam-
matory strictures. Future work will focus on improving the software to handle
pCLE sequences of various quality. The resulting case-based reasoning software
could be used as an educational tool to train non-expert endoscopists, but also as
a second- reader tool to assist any endoscopist in real-time diagnosis of biliary
strictures using pCLE.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP018 ENDOSCOPIC PAPILLARY LARGE BALLOON DILATION
(EPLBD) VERSUS ADDITIONAL FULL ENDOSCOPIC
SPHINCTEROTOMY (EST) FOR THE ENDOSCOPIC REMOVAL OF
RECURRENT LARGE BILE DUCT STONES AFTER NON-FULL EST
D. Kim1,1,*, G. Song1, B. Lee1, D. Baek1, J. Seo1, S. Lee1, T. Kim1, K. Lee1, J. Lee
1
1
Department of Internal Medicine, Pusan National University School of Medicine,
Busan, Korea, Republic Of
Contact E-mail Address: dhbeak@naver.com
INTRODUCTION: There were no reports about the comparative study between
endoscopic papillary large balloon diation (EPLBD) and additional endoscopic
sphincterotomy (EST) for endoscopic treatment of common bile duct stones
which were recurred after endoscopic stone removal with previous non-full EST.
AIMS & METHODS: The aim of this study was to compare the safety and
efficacy of EPLBD with additional EST for recurrent difficult bile duct stones
after previous non-full EST.
We retrospectively reviewed the records from twelve hundred four patients who
received the first ERCP for the removal of bile duct stones from August 2004 to
July 2013. We enrolled a total of 89 patients who had large bile duct stones
recurred after previous non-full EST, and need to receive the additional papillo-
plasty. The patients were classified into three groups: Group A who underwent
EPLBD (group A, n 59) by using 12 18 mm sized balloon, and group B who
underwent additional full EST (group B, n 30). When necessary, mechanical
lithotripsy was performed. The therapeutic outcomes and complications were
reviewed and compared between two groups.
RESULTS: There were no differences between two groups with regard to age,
stone size, number of stones and mean procedure time. Complete stone removal
was achieved in all patients, but group B had higher using rate of mechanical
lithotripsy for complete removal of the large bile duct stones, compared to group
A (16.9% vs. 36.7%, P .037). There were no differences in procedure-related
complications between two groups: pancreatitis(1.7% vs 0%, P .663),
Hyperamylasemia (5.1% vs 6.7%, P .550) and bleeding (1.7% vs 13.3%, P
0.042).
CONCLUSION: EPLBD showed results similar to those with additional full
EST for removing recurrent large stone. But additional full EST group had
more bleeding and increasing the need for lithotripsy, compared with EPLBD
group.
Disclosure of Interest: None declared
OP019 IMPACT OF PCLE ON THE MANAGEMENT OF PATIENTS
WITH INDETERMINATE BILIARY STRICTURE: RESULTS OF A
LARGE MULTICENTRIC STUDY
M. Giovannini1,*, A. slivka2, G. costamagna3, M. Kahaleh4, P. jamidar5, I. Gan6,
P. Cesaro7
1
GI, Institu Paoli Calmettes, Marseille, France, 2UPMC, Pittsburgh, United
States, 3Gemelli, Rome, Italy, 4GI, Cornell, New York, 5Yale, New Haven,
6
VMMC, Seattle, United States, 7Fondazione Poliambulanza, Brescia, Italy
Contact E-mail Address: giovaninim@wanadoo.fr
INTRODUCTION: Diagnosis of indeterminate biliary strictures remains a clin-
ical problem largely due to a low sensitivity of ERCP with tissue sampling
(550%). It has been previously shown that the use of probe-based confocal
laser endomicroscopy during ERCP for indeterminate biliary strictures, detects
more malignant lesions, doubles sensitivity compared to that of standard tissue
sampling (98% vs. 45%).
This study presents the final results of an international multicenter trial (FOCUS,
NCT01392274) aiming at evaluating the impact of optical biopsy in patients with
indeterminate biliary stricture using criteria for normal, inflammatory and malig-
nant strictures.
AIMS & METHODS: Patients were enrolled at 6 international centers (2
European, 4 US) from April 2012 to September 2013 and underwent pCLE
during standard ERCP. For each patient, the investigator was asked to provide
a diagnosis and a patient management recommendation based on clinical data
and ERCP findings before and after pCLE and again after tissue results returned.
Malignancy was confirmed by positive tissue sampling at ERCP or surgery or by
a deteriorating clinical course with consistent radiographs. Benign disease man-
dated negative histology at surgery or at least a 6 month follow period for a
benign course after negative ERCP tissue sampling.
RESULTS: 107 patients presenting with an indeterminate stricture where
enrolled (68 benign, 39 malignant).
Presumptive diagnosis based on clinical history and ERCP alone resulted in a
sensitivity of 84.6% and a specificity of 74.3%. The addition of pCLE increased
specificity up to 88.3% whereas the specificity declined to 89.7%. Finally, The
addition of tissue sampling resulted in a sensitivity of 89.7% and a specificity of
87.2%. Investigators would have immediately proceed with patient management
in 24 cases based on clinical history and ERCP, and in 33 cases based on clinical
history, ERCP and pCLE. Out of the 33 patients, pCLE would have had a
positive impact on 37% of them, a negative impact on 6% of them and would
have been in accordance with the actual patient management in 57% of the
patients.
CONCLUSION: pCLE is a safe and sensitive minimally invasive method for
evaluating patients with indeterminate biliary stricture Our observations further
suggest that the results of pCLE may have a favorable impact on patient manage-
ment. In centers in which pCLE expertise is available, our results suggest a more
rationalized approach to the diagnosis and management of biliary tumors.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP020 ESWL FOR LARGE PANCREATIC CALCULI. A DECADES
EXPERIENCE
M. Tandan1,*, D. N. REDDY2
1
GASTROENTEROLOGY, ASIAN INSTITUTE OF
GASTROENTEROLOGY, 2GASTROENTEROLOGY, ASIAN INSTITUTE
OF GASTROENTROLOGY, HYDERABAD, India
Contact E-mail Address: mantan_05@rediffmail.com
INTRODUCTION: ESWL is established as the standard of care for management
of pancreatic ductal calculi larger than 5mm in size. We share a single tertiary
care centre experience of 10 years using this technique.
AIMS & METHODS: This is a retrospective analysis of prospectively collected
data at the Asian Institute of Gastroenterology Hyderabad India from February
2004 to February 2014. All patients having pain as the dominant symptom, with
main pancreatic ductal calculi not amenable to standard endoscopic extraction,
were subjected to lithotripsy using a 3rd generation electro magnetic lithotripter.
Fragmentation was considered successful when the calculi were broken down to
53mm in size. Upto 5000 shocks were delivered per session till this result was
achieved. ERCP was done within 24 - 48 hours after successful fragmentation
and the main pancreatic duct was cleared following a sphincterotomy. Stents
were placed as and when required.
RESULTS: A total of 2779 patients underwent ESWL during this period. A
majority (69%) were under the age of 40 years and did not consume alcohol.
Males accounted for 64% of patients. Single stones were seen in 24%, whereas in
the rest they were multiple. The head was the commonest location of the calculi
(59%). Sixty eight percent of patients needed 3 sessions or less for fragmentation.
Endoscopic sphincterotomy was done in 69% of patients. Complete clearance
was achieved in 79%, partial in 14% while in the rest it was unsuccessful.
Complications were minimum and not life threatening. From our earlier experi-
ence short term pain relief was seen in 84% and long term relief (upto 8 years) in
60% of patients. There war significant improvement in quality of life.
CONCLUSION: ESWL should be offered as first line therapy in properly
selected patients with large main pancreatic duct calculi.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 11:0012:30
CELLULAR CROSSTALK IN PANCREATIC CANCER HALL O_____________________
OP021 PARASYMPATHOMIMETIC AGENTS LIMIT PANCREATIC
CANCER GROWTH BY SUPPRESSION OF THE P44/42 MAPK
SIGNALING PATHWAY
P.L. Pfitzinger1,*, I.E. Demir1, E. Tieftrunk1, K. Wang1, H. Friess1,
G.O. Ceyhan1
1
Surgery, Klinikum Rechts der Isar, Munich, Germany
Contact E-mail Address: paulo.pfitzinger@online.de
INTRODUCTION: The vagus nerve and parasympathetic nervous system play a
major role in the regulation of pancreatic physiology and also feature a suppres-
sive effect on acute and chronic inflammation. It is therefore conceivable that the
parasympathetic nervous system may also play a role in pancreatic
carcinogenesis.
AIMS & METHODS: The aim of this study was to investigate the potential
effect of the parasympathetic nervous system on proliferation and invasion of
pancreatic cancer (PCa) and enlighten the linked intracellular signalling path-
ways in vitro and in vivo. Therefore, human PCa cell lines were exposed in vitro to
direct and indirect parasympathomimetic agents (Carbachol, Physiostigmine and
Pyridostigmine) and their proliferation was quantified via the MTT proliferation
assay, their invasiveness via the matrigel invasion assay, and the extent of phos-
phorylation of p44/42 mitogen-activated protein kinase (MAPK) was determined
by immunoblotting. In an in vivo xenograft model, human PCa cells were injected
subcutaneously into Crl:NMRI-Foxn1nu nude mice and tumor area and metas-
tasis were compared between treated and untreated groups.
RESULTS: The MTT proliferation assay showed significant dose dependent
suppression of PCa cell proliferation after treatment with both direct and indirect
parasympathomimetic agents. The matrigel invasion assay experiments revealed
a dose dependent inhibition of PCa cell invasiveness. These results were asso-
ciated with a lower intracellular phosphorylation of p44/42 MAPK and corre-
sponded with the results obtained in the in vivo experiments, in which both tumor
size and local invasiveness were inhibited subsequent to prophylactic and ther-
apeutic treatment.
CONCLUSION: The systemic administration of activators of the parasympa-
thetic nervous system restrains PCa proliferation and invasiveness via suppres-
sing the intracellular phosphorylation of the p44/42 MAPK signalling pathway,
implicating a potential novel understanding of neuro-cancer interactions and
treatment of human malignancies.
Disclosure of Interest: None declared
A7
OP022 THE PHENOMENON OF BONE MARROW DERIVED STEM
CELLS MOBILIZATION IN PANCREATIC DISEASES IS PRESENT
ONLY IN CANCER PATIENTS
K. Dabkowski1,*, W. Blogowski1, A. Labedz Maslowska2, E. Zuba-Surma2,
M. Ratajczak3,4, T. Starzynska5
1
Department of Gastroenterology, Pomeranian Medical University, Szczecin,
2
Department of Cell Biology, Jagiellonian University, Krakow, 3Department of
Physiology, Pomeranian Medical Univeristy, Szczecin, Poland, 4Stem Cell Biology
Institute, James Graham Brown Cancer Center, University of Louisville, Louisville,
KY, United States, 5Department of Gastroenterology, Pomeranian Medical
Univeristy, Szczecin, Poland
Contact E-mail Address: dabkowskikrzysztof@wp.pl
INTRODUCTION: Various studies indicate potential involvement of various
populations of bone marrow derived stem cells (BMDSCs) into process of
tissue regeneration and tumor development. Our team demonstrated recently
that in patients with pancreatic cancer intensified peripheral trafficking of
selected populations of BMSCs occurres (J Cell Mol Med 2013: 17:792-9).
There is no data on this phenomenon in benign pancreatic disorders.
AIMS & METHODS: The purpose of the study was to comprehensively analyze
systemic trafficking of various populations of BMSCs: mesenchymal, hemato-
poietic, endothelial stem/progenitor cells (MSCs, HSCs, EPCs respectively), as
well as, of recently discovered population of very small embryonic/epiblast-like
SCs (VSELs) in patients chronic and acute pancreatitis with comparison to pan-
creatic cancer patients and controls. The circulating CD133/Lin-/CD45-/
CD34 cells enriched for HSCs, CD105/STRO-1/CD45- cells enriched for
MSCs, CD34/KDR/CD31/CD45- cells enriched for EPCs, and small
CXCR4CD34CD133 subsets of Lin-CD45- cells that correspond to
VSELs were enumerated and sorted from blood samples derived from 16 patients
with acute pancreatitis, 13 with chronic pancreatitis, 30 cancer patients and 19
healthy controls.
RESULTS: We noticed significant decrease of a number of circulating CD45(-
)STRO-1()CD105() (P0.03); CD45(-)STRO-1()CD105(-) (P0.02) LIN(-
)CD45()CD133() (P0.04), and LIN(-)CD45(-)CD133() (P50.04) in
patients with acute pancreatitis and decrease of number of circulating LIN(-
)CD45()CD133() (P0.04); LIN(-)CD45(-)CD133() (P50.04); LIN(-
)CD45()CD34 () (P50.04) in patients with chronic pancreatitis. The
number of circulating CD45(-)STRO-1()CD105(-)(p0,02) cells was signifi-
cantly higher in patients with chronic pancreatitis than in patients with acute
pancreatitis.
CONCLUSION: In contrast to heart infarction, brain stroke, skin burns and
pancreatic cancer, there is no significant mobilization of the BMDSCs to the
peripherial blood in patients with acute and chronic pancreatitis. Interestingly,
even significant decrease of the number of circulating cells was noted. The mobi-
lization of BMDSCs to the peripherial blood, in pancreatic disorders, seems to be
connected only with pancreatic cancer.
Acknowledgment:Study financed from Ministry of Science and Higher
Education Grant(402423038)
REFERENCES
1. Paczkowska E, Kucia M, Koziarska D, et al. Clinical evidence that very small
embryonic-like stem cells are mobilized into peripheral blood in patients after
stroke. Stroke 2009; 40: 1237-1244.
2. Starzynska T, Dabkowski K, Blogowski W, et al. An intensified systemic
trafficking of bone marrow-derived stem/progenitor cells in patients with pan-
creatic cancer. J Cell Mol Med 2013; 17: 792-799.
3. Wojakowski W, Landmesser U, Bachowski R, et al. Mobilization of stem and
progenitor cells in cardiovascular diseases. Leukemia 2012; 26: 23-33.
Disclosure of Interest: None declared
OP023 INCREASING THE INFLAMMATORY COMPETENCE OF
MACROPHAGES WITH IL-6 OR WITH COMBINATION OF IL-4
AND LPS RESTRAIN THE INVASION OF PANCREATIC CANCER
CELLS
A. Koski1,*, H. Mustonen1, S. Vainionpaa1, Z. Shen2, E. Kemppainen1,
H. Seppanen1, P. Puolakkainen1
1
Department of Surgery, Helsinki University Central Hospital, Helsinki, Finland,
2
Department of Gastroenterological Surgery, Peking University Peoples Hospital,
Beijing, China
Contact E-mail Address: aino.koski@helsinki.fi
INTRODUCTION: Inflammation plays a critical role in the development and
progression of cancer; local inflammation in chronic pancreatitis multiplies the
risk of pancreatic cancer. Recent studies suggest that pro-inflammatory type M1
macrophages work against tumour progression and anti-inflammatory M2
macrophages enhance tumour progression.
AIMS & METHODS: The aim of this study was to examine the interaction of
pro-inflammatory M1 and anti-inflammatory M2 macrophages with pancreatic
cancer cells.
We studied the migration rate of fluorescein stained pancreatic cancer cells
(MiaPaCa-2 and HPAF-II) in Matrigel cultured alone or with GM-CSF differ-
entiated M1 macrophages or with M-CSF differentiated M2 macrophages. We
studied the changes the pancreatic cancer cells induce in the differently stimulated
macrophages cytokine expression with cytokine array. Cytokine array results are
given as percentage between negative and positive control recorded on each
array.
RESULTS: GM-CSF differentiated M1 macrophages increased the migration
rate of primary pancreatic adenocarcinoma cell line (MiaPaCa) from 11.5m/h
0.2 to 24.7m/h 0.3 (p50.001) and metastatic cell line (HPAF) from 4.0m/h
0.2 to 19.1m/h 0.3 (p50.001). M-CSF differentiated macrophages M2
increased the invasion rate of MiaPaCa cells from 8.4m/h 0.1 to 14.8m/h
A8
0.1 and of HPAF from 4.5m/h 0.2 to 20.8m/h  0.3 (p50.001). When the
cells were stimulated with IL6 or IL4LPS, the macrophages increasing effect
on the migration rate was completely reversed in the case of primary pancreatic
cancer cell line and partly reversed in the case of metastatic cancer cell line. When
stimulated with IL6 (GM-CSF differentiated M1 cells) the migration rate of
MiaPaCa cells was 11.7m/h 0.2 and of HPAF cells 13.8m/h 0.2. The
migration rate of MiaPaCa cells co-cultured with IL4LPS stimulated macro-
phages (M-CSF differentiated M2) was 8.5m/h 0.4 and with HPAF 8.3m/h
0.4.
GM-CSF differentiated M1 macrophages co-cultured with MiaPaCa cells
released less inflammatory cytokines than macrophages cultured alone (TNF RESULTS: Here, we reveal the inflammation-induced transcription factor
from 0.64% to 0.03% 0.30, p0.009; IL23 from 1.14 to 0.63% 0.15, p0.009;
INF
from 1.30 to 0.54% 0.26, p0.038). Adding IL6 to GM-CSF differen-
tiated cell culture with macrophages and MiaPaCa cells increases the expression
of inflammatory cytokines IL23 (from 0.65 to 1.22% 0.12 p0.013), TNF complex mediated PDAC dedifferentiation is opposed by antithetical p53-
(from 0.58 to 1.34% 0.10, p0.007). M-CSF differentiated M2 macrophages
did not secrete inflammatory cytokines but adding IL4LPS to the cell culture
with macrophages and MiaPaCa cells increased the expression of IL6 (from 0.52
to 5.03% 2.21, p50.001), CCL5 (from 0.58 to 23.27% 7.65, p50.001), TNF CONCLUSION: Based on these findings, we propose a hierarchical signalling
(from 0.84 to 5.81% 0.52, p50.001) but also anti-inflammatory IL10 expres-
sion increased (from 0.31 to 1.08% 0.10, p0.007).
CONCLUSION: Our study shows that pancreatic cancer cells have an ability to
reduce the inflammatory cytokine expression of GM-CSF differentiated pro-
inflammatory M1 macrophages. This explains why both GM-CSF (M1) and
M-CSF (anti-inflamatory M2) differentiated macrophages promoted the inva-
sion of pancreatic cancer cells. IL6 and IL4LPS activated the inflammatory
cytokine expression in macrophages and this might contribute to the reversion of
the macrophage induced increase of cancer cell migration rate.
Disclosure of Interest: None declared
OP024 LOSS OF ATM ACCELERATES PANCREATIC CANCER
FORMATION AND EPITHELIAL-MESENCHYMAL-TRANSITION
VIA AN AUTOCRINE BMP4-SIGNALLING LOOP
A. Kleger1,*, R. Russell1, Q. Lin2, J. Lennerz3, M. Wagner1, T. Seufferlein4
1
Department of Internal Medicine 1, Ulm University Hospital, Ulm, 2Department
of Cell Biology, Institute for Biomedical Engineering, RWTH Aachen University,
Aachen, 3Institute of Pathology, Ulm, Germany, 4Ulm University Hospital, Ulm,
Germany
INTRODUCTION: Onset and progression of pancreatic ductal adenocarcinoma
(PDAC) is associated with accumulation of particular oncogenic mutations.
Recent genome-wide exome sequencing studies have identified ATM mutations
in independent PDAC cohorts but to date, the role of ATM in PDAC tumour
biology is unclear.
AIMS & METHODS: We use a conditional PDAC mouse modell and ex vivo
acinar cultures to delineate the role of ATM during mouse pancreatic
carcinogenesis.
RESULTS: Here we report that conditional deletion of ATM in a mouse model
of PDAC enhanced pancreatic cancer formation via enhanced ductal reprogram-
ming. ATM-targeted mice had significantly shortened survival compared to con-
trols and interestingly, loss of a single ATM allele was sufficient to induce this
phenotype. Depletion of ATM gave rise to a greater number of proliferative
acinar-to-ductal metaplastic (ADM) lesions and pancreatic intraepithelial neo-
plasias (PanIN), coupled with a pronounced fibrotic reaction. These precursor
lesions in ATM-deficient mice were broadly associated with altered epithelial-to-
mesenchymal transition (EMT) and a gain of tumor initiating cells. Finally,
we are able to define a Bmp4-signalling loop originating within the acinar com-
partment, which initiates ductal programming in an autocrine manner and
subsequent EMT. Notably, our mouse model recapitulates many features of
more aggressive human PDAC subtypes, namely mesenchymally differentiated
PDAC.
CONCLUSION: We show that ATM also acts as a tumor suppressor molecule
in human PDAC, where low expression of ATM serves as an independent pre-
dictor for EMT and poor prognosis. Taken together, our data suggests an inti-
mate link between ATM expression and pancreatic cancer progression in mice
and men.
Disclosure of Interest: None declared
OP025 ANTITHETICAL NFATC1-SOX2 AND P53-MIR-200 SIGNALLING
NETWORKS GOVERN PANCREATIC CANCER CELL PLASTICITY
AND TUMOUR PROGRESSION
S. Singh1,2,*, N.-M. Chen1, E. Hessmann1, A. Koenig1, I. Esposito3, M. Hebrok4,
V. Ellenrieder5
1
Gastroenterology, Philipps-Unoversity of Marburg, Marburg, Germany, 2Barrow
Brain Tumor Research Center, The Barrow Neurological Institute, Phoenix, United
States, 3Gastroenterology, 5Institute of Pathology, Helmholtz Zentrum, Munich,
Germany, 4Diabetes Center, USCF, California, United States, 5Gastroenterology,
Georg-August-Universitat, Gottingen, Germany
Contact E-mail Address: shivkishor@gmail.com
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) cells undergo
epithelialmesenchymal transdifferentiation (EMT) in adaption to environmen-
tal clues, including inflammation, a process that combines tumour cell dediffer-
entiation with dissemination and acquisition of stemness features. However, the
mechanisms coupling inflammation-induced signalling pathways with EMT and
stemness remain largely unknown. We have shown that activation of the
NFATc1 transcription factor promotes pancreatic cancer development and
metastasis through its ability to integrate extrinsic stimuli into coordinated
gene regulation.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: To assess whether NFATc1 controls transcription of
EMT genes and stemness in PDAC, particularly upon p53 inactivation. We
generated mouse strains with combined pancreas-specific expression of
KrasG12D, p53R172H or p53fl/wt and NFATc using Cre-Lox technology. These
mice showed a highly aggressive tumor growth (median survival of 550 or 61
days). Mouse primary tumour cells were used to identify NFATc1 targets by gene
expression profiling and pathway analyses (ChIP seq, miRNA analyses and
GSEA). NFATc1 mediated EMT and stemness were assessed in human and
murine pancreatic cancer models using migration and spheroid assay as well as
xenograft mouse models.
NFATc1 as a central regulator of pancreatic cancer cell plasticity. We show
that NFATc1 drives EMT programming and maintains cancer cells in a stem
cell-like state through Sox2-dependent transcription. Intriguingly, NFATc1-Sox2
miR200c signalling. Inactivation of the tumour suppressor pathway is essential
for tumour dissemination and dedifferentiation both in genetically engineered
mouse models and human PDAC.
network regulating PDAC cell plasticity and suggest that molecular decisions
between epithelial cell preservation and conversion into a dedifferentiated
cancer stem cell-like phenotype depends on opposing levels of p53 and
NFATc1 activities.
REFERENCES
Rhim AD et al. EMT and dissemination precede pancreatic tumor formation.
Cell 2012; 148: 349361.
Hezel AF, Kimmelman AC, Stanger BZ, et al. Genetics and biology of pancreatic
ductal adenocarcinoma. Gene Dev 2006; 20: 12181249.
Rustgi AK. The molecular pathogenesis of pancreatic cancer: clarifying a com-
plex circuitry. Gene Dev 2006; 20: 30493053.
Disclosure of Interest: None declared
OP026 NEURAL REMODELING IN PANCREATIC NEUROPATHY IS
CHARACTERIZED BY NEUROTROPHIN-3-MEDIATED INCREASE
IN THE PANCREATIC NOCICEPTIVE INNERVATION,
DEMYELINATION AND SELECTIVE GLIAL ACTIVATION
I.E. Demir1,*, D. Carty1, K. Wang1, C. Waldbaur1, L. Krauss1, E. Tieftrunk1,
H. Friess1, G.O. Ceyhan1
1
Department of Surgery, Klinikum rechts der Isar, TU Munchen, Munchen,
Germany
Contact E-mail Address: ekin.demir@tum.de
INTRODUCTION: Neural remodelling in pancreatic cancer (PDAC) and
chronic pancreatitis (CP) is characterized by reduced sympathetic pancreas inner-
vation among patients with severe pain. However, it remains unknown which
types of nerve fibers replace sympathetic fibers in panful PDAC and in CP.
AIMS & METHODS: In the current study, we aimed to elucidate wheter the
sympathetic innervation in PDAC and CP is replaced by increased nociceptive
innervation and glial activation, and which molecular agents mediate this switch.
For this purpose, normal human pancreas (NP, n16), CP (n 26) and PCa
(n25) tissues were quantitatively analyzed for the neuro-immunoreactivity of a)
nociceptive fiber markers substance-P (SP) and calcitonin-gene-related-peptide
(CGRP), b) myelination markers neurofilament-H (NFH) and peripheral-
myelin-protein-22 (PMP22), c) glial activation markers p75NTR and glial-fibril-
lary-acidic-protein (GFAP) and correlated to pain, neural invasion (NI) and
pancreatic neuritis. Nociceptive neurite density of dorsal-root-ganglia-(DRG)-
neurons that were cultivated in human NP, CP or PDAC tissue extracts was
analyzed in the presence of neutralizing antibodies against nerve-growth-factor
(NGF), neurotrophin-3 (NT-3) or brain-derived-neurotrophic-factor (BDNF).
RESULTS: SP- and CGRP-containing nerve fibers were prominently increased
in CP independently of the pain status. Accordingly, the neuro-immunoreactivity
of NFH and PMP22 was remarkably decreased in CP and PCa. NI and pan-
creatic neuritis were more pronounced around nerves with decreasing SP- and
CGRP-content, increasing myelination and enhanced glial activation.
Cultivation of DRG neurons in CP extracts induced the sprouting of SP- and
CGRP-containing neurites, which was reversed upon blockade of NT-3 within
CP extracts.
CONCLUSION: Neural remodeling in CP and PDAC involves pain-indepen-
dent, NT-3-mediated upregulation of nociceptive innervation, loss of myelina-
tion, and glial activation around nerves with NI and pancreatic neuritis. These
alterations show that the sympathetic innervation in CP is replaced by pain-
transmitting, i.e. nociceptive innervation. This switch to increased nociception,
myelination and glial activity may be the determinants of the pathologic pain
response in PDAC and CP.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 11:0012:30
CLINICO-PATHOLOGICAL FEATURES OF GI CANCER LOUNGE 5_____________________
OP027 INTERVAL GASTRIC CANCERS: PRECISE REVIEW OF PAST
ENDOSCOPIC IMAGES, CLINICOPATHOLOGICAL FEATURES
AND MICROSATELLITE INSTABILITY
K. Yamashita1,*, Y. Arimura1, K. Onodera1, H. Isshiki1, K. Murakami1,
M. Saito1, Y. Shinomura1, T. Endo2
1
Department of Gastroenterology, SAPPORO MEDICAL UNIVERSITY,
2
Department of Gastroenterology, SAPPORO SHIRAKABA-DAI HOSPITAL,
Sapporo, Japan
INTRODUCTION: There are few studies about interval gastric cancers, which
are diagnosed after preceding negative upper endoscopy. Microsatellite instabil-
ity (MSI), frequently observed in interval colorectal cancers, might be also a
genetic feature of interval gastric cancers.
AIMS & METHODS: The aims of this study were to speculate natural history of
early gastric cancer from precise review of past endoscopic images of interval gastric
cancers and to elucidate clinicopathological features of internal gastric cancers. The
study cohort consisted of 260 gastric cancer patients diagnosed at Sapporo Medical
University Hospital. Patients who had experience of upper endoscopy within the
past 10 years were stratified according to interval between past and current endo-
scopy. Images of past endoscopy performed at our hospital were scrutinized by two
endoscopy specialists independently. Five microsatellite markers were used for MSI
analysis and instability of two or more markers was defined as MSI-H.
RESULTS: Of 260 gastric cancer patients, 60 (23%) had experience of upper
endoscopy within 10 years prior to the cancer diagnosis; 27 patients with endo-
scopy interval of 24 months or less (short interval), 19 patients with 25 to 48
months interval (intermediate) and 14 patients with 49 to 120 months interval
(long interval). Rates of advanced gastric cancers (T2 or more) to all cancers were
19%, 37% and 57% for the short, the intermediate and the long interval group,
respectively. For patients with over 120 months interval or without experience of
endoscopy, rate of advanced gastric cancer was 51%.
High-quality images of past endoscopy performed at our hospital were available
for precise review in 32 patients. Rates of advanced gastric cancers of these 32
patients were 0%, 33% and 43% for the short, the intermediate and the long
interval group, respectively. At past endoscopy, existence of early (T1) gastric
cancers were strongly suspected in 17 patients while there were no lesions at current
cancer sites in 15 patients. Of 17 early gastric cancers observed at past endoscopy,
11 were unchanged for an average of 20.4 months (range 12-40) while 6 had grown
in 43.0 months (20-64). Of 6 growing gastric cancers, 3 had grown but remained as
T1 for 36.7 months while another 3 had become unresectable in 49.7 months.
Interval gastric cancers had no clinicopathological features such as age, site,
macroscopic and histological type. Seven percent (3/41) of interval gastric cancers
while 11% (12/106) of all other gastric cancers were MSI-H (P0.35). All MSI-H
interval gastric cancers were intramucosal (T1a) and Laurens intestinal type.
CONCLUSION: Most early gastric cancers are unchanged for 2 years while
some will become advanced or unresectable in 3 to 5 years. Endoscopy with 2-
year interval might be reasonable for gastric cancer surveillance, if quality of
endoscopy is warranted. MSI was not frequent in interval gastric cancers.
Disclosure of Interest: None declared
OP028 MANAGEMENTS AND CLINICAL OUTCOMES OF NON-
AMPULLARY NEUROENDOCRINE TUMORS OF THE
DUODENUM: A RETROSPECTIVE, MULTICENTER STUDY IN
JAPAN
W. Hatta1,*, T. Koike1, K. Iijima1, G. Kusaka1, Y. Kondo1, N. Ara1, K. Uno1,
N. Asano1, A. Imatani1, T. Shimosegawa1
1
Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Japan
Contact E-mail Address: waku-style@festa.ocn.ne.jp
INTRODUCTION: Duodenal neuroendocrine tumor (D-NET) is a rare tumor.
According to the latest European Neuroendocrine Tumor Society, surgical resec-
tion is recommended for ampullary D-NET, due to the anatomical location and
different growth patterns from non-ampullary D-NET (NAD-NET). In contrast,
endoscopic resection (ER) is recommended for small size (5 10 mm) NAD-NET,
and there is no standardized therapeutic approach for intermediate size (10 to
20mm) NAD-NET. However, it is reported that 13.2 % of small D-NET had
lymph node metastases. Furthermore, there are no reports on the criteria for
deciding the additional treatment after ER in NAD-NET.
AIMS & METHODS: The aim of this study was to investigate the detailed char-
acteristics of NAD-NET for detecting risk factors for metastasis by a multicenter,
retrospective study. The patients with NAD-NETs diagnosed and treated between
1992 and 2012 at 7 institutions in Japan were enrolled. The patients with follow-up
period of less than 24 months, except for NAD-NET-related death, were excluded
from this study. As a result, a total of 39 patients with NAD-NETs were analyzed,
comprising 29 men and 10 women, with a median follow-up of 46 months. The
clinical and pathological records were reviewed to investigate the therapeutic pro-
cedure, tumor size, presence of lymph node and distant metastasis, and prognosis.
In addition, depth of invasion, presence of lymphatic or venous invasion, World
Health Organization (WHO) grading (Ki-67 index, mitotic count per 10 high
power microscopic fields), peptide products (gastrin, somatostatin, and serotonin)
were re-evaluated by one pathologist who was blind to the clinical information. To
identify the risk factors for metastasis, we calculated odds ratio (OR) and 95 %
confidence interval (CI) of age (over 60 years), size (over 10 mm), location (bulbs),
number of lesions (multiple), each peptide product, lymphatic invasion, venous
invasion, and WHO grading (G2, compared to G1) by univariate analysis.
RESULTS: Thirty patients were treated with ER, and 9 were treated surgically,
and all of the tumors were less than 20 mm. There were 6 lymph node metastases
(15.4 %) and 2 distant metastases (5.1 %). With regard to peptide products, NAD-
A9
NETs showed immunoreactivity for gastrin, somatostatin, and serotonin in 75.7
%, 35.1 %, and 37.8 % of the cases, respectively, all of which were not significantly
associated with metastasis. Two of patients with immunoreactivity for gastrin
showed Zollinger-Ellison syndrome. On univariate analysis, risk factors for metas-
tasis were lymphatic invasion (OR 31.0; 95% CI: 3.37-282; P 0.002), venous
invasion (OR 14.5; 95% CI: 1.98-106; P 0.009), and G2 (OR 10.0; 95% CI:
1.36-73.3; P 0.024). Five-year overall survival was 78.9 %, and 5-year disease-
specific survival was 94.7 %. In one patient with 2 mm NAD-NET which had
vascular invasion and classified as G2 (Ki-67 index; 20 %), lymph node and liver
metastases were confirmed 18 months after ER, resulting in death.
CONCLUSION: To our knowledge, this is the first study to demonstrate that
lymphatic invasion, venous invasion, and WHO grading G2 were risk factors for
metastasis in NAD-NET less than 20 mm. These pathological findings could
provide useful information in considering additional treatment after ER.
Disclosure of Interest: None declared
OP029 DUODENAL POLYPOSIS OUTCOMES IN MYH-ASSOCIATED
POLYPOSIS
S.-J. Walton1,*, S. Clark1, A. Latchford1
1
The Polyposis Registry, St Marks Hospital, London, United Kingdom
Contact E-mail Address: s.j.walton@hotmail.co.uk
INTRODUCTION: MUTYH-associated polyposis (MAP) is an autosomal reces-
sive adenomatous condition. MAP (like familial adenomatous polyposis (FAP)),
predisposes to colorectal and duodenal adenoma formation. However, duodenal
polyposis is less frequently seen in MAP than in FAP, occurring in up to 25% and
90%, respectively. The rationale for adopting the same upper gastrointestinal
(UGI) surveillance protocol for both polyposis syndromes is questionable.
AIMS & METHODS: The aim of this study was to assess the incidence, extent
and progression of duodenal adenomas in an MAP population over time and
evaluate the suitability of the current FAP UGI surveillance protocol in MAP.
All genetically confirmed MAP cases followed-up at a single institution were
identified from a prospectively maintained registry database. Case notes, endo-
scopy and histology reports were analysed. The primary outcome measure was
the occurrence of duodenal adenomas. Secondary outcomes included age of
adenoma onset, time interval to advancing Spigelman stage, MAP mutation,
polyp morphology and distribution.
RESULTS: 34 MAP patients were identified, of which 13 (38%) developed
duodenal adenomas, with a median follow-up of 7.5 years (range 0-16 years).
Median age at first (baseline) OGD in the adenoma group was 50 years (range
38-66) with a median age of adenoma development of 52 years (range 39-66). In
92% (12/13 cases) only 1 to 4 polyps were found. 8/13 patients had a polyp
detected at their baseline OGD (median age 51 years), with the remaining 5
(with normal baseline OGDs) developing polyps over an average of 12 years
subsequently. All polyps involved D2, whilst most spared D1 and the ampulla.
8/13 cases were Spigelman stage 1 at first adenoma detection, and in only 1 case
did progression of Spigelman stage occur between OGDs (from stage 1 to 2, over
5 years, due to an increase in polyp size only). Stage 3 disease was seen in only 2
cases, both over 60 years and at their first OGD.
CONCLUSION: Duodenal polyposis is seen much less frequently in MAP com-
pared to FAP patients and this study supports that finding. Adenomas had a late
age of onset, although many had their 1st OGD at a late stage due to the timing
of their MAP diagnosis. Duodenal polyps appear to progress slowly in MAP and
it may be inappropriate to determine surveillance interval using the Spigelman
staging system given the lack of polyp multiplicity and histological progression.
A new protocol for MAP duodenal polyposis surveillance is therefore proposed.
Disclosure of Interest: None declared
OP030 POST COLONOSCOPY COLORECTAL CANCER (PCCRC). HOW
SHOULD WE CALCULATE A RATE? IMPLICATIONS FOR QUALITY
PROGRAMS
D.C. Sadowski1,*, Q., I. Ibrahim2
1
Division of Gastroenterology, Royal Alexandra Hospital, Edmonton,
2
Epidemiology Coordinating and Research Centre (EPICORE), University of
Alberta, Edmonton, Canada
INTRODUCTION: A significant proportion of detected colorectal cancers are
found in individuals who have had a colonoscopy in the previous 36 months.
These malignancies can be due to missed cancer, or cancer arising from missed or
incompletely removed polyps. The rate of post-colonoscopy colorectal cancer
(PCCRC) has been proposed as a key quality indicator for colonoscopy. A quality
indicator should be clearly defined, reproducible over time and relevant to colonos-
copists. Studies to date have calculated the rate of PCCRC as a percentage of
w n
detected colorectal cancers. This rate calculation is problematic for quality pro-
a
ithdr
grams in that the rate may fluctuate due to changes in the incidence of detected
cancers quite apart from any real improvements in colonoscopy quality. We propose
that PCCRC rates be expressed relative to the number of screening colonoscopies.
W
AIMS & METHODS: The aim of our study was to examine the feasibility of
reporting PCCRC rates relative to the number of screening colonoscopies as a
denominator and to test whether meaningful comparisons can be made when
rates vary due to colonoscopy quality interventions. We used service log data to
identify colonoscopies carried out during the last fiscal year in a regional color-
ectal cancer-screening program (Edmonton, Canada). This program serves a
population of 817,000 and delivers colonoscopy in 8 separate endoscopy units
in response to positive FIT tests, positive family history and previous history of
colonic neoplasms. A PCCRC was defined as the diagnosis of a colorectal cancer
in a patient who had undergone colonoscopy in the time period of 6-36 months
prior to diagnosis. We estimated the occurrence PCCRC from previous Canadian
studies that observed the rate of PCCRC to be approximately 8% of detected
A10
cancers. From this data we normalized PCCRC as a rate relative to the number
of screening colonoscopies performed. We then hypothesized a colonoscopy
quality intervention that would reduce the rate of PCCRCs by 50%. We calcu-
lated PCCRC rates for the region, individual endoscopy unit and individual
physician to determine the granularity by which meaningful statistical compar-
isons could be made. Confidence intervals for proportions were constructed using
RESULTS:
a w n
a Poisson distributions for rare events.
ithdr
W
Estimated # # of ScreeningRate/1000
of PCCRCsColonoscopies Colonoscopies95% CI
Regional Screening Program 10 11,374 0.88 0.42-1.62
50% Reduction in PCCRC Rate5 11,374 0.44 0.14-1.03
Single Endoscopy Unit 2 3680 0.54 0.07-1.96
Single Physician 0.4 460 0.87 0-3.56
Polish Program (6-36 Months) 33 45,000 0.73 0.50-1.03
50% Reduction in PCCRC Rate17 45,000 0.37 0.22-0.60
Kaiser Permanente (10 year) 712 314,872 2.26 2.10-2.43
50% Reduction in PCCRC Rate356 314,872 1.13 1.02-1.25
CONCLUSION: Expressing PCCRC as a rate relative to number of screening
colonoscopies is a feasible method to provide meaningful comparisons of colo-
noscopy quality. However, since PCCRC is a relatively rare event relative to the
number of colonoscopies performed, meaningful comparisons can only be pro-
vided for programs of more than 300,00 of colonoscopies per year.
Benchmarking of PCCRC across programs requires a standard definition and
calculation method.
Disclosure of Interest: None declared
OP031 GENETIC VARIANTS ASSOCIATED WITH COLORECTAL
CANCER AND ADENOMA SUSCEPTIBILITY
M. Andreu1,*, A. Abul 1, A. Castells2, L. Bujanda3, J.J. Lozano4, X. Bessa1,
C. Hernandez5, A.C. Alvarez-Urturi1, M. Pellise2, E. Hijona6, A. Buron5, and Hepatology, University Hospital Basel, Basel, Switzerland
F. Macia`5, J. Grau7, R. Guayta8, S. Castellvi2
1
Gastroenterology, Hospital del Mar, 2Gastroenterology, Hospital Clnic,
CIBERehd, IDIBAPS, Barcelona, 3Gastroenterology, Hospital Donostia/Instituto
Biodonostia, San Sebastian, 4Plataforma de Bioinformatica, CIBERehd,
5
Epidemiology and Evaluation, Hospital del Mar, 6Gastroenterology, Hospital
Donostia/Instituto Biodonostia, 7 Evaluation and prevention, Hospital Clnic,
8
Planning and Research Unit, Consell de Col.legis Farmace`utics de Catalunya,
Barcelona, Spain
INTRODUCTION: Thirty common, low-penetrant genetic variants have been
consistently associated with colorectal cancer (CRC) risk, but only few studies
have explored the contribution of these variants in colorectal adenoma suscept-
ibility. Age over 50 is the only identified and implemented stratification variable
in population-based CRC screening programs.
AIMS & METHODS: We assessed whether genetic variants associated to ade-
noma susceptibility could improve selection of average-risk population for CRC.
We selected 1,326 patients with high-risk adenomas (HRA) and 1,252 controls
were selected from population-based CRC screening programs at 3 hospitals
from Spain. We conducted a case-control association study analyzing 30 CRC
susceptibility variants in order to investigate the contribution of these variants to
the development of HRA. In addition, we built an individualized risk prediction
model in which common genetic variants were incorporated as risk factors.
RESULTS: We found that 14 of the 30 SNPs analyzed showed a statistically
significant association for HRA. We also observed that the risk of developing
HRA increased with increasing number of risk alleles, with a 2.3-fold increased
risk in individuals with  17 risk alleles. In the predictive model for HRA, ROC
curves demonstrated better discrimination ability for individuals at a younger
age, although with modest predictive performance.
CONCLUSION: Our results provided strong evidence that most genetic variants
increase CRC risk by adenoma predisposition. The risk of developing HRA
increased with multiple number of risk alleles, which may allow identifying a
subgroup of individuals at a higher risk. However, there are limitations of using
genetic variants associated with HRA to assess the risk at the individual level.
Disclosure of Interest: None declared
OP032 EVALUATION OF RECTAL CANCER RESPONSE TO THERAPY:
ROLE OF MAGNETIC RESONANCE TUMOR REGRESSION GRADE
(MR-TRG) TO PREDICT PATHOLOGICAL COMPLETE RESPONSE
M. Rengo1,*, D. Caruso1, C.N. De Cecco1, D. Bellini1, A. Laghi1
1
Department of Radiological Sciences, Oncology and Pathology, SAPIENZA
University of Rome, rome, Italy
Contact E-mail Address: marco.rengo@uniroma1.it
INTRODUCTION: To determine if a pathological complete response to therapy
in rectal cancer can be predicted by tumor regression grade evaluated by MR
(MR-TRG).
AIMS & METHODS: Thirty-seven patients, diagnosed with locally advanced
rectal cancer were prospectively enrolled in the study. All patients underwent
MRI on a 3 Tesla before, during and after chemoradiotherapy (CRT). All
patients underwent total mesorectal excision (TME). MR-TRG was evaluated
on T2-weighted fast spin-echo (FSE) multi-planar imaging. The MR-TRG was
determined by the fibrosis/tumor ratio and was divided into 4 grades based on
United European Gastroenterology Journal 2(5S)
the percentage of fibrosis (5 25%, 5 50%, 5 75%, 100%). Measurements were
performed on all axial images including the tumor. MR-TRG evaluated on the
second examination (during therapy) was correlated to the pathological finding
after surgery, defined as partial response or complete response.
RESULTS: A complete pathologic response was observed only in patients (17)
with MR-TRG 4 (100% fibrosis) with a negative predictive value of 100%. In
lower MR-TRG groups (1, 2 and 3) a partial response was observed (20 patients).
CONCLUSION: MR-TRG 4 is a accurate predictor of complete response after
CRT. When a lower MR-TRG is observed the persistence of disease should be
suspected. This method, applied during therapy, may reduce the time to surgery.
REFERENCES
Sauer R, Becker H, Hohenberger W, et al. Preoperative versus postoperative
chemoradiotherapy for rectal cancer. N Engl J Med 2004; 351: 17311740.
Valentini V, Aristei C, Glimelius B et al. Multidisciplinary Rectal Cancer
Management: 2nd European Rectal Cancer Consensus Conference (EURECA-
CC2). Radiother Oncol 2009; 92: 148163.
Guillem JG, Chessin DB, Cohen AM, et al. Long-term oncologic outcome fol-
lowing preoperative combined modality therapy and total mesorectal excision of
locally advanced rectal cancer. Ann Surg 2005; 241: 829836.
Ruo L, Tickoo S, Klimstra DS, et al. Long-term prognostic significance of extent
of rectal cancer response to preoperative radiation and chemotherapy. Ann Surg
2002; 236: 7581.
Rodel C, Martus P, Papadoupolos T, et al. Prognostic signif- icance of tumor
regression after preoperative chemoradiotherapy for rectal cancer. J Clin Oncol
2005; 23: 86888696.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 11:0012:30
SMALL BOWEL IMAGING AND ENDOSCOPIC INTERVENTIONS LOUNGE
6_____________________
OP033 DIAGNOSTIC VALUE OF FECAL CALPROTECTIN TO DETECT
SMALL BOWEL PATHOLOGY IN PATIENTS WITH PREVIOUS
NEGATIVE ENDOSCOPY
E. Burri1,2,*, N. Meuli2, C. Beglinger2
1
Medical University Clinic, Cantonal Hospital Liestal, Liestal, 2Gastroenterology
Contact E-mail Address: emanuel.burri@ksbl.ch
INTRODUCTION: The assessment of small bowel pathology with capsule endo-
scopy is laborious and costly. Therefore, the appropriate selection of patients to
increase diagnostic yield is highly anticipated. Increased levels of fecal calprotec-
tin have been measured in NSAID enteropathy and Crohns disease of the small
bowel.
AIMS & METHODS: Our aim was to examine the diagnostic value of fecal
calprotectin to detect significant small bowel pathology. We performed a post-
hoc analysis of a prospective cohort of 70 consecutive patients who had received
capsule endoscopy (Pillcam, Given Imaging, Israel), after negative bidirectional
endoscopy. Calprotectin was measured in stool samples collected within 24 hours
before the investigation using an enzyme-linked immunosorbent assay
(Buhlmann Laboratories, Switzerland). The presence of mucosal breaks in the
small bowel (erosion, ulcer, tumor) was the primary endpoint of the study. Final
diagnoses were adjudicated blinded to calprotectin values.
RESULTS: Indications for capsule endoscopy were anemia (51.4%), hematochezia
(14.3%), suspected Crohns disease (14.3%), abdominal pain (10%), suspected
malignant disease (8.6%) and unexplained diarrhea (1.4%). The prevalence of
mucosal breaks was 48.6% (n34) but 4 patients had significant lesions strictly
outside the small bowel and were not included in the analysis. Calprotectin testing
was more often positive (450g/g) in patients with mucosal findings (61.4% vs.
38.6%, P0.001) and mean calprotectin values were higher (meanstandard devia-
tion, 305289g/g vs 148228g/g, P50.001). Receiver Operating Characteristics
analysis showed an area under the curve of 0.760 (95% confidence interval 0.639-
0.857). At the optimal cut-off (63g/g), fecal calprotectin had 90.0% sensitivity and
63.9% specificity to detect mucosal inflammation. This translated in a positive and
negative likelihood ratio of 2.49 and 0.16, respectively, and resulted in a high nega-
tive predictive value (88.5%). The overall accuracy (true positive test results true
negative test results)/total population was 69.7%. In a subgroup analysis we
excluded patients with gross intestinal bleeding (N10) as this may increase fecal
concentrations of calprotectin in absence of mucosal inflammation. Fecal calpro-
tectin performed slightly better in this subset of patients (area under the curve 0.787,
overall accuracy 71.4%) but the positive and negative likelihood ratios remained
virtually unchanged (2.64 and 0.17, respectively).
CONCLUSION: Fecal calprotectin is a valid marker of intestinal inflammation
in the small bowel and might be helpful to guide diagnostic investigations.
Disclosure of Interest: None declared
OP034 CONFOCAL LASER ENDOMICROSCOPY A NEW METHOD
FOR ENDOSCOPIC ASSESSMENT OF CROHNS DISEASE
J.G. Karstensen1,*, J. Brynskov1, L.B. Riis2, P. Klausen1, J. Hendel1,
A. Saftoiu1,3, P. Vimann1
1
Gastro Unit, Division of Endoscopy, 2Department of Pathology, Copenhagen
University Hospital Herlev, Herlev, Denmark, 3Research Center of
Gastroenterology and Hepatology, University of Medicine and Pharmacy, Craiova,
Romania
Contact E-mail Address: johngkarstensen@hotmail.com
INTRODUCTION: Endoscopy is crucial to evaluate the extent and severity of
inflammation in patients with Crohns disease (CD), including the response to
treatment. Endoscopic remission is a predictor for extended surgery-free periods;
United European Gastroenterology Journal 2(5S)
however, approximately 50% of patients in deep remission on biological treat-
ment relapse within the first year after treatment cessation. Recently, confocal
laser endomicroscopy (CLE) has enabled in vivo microscopic evaluation during
endoscopy.
AIMS & METHODS: The aim of this study was to evaluate whether CLE can
identify subtle lesions in CD patients, and thus delineate deep remission and
contribute to better treatment algorithms. Patients with CD referred for ileoco-
lonoscopy were included in the study using the endoscope-based CLE system (EC
3830FK; Pentax, Tokyo, Japan). CLE images, macroscopic assessment (simple
endoscopic score for Crohns disease - SES-CD), and histopathological features
from biopsies obtained from the terminal ileum were registered. CLE findings in
terminal ileum were analysed assessing the images for fluorescein leakage over
the mucosal barrier and microerosions using the Watson Grading system, which
scores endomicroscopic changes as normal (1), functional defects (2) or structural
defects (3)[1]. These findings were correlated with the severity of disease (Fishers
Exact Test and two-side t-test). In patients with inactive CD, CLE changes were
registered and correlated to treatment escalation and all surgical interventions
during the follow-up period.
RESULTS: A total of 51 patients were enrolled in the study. Two patients were
excluded due to indeterminate colitis. Of the 49 patients in the final study group,
38 were known with CD (19 in endoscopic remission), while 11 patients (polyp
control or irritable bowel syndrome) served as controls. The mean age was 42
(18-71) years and 26 patients were female. The ileal intubation rate was 92% and
CLE imaging was obtained in 86% of patients. Comparing CD patients with the
control group fluorescein leakage and microerosions were seen in 50% vs. 10%
(p0.03) and 24% vs. 0 patients (p0.09), respectively. The Watson Score was
significantly higher in CD patients compared to controls (1,7 vs 1,2, p0.02). Of
note, fluorescein leakage and microerosions were also identified in patients with
quiescent CD (35% and 12%, respectively) despite no macroscopically or histo-
pathological abnormalities. Moreover, the Watson score was increased (2 or 3) in
35% of these patients. Three patients with endoscopic remission relapsed within
the limited follow-up period of 34 weeks (2-69); all of them had a Watson score of
2 or 3. In contrast, all of the patients with a Watson score of 1 remained in
remission.
CONCLUSION: CLE identified microscopic changes in the terminal ileum of
CD patients, even in patients with otherwise quiescent disease, suggesting that
this method may be a useful adjunct to routine endoscopy to predict relapse.
REFERENCES
[1] Kiesslich R et al. Local barrier dysfunction identified by confocal laser endo-
microscopy predicts relapse in inflammatory bowel disease. Gut 2012; 61: 1146-
1153.
Disclosure of Interest: None declared
OP035 CAN NARROW BAND IMAGING PREDICT DUODENAL
HISTOLOGY IN CELIAC DISEASE? A PROSPECTIVE DOUBLE
BLIND PILOT STUDY
S.K. Sinha1, P.K. Siddappa1,*, J. Basha1, K. Vaiphei2, K.K. Prasad1,
S. Appasani1, N. Berry1, M. Ashat1, K. Singh1, R. Kochhar1
1
Gastroenterology, 2Postgraduate Institute of Medical Education and
Research(PGIMER), Chandigarh, India
Contact E-mail Address: dr_kochhar@hotmail.com
INTRODUCTION: Celiac disease (CD) is characterized by varying degrees of
villous atrophy. Image enhancement with narrow band imaging(NBI) delineates
villous patterns better than routine endoscopy. Role of NBI in delineating villous
morphology of CD is sparsely reported.
AIMS & METHODS: To compare the diagnostic accuracy of NBI with histo-
pathology in predicting the duodenal villous morphology in CD.
Amongst the 80 subjects (mean age-26.5 12.24 years, 35-females) included in
the study, 60 were suspected to have CD (serology positive), 6 were follow up
patients of CD on gluten free diet and 14 had dyspepsia with no evidence of CD
on complete evaluation. CD was diagnosed on the basis of modified ESPGHAN
criteria. They underwent esophagogastroduodenoscopy (EGD) along with NBI
using an Olympus GIF-180 gastroscope to evaluate the villous pattern of duo-
denal mucosa. These images were digitally recorded for further characterization.
Four duodenal biopsies were taken from second part of duodenum for histo-
pathology. Digitally recorded images were analyzed by two experienced endos-
copists and biopsy specimens by an experienced pathologist all of whom were
blinded to clinical details and serological investigations. Villous patterns on NBI
were classified into normal-villous pattern (NVP), distorted & blunted-villous
pattern (DVP) and absent-villous pattern (AVP). NBI findings were correlated
with histopathology.
RESULTS: NBI revealed AVP in 27, DVP in 27 and NVP in 26 patients. In the
study group of CD (n60), 26 had AVP, 24 had DVP and 10 had NVP on NBI,
while on histopathology 27 had total villous atrophy, 20 had partial villous
atrophy and 13 had no villous atrophy. 4 CD patients on gluten free diet(n6)
and the 12 dyspepsia patients (control group) had normal villous pattern on both
NBI and histopathology. Significant correlation was observed between NBI and
histopathological examination(p50.001). The overall sensitivity and specificity
of NBI for delineating villous pattern were 87.03% and 84.61% and the positive
and negative predictive values were 92.16 % &75% respectively.
CONCLUSION: NBI can predict villous atrophy with high sensitivity and nega-
tive predictive value in CD.
Disclosure of Interest: None declared
A11
OP036 CLINICAL USEFULNESS OF VIRTUAL ENTEROSCOPY FOR
CROHNS DISEASE
T. Yoshikawa1,*, N. Suzuki1, N. Shirane1, T. Kurokami1, M. Shigetomo1,
H. Aoyama1, K. Enokida1, M. Kikuyama1
1
Gastroenterology, Shizuoka General Hospital, Shizuoka, Japan
Contact E-mail Address: t-yoshi@med.nagoya-u.ac.jp
INTRODUCTION: The technique of virtual colonoscopy can be used to explore
the colon as well as the small bowel. The clinical performance of Virtual
Enteroscopy (VE) was analyzed to evaluate the safety, feasibility, and the useful-
ness in Crohns disease.
AIMS & METHODS: VE was performed using the protocol reported pre-
viously1) with some modifications. The data of 130 examinations of VE per-
formed in our hospital from November 2006 to February 2014 were reviewed,
and the data of patients with Crohns disease were analyzed.
RESULTS: Thirty-nine VEs were performed in Crohns disease, for 27 males and
12 females. The examinations were indicated when Crohns disease was suspected
in 3, when diagnosis of Crohns disease was made in 8, when biologic response
modifier was planned or started in 4, when the disease was exacerbated in 19, and
during remission in 5 cases. The mean years after the diagnosis of Crohns disease
was 10.1; mean age was 35.4 /- 11.0 at the examination. The volume of air and
intraintestinal pressure were recorded in 19 examinations for patients without
previous resection of the small bowel with the indicators specially produced for
this examination. The mean total volume of the injected air was 1802 /- 784 ml,
the mean maximum intraintestinal pressure was 2.45 /- 0.67 kPa, the mean
length of depicted small bowel was 472 /- 80 cm, and whole small bowel
trace was achieved in 79% of these 19 examinations. In 39 examinations, stenoses
with wall thickness were found in 35. Resection of the small bowel was performed
and comparisons of the findings in the VE examination and the resected sample
were possible in 5 patients. The appearance of new stenoses was observed
between two examinations in one patient. The cobble stone appearance was
depicted and confirmed by balloon enteroscopy in one case. The ileo sigmoid
colonic fistula was depicted in one case. Balloon dilation therapy was planned
according to the results of the examination and performed successfully. The
mean length of the remaining small bowel was 246.5 /- 133.9 cm in 11 patients
with previous resection of the small bowel and the risk of short small bowel
syndrome was assessed when re-resection was considered. In 39 examinations,
vomiting and abdominal pain (requiring pain medication) were noted in 4 and 3
patients, respectively, but no additional treatments were necessary. No other
complication was observed.
CONCLUSION: VE can be performed safely and examination of the whole
small bowel was possible in most of the cases with Crohns disease, despite the
presence of stenosis. VE can depict characteristic findings, locate the position of
the lesions, and measure the length of the small bowel objectively. VE is a power-
ful new tool for diagnosis, pre-treatment evaluation, and follow up for Crohns
disease.
REFERENCES
1) Yoshikawa T, Takehara Y, Kikuyama M, et al. Computed tomographic
enteroclysis with air and virtual enteroscopy: protocol and feasibility for small
bowel evaluation. Dig Liver Dis 2012; 44; 297-302.
Disclosure of Interest: None declared
OP037 EFFECTIVENESS AND SAFETY OF ENDOSCOPIC BALLOON
DILATATION FOR STRICTURES IN CROHNS DISEASE A
MULTICENTER STUDY
Z. Szepes1,*, A. Balint1, D. Torocsik1, K. Palatka2, M. Szucs3, F. Nagy1,
K. Farkas1, R. Bor1, T. Wittmann1, T. Molnar1
1
First Department of Medicine, University of Szeged, Szeged, 22nd Department of
Medicine, University of Debrecen, Debrecen, 3Department of Medical Physics and
Informatics, University of Szeged, Szeged, Hungary
Contact E-mail Address: molnar.tamas@med.u-szeged.hu
INTRODUCTION: Crohns disease (CD) is a chronic inflammatory disease
which frequently complicates by obstructive symptoms secondary to develop-
ment of intestinal strictures.
AIMS & METHODS: The aim of this study was to assess effectiveness, safety of
endoscopic balloon dilatation (EBD). Data of 92 EBD in 45 CD patients were
retrospectively analyzed. 15.2 % of procedures were performed in upper gastro-
intestinal (GI) tract and 84.8% in lower GI tract. Short-term success rate was
defined as the ability of endoscope to traverse the stenosis after dilatation. Long-
term clinical success rate was claimed if a patient remained asymptomatic and did
not require surgery or further EBD, following technical success. Prognostic fac-
tors of outcome were statistically assessed.
RESULTS: 63.04 % of strictures were de novo and 36.96% anastomotic. The
mean time between diagnosis and development of strictures with symptoms was
7.26 (0-27) years. The elapsed time between diagnosis and the first balloon dila-
tation was 9.55 (0-35) years. 72.8 % of dilatations were successful on short-term
period without serious complications. 21 (46.6 %) patients showed that EBD is
effective on long-term period. Type of strictures, biological therapy before or
after dilatation, immunomodulatory therapy and the time between diagnosis and
first EBD did not have influence on long-term effectiveness. 7 subjects had need
for surgery due to strictures after EBD.
CONCLUSION: The result of this study highlights that EBD is an effective
therapy of the short strictures in CD with low complication rate. Using this
endoscopic method we can avoid surgical interventions in most of the cases.
The success rate is independent of the previous and current therapy, duration
of the disease and the type of stenosis.
Disclosure of Interest: None declared
A12
OP038 EFFICACY OF ENDOSCOPIC BALLOON DILATION FOR
SMALL BOWEL STRICTURES IN PATIENTS WITH CROHNS
DISEASE: A NATIONWIDE, MULTI-CENTER, OPEN-LABEL,
PROSPECTIVE COHORT STUDY
F. Hirai1,*, T. Matsumoto2, T. Matsui1
1 1
Department of Gastroenterology, Fukuoka University Chikushi Hospital,
Chikushino, 2Division of Gastroenterology, Department of Internal Medicine, Iwate
Medical University, Morioka, Japan
INTRODUCTION: Endoscopic balloon dilation (EBD) has been known to be
useful for strictures in Crohns disease (CD) that can be approached by colono-
scopy. Recently, EBD by means of balloon-assisted enteroscopy (BAE) has
become a possible procedure for small bowel strictures as an alternative to
surgery.
AIMS & METHODS: The efficacy and safety of this treatment remain unclear.
Therefore, a nationwide, multi-center, open-label, prospective cohort study was
conducted.This study was carried out prospectively within the framework of a
study project undertaken by the Study Group on Intractable Diseases, the Health
and Labor Sciences Research Grants from the Ministry of Health, Labour and
Welfare of Japan. Subjects from twenty-three institutions were registered in this
study. The study subjects were CD patients who had symptomatic small bowel
strictures. Patients with strictures of the colon or in the neo-terminal ileum were
excluded. Symptoms associated with small bowel strictures (abdominal pain,
abdominal bloating, and nausea) were evaluated by visual analogue scale
(VAS) scores before and 4 weeks after the initial EBD. A short-term success of
EBD was defined as improvement of all three VAS scores. As an interim analysis,
the short-term success rate and the adverse events in patients registered from Aug
2011 to Oct 2013 were analyzed.
RESULTS: One hundred and twelve patients were included in this study. EBD
could not be performed in 10 patients for various reasons. Of the remaining 102
patients, VAS scores of both before and 4 weeks after EBD were available in 69
patients at the time of this analysis. The treatment outcome was therefore ana-
lyzed in those 69 patients (50 male, 19 female, disease duration: 10.7 8.2 years).
The short-term success rate was 73% (50/69). After EBD, the scope could pass
through the stricture in 76% (54/69). There was not any significant difference in
patients characteristics or in the nature of stricture between successful and
unsuccessful cases. Complications were encountered in two of the 69 patients
(2.9%). These were all hemorrhage and the patients recovered by conservative
therapy.
CONCLUSION: EBD was effective and safe for small bowel strictures in CD
patients. We are going to clarify the long-term outcome of EBD in this study.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 14:0015:30
NEW THOUGHTS ON FUNCTIONAL DYSPEPSIA HALL B_____________________
OP039 FASTING PYLORIC PRESSURE AND COMPLIANCE IN
GASTROPARESIS
F. Tissier1,2, C. Melchior1, O. Touchais1, A.-M. Leroi1,3, P. Ducrotte1,2,
G. Gourcerol1,4,*
1
Digestive Physiology Department, 2HepatoGastroenterology Department,
3 F1_____________________
Clinical Investigation Center, 4Nutrition, Brain and Gut Laboratory, INSERM
unit 1073, Rouen University Hospital, Rouen, France
INTRODUCTION: Gastroparesis is defined by a delayed of gastric emptying
associated with dyspeptic symptoms. Delayed gastric emptying may result from
impairment in gastric and/or pyloric motility. To date, the role of pyloric pres-
sure and/or compliance in gastroparesis has however been poorly investigated.
AIMS & METHODS: Fasting pyloric pressure and compliance were assessed
using EndoFLIP technique (intrapyloric balloon inflated to 40 ml) in 21
healthy volunteers (HV), 24 Gastroparetic Patients (GP; diabetic: n3; post-
surgical: n3; idiopathic: n16), and in 4 patients who underwent esophagect-
omy without pyloroplasty as positive controls. Endoflip probe was positioned
without anesthesia, under videofluoroscopic control. Gastric half-emptying time
(T1/2) was measured using the 13Coctanoic acid breath test. Dyspeptic symp-
toms were recorded using a 5 point-rated scale and quality of life using gastro-
intestinal quality of life index (GIQLI).
RESULTS: Using Endoflip, the mean fasted pyloric compliance was 25.22.4
mm2/mmHg in HV. Fasted pyloric compliance decreased both in GP (17.62.4
mm2/mmHg; p50.05) and patients with esophagectomy (11.23.7 mm2/mmHg;
p50.05). By contrast, fasting pyloric pressure was not different between HV
(9.61.0), GP (12.11.0 mmHg; p40.05) and control (12.51.6 mmHg;
p40.05). Fasting pyloric compliance was inversely correlated with T1/2 in GP
(R-0.43; p0.03), while fasting pyloric pressure did not (R0.28; p0.15). AIMS & METHODS: 380 patients with Child-Pugh A cirrhosis were rando-
Fasting pyloric compliance was also inversely correlated with nausea, vomiting,
regurgitation, gastric fullness, early satiety, and dyspeptic symptomatic score. In
contrast, fasting pyloric pressure was only correlated with nausea and regurgita-
tion. Fasting pyloric compliance, but not pressure, was correlated with the
GIQLI score (R0.31; p0.02 and R-0.23; p0.10). In 8 GP with low fasting treatment and post-treatment periods, and summarized by treatment group.
pyloric compliance (510 mm2/mmHg) an hydraulic dilation of the pylorus
(20mm), improved fasting pyloric compliance from 7.40.4 to 20.14.9 mm2/
mmHg (p50.01). Dilatation also improved the T1/2 in 6/7 patients and quality
of life in 5/8 patients.
CONCLUSION: This study is the first to assess the pyloric compliance in GP.
Fasting pyloric compliance seems to be decreased in GP. Fasting pyloric com-
pliance, but not pressure, was inversely correlated with T1/2, dyspeptic symptoms
and quality of life. This suggests that pyloric compliance may play a role in
gastric emptying.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP040 ASSOCIATION OF SERUM ADIPOCYTOKINE AND GUT
HORMONE LEVELS WITH GASTRIC EMPTYING AND SYMPTOM
PERCEPTION IN PATIENTS WITH FUNCTIONAL DYSPEPSIA
P.-H. Tseng1,*, J.-M. Liou1, Y.-C. Lee1, J.-T. Lin1,2, M.-S. Wu1 on behalf of
Taiwan, GI disease and, Helicobacter consortium
Department of Internal Medicine, National Taiwan University Hospital, Taipei,
2
School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan,
Province of China
Contact E-mail Address: pinghuei@ntu.edu.tw
INTRODUCTION: The pathogenesis of functional dyspepsia (FD) is complex
and has been associated with a variety of gastrointestinal motor and sensory
dysfunction. Several peptide hormones secreted by the adipose tissue and the
gut play an important role in regulating food intake, gastrointestinal motility
and energy balance.
AIMS & METHODS: To investigate the association of circulating adipocyto-
kines and gut hormones with gastric emptying and symptom perception in FD
patients, we conducted a case-control study in 40 FD patients (16 male and 24
female; age: 5012) and 40 asymptomatic healthy volunteers matched for age
and gender. Basic demographics, including complete anthropometric measures,
were obtained. All subjects underwent a 3-h gastric emptying scintigraphy using
radiolabeled oatmeal as the test meal and quantitative emptying parameters were
determined. On the day of scintigraphy, dyspeptic symptoms during the preced-
ing two weeks were evaluated using the 9-item Gastroparesis Cardinal Symptom
Index. Fasting serum levels of adipocytokines (adiponectin and leptin) and gut
hormones (ghrelin, obestatin and peptide YY) were assayed in all subjects with
ELISA methods.
RESULTS: Anthropometric measures, including body mass index and waist
circumference, were similar between the 2 groups. FD patients had significantly
longer gastric half-emptying time T1/2(57.119.2 vs. 48.78.0 min, p50.001) and
greater gastric retention at 1 h and 2 h (46.418.8 vs. 39.411.3, p0.046;
11.710.3 vs. 7.54.8, p0.023) when compared with healthy controls. Five
patients with FD (12.5%) had delayed gastric emptying. FD patients had sig-
nificantly lower adiponectin levels (7.63.4 vs. 11.45.0, p50.001) but higher
obestatin levels (4.91.8 vs. 3.90.6, p0.003). Both adiponectin and leptin
levels correlated with gastric retention at 1 h (r0.619 and -0.582; p0.011
and 0.018, respectively) in male but not in female FD patients. All adipocytokine
and gut hormone levels were not significantly different between FD subjects with
or without delayed gastric emptying. Leptin levels positively correlated with
visibly larger stomach or belly after a meal (r0.358, p0.024) while ghrelin
levels positively correlated with early satiety (r0.364, p0.023) and loss of
appetite (r0.353, p0.028).
CONCLUSION: Gastric dysmotility and derangement of various circulating
adipocytokines and gut hormones might participate in the heterogenous mani-
festations of FD patients. Further studies to elucidate the potential roles of these
peptide hormones in the pathophysiology of FD and their clinical implication are
warranted.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 14:0015:30
CLINICAL CHALLENGES IN HEPATITIS C VIRUS THERAPY HALL
OP041 NORMALIZATION OF LIVER-RELATED LABORATORY
PARAMETERS IN HCV GENOTYPE 1-INFECTED PATIENTS WITH
CIRRHOSIS AFTER TREATMENT WITH ABT-450/R/OMBITASVIR,
DASABUVIR AND RIBAVIRIN
S. Zeuzem1,*, P. Andreone2, S. Pol3, M. Bourlie`re4, A. Castro5, M. Berenguer6,
S. Lee7, G. Everson8, S. Lovell9, M. Pedrosa9, R. Trinh9
1
J.W. Goethe University, Frankfurt, Germany, 2University of Bologna, Bologna,
Italy, 3Groupe Hospitalier Cochin-Saint Vincent De Paul, Paris, 4Hopital Saint
Joseph, Marseille, France, 5Hospital Universitario La Fe, Valencia, 6Complejo
Hospitalario Universitario A Coruna, A Coruna, Spain, 7University of Calgary,
Calgary, Canada, 8University of Colorado Denver and Hospital, Aurora, 9AbbVie
Inc., North Chicago, United States
INTRODUCTION: HCV-infected patients with cirrhosis are at increased risk for
hepatocellular carcinoma and liver-related mortality, which can be significantly
reduced if treated and the patient achieves a sustained virologic response. We
report the changes in liver-related laboratory parameters after 12 or 24 weeks of
treatment with the 3 direct-acting antiviral (3D) regimen of ABT-450/r/ombitas-
vir, dasabuvir, and ribavirin (RBV) among 380 treatment-na ve and peginter-
feron/RBV-experienced HCV genotype 1-infected patients with cirrhosis.
mized (approximately 1:1) to receive the 3DRBV regimen for 12 or 24 weeks.
Key eligibility criteria included platelet count 60,000 cells/mm3, serum albumin
2.8 g/dL, and total bilirubin 53 mg/dL. Laboratory testing, including chem-
istry, hematology, and urinalysis, were conducted at each study visit during the
RESULTS: SVR12 was achieved in 92% and 96% of patients receiving the 12-
and 24-week treatments, respectively. At the end of treatment with 3DRBV,
liver enzymes were normalized in most patients with baseline elevations regard-
less of treatment duration (ALT, 323/347 [93.1%]; AST, 316/360 [87.8%]; GGT,
284/307 [92.5%]). Mean liver enzyme values were normalized by Week 4. Of
patients with platelet counts 5LLN at baseline, counts were normalized in
28.8% of patients at the end of treatment. Activated partial thromboplastin
time was normalized at the end of treatment in 47/67 (70.1%) and 46/51
(90.2%) of 12-week and 24-week 3DRBV patients with values 4ULN at base-
line. Mean total bilirubin values peaked at Week 1 (predominantly indirect),
subsequently decreased to the end of treatment, and normalized post-treatment.
United European Gastroenterology Journal 2(5S) A13
OP041

12-Wk 3DRBV 24-Wk 3DRBV

Post-treatment Post-treatment
Parameter Baseline Wk12 Wk12 Baseline Wk12 Wk24 Wk12

Alanine aminotransferase, U/L 99 24 32 100 22 19 28

Aspartate aminotransferase, U/L 88 27 33 92 26 24 29
Gamma glutamyl transferase, U/L 123 28 47 132 29 28 46
Total bilirubin, mg/L 8.5 11.5 7.1 8.8 10.2 9.7 6.5
Indirect bilirubin, mg/L 5.5 8.3 5.3 5.7 7.3 7.1 4.9
Activated partial thromboplastin time, sec 31 28 29 30 27 28 28
Platelet count, x103/mL 151 175 155 152 179 172 159
International normalized ratio 1.1 1.1 1.1 1.1 1.1 1.1 1.1

CONCLUSION: Treating HCV genotype 1-infected patients with the 3DRBV OP043 REVISITING LIVER DISEASE PROGRESSION IN HIV/HCV-
regimen resulted in high SVR rates and normalization of liver-related chemistry COINFECTED PATIENTS: THE INFLUENCE OF VITAMIN D,
and coagulation profile abnormalities often present in patients with cirrhosis. INSULIN RESISTANCE, IMMUNE STATUS, IL28B AND PNPLA3
Disclosure of Interest: S. Zeuzem Consultancy for: AbbVie, Achillion, BMS, M. Mandorfer1,*, B.A. Payer1, P. Schwabl1, S. Steiner1, A. Ferlitsch1,
Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Novartis, Roche, M.C. Aichelburg2, A.F. Stattermayer1, P. Ferenci1, B. Obermayer-Pietsch3,
Santaris, Vertex, P. Andreone Financial support for research from: Roche, K. Grabmeier-Pfistershammer2, M. Trauner1, M. Peck-Radosavljevic1,
Merck, Gilead, Consultancy for: Roche, Merck, Janssen Cilag, AbbVie, T. Reiberger1 on behalf of Vienna HIV &, Liver Study Group
Boehringer Ingelheim, Gilead, BMS, S. Pol Lecture fee(s) from: GSK, 1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
Consultancy for: Sanofi, BMS, Boehringer Ingelheim, Tibotec, Janssen Cilag, III, 2Division of Immunology, Allergy and Infectious Diseases, Department of
Vertex, Gilead, Roche, MSD, Novartis, AbbVie, M. Bourlie`re Lecture fee(s) Dermatology, Medical University of Vienna, Vienna, 3Division of Endocrinology
from: D, Janssen, Gilead, AbbVie, Consultancy for: BMS, Vertex, MSD, and Metabolism, Department of Internal Medicine, Medical University Graz, Graz,
Janssen, Gilead, AbbVie, Roche, A. Castro Consultancy for: AbbVie, BMS, Austria
Janssen, Merck, Roche, M. Berenguer Consultancy for: BMS, Janssen, Roche, Contact E-mail Address: thomas.reiberger@meduniwien.ac.at
MSD, Novartis, AbbVie, S. Lee Financial support for research from: AbbVie,
BMS, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, Vertex, INTRODUCTION: The importance of endocrine, metabolic, genetic and immu-
Lecture fee(s) from: BMS, Gilead, Merck, Roche, Vertex, Consultancy for: nologic factors in the natural history of HIV/hepatitis C virus (HCV) coinfection
AbbVie, BMS, Boehringer Ingelheim, Gilead, Idenix, Janssen, Merck, Roche, has increasingly gained recognition.
Vertex, G. Everson Financial support for research from: AbbVie, Vertex, BMS, AIMS & METHODS: We aimed to perform a comprehensive study on indepen-
Merck, Roche/Genentech, Gilead/Pharmasset, GSK, Novartis, Tibotec, Janssen, dent modulators of liver fibrosis progression and determinants of portal pressure
Consultancy for: AbbVie, Vertex, BMS, Merck, Roche/Genentech, Gilead, considering immune status, insulin resistance (IR), serum 25-hydroxyvitamin D
GSK, Novartis, Esai, Biotest, Other: HepQuant LLC, S. Lovell Shareholder levels (25(OH)D), genetic variants of patatin-like phospholipase domain-contain-
of: AbbVie, Other: AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: ing protein 3 (PNPLA3) and interleukin 28B (IL28B) in a thoroughly documen-
AbbVie, R. Trinh Shareholder of: AbbVie, Other: AbbVie ted cohort of HIV/HCV-coinfected patients.
25. OH)D deficiency (25(OH)DDEF), IR and low CD4 T-lymphocyte nadir
(lowCD4NAD) were defined as 25(OH)D520ngxmL-1, HOMA-IR42 and
OP042 CORRECTION OF VITAMIN D DEFICIENCY CORRELATED CD4nadir5200cellsxL-1, respectively. Liver fibrosis progression rate (FPR)
WITH SUPPRESSION OF SOLUBLE CD26 LEVELS (SCD26) AND was calculated as METAVIR F units divided by the number of years since
INTERFERON-GAMMA-INDUCIBLE PROTEIN 10 (IP-10) IN HCV-infection. Patients with a FPR 4median FPR were assigned to the
PATIENTS WITH CHRONIC HEPATITIS C: A RANDOMIZED, highFPR group.
DOUBLE-BLINDED, PLACEBO-CONTROLLED PILOT STUDY RESULTS: Among 86 HIV/HCV, the median FPR was 0.1667unitsxyears-1.
K. Charoensuk1,2,*, C. Chirathaworn3, S. Suksawatamnuay2, P. Komolmit2 While the prevalence of prior alcohol abuse, lowCD4NAD and 25(OH)DDEF
1
Gastroenterology, Department of Internal Medicine, Buddhachinaraj hospital was higher among highFPR patients, the prevalence of IR was comparable. The
School of Medicine, Phitsanulok, 2Gastroenterology, Department of Internal association between 25(OH)DDEF and FPR
medicine, Chulalongkorn university, 3Division of Immunology, Department of (highFPR:90%vs.lowFPR:31%;P50.001) was confirmed in a subgroup of
Microbiology, Chulalongkorn university, Bangkok, Thailand patients with METAVIR F0/F1/F2 in which 25(OH)D levels are not affected
Contact E-mail Address: hut_kriangsak@hotmail.com by the severity of liver disease. The distribution of IL28B C/C and PNPLA3 non-
C/C was similar, while PNPLA3 G/G was exclusively observed in highFPR
INTRODUCTION: Vitamin D deficiency, serum IP-10 levels and IL28B poly- patients.
morphisms are used to predicted favorable treatment outcome in chronic hepa-
titis C (CHC). CD26 (DPPIV) truncates the chemokine IP-10 into a shorter
antagonistic form. Previous studies, this truncated IP-10 and CD26 has been Patient characteristics lowFPR n49 highFPR n37 P value
shown to correlate with disease activity and also influence treatment outcome
in CHC patients. We hypothesized that vitamin D supplement, which shown to Prior alcohol abuse 12 (25%) 17 (46%) 0.037
improve CHC treatment response, might restore immune dysregulation in these 25(OH)DDEF 20 (41%) 29 (78%) 50.001
patients through a pathway linked to the Th1/Th2 cytokines, IP-10 or CD26. The
purpose of this study was to investigate the association between vitamin D sup- IR 27 (55%) 18 (49%) 0.553
plement, IP-10 and sCD26 levels in these patients. lowCD4NAD 11 (22%) 16 (43%) 0.04
AIMS & METHODS: We conducted the double-blind, placebo-controlled, inter- IL28B C/C 15 (31%) 14 (38%) 0.483
ventional study; CHC patients with vitamin D deficiency were assigned to receive PNPLA3 non-C/C 21 (43%) 17 (46%) 0.775
vitamin D supplement or placebo for 6 weeks. 25-hydroxyvitamin D (25(OH)D)
levels, Th1/Th2 cytokines, IP-10 and sCD26 levels were measured at baseline and PNPLA3 G/G 0 (0%) 4 (11) 0.031
at 6 weeks. Baseline characteristics were assessed. LowCD4NAD (OR:2.947;95%CI:1.05-8.24;P=0.034) and 25(OH)DDEF
RESULTS: A total of 80 CHC patients with vitamin D deficiency were rando- (OR:5.62;95%CI:2.05-15.38;P50.001) were independently associated with
mized into two groups, 40 patients in each group. There were no significant highFPR and showed an additive effect. Portal pressure correlated with prior
differences in all baseline characteristics between two groups. At the end of alcohol abuse (=0.447;P50.001), HCV-genotype 3 (=0.252;P=0.034),
study, only the mean 25(OH)D levels in vitamin D group were significantly CD4+ nadir (=-0.288;P=0.015), lowCD4NAD (=0.286;P=0.016) and
increased from 21.07 to 48.44 ng/ml, (p50.001).While no significant changes 25(OH)D (=-0.246;P=0.038).
of the IP-10 levels was demonstrated in placebo group, there were significant CONCLUSION: Two potentially modifiable factors, CD4 nadir and
decreasedin serum IP-10 and sCD26 in vitamin D group after 6-week of vitamin 25(OH)D, were both independent modulators of liver fibrosis progression and
D supplement (p5 0.05). However, there were no significant differences in serum determinants of portal pressure. Further studies are warranted to assess the
levels of all Th1/Th2 cytokines studied both groups. relevance of PNPLA3 for FPR in HIV/HCV. The findings of our study suggest,
CONCLUSION: This study demonstrated that vitamin D supplement and that early initiation of combined antiretroviral therapy, as well as vitamin D
restoration of 25(OH)D level in CHC patients resulted in suppression of serum supplementation and vitamin D receptor ligands could be of therapeutic value
IP-10 and sCD26 levels without changes in systemic Th1/Th2 immune cytokines. for the reduction liver fibrosis progression in HIV/HCV-coinfected patients.
These results connect the link and give one explanation of why vitamin D defi- Disclosure of Interest: None declared
ciency, pre-treatment high serum IP-10 levels, sCD26 level and by treatment of
vitamin D deficiency could have effects on CHC treatment responses.
Disclosure of Interest: None declared
A14
OP044 MICRORNA-21 AND PTEN: A SIMPLE PREDICTIVE MODEL
FOR FIBROSIS IN CHC PATIENTS
S.J. Chowdhury1,*, V. Karra1, P. Gumma1, P. Kar1
1
Medicine, Maulana Azad Medical College, New Delhi, India, New Delhi, India
Contact E-mail Address: soumya.molbio@gmail.com
INTRODUCTION: Down regulation of PTEN in Chronic Hepatitis C has been
associated with steatosis and increase in fibrosis. Even though many predictive
model have been evaluated on the basis of biochemical parameter, PTEN expres-
sion and factors affectng its expression has not been studied.
AIMS & METHODS: This study aims at finding if there is any correlation
between increasing fibrosis and variables like PTEN, miR-21, HCV RNA
levels, HCV genotype and other biochemical parameters and to draw a predic-
tion model out from the dependable variables. Study consisted of 84 CHC
patients whose miR-21, PTEN expression, HCV RNA levels were estimated by
Real Time QPCR. All the CHC patients had undergone liver biopsy and were
grouped into 3 fibrosis group, viz. F0 (Fibrosis score 0), FM(Fibrosis 1& 2), TREATED WITH ABT-450/RITONAVIR/OMBITASVIR AND
FH (Fibrosis 3). 76 Healthy blood donors were selected randomly and were
evaluated for any history of liver disease. The PTEN and mir21a expression levels
have been described in 2Cp where CpCt (Household gene)-Ct(target gene) and so
positive 2Cp values depicts decrease in expression against the housekeeping gene
concentration which is, in this case, GAPDH for RNA expression and U6 for
micro RNA.
RESULTS: The average age (MeanS.D) of CHC and control group was
42.5511.258 and 33.426.293 years respectively. There was statistical signifi-
cant difference in PTEN(2Cp) between the mean rank of control (22.93) and
Cases(56.93) (U130.5, p50.001). There was statistical significant difference
miR-21(2Cp) levels between the mean rank of control (60.09) and CHC(22.7)
(U53.5, p50.001). Univariate analysis and post-Hoc test between the fibrosis
group (F0,FM&FH) resulted in statistical significant difference in T.Bil
FM(0.70.306)mg/dl & FH(1.13.563)mg/dl (p.014), PTEN(2Cp) expression
FM(4.770.415) & FH(37.5210.37) (p50.0001), miR21(2Cp) expression
F0(3.66.08), FM(2.70.50)&FH (1.480.09), (p50.0001). Multinominal logis-
tic regression was done to find out the predictor of increasing fibrosis with above
variables and it was found that only PTEN(2Cp) predicted FH from FM with
statistical significance (B-1.5, p50.0001). Multiple regression was carried
out to predict PTEN(2Cp) from T.Bil and miR21(2Cp). These variables signifi-
cantly predicted PTEN(2Cp), F(2,39)46.69, p50.0001, R20.705 and the
two variables added statistically significantly to the prediction, p50.001. The
regression equation obtained predicted PTEN(2Cp)40.63-
(13.85xmi21a(2Cp))(10.65xT.Bil). Using this model new cut-off value of
PTEN(2Cp) was calculated using ROC with Area under curve 0.983 and cut-
off level 424.22 was found to predict advance fibrosis (Fibrosis 3)
(sensitivity92.86, Specificity89.29). It had a positive predictive value (PPV)
of 82.35% and negative predictive value (NPV) of 100%.
CONCLUSION: From our study we conclude that decrease in PTEN mRNA
expression is significantly associated with increase in fibrosis and that there is
negative correlation between PTEN expression and miR21 expression. Other
than PTEN, miR21 expression levels and Total bilirubin none of the other fac-
tors significantly correlated to either PTEN, miR21 or fibrosis. Our predicitive
model predicted PTEN(2Cp) using T.Bil and miR21(2Cp) which predicted advance
fibrosis(fibrosis 3) with PPV and NPV of 92.86 and 89.2 respectively.
Disclosure of Interest: None declared
OP045 ANTIVIRAL TREATMENT AND RISK OF END-STAGE RENAL
DISEASE IN PATIENTS WITH HEPATITIS C VIRUS INFECTION
Y.-C. Hsu1,*, J.-T. Lin2, H.J. Ho3, C.-Y. Chang1, C.-Y. Wu4
1
Department of Internal Medicine, E-DA HOSPITAL/I-SHOU UNIVERSITY,
Kaohsiung, 2School of Medicine, Fu Jen Catholic University, 3School of Medicine,
Fu Jen Catholic University, New Taipei, 4Department of Internal Medicine,
Taichung Veterans General Hospital, Taichung, Taiwan, Province of China
Contact E-mail Address: holdenhsu@gmail.com
INTRODUCTION: Hepatitis C virus (HCV) infection can lead to renal compli-
cations and increase the risk of end-stage renal disease (ESRD).1 It remains
unknown, however, whether antiviral treatment is associated with risk reduction
of ESRD in HCV-infected individuals.
AIMS & METHODS: This nationwide cohort study aimed to investigate
whether antiviral treatment for HCV infection is associated with attenuation in
the risk of ESRD.
We firstly screened all Taiwanese residents (n293,480) diagnosed with hepatitis
C virus infection from 1997 through 2011, based on analysis of the Taiwan
National Health Insurance Research Database, which has been prospectively
recording claim data of all reimbursed healthcare service in this country since
1995 Those with physical or psychiatric conditions that might contraindicate or
confound antiviral treatment were excluded. A total of 12,384 eligible patients
who had received pegylated interferon plus ribavirin between October 1, 2003
and December 31, 2010 were enrolled in the treated cohort, and were matched 1:2
with 24,768 untreated controls in the propensity score. Occurrence of end-stage
renal disease was compared between the treated and untreated cohorts after
adjustment for multiple confounders including the competing mortality.
RESULTS: During the follow-up for the years 2003 through 2011, the 8-year
cumulative incidence of ESRD was significantly lower in the treated than in the
untreated cohort, 0.15% (95% confidence interval [CI], 0.04-0.26%) versus
1.32% (95% CI, 1.01-1.64%; p50.001). Multivariate-adjusted analyses con-
firmed the association between antiviral therapy and a lower risk of end-stage
renal failure (adjusted hazard ratio [HR], 0.15; 95% confidence interval [CI],
0.07-0.31), whereas diabetes mellitus (adjusted HR, 20.85; 95% CI, 12.67-
34.29), male gender (adjusted HR, 1.79; 95% CI, 1.16-2.75), hypertension
(adjusted HR, 1.54; 95% CI, 1.04-2.28), and management in a local community
United European Gastroenterology Journal 2(5S)
hospital (adjusted HR, 1.99; 95% CI, 1.18-3.36) were associated with excessive
risks. Intriguingly, the risk was not attenuated in patients receiving incomplete
therapy shorter than 16 weeks.
CONCLUSION: Antiviral treatment for HCV is associated with risk reduction
in ESRD. These findings suggest the extrahepatic effectiveness of treating HCV
infection in improving renal outcome.
REFERENCES
1. Su FH, Su CT, Chang SN, et al. Association of hepatitis C virus infection with
risk of ESRD: a population-based study. Am J Kidney Dis 2012; 60: 553-560.
2. Hsu YC, Lin JT, Ho HJ, et al. Antiviral treatment for hepatitis C virus
infection is associated with improved renal and cardiovascular outcomes in dia-
betic patients. Hepatology 2014; 59: 1293-302.
Disclosure of Interest: None declared
OP046 MANAGEMENT OF HAEMOGLOBIN DECREASE IN PATIENTS
DASABUVIR WITH OR WITHOUT RIBAVIRIN IN HCV GENOTYPE
1-INFECTED PATIENTS
M. Diago1, P. Andreone2, D. Forton3, H. Reesink4, V. Rustgi5, D. Bernstein6,
T. Sepe7, J. Vierling8, W. King9, Y. Hu10, J. Enejosa10, D. Cohen10, Y. Luo10,
M. Pedrosa10, P. Ferenci11,*
1
Hospital Quiron de Valencia, Valencia, Spain, 2Azienda Ospedaliero Universitaria
Policlinico S. Orsola Malpighi, Bologna, Italy, 3St. Georges, University of
London, London, United Kingdom, 4Academisch Medisch Centrum, Universiteit
van Amsterdam, Amsterdam, Netherlands, 5Metropolitan Research, Fairfax,
6
North Shore University Hospital (BRANY), Manhasset, 7University
Gastroenterology, Providence, 8St. Lukes Episcopal Hospital / St. Lukes
Advanced Liver Therapies, Houston, 9Trial Management Associates, LLC,
Wilmington, 10AbbVie, North Chicago, United States, 11Medical University of
Vienna, Vienna, Austria
Contact E-mail Address: moisesdiagom@gmail.com, laurinda.cooker@abbvie.com
INTRODUCTION: Ribavirin (RBV), which may be associated with anaemia, is
commonly prescribed with direct-acting antivirals for treatment of hepatitis C
virus (HCV) infection. The randomized phase 3 PEARL trials evaluated the
safety and efficacy of the 3D regimen of ABT-450/ritonavir/ombitasvir (for-
merly ABT-267) and dasabuvir (formerly ABT-333) with or without RBV in
HCV genotype 1b-infected treatment-experienced (PEARL-II) or treatment-
na ve (PEARL-III) patients, and in genotype 1a-infected treatment-na ve
(PEARL-IV) patients.
AIMS & METHODS: The management of decreased haemoglobin was deter-
mined using data from the 910 patients enrolled in PEARL-II (n186), PEARL-
III (n419), and PEARL-IV (n305) trials. In each trial, HCV genotype 1-
infected patients were randomized to 12 weeks of treatment with the 3D regimen
RBV (co-formulated ABT-450/r/ombitasvir [150mg/100mg/25mg QD] and
dasabuvir [250mg BID] with weight-based RBV [1000 or 1200 mg daily divided
BID]), or 3Dplacebo for RBV (PEARL-III and -IV) or 3D without RBV
(PEARL-II). Haemoglobin was assessed at baseline and throughout treatment
and follow-up periods. Decreases from baseline in haemoglobin during the treat-
ment period and patient outcomes are reported.
RESULTS: Among patients with normal baseline haemoglobin values, on-treat-
ment grade 2 haemoglobin decrease (8 to 10 g/dL) occurred in 23 patients
(5.7%) receiving 3DRBV; grade 3 decrease (6.5 to 8 g/dL) occurred in 2
patients (0.5%). No patients receiving 3D without RBV experienced grade 2 or
greater haemoglobin decrease while on treatment (Table). There were no grade 4
haemoglobin decreases (56.5 g/dL). RBV dose was reduced in 23 patients
(5.7%) to manage anaemia or haemoglobin decrease, and all patients with
RBV dose modification achieved SVR12. Mean haemoglobin values decreased
by the second week of treatment, and returned to near-baseline by 4 weeks post-
treatment. 1 patient (0.1%) received a blood transfusion for haemoglobin 58 g/
dL. No erythropoietin use was required. No patient discontinued the study due
to decreased haemoglobin.
3DRBV 3D
N401 n (%) N509 n (%)
Haemoglobin decrease (n)
LLN to 10 g/dL (Grade 1) 209 (52.1) 34 (6.7)
10 to 8 g/dL (Grade 2) 23 (5.7) 0
8 to 6.5 g/dL (Grade 3) 2 (0.5) 0
56.5 g/dL (Grade 4) 0 0
RBV dose modification due 23 (5.7) 0
to haemoglobin decrease or anaemia
Study drug interruption due 1 (0.2) 0
to haemoglobin decrease or anaemia
Discontinuation due to 0 0
haemoglobin decrease or anaemia
CONCLUSION: The 3D regimen was well tolerated with and without RBV.
Clinically significant decreases in haemoglobin were uncommon. Haemoglobin
levels 510 g/dL were managed successfully with RBV dose modification, with-
out impact on treatment response.
Disclosure of Interest: M. Diago Financial support for research from: AbbVie,
Boehringer Ingelheim, Bristol-Myers Squibb, Gilead Sciences, Janssen, Roche,
United European Gastroenterology Journal 2(5S)
MSD, Novartis, Vertex, Lecture fee(s) from: MSD, Roche, Janssen, BMS,
Gilead Sciences, P. Andreone Financial support for research from: Roche,
Merck, and Gilead Sciences, Consultancy for: Roche, Merck, Janssen Cilag,
AbbVie, Boehringer Ingelheim, Gilead Sciences, and BMS, D. Forton
Financial support for research from: Roche, Gilead, Consultancy for: Abbvie,
Roche, BMS, Merck, Boehringer Ingelheim, Gilead, Janssen, H. Reesink
Financial support for research from: AbbVie, BMS, Boehringer Ingelheim,
Gilead Sciences, Janssen-Cilag, Merck, PRA-International, Roche, and
Santaris, Consultancy for: AbbVie, Astex, BMS, Gilead Sciences, GSK,
Janssen-Cilag, Merck, PRA-International, Roche, Tibotec, R-Pharm, and
Regulus, V. Rustgi Financial support for research from: Abbvie, Gilead, BMS,
Lecture fee(s) from: Gilead, Genentech, Janssen, Consultancy for: Abbvie,
Gilead, Janssen, D. Bernstein Financial support for research from: AbbVie,
BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from:
AbbVie, Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead,
Janssen, Vertex, Merck, T. Sepe Financial support for research from: AbbVie,
J. Vierling Financial support for research from: Abbvie, Biotest, BMS, Gilead,
Janssen, Vertex, Merck, Genentech, Genfit, Hyperion, Intercept, Ocera, Sundise,
Consultancy for: Abbvie, Boerhinger-Ingelheim, BMS, Gilead, Janssen, Merck,
Hyperion, Intercept, Sundise, W. King: None declared, Y. Hu Shareholder of:
AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, D.
Cohen Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie,
Other: AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: AbbVie, P. Ferenci
Financial support for research from: Roche, Lecture fee(s) from: Roche, MSD,
BMS, Gilead, Abbvie, Bohringer Ingelheim, Idenix, Janssen, Consultancy for:
Roche, MSD, BMS, Gilead, Abbvie, Bohringer Ingelheim, Idenix, Janssen
MONDAY, OCTOBER 20, 2014 14:0015:30
NEW IMAGING TECHNIQUES IN COLONOSCOPY HALL F2_____________________
OP047 NARROW BAND IMAGING MAGNIFICATION FOR THE
DIAGNOSIS OF COLORECTAL NEOPLASTIC LESIONS
M. Takahashi1,*, R. Chinzei1, H. Doi1, K. Sasajima1
1
Gastroenterology, SAITAMA RED CROSS HOSPITAL, Saitama, Japan
Contact E-mail Address: machat1215@yahoo.co.jp
INTRODUCTION: Narrow Band Imaging (NBI) magnification has been recog-
nized as a time-saving and convenient tool for the differentiation between neo-
plastic and nonneoplastic colorectal lesions. The aim of this study was to clarify
the clinical efficacy of NBI magnification for the diagnosis of colorectal neoplas-
tic lesions, compared to chromoendoscopic magnification.
AIMS & METHODS: The subjects of this prospective study were 569 colorectal
lesions, examined by an expert endoscopist with 12-year experience in magnifying
diagnosis. Endoscopic diagnosis was examined on the basis of Sanos classifica-
tion with NBI and Kudos classification with chromoendoscopic magnification;
capillary pattern (CP) type II, and IIIL or IV pit pattern were defined as indi-
cators of tubular adenoma (TA), CP type IIIA and IIIs or VI (low-grade) pit
pattern as intramucosal or submucosal slightly invasive cancer (M-SM-S), and
CP type IIIB and VI (high-grade) or VN pit pattern as submucosal massively
invasive cancer (SM-M). Additionally, both inter- and intraobserver agreement
were evaluated using kappa statistics among 150 lesions (50 lesions each in TA,
M-SM-S and SM-M) between the expert and three observers, that were endos-
copists with 10-, 2- and 1-year experience respectively in magnifying diagnosis.
RESULTS: 569 lesions included 180 TA, 277 M-SM-S and 112 SM-M.
Sensitivity, specificity and accuracy for TA were 98.5%, 75.9% and 81.9%
with NBI and 93.3% (N.S), 87.4% (p50.01) and 89.5% (p50.01) with chro-
moendoscopic magnification. Similarly, those for M-SM-S were 64.3%, 84.9%
and 81.9% with NBI and 82.3% (p50.01), 83.2% (N.S) and 82.8% (p50.01)
with chromoendoscopic magnification, and those for SM-M were 69.6%, 98.9%
and 89.8% with NBI and 81.3% (p50.05), 98.9% (N.S) and 95.4% (N.S) with
chromoendoscopic magnification. Additionally, among the lesions less than
10mm, accuracy with NBI magnification for TA was comparable to that with
chromoendoscopic magnification (93.0% and 94.8%, N.S). Interobserver agree-
ment of NBI magnification varied according to the year of experience, with
similar result to chromoendoscopic magnification (kappa value of 0.73, 0.54
and 0.45 with NBI and 0.64, 0.57 and 0.53 with chromoendoscopic magnifica-
tion), whereas intraobserver agreement was similar among three observers in
both two modalities (0.76-0.77 and 0.71-0.84, respectively). Concordance rates
of CP type II and IIIB between the expert and observers, didnt significantly
differ respectively among the three (87.0%, 79.6% and 68.5% with CP type II
and 76.5%, 94.1% and 88.2% with CP type IIIB), although those of CP type
IIIA significantly decreased according to the year of experience (83.9%, 59.7%
and 48.4%, p50.01). Moreover, overestimated diagnosis with NBI magnifica-
tion increased according to the fewer experience (6.0%, 19.0% and 35.3%,
p50.01), while underestimated diagnosis tended to be higher according to the
year of experience (18.8%, 16.7% and 12.5%, respectively).
CONCLUSION: NBI magnification would have the clinical benefits for the
diagnosis of colorectal neoplastic lesions, although sensitivity for early colorectal
cancer was low compared to chromoendoscopic magnification. Moreover, NBI
magnification has good concordance rate of intraoberver agreement, but it would
take years of experience to achieve good diagnostic skill even in NBI
magnification.
Disclosure of Interest: None declared
A15
OP048 NOVEL 3D IMAGE OF COLON NEOPLASM MUCOSAL
TISSUES USING MULTIPHOTON MICROSCOPY
I.K. Yoo1, J.M. Lee1, S.H. Kim1, S.J. Nam1,*, H.S. Choi1, E.S. Kim1, B. Keum1,
Y.T. Jeen1, H.J. Chun 1, H.S. Lee 1, C.D. Kim1
1
Department of Internal Medicine, Institute of Digestive Disease and Nutrition,
Korea University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: ikyoo82@hanmail.net
INTRODUCTION: During recent years, multiphoton microscopy became one of
the most important optical imaging techniques for in vivo basic research.
Multiphoton microscopy (MPM) can allow a detailed 3D structure analysis of
tissue and can be used for the early diagnosis of dysplastic mucosal lesion.
AIMS & METHODS: The aim of this study was to make the gastrointestinal
mucosa 3D structure using DNA probe of multiphoton microscopy and to com-
pare normal mucosa with adenoma and adenocarcinoma tissues. This study was
a single center study during Jury to September 2013. We obtained normal, ade-
noma and adenocarcinoma colon tissue samples by biopsy or endoscopic muco-
sal resection during colonoscopy from 7 patients. Then the tissues were placed in
sterile specimen bottles containing PBS(phosphate buffer solution). Multiphoton
images were collected using a DM IRE2 Microscope (Leica Microsystems
GmbH, Wetzlar, Germany).
RESULTS: Total 7 Patient was composed of 4 adenoma and 7 adenocarcinoma.
Among them, 4 patients were diagnosed adenoma and adenocarcinoma at the
same time. We were able to get 3D structural images at depths of 90-140 m.
Normal tissue had a defined texture, whereas adenoma and cancer tissue was
amorphous. And cancer tissues increased nucleus/cytoplasm ratio compared to
normal mucosa.
CONCLUSION: Colon mucosa 3D structure analysis using multiphoton micro-
scopy can be successfully used to determine colon mucosa architecture and may
help to diagnose early colon cancer together with histopathologic examination.
REFERENCES
1. Cicchi R, Sturiale A, Nesi G, et al. Multiphoton morpho-functional imaging of
healthy colon mucosa, adenomatous polyp and adenocarcinoma. Biomedical
Optics Express 2013; 4: 1204-1213.
2. Decencie`re E, Tancre`de-Bohin E, Dokladal P, et al. Automatic 3D segmenta-
tion of multiphoton images: a key step for the quantification of human skin. Skin
Res Technol 2013; 19: 115-124.
3. Liu N, Chen J, Xu R, et al. Label-free imaging characteristics of colonic
mucinous adenocarcinoma using multiphoton microscopy. Scanning 2013; 35:
277-282.
4. Smith PJ, Blunt N, Wiltshire M, et al. Characteristics of a novel deep red/
infrared fluorescent cell-permeant DNA probe, DRAQ5, in intact human cells
analyzed by flow cytometry, confocal and multiphoton microscopy. Cytometry
2000; 40: 280-291.
Disclosure of Interest: None declared
OP049 FEASIBILITY STUDY FOR THE EVALUATION OF
MORPHOPATOLOGICAL PATTERN OF NEOANGIOGENESIS IN
HUMAN COLORECTAL CANCER USING CONFOCAL LASER
ENDOMICROSCOPY AND TARGETED ANTI- CD105 ANTIBODIES
A. Ciocalteu1,*, A. Saftoiu1, T. Cartana1, I. Cherciu1, L. Gruionu2, D. Pirici3,
C. Georgescu4, G. Gruionu1,5
1
Research Center of Gastroenterology and Hepatology, University of Medicine and
Pharmacy of Craiova, 2Department of Mechanical Engineering, University of
Craiova, 3Department of Histology, University of Medicine and Pharmacy of
Craiova, 4Department of Pathology, Emergency County Hospital, Craiova,
Romania, 5Edwin L. Steele Laboratory of Tumor Biology, Department of
Radiation Oncology, Massachusetts General Hospital, Harvard Medical School,
Boston, Massachusetts, United States
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) is an imaging tech-
nique for gastrointestinal endoscopy providing in vivo microscopy at subcellular
resolution. An important question in validating tumor angiogenesis is what pro-
portion of the tumor vascular network is represented by pre-existing parent tissue
vessels or newly formed vessels. CD105 (endoglin) represents a proliferation-
associated endothelial cell adhesion molecule. In contrast to pan-endothelial
markers, such as CD31, CD105 is preferentially expressed in activated endothe-
lial cells that participate in neovascularization.
AIMS & METHODS: The aim of the study was to evaluate neoangiogenesis and
vessel density in colorectal cancer patients by using two fluorescently labeled
antibodies on fresh biopsy samples imaged with CLE. We evaluated CD105
and CD31 expression from samples of five patients with primary colon adeno-
carcinoma, using a dedicated endomicroscopy system (EC-3870 CIFK, Pentax,
Japan). Image J (National Institutes of Health, USA) software was used to
obtain the Z projection of the confocal serial images from each biopsy sample
previously combined into stacks. Vascular density and vessel diameters were
measured within two 50x475 mm rectangular regions of interest centered in the
middle of each image in the horizontal and vertical direction. The results were
averaged over all the patients and were expressed as the mean standard error.
RESULTS: The use of CD105-antibody was found to be suitable for the detec-
tion of blood vessels only in colorectal cancer. Whereas anti-CD31 antibodies
stained blood vessels in both normal and pathologic colon equally, CD105
expression was observed primarily in malignant lesions, with little or no expres-
sion in the vessels of the normal mucosa (252.63195.6 vessels/mm3 in only two
patients). We could measure the average diameter of anti-CD105 antibodies
stained vessels of 11.220.8 m in tumor tissue, counting 2812.61147.3 ves-
sels/mm3. When using anti-CD31 antibodies, the average diameter of vessels in
the normal sample was 6.220.3 m and the vessel density was 3199.98478.5
vessels/mm3, while in the tumor sample we obtained an average diameter of
10.38  0.4 m and a vessel density of 4816.81 620.7vessels/ mm3. Thus,
A16
there were more vessels stained with CD31 than by CD105 (p50.05). The results
were also confirmed by immunohistochemistry.
CONCLUSION: Specific imaging and quantification of tumor microvessels is
feasible using CLE examination and CD 105 immunostaining of samples. CD
105 is a more specific marker for tumour angiogenesis, as compared to com-
monly used panendothelial markers. The combination of CD 105 staining with
CLE analysis could provide a more reliable evaluation of the angiogenetic status
of patients with colorectal cancer.
Disclosure of Interest: None declared
OP050 CLINICAL PATHOLOGY AND MOLECULAR BIOLOGY FOR
MIXED SERRATED LESIONS DIAGNOSED IN MAGNIFYING
ENDOSCOPY
H. Aoki1,2,*, H.-O. Yamano3, E. Yamamoto2, K. Yoshikawa3, R. Takagi3,
E. Harada3, Y. Tanaka3, R. Himori3, T. Endo1, T. Sugai4, H. Suzuki2
1
Department of Gastroenterology, Sapporo Shirakaba-dai Hospital, 2Department
of Molecular Biology, Sapporo Medical University, Sapporo, 3Department of
Gastroenterology, Akita Red Cross Hospital, Akita, 4Department of Molecular
Diagnostic Pathology, Iwate Medical University, Morioka, Japan
Contact E-mail Address: hironori_a1123@yahoo.co.jp
INTRODUCTION: We have previously reported that a novel surface micro-
structure Type II-Open pit patterns (Type II-O), which is highly specific to
SSA/P with BRAF mutation and CpG island methylator phenotype (CIMP)
(1). SSA/P with cytological dysplasia has been established in the field of serrated
lesions in the fourth edition of the WHO classification of tumors of the digestive
system. Progression of SSA/Ps to cytological dysplasia was suggested to be asso-
ciated with additional morphological changes, including the tumor-like pits
(similar to Type III, IV and V pits in Kudos classification), but the clinical
findings are still not clear.
AIMS & METHODS: We examined the characteristics of clinical pathology and
molecular biology of the mixed serrated lesions in which conventional Type II
pits, Type II-O pits and tumor-like pits coexisted in magnifying endoscopy. From
April 2009 to September 2013, 54 patients (56 mixed serrated lesions) were
enrolled in this study. Surface microstructures were analyzed using magnifying
endoscopy. A gastrointestinal pathologist who was blinded to the clinical and
molecular information evaluated histological findings for all lesions. Biopsy spe-
cimens were obtained for each respective pit pattern for the extraction of genomic
DNA. Mutation in BRAF and KRAS was examined by pyrosequencing.
Methylation of p16, MLH1 and MINT1, -2, -12 and -31 was analyzed using
bisulfite pyrosequencing. Tumors were defined as CIMP-positive when methyla-
tion was detected in three or more loci of the five markers (MINT1, -2, -12, -31
and p16). The baseline characteristics, the histological findings, and the molecu-
lar analyses in the mixed serrated legions were assessed.
RESULTS: Endoscopic characteristics of these lesions were Type II Type IV 1,
Type II Type IV with serration 24, Type II-O Type IV 3, Type II Type IV
with serration 21, Type II-O Type V 7. Histopathological results of these
lesions were SSA/P alone 3, traditional serrated adenoma (TSA) alone 28,
SSA/PTSA 8, SSA/P with cytological dysplasia 10 and SSA/P adenocarci-
noma 7. All Type II-O plus Type IV lesions showed SSA/P with cytological
dysplasia histology, and both the Type II-O subcomponents and the Type IV
subcomponents showed BRAF mutation and CIMP-positive. By contrast, major-
ity of the serrated lesions (76%) presenting with Type IV with serration were
traditional serrated adenoma (TSA) with BRAF mutation and CIMP-negative.
These results suggest that serrated lesions with Type IV pit and Type IV with
serration appear to develop through distinct tumorigenic pathways. All lesions
presenting with Type II-O Type V pits were SSA/P adenocarcinoma with
BRAF mutation and CIMP-positive. MLH1 methylation and MSI was observed
only in portions with a Type V pit pattern.
CONCLUSION: Our results may provide a model that variation in surface
microstructure and molecular alterations are directly linked each other.
Analysis based on magnified endoscopy may have an importance in understand-
ing the developmental progress of serrated lesions.
REFERENCES
(1) Kimura T, Yamamoto E, Yamano HO, et al. A novel pit pattern identifies the
precursor of colorectal cancer derived from sessile serrated adenoma. The
American Journal of Gastroenterology 2012; 107: 460-469.
Disclosure of Interest: None declared
OP051 AN INVESTIGATION INTO THE DIAGNOSIS OF INVASION
DEPTH IN COLORECTAL TUMORS BY MORPHOLOGICAL TYPE
USING MAGNIFYING AND ULTRA-HIGH MAGNIFYING
ENDOSCOPY
T. Kudo1,*, S.-E. Kudo1, K. Wakamura1, Y. Mori1, M. Misawa1, T. Hayashi1,
K. Ichimasa1, M. Kutsukawa1, Y. Ogawa1, H. Miyachi1, F. Ishida1
1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
HOSPITAL, yokohama city, Japan
Contact E-mail Address: s6027@nms.ac.jp
INTRODUCTION: Pit pattern diagnosis used for endoscopic diagnosis of inva-
sion depth colorectal tumors has high diagnostic accuracy. However, there is a
tendency toward disparities in diagnostic accuracy depending upon the morpho-
logical type of the tumor.
AIMS & METHODS: The aim of this study was to investigate the diagnostic
characteristics of magnifying and ultra-high magnifying endoscopy by morpho-
logical type of colorectal lesions and evaluated the diagnostic differences and
clinical applicability of the technique. We investigated 292 lesions [129 protrud-
ing lesions, 47 laterally spreading tumors-granular (LST-G), and 116 LST-non-
granular (NG) 10 mm] that could be observed under magnification and under
United European Gastroenterology Journal 2(5S)
ultra-high magnification using endocytoscopy in patients treated at our facility
between May 2005 and March 2013. Pit pattern classifications of III and IV were
considered as tubular adenoma (TA), VI slight pit pattern was considered as
carcinoma with intramucosal to submucosal shallow invasive carcinoma (M/
SM-s), and VI highly disorganized and VN pit patterns were considered as carci-
noma with submucosal deep invasion (SM-d). Using the EC classification with
endocytoscopy, EC2 was considered as TA, EC3a was considered as M/SM-s,
and EC3b was considered as SM-d. We investigated the diagnostic accuracy of
each of these classifications.
RESULTS: The diagnostic accuracies using pit pattern classification and EC
classification for all lesions were 83.6% and 85.8%, respectively. Diagnostic
accuracy by morphological type under magnification using the former was
86.1%, 78.7%, and 79.3% for protruding lesions, LST-G, and LST-NG, respec-
tively, whereas that using the latter was 80.6%, 83.0%, and 90.5%, respectively.
There was no significant difference of diagnostic accuracies between each mor-
phological type using pit pattern classification, whereas the diagnostic accuracy
using EC classification for LST-NG was significantly higher than that for pro-
truding lesions (90.5% vs 80.6%, p 5 0.05). We also compared the diagnostic
accuracies of each classification for LST-NG. The results (pit pattern classifica-
tion, EC classification) were 79.3% and 90.5%, respectively, so these results
indicate that, for LST-NG, the diagnostic accuracy of EC classification was
significantly higher (p 5 0.01).
CONCLUSION: This study showed that there was a difference in diagnostic
accuracy by morphological type when performing endocytoscopy on colorectal
tumors. EC diagnosis was significantly more useful for LST-NG lesions than for
protruding lesions, and the diagnostic accuracy was higher than that of pit pat-
tern diagnosis.
Disclosure of Interest: None declared
OP052 THREE-DIMENSIONAL ENDOSCOPIC MEASUREMENT
SYSTEM THAT EXPLOITS GRID-BASED ACTIVE STEREO FOR
PRECISE MEASUREMENT OF GASTROINTESTINAL MUCOSAL
LESIONS
S. Yoshida1,*, Y. Kominami2, Y. Sanomura1, S. Oka1, S. Tanaka1, R. Masutani3,
R. Furukawa3, H. Aoki4, R. Sagawa5, H. Morinaga6, H. Kawasaki6,
K. Chayama2
1
Department of Endoscopy and Medicine, 2Department of Gastroenterology and
Metabolism, Hiroshima University, 3Faculty of information sciences, Hiroshima
City University, Hiroshima, 4Chitose Institute of Science and Technology, Chitose,
5
National Institute of Advanced Industrial Science and Technology, Tsukuba,
6
Faculty of Engineering, Kagoshima University, Kagoshima, Japan
Contact E-mail Address: yoshida7@hiroshima-u.ac.jp
INTRODUCTION: Endoscopy is essential for clinical diagnosis and treatment
of gastrointestinal (GI) disorders and for gastroenterological research. A major
disadvantage, however, is that the size of a lesion cannot be determined precisely
by endoscopic visual estimation. Although several techniques for precise endo-
scopic measurement have been proposed, none have been applied clinically
because of costs or inaccuracies. We have proposed a 3-dimensional (3D) recon-
struction method called active stereo. Active stereo measurement is based on a
mono/multi-projector, mono-/multi-camera system. An image of patterned light
projected onto a target object is obtained, and the 3D shape of the object is
reconstructed by analysing the distribution of the light pattern in the image.1)
We have also developed an endoscopic system that allows 3D measurement
based on active stereo techniques and projection of a static pattern.
AIMS & METHODS: The aim of this study was to evaluate the accuracy of our
3D endoscopic system, which exploits grid-based active stereo techniques. We
evaluated the system as applied to 17 sites, each between two points marked on
GI mucosa. Lesions were examined with the use of a video endoscopy system
(EG-590WR; Fujifilm Medical Co. Ltd., Japan) and a micro-pattern projection
catheter. Study samples were 1 esophageal cancer, 2 gastric cancers, and 2 colonic
tumor specimens obtained by endoscopic resection at our institution. We eval-
uated the characteristics of error (E degree of under- or over-estimation: E
average value of (measured value true value)/true value), the magnitude of
error (jEj absolute degree of error: jEj average value of jmeasured value
true valuej/true value), and correlation between the true value (actual measure-
ment) and the measured value (active stereo endoscopy system measurement).
RESULTS: E was 2.22% [6.62, 2.22] (mean [95% CI(%)]), and jEj was
6.78% [3.96, 9.60]. Strong positive correlation was found between the true
value and the value measured by the active stereo endoscopy system (r 0.99:
99% CI [0.97, 1.00]; P 50.01).
CONCLUSION: Our newly developed 3D endoscopic system provided for suc-
cessful measurement of lesions in GI mucosa. Further development of our system
will allow for accurate, real-time measurement of GI lesions in vivo. With attach-
ment of a micro-pattern projector to a normal, unaltered endoscope, it is possible
to measure the 3D shapes of target surfaces. This work was supported in part by
NEXT program No.LR030 in Japan.
REFERENCES
1. Aoki H, Furukawa R, Aoyama M, et al. Endoscope by using grid-based active
stereo. In: The proceeding of 35th Annual International Conference of the IEEE
Engineering in Medicine and Biology Society (EMBC2013), 2013, pp. 5694-5697.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 14:0015:30
LATE BREAKING DIGESTIVE ONCOLOGY ABSTRACTS HALL I/K_____________________
OP052-LB1 METAL OR PLASTIC STENTS FOR PREOPERATIVE
BILIARY DRAINAGE IN RESECTABLE PERIAMPULLARY
CANCER: PROSPECTIVE MULTICENTER STUDY
1, 2 3 4 5
J. Tol *, J. van Hooft , R. Timmer , F. Kubben , E. van der Harst , I. de
Hingh6, F. Vleggaar7, I. Molenaar8, Y. Keulemans9, D. Boerma10, N. van der
Gaag11, M. Besselink1, P. Fockens2, T. van Gulik1, E. Rauws2, O. Busch1,
D. Gouma1 on behalf of DPCG
1
Surgery, 2Gastroenterology and Hepatology, Academic Medical Center,
Amsterdam, 3Gastroenterology, St. Antonius hospital, Nieuwegein, 4Maasstad
hospital, Rotterdam, Netherlands, 5Surgery, Maasstad hospital, Rotterdam,
6
Surgery, Catharina hospital, Eindhoven, 7Gastroenterology and Hepatology,
8
Surgery, University Medical Center Utrecht, Utrecht, 9Gastroenterology,
University Medical Center Maastricht, Maastricht, 10Surgery, St. Antonius hos-
pital, Nieuwegein, 11Neurosurgery, Leiden University Medical Centre, Leiden,
Netherlands
Contact E-mail Address: JAMG Tol j.tol@amc.uva.nl
INTRODUCTION: A recent randomised controlled multicenter trial (RCT)
found a higher complication rate after preoperative biliary drainage (PBD) as
compared to direct pancreatoduodenctomy in jaundiced patients with resectable
pancreatic tumors, which might be related to the plastic endoprotheses used.
However, PBD is still frequently indicated due to logistic hurdles and neoadju-
vant therapy. Aim of this study was to compare the complication rates after PBD
with metal stents to plastic stents.
AIMS & METHODS: A prospective cohort of patients with obstructive jaundice
due to a periampullary or pancreatic tumor who were scheduled to undergo PBD
before resection was added to the study cohort of the earlier RCT. PBD with a
metal stent was performed in jaundiced patients when early surgery was not
appropriate. The multidisciplinary setting and inclusion criteria were identical
to the criteria reported in the RCT. Metal stent and plastic stent groups were
compared for the primary outcome, PBD-related complications. A three-group
comparison with early surgery patients was performed to compare overall
complications.
RESULTS: A total of 53 patients underwent drainage with a metal stent and
were compared with the plastic stent group (n102). Patients characteristics did
not differ. PBD related complications rates were 24% in the metal stent group
compared to 46% in the plastic stent group (relative risk (RR) of the plastic stent
use 1.9, lower limit 90% confidence interval (CI) 1.2, P0.006). Specific stent
related complications (occlusion and exchange) were 6% in the metal stent group
compared to 31% in the plastic stent group (P0.001). RR of plastic stent use 5
(lower limit 90% CI 1.9). In the three-group comparison overall complication
rates for the metal stent, plastic stent and early surgery groups were resp. 51% vs.
74% vs. 39% (p50.001) (metal vs. early surgery: p 0.09).
CONCLUSION: Metal stents are superior to plastic stent for selective PBD in
jaundiced patients. Although early pancreatoduodenectomy is still the preferred
treatment of choice in jaundiced patients, metal stent should be used when PBD
is indicated.
Disclosure of Interest: None declared
OP052-LB2 FEATURES PREDICTING MALIGNANCY IN BRANCH
DUCT INTRADUCTAL PAPILLARY MUCINOUS NEOPLASM OF
THE PANCREAS
E. Perez-Cuadrado Robles1,*, J. Cros2, M.P. Vullierme3, N. Muller 1, V. Rebours
1
, F. Maire1, A. Sauvanet4, P. Hammel 1, A. Aubert 1, O. Hentic1, P. Levy1,
P. Ruszniewski1
1
Gastroenterology, 2Pathology, 3Radiology, 4Surgery, Beaujon Hospital, Clichy,
France
Contact E-mail Address: kikemurcia@gmail.com
INTRODUCTION: The aim of this study was to determine the features predict-
ing malignancy and analyze their diagnosis value in a large single-center cohort
that includes resected branch duct Intraductal Papillary Mucinous Neoplasm
(BD-IPMN) histologically proven.
AIMS & METHODS: This study included all consecutive patients who under-
went surgical pancreatic resection with final pathological diagnosis of BD-IPMN
by histological examination between 2006 and 2014. Neoplasms were classified as
malignant if high grade dysplasia (HGD) or invasive carcinoma was found.
Medical and radiological records were retrospectively reviewed, with a special
focus on features that predict malignancy according to 2012 Sendai guidelines.
Endoscopic ultrasound (EUS) was also considered.
RESULTS: 120 patients (65 males, 55 females, mean age: 57.75 years) were
included. 53 patients had at least one acute pancreatitis (AP).
Of the 120 patients, 89 (74.1%) had at least one surgical indication, 23 underwent
surgery for relief of symptoms, 5 because of their family history of pancreatic
cancer, 3 because of multifocality. 36 patients had a malignant tumor. Within
those 89 patients (Sendai positive), 34 had a malignant tumor (sensitivity: 94.4%,
specificity: 34.5%). Among the 31 Sendai-negative patients, 29 (93.5%) had a
benign tumor and only 2 harbored HGD. Patients with malignant neoplasms had
significantly more indications for resection than those with low or moderate
dysplasia (2.06 /- 0.98 vs. 0.99 /- 0.95, P 5 0.001).
The univariate and multivariate analysis clarified the significant factors asso-
ciated with malignancy, these being the obstructive jaundice (p0.002), mural
nodule (MN) (median diameter: 10mm) (p0.005), thickened/enhancing walls
(p0.019), the main pancreatic duct (MPD) from 5 to 9mm (p0.004). Age,
family history of pancreatic cancer, AP, mutifocality and cyst size  30mm
were not statistically associated with malignancy.
A17
Table to abstract OP052-LB2
Analysis of predictive features of malignancy in BD-IPMN
N Sensitivity Specificity PPV NPV
Obstructive jaundice 5 13.9% 100% 100% 73%
Thickened/enhancing walls 27 36.1% 83.3% 48.1% 75.3%
MPD 5-9 mm 44 59.4% 69.9% 43.2% 81.7%
Mural nodule (MN) 17 27.8% 91.7% 58.8% 74.8%
MN in EUS 17 25% 90.5% 52.9% 73.8%
CONCLUSION: Sendai guidelines increased surgical indications due to high
sensitivity and low specificity. The 61.8% of the patients with surgical indications
in our study harbored low or moderate dysplasia.
Disclosure of Interest: None declared
OP052-LB3 PREOPERATIVE BILIARY DRAINAGE IN PERIHILAR
CHOLANGIOCARCINOMA: IDENTIFYING PATIENTS THAT
BENEFIT FROM IMMEDIATE PERCUTANEOUS INSTEAD OF
ENDOSCOPIC DRAINAGE
J. Wiggers1,*, B. Groot Koerkamp2, M. Gonen3, S. van Dieren4, E. Rauws5,
M. Schattner6, O. van Delden7, K. Brown8, P. Allen2, O. Busch1,
M. DAngelica2, R. Dematteo2, D.-J. Gouma1, P. Kingham2, W. Jarnagin2,
T. van Gulik1
1
Surgery, Academic Medical Center, Amsterdam, Netherlands, 2Surgery,
3
Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New
York, United States, 4Epidemiology and Biostatistics, 5Gastroenterology,
Academic Medical Center, Amsterdam, Netherlands, 6Gastroenterology, Memorial
Sloan Kettering Cancer Center, New York, United States, 7Interventional
Radiology, Academic Medical Center, Amsterdam, Netherlands, 8Interventional
Radiology, Memorial Sloan Kettering Cancer Center, New York, United States
Contact E-mail Address: j.k.wiggers@amc.nl; t.m.vangulik@amc.nl
INTRODUCTION: Preoperative biliary drainage in perihilar cholangiocarci-
noma is mostly initiated with endoscopic biliary drainage (EBD), but additional
percutaneous transhepatic biliary drainage (PTBD) is frequently required to
establish optimal biliary drainage prior to surgery. This study aimed to develop
and validate a simple prediction model that identifies patients likely to require
pre-operative PTBD.
AIMS & METHODS: Two databases from specialty centers were used (Europe
and USA), and patients that underwent (attempted) EBD with plastic stents prior
to surgery for presumed perihilar cholangiocarcinoma between 2001-2013 were
included. A prediction model was derived from the European population based
on variables uniformly available prior to biliary drainage. Performance of the
risk model was assessed for discrimination and calibration in the validation
population (USA).
RESULTS: 108 patients of 288 patients (38%) required additional PTBD prior
to surgery. Incremental risk factors of the need for pre-operative PTBD included
bile duct obstruction at the left, right, or bilateral segmental level as assessed on
preoperative CT and/or MRI, and a pre-drainage total bilirubin level above 150
mmol/L. The prediction model identified three subgroups: Patients with a pre-
dicted low risk of 7%, a moderate risk of 40%, and high risk of 62% of the need
for pre-operative PTBD. The high risk group consisted of patients with obstruc-
tion at the level of the right or bilateral segmental bile ducts in combination with
a total bilirubin above 150 mmol/L. The prediction model had good discrimina-
tion (area under the curve 0.74) and adeqaute calibration in the external valida-
tion dataset.
CONCLUSION: Patients with perihilar cholangiocarcinoma likely to need addi-
tional PTBD after initial attempt at endoscopic stent placement can be identified
using the predictive model described. These patients should be treated with initial
PTBD instead of initial EBD, thereby potentially reducing the number of pre-
operative biliary drainage procedures and associated complications.
Disclosure of Interest: None declared
OP052-LB4 INTERVAL CANCERS USING A FAECAL
IMMUNOCHEMICAL TEST FOR HAEMOGLOBIN WHEN
COLONOSCOPY CAPACITY IS LIMITED
J. Digby1,*, C.G. Fraser2, F.A. Carey3, J. Lang4, R.J. Steele5
1
Scottish Bowel Screening Research Unit, 2Centre for Research into Cancer
Prevention and Screening, University of Dundee, 3Department of Pathology,
Ninewells Hospital & Medical School, Dundee, 4NHS National Services Scotland,
Glasgow, 5Medical Research Institute, University of Dundee, Dundee, United
Kingdom
Contact E-mail Address: jaynedigby@nhs.net
INTRODUCTION: Introduction of faecal immunochemical tests for haemoglo-
bin (FIT) for colorectal cancer (CRC) screening poses considerable challenges for
countries with limited colonoscopy capacity. To secure low positivity rates, high
faecal haemoglobin concentration (f-Hb) cut-offs must be used. This decreases
sensitivity, particularly for adenoma. Interval cancers (IC) are an important
consideration but little examined for FIT-based programmes. We assessed IC
using an 80 mg Hb/g faeces cut-off in an established screening programme.
AIMS & METHODS: A single estimate of f-Hb using quantitative automated
immunoturbidimetry (OC-Sensor, Eiken, Japan) was obtained for 30894 partici-
pants aged 50-75 who took part in a six-month evaluation of FIT as a first-line
test within the Scottish Bowel Screening Programme. 754 participants with f-Hb
 80 mg Hb/g were referred for colonoscopy. IC, defined as CRC diagnosed
A18
within two years of a negative screening test result, or the time to next invitation,
were identified from the Cancer Registry.
RESULTS: We identified 31 IC and 30 screen-detected CRC, giving an IC rate of
50.8%. IC rate was 46.9% for men and 55.2% for women. CRC site distribution
did not differ between IC and screen-detected CRC, but IC were later stage
(Dukes C or D): 46.7% and 37.0%, respectively. Of the 31 IC, 23 had f-Hb
510 mg Hb/g, the lower limit of quantitation. Of these 23, 6 had undetectable f-
Hb. Lowering the f-Hb cut-off to 10 mg Hb/g would increase positivity rate from
2.4% to 9.4%, colonoscopy demand from 754 to 2137, and reduce the IC rate to
37.7%.
CONCLUSION: Our results provide unique insight into IC rates using FIT in a
screening programme with limited colonoscopy capacity. Our IC rate was similar
to the ca. 50% commonly reported with guaiac faecal occult blood tests, but
much higher than the 14.4% IC rate with f-Hb cut-off of 20 mg Hb/g1. Thus, a
high f-Hb cut-off limits the improved sensitivity of FIT. The more advanced
stage distribution of IC highlights the need for improved CRC detection with
screening. However, with 19.4% of IC having undetectable f-Hb, some cancers
would always be missed, even with significant lowering of the f-Hb cut-off. With
more CRC missed in women than in men, it appears that women may be dis-
advantaged by the use of one f-Hb cut-off for all and we propose better indivi-
dualized use of FIT in CRC screening.
REFERENCES
1. Zorzi M, Fedato C, Grazzini G, et al. High sensitivity of five colorectal screen-
ing programmes with faecal immunochemical test in the Veneto Region, Italy.
Gut 2011; 60: 944-949.
Disclosure of Interest: J. Digby: None declared, C. Fraser Consultancy for:
Immunostics Inc, Other: Alpha Labs Ltd, F. Carey: None declared, J. Lang:
None declared, R. Steele: None declared
OP052-LB5 ASSOCIATION OF THE 3UTR HLA-G 3187A/G
POLYMORPHISM WITH RELAPSE AND SURVIVAL IN
COLORECTAL CANCER PATIENTS IN ADJUVANT REGIMEN. A
MULTICENTER STUDY
M. Garziera1,*, E. Bidoli2, E. Cecchin1, C. Zanusso1, F. De Marchi3, A. De
Paoli4, E. Mini5, G. Toffoli1
1 13-16 weeks
Experimental and Clinical Pharmacology Unit, 2Epidemiology Unit, 3Dept
Surgical Oncology, 4Dept Radiotherapy, CRO Aviano National Cancer Institute,
Aviano, 5Experimental and Clinical Medicine, University of Florence, Florence,
Italy
Contact E-mail Address: mgarziera@cro.it
INTRODUCTION: HLA-G is involved in cancer immune tolerance. HLA-G
expression is linked to 3UTR regulation. To date, the prognostic value of
3UTR HLA-G SNPs has never been explored in colorectal cancer (CRC) in
the adjuvant chemotherapy (ADJ-CT) regimen.
AIMS & METHODS: To quantify in CRC patients the association between SNPs,
alleles and haplotypes of HLA-G 3 UTR region with disease free survival (DFS)
and OS. 274 CRC patients (stage II-III) after primary surgery were included in 2
independent cohorts: 1) the discovery set (N124); 2) the validation set (N150).
All patients received fluoropyrimidines (FL) as ADJ-CT; of them, 164 received FL
plus oxaliplatin. 3UTR of the HLA-G gene was amplified by PCR from genomic
DNA. 9SNPs: 14bp INDEL, 3003T/C, 3010G/C, 3027C/A, 3035C/T,
3142C/G, 3187A/G, 3196C/G, 3227G/A, were analysed by direct sequen-
cing. UTR haplotypes frequencies were determined by PHASE method. We eval-
uated data by means of Cox models. Multivariate Hazard ratios (HRs) and 95% CIs
of DFS and OS were computed adjusting for age, sex, stadium and type of ADJ-CT.
Data validation was performed between the 2 cohorts.
RESULTS: Relapses were 79/274 and deaths were 45/274. Mean follow-up time
was 67.2 months (range: 4.6-186.3). The association between DFS and 3UTR
3187G/G genotype was statistically significant (HR2.2; 95%CI:1.1-4.6). The
3187A/G SNP was also significantly associated to DFS under a recessive
genetic model (HR2.1; 95%CI:1.1-4.3). 20 haplotypes were identified (6
novel); 8 with frequencies 41% (93% of total): UTR-2(33%), UTR-1(24%),
UTR-3(13%), UTR-4(12%), UTR-7 (5%), UTR-5(3%), UTR-18(2%) and
UTR-15(1%). The 3UTR-1 in homozygous state was significantly associated
to DFS (HR2.2;95%CI:1.0-4.5). OS was directly associated to these variants
but not statistically significant. HR heterogeneity tests across the two cohorts,
were not significant for 3187A/G and 3UTR1/UTR1 (i.e. p0.24 for DFS and
p0.61 for OS).
CONCLUSION: For the first time, the 3UTR of the HLA-G gene was explored
in CRC patients. Analyses showed that 3UTR 3187A/G and 3UTR-1, which
includes 3187G allele, were associated to an unfavourable DFS and OS.
3187A allele was related to a decreased HLA-G expression, while 3187G
allele and UTR-1 haplotype were associated to higher soluble HLA-G levels.
Next analyses will explore, at germinal level, the 3UTR HLA-G region novel
prognostic role to better manage CRC patients in FL based ADJ treatment.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP052-LB6 ADJUVANT CHEMOTHERAPY FOLLOWING
COLORECTAL CANCER RESECTION - WHAT TIMEFRAME
CONSTITUTES A DELAY AND HOW DOES THIS IMPACT
OVERALL SURVIVAL?
S. Nachiappan1,*, A. Askari1, R. Mamidanna1, A. Munasinghe1, A. Currie1,
J. Stebbing2,3, O. Faiz1,3
1
Surgical Epidemiology, Trials & Outcome Centre, St Marks Hospital &
Academic Institute, Harrow, 2Hammersmith Hospital, 3Department of Surgery &
Cancer, Imperial College, London, United Kingdom
Contact E-mail Address: s.nachiappan12@imperial.ac.uk
INTRODUCTION: The ideal timing of adjuvant chemotherapy in colorectal
cancer surgery and the impact of its delay has been extensively studied.
However there has been no real consensus on a specific timeframe.
AIMS & METHODS: Elective colorectal cancer resections between April 1997
and March 2012 were collated from prospectively recorded Hospital Episode
Statistics in England. Reoperation rates and time to adjuvant chemotherapy
were ascertained and their impacts on overall survival were analysed utilising
multivariate logistic regression and survival statistics. Patients who received adju-
vant chemotherapy were grouped depending on their timing of initiation into 4-
week cohorts. These groups were then compared to assess the impact of increas-
ing adjuvant chemotherapy delay, on overall survival.
RESULTS: 210,581 individuals underwent colorectal cancer resection. 40,479
(19.2%) received chemotherapy within 24 weeks of surgery. Patients receiving
adjuvant chemotherapy in the first month were taken as a reference and each
subsequent month of patients was compared to it sequentially.
Overall Survival
Timing of adjuvant chemotherapy initiation Hazard Ratio (95% CI) Sig.
0-4 weeks Ref
5-8 weeks 0.81 (0.75-0.87) 50.001
9-12 weeks 0.92 (0.85-0.99) 0.028
1.10 (1.01-1.19) 0.029
17-20 weeks 1.35 (1.23-1.48) 50.001
21-24 weeks 1.31 (1.18-1.45) 50.001
33,435 (82.6%) of the 40479 patients received it within 12 weeks. Adjuvant
chemotherapy beyond 12 weeks resulted in poorer survival, compared to
within 12 [Hazard Ratio (HR) 1.39, 95% CI 1.34-1.44, p50.001]. Reoperation
was an independent predictor of adjuvant chemotherapy delay (HR 2.22, CI
1.98-2.48, p50.001). Patients who avoided a reoperation and received timely
adjuvant chemotherapy demonstrated the greatest median survival [no delay
no reoperation 90 months (m); no delay reoperation 75m, delay no
reoperation 50m, delay reoperation 50m, Log rank p value50.001)].
CONCLUSION: Twelve weeks may be an appropriate cut-off for timely initia-
tion of adjuvant chemotherapy and with such a delay adversely impacting color-
ectal cancer patients overall survival. Reoperation is a significant cause of
delayed adjuvant chemotherapy. Efforts to prevent complications necessitating
reoperation and to improve access to chemotherapy services will improve survi-
val in this patient group.
REFERENCES
1. Biagi JJ et al. PMID: 21642686
2. Des Guetz G et al. PMID: 20138505
Disclosure of Interest: None declared
OP052-LB7 ADM RECEPTOR WAS RELATED WITH THE METASTASIS
OF COLORECTAL CANCERS THROUGH WNT AND NO
PATHWAYS
L. Wang1,2,*, Y. Fang2,3, S. Chen2,3
1
Gastroenterology, the Second Affiliated Hospital, School of Medicine, Zhejiang
University, 2Institute of Gastroenterology, Zhejiang University School of Medicine,
3
Gastroenterology, Sir Runrun Shaw Hospital, Zhejiang University School of
Medicine, Hangzhou, China
Contact E-mail Address: 1400927291@qq.com
INTRODUCTION: ADM is significantly overexpressed in human colorectal
cancer (CRC) samples with a mutant KRAS oncogene and it can promote cell
invasion. ADM acts as a peptide ligand that activates receptors including the
adrenomedullin receptor (ADMR, also known as L1-R) and the calcitonin-recep-
tor-like-receptor (CRLR). However, the role of ADM receptors remains
unknown.
AIMS & METHODS: We first detected the expression of ADM, ADMR and
CRLR in human colon tissues by immunohistochemistry and correlated the
expression levels with clinicopathological features. The expression of ADMR
and CRLR was interfered by lentivirus and their effects on the proliferation,
cell cycle, apoptosis, migration and invasion were evaluated by MTS, flow cyto-
metry and transwell assays, respectively. We screened the downstream targets
related with the metastasis-related signaling pathways of ADMR and CRLR in
CRC by metastasis Gene-expression Array and validated the results by PCR.
RESULTS: The expression level of ADM and CRLR were statistically higher in
CRC tissues than those in adjacent tumor-free tissues (p50.01). The expression
of ADMR and CRLR mRNA was correlated with lymph node metastasis of
colon cancer (p50.01). ADMR or CRLR shRNA-transfected RKO and HT-29
cells inhibit the cell viability and induced a significant increase in early and
total apoptosis of RKO and HT-29 cells. In addition, dual interference with
ADMR and CRLR significantly inhibited cell migration and invasion in RKO
United European Gastroenterology Journal 2(5S)
and HT-29 cells (p50.01). Exogenous ADM administration (50nmol/L) can
promote cell migration and invasions, and these effects were blocked with silen-
cing of ADMR and CRLR. cDNA microarray and qPCR validation analysis
showed that APC, EGF, PIK3CA, PIK3CB and DVL1 were up-regulated, while
NOS2 is down-regulated by silencing of ADMR and CRLR.
CONCLUSION: High expression of ADM and its receptors- ADMR and CRLR
was associated with lymph node metastasis. Silencing expression of ADMR and
CRLR significantly inhibited proliferation, impaired migration and invasion of
colon cancer cells, which might be mediated through Wnt and NO signaling
pathways.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 14:0015:30
NEW IMAGING TOOLS FOR IBD HALL N_____________________
OP053 DEVELOPMENT AND INITIAL VALIDATION OF A UNIQUE
SCORE FOR IN VIVO DIFFERENTIATION OF ULCERATIVE
COLITIS AND CROHNS DISEASE FEATURING CONFOCAL LASER
ENDOMICROSCOPY
G.E. Tontini1,2,*, J. Mudter1, M. Vieth3, R. Atreya1, C. Gunther1, R. Kiesslich4,
M. Vecchi2,5, M.F. Neurath1, H. Neumann1
1
Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany,
2
Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato,
Milano, Italy, 3Institute of Pathology, Klinikum Bayreuth, Bayreuth, 4Medicine,
St. Marienkrankenhaus Katharina-Kasper, Frankfurt am Main, Germany,
5
Biomedical Sciences for Health, University of Milan, Milano, Italy
Contact E-mail Address: gianeugeniotontini@libero.it
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) allows on demand
in vivo characterization of architectural and cellular tissue details during endo-
scopy. Recent evidences have shown that CLE can detect Crohns disease (CD)
and ulcerative colitis (UC) associated histological changes in vivo.
AIMS & METHODS: We prospectively assessed the efficacy of CLE for in vivo
differentiation of IBD by developing a unique CLE scoring system based on
histopathological hallmarks of colonic IBD involvement. Consecutive patients
with a well-established diagnosis of UC and CD and no disease reclassification
during the last three years underwent colonoscopy with biopsies and blind fluor-
esceine-aided confocal imaging. Analysis of contingency tables was performed
using the Fishers Exact test, thereby considering significant a two-sided P value
50.05.
RESULTS: Seventy-nine patients were prospectively included (40 CD, 39 UC).
In CD, CLE showed significantly more often discontinuous inflammation (90%
vs. 5%), focal cryptitis (75% vs. 13%) and discontinuous crypt architectural
abnormality (90% vs. 5%). Conversely, UC was associated with severe, wide-
spread crypt distortion (87% vs. 17%), decreased crypt density (79% vs. 22%)
and frankly, irregular surface (90% vs. 17%). Significant differences were not
seen for heavy, diffuse lamina propria cell increase or mucin preservation.
Granulomas were not visible in any case. Based on these findings, we developed
a scoring system for in vivo IBD differentiation based on endomicroscopic assess-
ment (IDEA). Compared to the historical clinical diagnosis and histopathology,
the IDEA score revealed excellent validity measures in both UC and CD subjects
(sensitivity 97% and 90%, specificity 90% and 97%, positive predictive value
91% and 97%, negative predictive value 97% and 91%, accuracy 94% for both).
CONCLUSION: CLE enables in vivo characterization of most microscopic tissue
features and inflammatory changes of tissue and cellular characteristics conven-
tionally used by standard histopathology both to confirm diagnosis and to dis-
tinguish UC from CD. However, according to the penetration depths of CLE,
submucosal details or granulomas are not visible. The new scoring system
"IDEA" allows for on demand in vivo differential diagnosis of UC and CD
with high accuracy.
Disclosure of Interest: G. E. Tontini Financial support for research from: Italian
Group for the study of IBD (IG-IBD), J. Mudter: None declared, M. Vieth:
None declared, R. Atreya: None declared, C. Gunther: None declared, R.
Kiesslich: None declared, M. Vecchi: None declared, M. Neurath: None
declared, H. Neumann: None declared
OP054 THE NOVEL PILLCAM CROHNS DISEASE CAPSULE
DEMONSTRATES SIMILAR DIAGNOSTIC YIELD AS
ILEOCOLONOSCOPY IN PATIENTS WITH ACTIVE CROHNS
DISEASE - A PROSPECTIVE MULTICENTER INTERNATIONAL
COHORT STUDY
D. Helper1,*, P. Malik2, R. Havranek3, K. Isaacs4, I. Dotan5, A. Lahat6,
J. Horlander7, A. Tinsley8, J. Leighton9, I. Fernandez-Urien Sainz10, B. Rosa11,
G. Mullin12, I. Gralnek13
1
Indiana University School of Medicine, Indianapolis, 2Gastroenterology
Associates of Tidewater, Chesapeake, 3Gastroenterology Clinic of San Antonio,
San Antonio, 4University of North Carolina, Chapel Hill, United States, 5Tel Aviv
Sourasky Medical Center, Ichilov, 6Sheba Medical Center, Ramat Gan, Israel,
7
Gastroenterology Associates of Louisville, Louisville, 8Penn State Hershey
Medical Center, Hershey, 9Mayo Clinic Arizona, Scottsdale, United States,
10
Hospital de Navarra, Pamplona, Spain, 11CentroHospitalar do Alto Ave,
Guimaraes, Portugal, 12Johns Hopkins Medical Center, Baltimore, United States,
13
Rambam Medical Center, Haifa, Israel
Contact E-mail Address: dhelper@iu.edu
INTRODUCTION: Mucosal lesions in Crohns disease (CD) can be found
throughout the GI tract. While an endoscopist may visualize to D3 with EGD
and from anus to terminal ileum with ileocolonoscopy (IC), visualization of the
entire small bowel (SB) is challenging. The novel PillCamCD is designed to
A19
examine the entire GI tract. This study compares the diagnostic yield of
PillCamCD to IC.
AIMS & METHODS: In 8 centers, the PillCamCD capsule (Given Imaging,
Yoqneam, Israel) was prospectively compared to IC in a cohort of patients
with known CD presenting with objective signs and symptoms of active disease.
Patients underwent patency capsule testing if they did not have recent radio-
graphic evidence of small bowel patency. Subjects underwent standardized
bowel prep. Ingestion of PillCamCD was followed by IC the same or following
day per investigator discretion. RAPID videos were reviewed by one of three
central readers. Mucosal lesions identified during PillCamCD and IC were ana-
lyzed by type and location. A priori, Active CD was defined as the presence of
aphthae, ulcerations, inflammatory stricture or bleeding. Other lesions were
defined Non-active CD. Localization was to SB, ileum, cecum, ascending,
transverse, descending, sigmoid or rectum. Each segment was reported as
Active disease likely or Active disease NOT likely.
RESULTS: Total of 114 subjects screened; 76 enrolled. Screen failures were due
to lack of evidence of inflammation or failure to pass the patency capsule. Of 76
subjects, 66 were included in the efficacy analysis (mean age 37yrs, 67% F). The
majority of exclusions was due to capsule retention in the SB or stomach. Forty-
six of 66 (70%) had Active CD likely by IC. PillCamCD identified 43 (94%)
similarly. There was no significant difference between PillCamCD and IC for
classifying subjects as having active CD (p 0.43). Fifty-five subjects (83%) were
identified with Active CD likely by PillCamCD including 12 identified by
PillCamCD only. The proximal SB was evaluated only by PillCamCD; however,
5 of 12 were found to have lesions in the TI as defined by the last 10 minutes of
the SB portion of the study. Thirty subjects (46%) were identified with Active
CD likely in the SB. There was no significant difference between PillCamCD
and IC in classifying segments as having Active CD likely (p50.09). There
were three (3%) adverse events: 1 bowel obstruction due to CD capsule retention,
1 abdominal pain due to prep, 1 episode of fever, nausea, vomiting, abdominal
pain and bloating (without obstruction) related to the patency capsule.
CONCLUSION: As compared to IC, the novel PillCamCD capsule was equally
effective in identifying active CD in the colon and TI in patients with signs and
symptoms of active CD, identified more overall patients with active CD, and
provides the advantage of imaging the entire small bowel and colon in a single
procedure.
Disclosure of Interest: D. Helper Financial support for research from: Given
Imaging, P. Malik Financial support for research from: Given Imaging, R.
Havranek Financial support for research from: Given Imaging, Lecture fee(s)
from: Given Imaging, K. Isaacs Financial support for research from: Given
Imaging, I. Dotan Financial support for research from: Given Imaging, A.
Lahat Financial support for research from: Given Imaging, J. Horlander
Financial support for research from: Given Imaging, A. Tinsley Financial sup-
port for research from: Given Imaging, J. Leighton Financial support for
research from: Given Imaging, Consultancy for: Given Imaging, I. Fernandez-
Urien Sainz Financial support for research from: Given Imaging, B. Rosa
Financial support for research from: Given Imaging, G. Mullin Financial sup-
port for research from: Given Imaging, I. Gralnek Consultancy for: Given
Imaging
OP055 CONFOCAL LASER ENDOMICROSCOPY PREDICTS
RELEVANT CLINICAL OUTCOMES IN CROHNS DISEASE: A
PROSPECTIVE, OBSERVATIONAL, FOLLOW-UP STUDY
G.E. Tontini1,2,*, J. Mudter1, M. Vieth3, R. Atreya1, C. Gunther1, M. Vecchi2,4,
M.F. Neurath1, H. Neumann1
1
Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany,
2
Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato,
Milano, Italy, 3Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany,
4
Biomedical Sciences for Health, University of Milan, Milano, Italy
Contact E-mail Address: gianeugeniotontini@libero.it
INTRODUCTION: Assessment of prognostic factors in Crohns disease (CD)
patients is crucial for early intervention and treat to target strategies [1].
Confocal Laser Endomicroscopy (CLE) enables on demand in vivo characteriza-
tion of architectural changes during endoscopy [2].
AIMS & METHODS: Here, we prospectively evaluated the value of CLE, endo-
scopic index of severity (CDEIS) and serum C-reactive protein (CRP) for pre-
diction of clinical outcomes in CD. Consecutive CD patients undergoing
colonoscopy with fluoresceine-aided confocal imaging were enrolled in a blind,
observational, follow-up study. Consistent with previous reports [2], CLE ana-
lysis focused on two highly reproducible architectural microscopic tissue changes
referred as histological hallmarks of acute inflammation in CD: focal cryptitis
and discontinuous crypt architectural abnormality.
RESULTS: Thirty-two CD patients were included (14 men; median age/range
37/18-60 years; mean distance from diagnosis 11 years). Baseline CRP was 5
mg/L in 46% and CDEIS 3 in 73% of patients. Mean follow-up period was 2.5
years (range6-48 months). Focal cryptitis and discontinuous crypt architectural
abnormality were observed in 63% of patients. This finding showed a weak
correlation with CDEIS (P0.068, RR1.6) and no correlation with CRP
(P0.4, RR1.6). Focal cryptitis and discontinuous crypt architectural abnorm-
ality were significantly associated with an increased risk of medical treatment
escalation with biologics, immunosuppressant or systemic steroids within 6
months (P0.045, RR2.0), showing 75% sensitivity and 70% specificity. This
finding was also confirmed at 12 month follow up (P0.012, RR2.1;
sensitivity76%, specificity78%). Patients with positive CLE findings devel-
oped significantly more transmural complications such as stenosis or perianal
disease during the first 12 months (P0.023, RR6.0; sensitivity91%,
specificity52%). Conversely, basal CDEIS 3 was only associated with treat-
ment escalation at month 12th (P0.022, RR2.27; sensibility85%,
specificity37%). CRP was not correlated with prognostic clinical outcomes.
A20
CONCLUSION: In vivo characterization of CD-related signs of acute inflamma-
tion by means of CLE showed moderate correlation with CDEIS but not with
CRP. CLE appeared as a good predictor of relevant clinical outcomes such as
treatment escalation and transmural complications, performing better than CRP
and CDEIS. This finding was substantial in the short term but disappeared after
one year follow up. Therefore, endomicroscopic assessment of acute mucosal
inflammation appears to be a promising prognostic tool, which may allow
early risk stratification of strong clinical outcomes with high sensitivity and
moderate to good specificity, thereby potentially improving the timing of treat-
ment strategies targeting mucosal inflammation in CD.
REFERENCES
1. Bouguen G, et al. Treat to target: a proposed new paradigm for the manage-
ment of Crohns disease. Clin Gastroenterol Hepatol. Epub ahead of print 2013.
2. Neumann H, et al. Assessment of Crohns disease activity by confocal laser
endomicroscopy. Inflamm Bowel Dis 2012; 18: 2261-2269.
Disclosure of Interest: G. E. Tontini Financial support for research from: Italian
Group for the study of IBD (IG-IBD), J. Mudter: None declared, M. Vieth:
None declared, R. Atreya: None declared, C. Gunther: None declared, M.
Vecchi: None declared, M. Neurath: None declared, H. Neumann: None
declared
OP056 MR ENTEROCOLONOGRAPHY CAN IDENTIFY PATIENTS
WHO NEED ADDITIONAL TREATMENT BY PREDICTING
RECURRENCE, HOSPITALIZATION AND SURGERY OF CROHNS
DISEASE PATIENTS IN REMISSION
T. Fujii1,*, M. Naganuma1, Y. Kitazume2, K. Takenaka1, M. Nagahori1,
E. Saito1, K. Ohtsuka1, M. Watanabe1
1
Gastroenterology, 2Radiology, TOKYO MEDICAL AND DENTAL UNIV,
Tokyo, Japan
Contact E-mail Address: tfujii.gast@tmd.ac.jp
INTRODUCTION: Crohns disease (CD) is a lifelong chronic inflammatory
bowel disease. Evaluating the extension and severity of the disease is critical to
determine appropriate therapeutic strategies in patients with CD. MR enterogra-
phy (MRE) can investigate not only intraluminal changes, but also extraluminal
abnormalities without ionizing radiation and anesthesia, which makes it appro-
priate for frequent examinations in CD patients. We developed novel magnetic
resonance enterocolonography (MREC) for simultaneously evaluating both
small and large bowel lesions in patients with CD and recently we reported its
excellent correlation with endoscopy. However, there are few reports about pre-
dictability of CD recurrence by MRE. The aim of this study was to evaluate the
capability of MREC for prediction of recurrence, hospitalization, and surgery
among CD patients in clinical remission.
AIMS & METHODS: A total of 284 patients with established CD were pro-
spectively examined by MREC between July 2009 and February 2014. Among
them, 213 patients were in clinical remission (Crohns Disease Activity Index
(CDAI) 150). Patients underwent ileocolonoscopy (ICS) after MREC on the
same day. MREC score (0-60) was defined by modifying SES-CD. Presence and
size of ulcers, extent of ulcerated surface, extent of affected surface and presence
of narrowings were scored (0-3) in each segment of small and large intestine.
MREC score, simplified endoscopic activity score for Crohns disease (SES-CD),
CDAI and CRP was evaluated. The patients were followed up for a maximum of
58 months unless clinical recurrence occurred earlier.
RESULTS: 126 patients (59.2%) in clinical remission had active lesion on
MREC (MREC score =2; reflecting active disease). Over a median follow up
of 12 months (3-58), 81 patients recurred, 57 needed hospitalization and 49 had
operation. Patients who had active lesion on MREC more often experienced
recurrence than those who didnt (88.9% vs 11.1%. p50.001). Higher SES-
CD, higher CDAI and higher CRP at baseline also predicted clinical recurrence.
But only active lesion on MREC was a predictor for both hospitalization (37.3%
vs 11.5%, p 50.001) and operation (32.5% vs 9.2%, p 50.001). Even in 152
patients in remission with negative CRP, the detection of active lesion on MREC
significantly predicted clinical recurrence (52.6% vs 10.5%, p50.001), hospita-
lization (40.8% vs 11.8%, p50.001) and operation (35.5% vs 10.5%, p50.001).
CONCLUSION: This prospective study suggested that MR enterocolonography
is useful for predicting recurrence of Crohns disease and identifying patients who
need additional treatment.
REFERENCES
Hyun SB, Fujii T, et al. Magnetic resonance enterocolonography is useful for
simultaneous evaluation of small and large intestinal lesions in Crohns disease.
Inflamm Bowel Dis 2011.
Takenaka K, FujiiT, et al. Comparison of magnetic resonance and balloon
enteroscopic examination of deep small intestine in patients with Crohns disease.
Gastroenterol 2014 in press.
Disclosure of Interest: None declared
OP057 MAGNETIC RESONANCE ENTEROCOLONOGRAPHY CAN
DETECT SMALL INTESTINAL ACTIVE LESIONS IN CROHNS
DISEASE; COMPARISON WITH BALLOON ENTEROSCOPY
K. Takenaka1,*, K. Ohtsuka1, Y. Kitazume1, M. Nagahori1, T. Fujii1, E. Saito1,
M. Watanabe1
1
Tokyo Medical and Dental University, Tokyo, Japan
Contact E-mail Address: ktakenaka.gast@tmd.ac.jp
INTRODUCTION: To assess active lesions such as ulcers or aphtha is important
in Crohns disease (CD). Magnetic resonance (MR) enterography is a recom-
mended imaging technique for detecting intestinal involvement in Crohns dis-
ease (CD). However, the diagnostic accuracy of MR enterograpy has not been
compared directly what that of enteroscopy of the jejunum and proximal ileum.
United European Gastroenterology Journal 2(5S)
In addition, there is no widely accepted endoscopic or MR scoring system for the
entire small intestine in CD. We evaluated the usefulness of MR enterocolono-
graphy (MREC) by comparing its findings with those from balloon-assisted
enteroscopy.
AIMS & METHODS: MREC and enteroscopy were performed within 3 days on
100 patients. The segmentation and assessment of the endoscopic findings were
defined based on modified SES-CD, and those of MREC findings were defined
based on modified MaRIA score as well. Physicians and radiologists were
blinded to results from other studies. Findings from MREC were directly com-
pared with those from enteroscopy; the sensitivity and specificity with which
MREC detected CD active lesions were assessed. Additionally, we are evaluating
the correlation between modified SES-CD and MaRIA scores.
RESULTS: The scope was passed in retrograde fashion and reached the prox-
imal ileum in 98 patients (98.0 %), the jejunum in 40 patients (40.0 %), and the
entire intestine in 11 patients (11.0 %). In the assessment of CD active lesions,
MREC detected ulcerative lesions and all mucosal lesions in the small intestine
with 82.4% sensitivity and 67.5% sensitivity, respectively; specificity values were
87.6% and 94.8%, respectively. Modified MaRIA scores correlated with mod-
ified SES-CD in the terminal ileum (r 0.75), but did not in the jejunum and
proximal ileum (r 0.48).
CONCLUSION: MREC is useful for detecting active lesions in deep small intes-
tine. Evaluation of active lesions is important to determine medical treatment.
Suitable imaging approaches should be selected to assess CD lesions in deep
small intestine. Alternatively, it is needed to develop the new scoring system of
enteroscopy or MR for the entire small intestine in CD.
Disclosure of Interest: None declared
OP058 LOOKING BEYOND MUCOSAL HEALING: EFFECT OF
BIOLOGIC THERAPY ON TRANSMURAL HEALING EVALUATED
BY ULTRASOUND IN PEDIATRIC CROHNS DISEASE
F. Civitelli1,*, F. nuti1, S. oliva1, M. murciano1, M. aloi1, L. Messina1, F. Viola1,
S. cucchiara1
1
Pediatrics, Gastroenterology and Liver Unit, Sapienza University of Rome, Italy,
Rome, Italy
Contact E-mail Address: fortunatacivitelli@gmail.com
INTRODUCTION: Therapeutic goals for Crohns disease (CD) have evolved
from a mere control of symptoms to the concept of deep remission (DR), includ-
ing clinical and biomarker remission and mucosal healing (MH). Biologic ther-
apy with anti-TNF is effective in achieving MH. Yet, CD is a transmural
disease, characterized by a progressive bowel damage leading to complications.
AIMS & METHODS: This is the first pediatric study prospectively evaluating
the efficacy of anti-TNF therapy in inducing clinical remission, MH and TH in
ileal CD. Pediatric patients (pts) with ileal CD starting biological therapy with
Infliximab or Adalimumab were prospectively enrolled. All pts were na ve to
biologics. Clinical activity (Pediatric Crohns Disease Activity Index, PCDAI),
laboratory tests (CRP, ESR), endoscopic activity (simple endoscopic score, SES-
CD) and transmural disease assessed by small intestine contrast ultrasonography
(SICUS) were evaluated before starting (T0) and after 9-12 months of therapy
(T1). Complete MH was defined as a SES-CD of 0-1, partial MH as 50%
decrease vs T0. At US the evaluated parameters were: extension of disease
(cm), bowel wall thickness 43 mm (BWT), BW vascularity (BWV), stratification
of the BW (BWS), presence of stricture, fistulae and abscess. Wilcoxon signed
rank test was used for pair comparison (T1T0).
RESULTS:
T0 T1 p value
PCDAI 33.77 18.20 13.10 12.86 50.0001
Ileal SES-CD 6.6 3.6) 2  2.3 50.001
PCR (mg/l) 30609 24539 8744 16330 50.001
ESR (mm/h) 69 35 35  26 50.0001
BWT (mm) 5.98 1.67 4.31  1.71 50.0001
Extension of ileal disease (cm) 13.63  5.78 9.08  5.74 50.0001
26 pts (mean age 13.3  4, 16 males) were included. The mean PCDAI, ileal SES-
CD, CRP, ESR, BWT and disease extension values significantly decreased at T1
(table; mean SD  values). Increased BWV was present in 80% of pts at T0 and
in 24% at T1 (p50.0001). In pts with complete and partial MH the extension of
disease and the mean BWT at US were significantly reduced at T1 (p50.02); in
pts without endoscopic response the US parameters didnt change significantly,
despite clinical response. Presence of strictures and BWS didnt modify during
therapy in any group.
CONCLUSION: Biologics are effective in inducing clinical and laboratory
remission and in achieving MH in pediatric CD. Transmural inflammation sig-
nificantly improves during therapy, however when a substantial bowel damage
(stricture) is present, the effect on TH might be poorer. Further studies are
needed to evaluate the impact of TH on the long term outcome of CD.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 14:0015:30
IMAGING IN PANCREATIC CANCER: STILL A CHALLENGE HALL O_____________________
OP059 PROSPECTIVE MULTICENTER RANDOMIZED CONTROLLED
TRIAL OF HISTOLOGICAL DIAGNOSTIC YIELD COMPARING 25G
EUS-FNA NEEDLES WITH AND WITHOUT A CORE TRAP IN SOLID
PANCREATIC MASSES: ANALYSIS OF FACTORS AFFECTING
TISSUE ACQUISITION AND DIAGNOSTIC ACCURACY
H. Nebiki1,*, A. Yanagisawa2, S. Yasukawa2, K. Kamata3, M. Kudo3,
T. Ogura4, K. Higuchi4, N. Fukutake5, R. Ashida5, T. Yamasaki1, S. Hirose6,
N. Hoki6, M. Asada7, S. Yazumi7, M. Takaoka8, K. Okazaki8, F. Matsuda9,
Y. Okabe9, M. Kitano3
1
Dept. of Gastroenterology, Osaka City General Hospital, Osaka, 2Dept. of
Surgical Pathology, Kyoto Prefectural University of Medicine, Kyoto,
3
Gastroenterology and Hepatology, Kinki University, Osaka-sayama, 4The Second
dept. of Int. Med., Osaka Medical College, Takatsuki, 5Dept. of Cancer Survey
and Gastrointestinal Oncology, Osaka Medical Center for Cancer and
Cardiovascular Diseasis, Osaka, 6Dept. of Gastroenterology, Bell Land General
hospital, Sakai, 7Digestive Disease Center, Kitano Hospital, Osaka,
8
Gastroenterology and Hepatology, Kansai Medical University, Hirakata, 9Dept.
of Gastroenterology and Hepatology, Osaka Red Cross Hospital, Osaka, Japan
Contact E-mail Address: nebiki@nn.iij4u.or.jp
INTRODUCTION: We have reported that a prospective multicenter randomized
controlled trial indicated that the novel EUS-FNA 25G needle with a core trap
by a single pass offers significantly higher tissue acquisition rate and the definite
histological diagnosis rate of solid pancreatic tumors compared with the 25G
standard needle (DDW May 3, 2014).
AIMS & METHODS: The aim of the present study was to assess factors affect-
ing the tissue acquisition and diagnostic rates for both needles. Consecutive
patients with pancreatic solid masses presenting to 8 referral centers for EUS-
FNA from April 2013 to Sept 2013 were prospectively recruited. All patients
were randomized to EUS-FNA performed with either the novel 25G EchoTip
ProCoreTM (PrC) with a core trap and the standard 25G EchoTip UltraTM
(Ult). Only a single pass was performed. The whole specimen was inserted into a
formalin bottle and processed for histological analysis. All tissue samples were
brought to one facility where experienced pathologists reviewed them. All sam-
ples were divided into three groups based on quality (rich, moderate, and poor
cellularity). The tissue acquisition and diagnostic rates were assessed for different
access routes and compared between the needles. Also, the diagnostic rates in
three groups with different sample quality were compared.
RESULTS: A total of 214 patients were enrolled with 106 patients in the PrC and
108 in the Ult. The tissue acquisition rate for histological analysis was signifi-
cantly higher in the PrC than the Ult (90.6% vs. 79.6%; p0.025). The definite
histological diagnosis achieved by the PrC was significantly higher than the Ult
(81.1% vs. 69.4%; p0.048). The samples of the PrC showed significantly super-
ior quality than the Ult (rich: moderate: poor 38: 29: 39cases in the PrC vs. 21:
28: 59cases in the Ult; p0.003). In terms of tissue-sampling, the tissue acquisi-
tion rate of the PrC (46/50 cases; 92.0%) was significantly higher than that of the
Ult (33/43 cases; 76.7%) in transduodenal EUS-FNA (p0.04), although these
values did not differ significantly in transgastric EUS-FNA. Overall sensitivity,
specificity, and accuracy in pathological diagnosis of malignancy were 100%,
100%, and 100%, for rich group, 90%, 100%, and 92.5% for moderate group,
83%, 100%, and 84% for poor group respectively. The sensitivity and accuracy
were significantly higher in rich group than moderate group (p 0.027, p 0.028)
and significantly higher in rich group than poor group (p0.003, p0.002).
CONCLUSION: The novel EUS-FNA 25G needle with a core trap by a single
pass offers significantly better sample quality for histological diagnosis of solid
pancreatic tumors compared with the 25G standard needle, especially in trans-
duodenal access. The high quality of EUS-FNA sample allows increasing accu-
racy for histological diagnosis.
Disclosure of Interest: None declared
OP060 USEFULNESS OF CONTRAST-ENHANCED ENDOSCOPIC
ULTRASONOGRAPHY FOR DIFFERENTIAL DIAGNOSIS OF
PANCEATIC SOLID LESIONS: A SINGLE-CENTER PROSPECTIVE
STUDY
Y. Yamashita1,*, K. Ueda1, H. Abe1, T. Tamura1, M. Itonaga1, H. Maeda1,
T. Maekita1, M. Iguchi1, H. Tamai1, J. Kato1, M. Ichinose1
1
Second Department of Internal Medicine, Wakayama Medical University,
Wakayama, Japan
Contact E-mail Address: yasunobu@wakayama-med.ac.jp
INTRODUCTION: Recently, contrast-enhanced endoscopic ultrasonography
(CE-EUS) has become available in the diagnosis of pancreatic lesions.
AIMS & METHODS: The aim of this study was to investigate the accuracy of
CE-EUS in differentiating pancreatic ductal carcinoma from other lesions.
Between, February 2009 and July 2013, we prospectively evaluated 147 patients
with pancreatic solid lesions. After intravenous injection of a contrast agent
(Sonazoid), CE-EUS was performed using a radial-type endoscope.
Pancreatic solid lesions were classified into three vascular patterns (hypervas-
cular, isovascular, and hypovascular) on the basis of CE-EUS imaging, and
these patterns were compared to the histological diagnosis.
RESULTS: The lesions were diagnosed as ductal carcinoma (n109), acinor cell
carcinoma (n2), inflammatory mass (n11), neuroendocrine tumor (NET)
(n8), autoimmune pancreatitis (AIP) (n9), invasive intraductal papillary
mucinous neoplasm (IPMN) (n5), metastatic lesion (n2; lung cancer 1, mel-
anoma 1) or intraductal tubular tumor (ITT) (n1) by operation, EUS-FNA,
biopsy of liver metastasis, or international consensus diagnostic criteria for AIP.
104 of 109 ductal carcinomas were hypovascular patterns (95%). 8 of 9 AIPs
A21
were isovascular patterns (89%). 6 of 8 NETs were hypervascular patterns
(75%). 8 of 11 inflammatory masses were isovascular patterns (73%). 3 of 5
invasive IPMNs were hypovascular patterns (60%). All 2 acinor carcinomas
were isovascular patterns (100%). A hypovascular pattern, determined by CE-
EUS, was calculated to diagnose ductal carcinoma with sensitivity and accuracy
of 95% and 89%, respectively.
CONCLUSION: CE-EUS was useful for characterization of pancreatic solid
masses with high sensitivity and accuracy.
Disclosure of Interest: None declared
OP061 LIQUID BIOPSY BASED ON CIRCULATING TUMOUR CELLS
(CTC) DETECTION IS A DIAGNOSTIC AND PROGNOSTIC
MARKER IN PATIENTS WITH PANCREATIC SOLID TUMOURS
P. Basile1,*, E. Toure2, D. Sefrioui1,3, I. Iwanicki-Caron1, C. Vasseur3,
M. Antonietti4, S. Lecleire4, F. Blanchard2, J.C. Sabourin2,3, F. Di Fiore1,3,
P. Michel1,3
1
Digestive oncology unit, Department of hepatogastroenterology, 2Department of
pathology, 3Inserm unit U1079, 4Endoscopy unit, Department of hepatogastroen-
terology, Rouen University Hospital, ROUEN, France
Contact E-mail Address: frederic.di-fiore@chu-rouen.fr
INTRODUCTION: The pancreatic cytology by endoscopic ultrasound-guided
fine needle aspiration (EUS-FNA) is considered as the standard procedure for
the diagnostic of pancreatic tumour. We recently showed that detection of cir-
culating tumour cells (CTC) had a diagnostic accuracy of 70% for pancreatic
adenocarcinoma (Am J Gastroenterol 2013;108:152-155). The aim of the study
was to evaluate both diagnostic and prognostic impact of CTC detection in an
extended series of patients referred for a EUS-FNA for a pancreatic solid
tumour.
AIMS & METHODS: It was a single center study including all consecutive
patients referred from 01/2011 to 07/2013 for a EUS-FNA procedure in a context
of pancreatic solid mass. EUS-FNA was performed with a 22 gauge needle and
analysed by two pathologists. A 10 ml peripheral blood sample was collected in
each patient before the EUS-FNA procedure. Samples were filtered using the
ScreencellsCyto method, stained with Giemsa and analyzed by a cytologist
blinded to clinical data and FNA results. The CTC detection was positive accord-
ing to the presence of the following parameters: nuclear diameter 4 7m, aniso-
cytosis, membrane irregularities, presence of a large nucleolus.
RESULTS: A total of 69 patients were included. Amon them, 57 (83%) have a
confirmed pancreatic tumours corresponding to 47 primitive adenocarcinoma, 4
others primitive tumours and 6 metastatic lesions. The sensitivity and the speci-
ficity of EUS-FNA was 83% and 100%, respectively. CTC were positive in 36/69
(52%) patients. The sensitivity and specificity of CTC was respectively 64.4%
and 73.3% in patients with pancreatic cancer and 64.1% and 81.8% in patients
with all types of cancer. The presence of CTC was significantly associated with
the diagnosis of cancer (p0.01) and with the presence of distant metastases
(p0.004). In contrast, tumour size, arterial involvement and CA19-9 serum
level were not associated with CTC. The 18 months survival rate was significantly
lower in patients with positive CTC as compared to those without detectable
CTC (33 vs 44%, p0.03).
CONCLUSION: Ours results highlighted that liquid biopsy based on circulating
tumour cells (CTC) detection may be a diagnostic and prognostic marker in
patients with pancreatic solid tumours.
REFERENCES
Iwanicki-Caron I, Basile P, Toure E, et al. Am J Gastroenterol 2013; 108: 152-
155.
Disclosure of Interest: None declared
OP062 EUS AND MRI AS SCREENING TOOLS FOR PANCREATIC
CANCER: A COMPARATIVE PROSPECTIVE BLINDED ANALYSIS
OF THEIR EFFECTIVENESS
I. Konings1,*, F. Harinck1, J.W. Poley1, N. Krak2, K. Biermann3, J. van Hooft4,
Y. Nio5, C. Aalfs6, A. van Rens7, C. van Eijck8, D. Gouma9, M. Dijkgraaf10,
H. van Dullemen11, R. Sijmons12, P. Fockens4, M. Bruno1 on behalf of the Dutch
research group on pancreatic cancer surveillance in high-risk individuals
1
Department of Gastroenterology and Hepatology, 2Department of Radiology,
3
Department of Pathology, Erasmus MC University Medical Center Rotterdam,
Rotterdam, 4Department of Gastroenterology and Hepatology, 5Department of
Radiology, 6Department of Clinical Genetics, Academic Medical Center
Amsterdam, 7Department of Clinical Genetics, The Netherlands Cancer Institute,
Antoni van Leeuwenhoek, Amsterdam, 8Department of surgery, Erasmus MC
University Medical Center Rotterdam, Rotterdam, 9Department of surgery,
10
Clinical Research Unit, Academic Medical Center Amsterdam, Amsterdam,
11
Department of Gastroenterology and Hepatology, 12Department of Clinical
Genetics, University Medical Center Groningen, Groningen, Netherlands
Contact E-mail Address: i.konings@erasmusmc.nl
INTRODUCTION: Previous studies suggest that endoscopic ultrasonography
(EUS) and magnetic resonance imaging (MRI) are promising tests to detect
asymptomatic, non-invasive precursor lesions and early stage pancreatic cancer
(PC) in high-risk individuals (HRI). However, most studies were not performed
in a blinded fashion. Therefore, it is still unclear which screening technique is to
be preferred. We aimed to compare the effectiveness of EUS and MRI in a
prospective blinded fashion in their ability to detect clinical relevant lesions in
individuals at high risk for developing pancreatic cancer.
AIMS & METHODS: In the interim-analysis of this ongoing Dutch multicenter
prospective study, the results of 139 asymptomatic HRI undergoing first time
screening by EUS and MRI are described. HRI (410% life time risk of PC) were
defined as (1) mutation carriers of pancreatic cancer prone gene mutations and
A22
(2) first-degree relatives of patients with familial pancreatic cancer. Clinical rele-
vant lesions included all solid lesion, MB-IPMNs, and all cystic lesions 10mm
and/or with malignant features. Results were compared in a blinded, independent
fashion.
RESULTS: Clinical relevant lesions were detected by either EUS and/or MRI in
9 out of 139 HRI (6%). Within these 9 HRI, a total of 11 clinical relevant lesions
were detected: 2 solid lesions and 9 cysts 10 mm. Both solid lesions were
detected by EUS only, one 11 mm and one 7 mm lesion, which, after resection,
proved to be a stage I adenocarcinoma and multifocal PanIN-2 lesions. Of the 10
cysts 10 mm, 6 were detected by both EUS and MRI and 3 were detected by
MRI only. There was a slight agreement between EUS and MRI for the detection
of clinical relevant lesions with a Kappa-value of -0.279 (55% agreement) and a
good agreement between EUS and MRI for the location (Kappa 1.000, agree-
ment 100%) and size of detected lesions (Spearmans rho 0.638).
CONCLUSION: EUS and/or MRI showed clinical relevant pancreatic lesions in
6% of high risk individuals. There was a slight agreement between EUS and MRI
on detection of lesions was, however, on location and size a good to perfect
agreement. EUS and MRI seem rather complementary of each other than corre-
sponding: contrary to EUS, MRI proved very sensitive for cystic lesions, how-
ever, MRI might have some important limitations with regard to the timely
detection of (small) solid lesions.
Disclosure of Interest: None declared
OP063 NEEDLE BASED CONFOCAL LASER ENDOMICROSCOPY
(NCLE) FOR THE DIAGNOSIS OF PANCREATIC MASSES:
CORRELATION BETWEEN PCLE AND HISTOLOGICAL CRITERIA
(CONTACT STUDY)
M. Giovannini1,*, F. Caillol1, D. Lucidarme2, B. Pujol3, F. Poizat1, G. Monges1,
B. Filoche2, A., I. Lemaistre4, B. Napoleon3
1
Institut Paoli Calmettes, Marseille, 2GHICL, Lille, 3Hopital Jean Mermoz,
4
Centre Leon Berard, Lyon, France
Contact E-mail Address: giovanninim@wanadoo.fr
INTRODUCTION: Needle-based Confocal Laser Endomicroscopy (nCLE) is an
imaging technique, which enables microscopic observation of solid organs, in vivo
and in real-time, during an EUS FNA procedure. The CONTACT study
(Clinical evaluation Of NCLE in The lymph nodes Along with masses and
Cystic Tumors of the pancreas) aims at building an image atlas, and define
interpretation criteria for nCLE images in the pancreatic masses.
AIMS & METHODS: 3 centres in France (7 investigators) took part in this
prospective study.
34 patients with a pancreatic mass of unknown nature were included prospec-
tively during the study (June 2012 to March 2013). There were 17 men, and 18
women, mean age 66 years, (range: 32-87 years old). The localization of the
pancreatic masses was: head (17 cases), body (12 cases), tail (6 cases). Mean
size was 30mm (/- 9mm). The puncture of the mass was done in all cases
with a 19G puncture needle with the nCLE probe preloaded. After examination
of the track of the puncture by nCLE, aspiration was done in the same track to
compare images and histological results. No complication occurred during the
nCLE procedure or the puncture. A definitive histological diagnosis was
obtained in 30/34 patients: adenocarcinoma (21 cases), fibrous stroma adenocar-
cinoma (1 case), neuroendocrine tumor (4 cases), pseudopapillary tumor (1),
chronic pancreatitis (3 diagnosis confirmed by a one year follow-up)).
Preliminary characteristic descriptive criteria were previously described [1].
To go further, nCLE sequences were re-visualized by two gastro-enterologists
and two pathologists to compare, for each type of lesion, their findings to the
pathology specimen.
RESULTS: During this review, normal pancreas shows an aspect of coffee beans
corresponding to the histological structure of acinis.
Adenocarcinomas showed dark cells aggregates with pseudo-glandular aspects
and straight hyperdense elements more or less thick. These criteria correlate with
the histological structure of those tumors which are characterized by tumoral
glands, surrounded by fibrosis in case of fibrous stroma tumor.
Neuroendocrine tumors showed a dense network of small vessels on a dark
background, which fits with the histological structure based on cord of cells
surrounded by vessels and by fibrosis in case of fibrosis area.
Chronic pancreatitis showed residual acinis, which corresponds to the pancreatic
regression.
CONCLUSION: This preliminary classification of nCLE images obtained in
pancreatic masses could help in the differentiation of adenocarcinomas and neu-
roendocrine tumors, and between malignant tumors from normal pancreatic
tissue. nCLE could therefore facilitate the diagnosis of these lesions, by bringing
in vivo microscopic information, in real-time.
REFERENCES
[1] Giovannini M. Needle-based confocal laser endomicroscopy for the diagnosis
of pancreatic masses: preliminary criteria (CONTACT study). Oral presentation
UEGW 2013 (OP 205).
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP064 DETECTION OF KRAS GENE MUTATION BY LIQUID BIOPSY
IN PATIENTS WITH PANCREATIC CANCER
H. KINUGASA1,*, K. NOUSO1, K. MIYAHARA1, Y. MORIMOTO1, C.
DOI1, K. TSUTSUMI1, H. KATO1, H. OKADA1, K. YAMAMOTO1
1
GASTROENTEROLOGY, OKAYAMA UNIVERSITY, OKAYAMA, Japan
Contact E-mail Address: gyacy14@gmail.com
INTRODUCTION: Circulating nucleic acids in plasma or serum have been
considered to be a candidate for noninvasive cancer diagnosis which is called
liquid biopsy. However, conventional mutation detection assays have not been
sufficiently sensitive, specific, nor quantitative for the clinical use, because the
number of circulating tumor cells and serum free DNA with somatic mutations
are very low compared to those of wild type. Newly developed technologies on
digital PCR such as droplet digital PCR (ddPCR) and next generation sequence
(NGS) have provided new insight to this area. The methods dramatically
improve the detection rate of rare mutations and are able to quantify the
mutant fraction among normal DNA molecules.
AIMS & METHODS: This study was designed to estimate the clinical utilities of
genetic analysis for circulating DNA in serum with pancreatic cancer by droplet
digital PCR (ddPCR) (QX200, Biorad). We compared KRAS mutation detected
in endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) biopsy tissue
DNA and in circulating serum DNA in 75 patients with pancreatic cancer
admitted in our institute between January 2008 and December 2010. Codon12
KRAS mutations were examined by ddPCR to detect circulating serum DNA
with rare mutations and compared with survival.
RESULTS: Median age of the patients were 66 years old. Two patients, 5
patients, and 68 patients were diagnosed as stage I/II, III and stage IV, respec-
tively. KRAS mutations were detected in 74.7% (56/75) of the EUS-FNA tissue
samples. The frequencies of the mutations at GTT, GAT, CGT, GCT, AGT and
TGT in codon12 were 28/56 (50%), 22/56 (39.3%), 6/56 (10.7%), 0/56 (0%), 0/56
(0%) and 0/56 (0%), respectively. On the other hand, the rate of KRAS muta-
tions in circulating serum DNA was 68% (51/75). The mutations at GTT, GAT
and CGT in codon12 were 30/51 (58.8%), 29/51 (56.8%) and 4/51 (7.8%),
respectively. Although the mutations detected in EUS-FNA samples were not
completely matched to those in serum DNA, the frequencies of mutations were
very similar between them (N.S.). Interestingly 12/75 (16%) circulating DNA
showed multiple mutations at GTT, GAT and/or CGT, whereas EUS-FNA
revealed only one kind of KRAS mutation. Survival was not different by
KRAS mutations at GTT, GAT, CGT, GCT, AGT and TGT in EUS-FNA
tissue DNA, but it was shorter in patients with KRAS mutation at GTT com-
pared to others in circulating serum DNA analysis (P50.01).
CONCLUSION: Analysis of circulating DNA in serum is a new useful procedure
to detect genetic mutations in pancreatic cancer. This method is simple and
noninvasive, and may have great potential as a new strategy for the diagnosis
of pancreatic cancer as well as to predict patients survival. The findings in this
study warrant further verification in other populations.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 14:0015:30
CLINICAL AND MOLECULAR FACTORS IN OESOPHAGO-GASTRIC CANCER OUTCOMES
LOUNGE 5_____________________
OP065 SURVIVAL AFTER PATHOLOGIC COMPLETE RESPONSE IN
PATIENTS WITH CANCER OF THE ESOPHAGUS OR GASTRO-
ESOPHAGEAL JUNCTION
S. Lagarde1, M. Anderegg1,*, W. Borstlap1, S. Gisbertz1, S. Meijer2, M. Hulshof3,
J. Bergman4, H. van Laarhoven5, M. van Berge Henegouwen1
1
Surgery, 2Pathology, 3Radiation Oncology, 4Gastroenterology, 5Medical
Oncology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: s.m.lagarde@amc.uva.nl
INTRODUCTION: The preferred curative strategy for esophageal cancer
patients with locally advanced tumors, but without distant metastases consists
of esophagectomy with preceding chemo(radio)therapy (CRT). In 10-40% of
patients who are neoadjuvantly treated, there is absence of viable tumor at the
time of surgery (pathologic complete response (pCR)). The aim of the present
study was to define the outcome of patients with a pCR and identify predictive
factors for survival in this group.
AIMS & METHODS: Between March 1994 and September 2013 all consecutive
patients with cancer of the esophagus or gastroesophageal junction who under-
went esophageal resection after neoadjuvant chemo (radio) therapy were
included in the present study. Multivariate Cox regression analysis was carried
out to identify independent prognostic factors.
RESULTS: Of the 463 included patients, 86 (19%) patients had a pCR
(pyT0N0M0R0) (54 men, 32 women, median age: 63yrs (range 33-82 years)).
48 (56%) patients had an adenocarcinoma. Eight (9%) patients underwent
neoadjuvant chemotherapy and 78 (91%) underwent neoadjuvant chemoradia-
tion therapy. During follow-up, 25 (29%) patients developed recurrent disease.
Nineteen (76%) patients developed haematogenous metastases, 6 developed lym-
phatic metastases (of which 3 patients with a distant lymphatic location). 5-year
disease free survival was 61%, 5-year overall survival was 58%. Cox regression
analysis revealed no prognostic factor for any of the tested variables (sex, age,
histologic subtype, tumor location, type of neoadjuvant therapy, cTNM stage).
CONCLUSION: Patients with a pathologic complete response have a relatively
good survival. However, one third of these patients developed recurrent disease.
Thus far it is unclear how these patients can be identified.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP066 TUMOR MICROENVIRONMENT IN ESOPHAGEAL
ADENOCARCINOMA: CD80 EXPRESSION PEAKS IN EARLY
STAGES, IT IS ENHANCED BY NEOADJUVANT THERAPY AND IT
IS AN ACCURATE PREDICTOR OF SURVIVAL
M. Scarpa1, A. Kotsafti1,*, M. Scarpa1, M. Cagol1, R. Alfieri1, E. Pinto1,
I. Castagliuolo2, C. Castoro1
1
Oncological Surgery Unit, Veneto Institute of Oncology (IOV-IRCCS), 2Dept
Molecular Medicine, University of Padova, Padova, Italy
INTRODUCTION: Esophageal adenocarcinoma (EAC) is an increasingly
common cancer with a poor prognosis. EAC microenvironment is characterized
by lack of cytokines with anti-cancer effect and by high expression of immuno-
suppressive factors. The aim of the study is to characterize the antigen presenting
cells (APC) and lymphocyte function in EAC investigating their relationship with
stage, response to neoadjuvant therapy and prognosis.
AIMS & METHODS: Mucosa samples from cancer and from healthy esophagus
were obtained during esophagectomy from 64 patients affected by EAC. Frozen
samples were analysed with Real Time qPCR for costimulatory molecules (Cd80,
Cd86), and lymphocytes activation (Cd38, Cd69) genes expression.
Immunohistochemistry for CD8 and NK cells cytolytic activity (CD107a) of
tumor infiltrating lymphocytes and for CD80 was performed. Flow cytometry
for epithelial cells (CytokeratineCd80 and CytokeratineHLA-ABC) acting
as APC and activated (CD8Cd28 and CD8CD38) tumor infiltrating lym-
phocyte (TIL) was performed. Non parametrical statistics, survival analysis and
ROC curve analysis were used.
RESULTS: In normal mucosa a lower level of epithelial cells expressing HLA-
ABC compared to neoplastic tissue was observed (p0.02) but the rate of
CD80epithelial cells was similar (p0.61) and well as the rate of activated
CD8 lymphocytes. In normal mucosa, a significant upregulation of Cd80
mRNA expression in patients who underwent neoadjuvant therapy compared
to that from patients who had no neoadjuvant therapy was observed (p0.02).
Immunohistochemistry showed a high level of CD80 expression in normal
mucosa of patients with stage I EAC compared to stage III and to yT0N0
(p0.02). A similar peak was observed in CD38 mRNA levels (p0.02).
Patients with CD80 normal mucosa survived significantly longer than CD80-
patients (p0.02) while the stage distribution of the two groups was equivalent
(p0.69). CD80 expression in normal mucosa had a great accuracy in predicting
cancer-related deaths (AUC0.87 (95% CI0,68-0,96): p0.001).
CONCLUSION: In EAC, tumor cells expressed more HLA-ABC but their CD80
expression was similar to normal tissue levels confirming an impaired APC func-
tion in cancer tissue. Neoadjuvant therapy seemed to induce a high expression of
CD80 in healthy mucosa suggesting an APC activation. CD80 expression was
highest in stage-1 EAC and this peak expression corresponded to a peak in
lymphocyte activation. Finally, CD80 expression in normal mucosa resulted an
accurate predictor of postoperative survival suggesting its possible role as a
biomarker in EAC management.
Disclosure of Interest: None declared
OP067 TRANSCRIPTIONAL FACTORS FOR EPITHELIAL-
MESENCHYMAL TRANSITION ARE ASSOCIATED WITH
PATHOGENESIS OF CARCINOSARCOMA OF THE ESOPHAGUS:
WITH EVIDENCE OF MONOCLONAL ORIGIN BY TP53
MUTATIONAL ANALYSIS
T. Nakazawa1,*, H. Ikota1, S. Nobusawa1, H. Yokoo1
1
Department of Human Pathology, Gunma University Graduate School of
Medicine, Maebashi, Japan
Contact E-mail Address: ntakuro3@yahoo.co.jp
INTRODUCTION: Carcinosarcoma of the esophagus is a rare malignant neo-
plasm composed of both carcinomatous and sarcomatous elements. The histo-
genesis of sarcomatous and carcinomatous components of the tumor has not
been elucidated. Epithelial-mesenchymal transition (EMT) is the conversion of
cells with an epithelial phenotype into cells with a highly motile fibroblastoid or
mesenchymal phenotype1. It is unclear whether EMT is involved in sarcomatous
differentiation in carcinosarcoma of the esophagus.
AIMS & METHODS: We carried out immunohistochemistry for Slug, Twist,
ZEB1 and ZEB2, genes associated with EMT1, in 14 cases of carcinosarcoma of
the esophagus to assess whether there is evidence of expression of these genes. We
also performed immunohistochemical analysis for E-cadherin, whose loss of
expression is considered as the key step of EMT1. The staining of Slug, Twist,
ZEB1, ZEB2 and E-cadherin was scored as follows: -, 0% of positive cells; , 1-
10%; , 11-50%; , 51-80%; , 480%. To verify the neoplastic 1
nature of sarcomatous components, we examined monoclonality between carci-
nomatous and sarcomatous components comparing TP53 mutation status and
p53 expression of both areas by DNA sequencing and p53 immunohistochem-
istry, respectively.
RESULTS: Nuclear ZEB1 was significantly more widely expressed in the sarco-
matous component (P 5 0.0001). Twelve cases showed ZEB1 expression in 4
80% neoplastic cells in the sarcomatous component. In contrast, neoplastic cells
in carcinomatous components were negative in these 12 cases. Nuclear Twist was
also significantly more widely expressed in the sarcomatous component (P
0.0256). Membranous E-cadherin was significantly more widely expressed in
the carcinomatous component in all cases (P 5 0.001), and neoplastic cells in
the sarcomatous component were largely negative. Nuclear Slug and ZEB2
expression showed no significant difference between carcinomatous and sarco-
matous components (P 0.1379, P 0.1292, respectively). TP53 mutation
analysis was carried out in 13 cases. Seven cases had mutations in both carcino-
matous and sarcomatous components and the mutations patterns were identical.
One case had mutation only in sarcomatous components. p53 immunohisto-
chemical study was carried out for all 14 cases. Immunohistochemistry detected
A23
moderate to strong p53 expression in 6 cases, and the sarcomatoid and epithelial
tumor components showed almost concordant p53 expression patterns and inten-
sities, except one case that had mutations only in sarcomatous components. Of
these 6 cases, 4 cases harbored TP53 mutations.
CONCLUSION: We found that ZEB1 and Twist were significantly widely
expressed in the sarcomatous component, and the expression of E-cadherin in
the sarcomatous area was lost. We also detected identical TP53 mutation pat-
terns and nuclear p53 immunohistochemical staining in both carcinomatous and
sarcomatous components. These findings suggest that this uncommon tumor has
a monoclonal origin and support the hypothesis that EMT may play an impor-
tant role in the pathogenesis of carcinosarcoma of the esophagus, mainly through
ZEB1 and Twist expression.
REFERENCES
1) Peinado H, Olmeda D and Cano A. Snail, ZEB and bHLH factors in tumor
progression: an alliance against the epithelial phenotype? Nat Rev 2007; 7: 415-
428.
Disclosure of Interest: None declared
OP068 THE THERAPEUTIC EFFECT OF IRREVERSIBLE
ELECTROPORATION ACCORDING TO TISSUE PROPERTIES OF
UPPER GASTROINTESTINAL TRACT: GENE EXPRESSION
SIGNATURE ANALYSIS
H.S. Choi1,*, J.M. Lee1, S.H. Kim1, S.J. Nam1, E.S. Kim1, B. Keum1, Y.T. Jeen1,
H.S. Lee1, H.J. Chun1, C.D. Kim1, H.B. Kim1
1
Internal Medicine, Korea University College of Medicine, Seoul, Korea, Republic
Of
Contact E-mail Address: mdkorea@gmail.com
INTRODUCTION: Irreversible electroporation (IRE) is a promising novel tech-
nique for the ablation of tumors. IRE has an advantage over other ablation
techniques in its mechanism to remove undesired cells by affecting the cell mem-
brane without thermally destroying blood vessels, nerves and the surrounding
tissues. This therapeutic modality has been considered to apply to Barretts
dysplasia or epithelial neoplasm of upper gastrointestinal tract instead of pre-
vious radiofrequency ablation. Recently, we have validated the effectiveness of
IRE tissue ablation on stomach, but there was no study about treatment effect of
IRE according to tissue property in upper gastrointestinal tract. Our purpose was
to study effectiveness of IRE according to tissue properties in rat stomach.
AIMS & METHODS: The Sprague-Dawley rats were used throughout this
study. IRE ablation was applied in upper stomach (squamous cell epithelium)
and lower stomach (columnar cell epithelium) with same energy parameters. The
energy delivered for each ablation was 50/100 pulses of 1KV/cm  3KV/cm. All
samples for histologic analysis and tunnel assay were got at 0hrs, 10hrs, 24hrs
and 72hrs after IRE. And we used DNA microarrays to measure the expression
levels of large numbers of genes in rat stomach according to different electrical
energy. And we measured several apoptotic gene expression using real time RT-
PCR.
RESULTS: All animals survived for their designated times. H-E staining showed
extensive cell death area, which were proved by a pyknotic nucleus and eosino-
philic cytoplasm near absence of cell at 10 hours after IRE ablation in upper
(squamous cell epithelium) and lower (columnar cell epithelium) gastric tissue.
We confirmed apoptotic cell death by Tunnel assay. The number of significantly
up-regulated apoptotic genes was higher in 2KV, 100 pulse and 10hr than that of
other electrical energy groups. The significantly up-regulated genes related to
apoptosis after IRE ablation in all IRE setting were s100a8/9, Ccl2, Timp1.
Aif1, Lcn2, hspb1 genes, but caspase-related genes were down-regulated in all
condition.
CONCLUSION: This study showed that IRE ablated stomach tissue through
cellular apoptosis. And the degree of apoptosis after IRE ablation was tissue and
electric energy specific in gastrointestinal tract. This study suggests the potenti-
ality of IRE application in the treatment of not only gastric neoplasm but also
esophageal neoplasm including dysplasia of Barretts esophagus without
metastasis.
Disclosure of Interest: None declared
OP069 THE RELEVANCE OF THE LOCATION OF INVOLVED NODES
IN PATIENTS WITH CANCER OF THE DISTAL ESOPHAGUS OR
GASTRO-ESOPHAGEAL JUNCTION
S. Lagarde1, M. Anderegg1,*, S. Gisbertz1, S. Meijer2, M. Hulshof3, J. Bergman4,
H. van Laarhoven5, M. van Berge Henegouwen1
Surgery, 2Pathology, 3Radiation Oncology, 4Gastroenterology, 5Medical
Oncology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: s.m.lagarde@amc.uva.nl
INTRODUCTION: Truncal node metastases as well as lymphatic dissemination
in the proximal field (subcarinal, paratracheal and aortopulmonary window
lymph nodes) after neoadjuvant chemoradiation therapy does not alter the
TNM classification. The incidence and impact of these relatively distant lymph
node metastases on long-term survival remains unclear. Therefore the aim of the
present study is to identify the incidence and prognostic significance of the loca-
tion of lymph node metastasis in patients who underwent neoadjuvant chemor-
adiation therapy followed by a transthoracic esophagectomy (TTE).
AIMS & METHODS: Between March 1994 and September 2013 a total of 286
consecutive patients with cancer of the mid-to-distal esophagus or gastroesopha-
geal junction (GEJ) who underwent potentially curative esophageal resection
after neoadjuvant chemoradiation therapy were included.
RESULTS: The majority of patients was male (219 patients, 76.6%) and had an
adenocarcinoma (208 patients, 72.7%). The tumor was located in the mid-eso-
phagus in 53 (18.5%), in the distal esophagus in 210 (73.4%) and at the GEJ /
A24
cardia in 23 (8.0%) patients. 279 (97.6%) patients underwent a radical (R0)
resection. 112 (39.2%) patients had a complete or near complete pathologic
response (tumor regression grade 1 or 2). 110 (38.5%) patients had nodal metas-
tases in the marked resection specimen. 63 (22.0%) patients were classified as N1,
33 (11.5%) patients as N2 and 14 (4.8%) patients as N3. Of the patients with
tumorpositive lymph nodes, 40 (36.4%) patients had metastases localized in
locoregional nodes, 35 (31.8%) patients had localisation of metastases in at
least one truncal node, 14 (12.7%) patients had positive nodes in the proximal
field and 5 (4.5%) patients had positive truncal nodes as well as positive proximal
lymph nodes. Median disease free-survival was 90.3 months for N0 patients, 65.7
months for patients with nodal metastases limited to locoregional nodes, 18.8
months for patients with truncal nodes, 15.4 months for patients with lymph
node in the proximal field and 10.1 months if nodes were positive in both the
truncal and the proximal field. In multivariate analysis yN stage as well as loca-
tion of lymph nodes were independently associated with a worse survival.
CONCLUSION: The present study demonstrated that the location of positive
nodes after neoadjuvant chemoradiation therapy harbors important prognostic
information.
Disclosure of Interest: None declared
OP070 ADIPOSE TISSUE PROMOTES PROLIFERATION,
DIFFERENTIATION AND INVASION OF ESOPHAGEAL
SQUAMOUS CELL CARCINOMA IN VITRO
A. Nakayama1,*, E. Takeshita1, N. Tsuruoka1, R. Shimoda1, T. Koyama2,
T. Noda3, H. Sakata1, R. Iwakiri1, K. Fujimoto1
1
Gastrointestinal Endoscopy, Saga university, Saga, 2Gastrointestinal Medicine,
Shimonoseki City Toyoura Hospital, Shimonoseki, 3Internal Medicine, Karatsu
Red Cross Hospital, Karatsu, Japan
Contact E-mail Address: sr20det14turbo@yahoo.co.jp
INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) develops
within squamous epithelial layer, and progressively invades into submucosal to
subadventitial layers. Given that abundant adipose tissue exists in the subadven-
titia, adipose tissue seems critical for the progression of ESCC. However, their
interaction is unknown.
AIMS & METHODS: We aimed to address an interaction between ESCC and
adipose tissue in vitro. ESCC cells (well and poorly differentiated types, EC-GI-
10 and TE-9, respectively) were cultured on rat or human subcutaneous adipose
tissue-embedded or -nonembedded collagen gel. Culture assembly was analyzed
by electron microscopy, immunohistochemistry, Western blotting, ELISA and
small interfering RNA (siRNA) transfection, in terms of cell survival, growth,
differentiation and invasion.
RESULTS: Adipose tissue promoted the expression of the growth markers, Ki-
67 antigen and bromodeoxyuridine (at 24 h-labeling) in the cancer cell types,
whereas it inhibited that of the apoptosis marker, cleaved caspase-3. Adipose
tissue promoted the basal and superficial expression of the differentiation mar-
kers, p63 and involucrin, respectively, within the epithelial layer formed by
cancer cell types. Adipose tissue accelerated the invasion of cancer cell types
into the gel, together with increased expression of filamin A, laminin-5 and
membrane type 1-matrix metalloproteinase (MT1-MMP), and with decreased
display of E-cadherin. Adipose tissue promoted the expression of mitogen-acti-
vated protein kinase (MAPK: pERK1/2) and phosphoinositide 3-kinase-AKT
(PI3K-AKT: pAKT1/2/3, p4E-BP1 and pS6) pathways, and insulin-like growth
factor-1 receptor (IGF-1R) in the cell types, while it decreased that of human
epidermal growth factor receptor 2 (HER2). Cancer cell types in turn decreased
IGF-1, adiponection, leptin and registin production in adipose tissue. IGF-1 (10
nM) promoted the growth of cancer cell types, while IGF-1R inhibitor (picro-
podophyllin, 1 mM) enhanced the apoptosis. Finally, IGF-1R siRNA-transfected
EC-GI-10 cells did not replicated the adipose tissue-induced phenomena above.
CONCLUSION: The data suggest, first, that adipose tissue may influence the
progression of ESCC with the increased growth/invasion and the decreased
apoptosis through MAPK, PI3K-AKT and IGF-1R up-regulation, although
adipose tissue seems to induce the differentiation of the cancer cells; second,
that adipose tissue may adversely affect the HER2-targeted therapy; and third,
that the cancer cells may affect adipokine production of adipose tissue.
Collectively, we conclude that adipose tissue may be involved in the progression
of ESCC under adipose tissue-cancer cell interaction.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 14:0015:30
OBESITY AND THE GUT LOUNGE 6_____________________
OP071 ACCELERATED INTESTINAL GLUCOSE ABSORPTION IN
MORBID OBESITY RELATIONSHIP TO GLUCOSE
TRANSPORTERS, INCRETIN HORMONES AND GLYCAEMIA
N.Q. Nguyen1,*, T. DEBRECINI1, J. BAMBRICK1, C. RAYNER2,
M. HOROWITZ2, R. YOUNG2
1
GASTROENTEROLOGY, ROYAL ADELAIDE HOSPITAL, 2MEDICINE,
UNIVERSITY OF ADELAIDE, ADELAIDE, Australia
Contact E-mail Address: QUOC.NGUYEN@HEALTH.SA.GOV.AU
INTRODUCTION: Glucose absorption in the small intestine is mediated by
sodium dependent glucose co-transporter 1 (SGLT-1) and glucose transporter-
2 (GLUT2), and is potentially linked to sweet taste receptor (STR) signaling and
incretin hormone secretion. Both glucose absorption and expression of SGLT-1
are increased in obese rats, but human data are lacking.
AIMS & METHODS: This study aimed to examine intestinal glucose absorption
in morbidly obese humans, and its relationship to glycemia, incretin responses,
and expression of SGLT-1, GLUT2, and STR.
United European Gastroenterology Journal 2(5S)
Methods: 17 non-diabetic, morbidly obese subjects (5M:12F; 45  3yrs, BMI: 48
 4kg/m2) and 11 lean controls (10M:1F; 44  6yrs, BMI: 25  1kg/m2) under-
went endoscopic duodenal biopsies immediately prior to intraduodenal (ID)
glucose infusion (30g glucose over 30 min, with 3g 3-O-methylglucose (3-
OMG) to assess glucose absorption). Blood glucose and plasma concentrations
of 3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like
peptide-1 (GLP-1), insulin, and glucagon were measured over 270 min. Absolute
expression of duodenal SGLT-1, GLUT2 and STR transcripts was quantified by
PCR.
RESULTS: The rise in plasma 3-OMG (P50.001) and blood glucose
(P50.0001) were greater in obese than lean subjects. Plasma 3-OMG was directly
correlated with blood glucose (r0.78, P50.01). After ID glucose, plasma GIP
(P50.001), glucagon (P50.001), and insulin (P50.001) were higher, but GLP-1
(P50.001) was less, in the obese than in the lean. Expression of SGLT-1
(P0.035), but not GLUT2 or T1R2, was higher in the obese than lean subjects,
and was related to peak plasma 3-OMG (r0.60, P0.01), GIP (r0.67,
P0.003) and insulin (r0.58, P0.02).
CONCLUSION: In morbid obesity, proximal intestine glucose absorption is
accelerated and related to increased SGLT-1 expression, leading to an incretin
profile that promotes hyperinsulinemia and hyperglycemia. These findings are
consistent with the concept that accelerated glucose absorption in the proximal
gut underlie the foregut theory of obesity and type 2 diabetes.
Disclosure of Interest: None declared
OP072 IMPACT OF A 2-WEEK VERY LOW CALORIE DIET (VLCD) ON
GLUCOSE SENSING, ABSORPTION, TRANSPORTERS, INCRETIN
HORMONES AND GLYCEMIA IN MORBIDLY OBESE HUMANS
N.Q. Nguyen1,*, T.L. Debreceni1, J.E. Bambrick1, B. Chia2, J.M. Wishart3,
G. Wittert3, C.K. Rayner1,3, M. Horowitz3, R.L. Young2,3
1
Department of Gastroenterology & Hepatology, Royal Adelaide Hospital, 2Nerve-
Gut Laboratory, 3Discipline of Medicine, University of Adelaide, Adelaide,
Australia
Contact E-mail Address: quocnam.nguyen@health.sa.gov.au
INTRODUCTION: Glucose absorption is accelerated in the proximal
intestine of morbidly obese humans, which is associated with increased
expression of sodium dependent glucose co-transporter 1 (SGLT1), an
altered incretin profile, hyperinsulinemia and hyperglycemia (Nguyen et al.
DDW 2014).
AIMS & METHODS: This study aimed to examine the effects of energy restric-
tion on glucose absorption, expression of intestinal glucose transporters and
sweet taste receptors (STR), incretin hormone responses and glycemia in the
morbidly obese.
14 morbidly obese subjects (BMI: 463kg/m2) were studied before and after a 2-
week VLCD (750kcal/day). On each occasion, endoscopic duodenal biopsies
were collected before and after a 30-min duodenal glucose infusion (30g glucose
with 3g 3-O-methylglucose (3-OMG)). Measurements of blood glucose, plasma
3-OMG, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like pep-
tide-1 (GLP-1), insulin, and absolute expression of SGLT-1, GLUT2 and STR
(T1R2) transcripts obtained.
RESULTS: Fasting expression of T1R2 (-5422%, P0.03), SGLT1 (-307%,
P0.004) and GLUT2 (-5015%, P0.008) were markedly reduced after 2
weeks VLCD, which were associated with reductions in fasting blood glucose
(-0.50.1mmol/L, P0.02), insulin, GIP and GLP-1, body weight (-5.60.5kg,
P50.001), and HbA1c (-0.320.08%, P0.001). Although intra-duodenal glu-
cose had no impact on T1R2, SGLT1 and GLUT2 expression prior to VLCD, it
increased the expression of T1R2 (4530%, P0.03) and GLUT2 (5714%,
P0.003) after 2-wk VLCD. The blood glucose (P0.002) and plasma insulin
(P0.002) responses to intra-duodenal glucose were all reduced after VLCD,
while plasma 3-OMG and GLP-1 concentrations were unchanged. The peak
plasma 3-OMG (at 60min), however, was higher after VLCD (0.570.04 vs.
0.510.04mmol/L; P0.05) and was associated with a small elevation of plasma
GIP (P0.03) at 60 to 90 min after glucose stimulation.
CONCLUSION: In morbid obesity, both fasting and glucose-stimulated expres-
sion of intestinal STR and glucose transporters are modulated by short-term
VLCD. Further studies with inhibitors of STR and glucose transporters are
warranted to determine whether the changes in STR and GTs expression,
rather than the associated weight loss, are responsible for the observed glycemic
and incretin responses.
Disclosure of Interest: None declared
OP073 EFFECTS OF VERTICAL SLEEVE GASTRECTOMY (VSG) AND
CALORIC RESTRICTION BY DIET ON GLUCOSE METABOLISM IN
OBESE PATIENTS WITH TYPE 2 DIABETES
B.A. Aulinger1,*, K. Piotrowski1, K. Widynski1, J. Zugwurst1, T. To Viet1, J. De
Heer1, B. Goke1, U. Brodl1, K.G. Parhofer1, J. Schirra1
1
Medizinische Klinik II, University of Munich, Munchen, Germany
Contact E-mail Address: benedikt.aulinger@med.uni-muenchen.de
INTRODUCTION: Vertical sleeve gastrectomy (VSG) effectively induces weight
loss and ameliorates hyperglycemia making it a successful treatment option for
obese diabetic patients. However, the exact mechanisms underlying its efficacy
and a direct comparison with a dietary intervention to mimic these effects are
elusive. Hence, we thought to compare the regulation of glucose metabolism
before and after a hypolcaloric diet (HD) or VSG in morbidly obese patients
with type 2 diabetes.
AIMS & METHODS: Obese diabetic subjects were studied before as well as 3
months after VSG (N 9, BMI 54.2 kg/m2, HbA1c 7.0%) or a HD (14, 45.6 kg/m2,
6.7%). During each visit a hyperinsulinemic euglycemic clamp to determine
United European Gastroenterology Journal 2(5S)
insulin sensitivity as well as a hyperglycemic clamp 100 mg/dl above basal glucose
was performed. After 120 min of stable hyperglycemia 50 ml of a liquid meal with
13C-acetate was consumed while constant hyperglycemia was maintained. This
allowed determining insulin in response to glucose during fasting as well as in a
postprandial state. Furthermore, postprandial changes in gut hormones, gastric
emptying and the incretin effect (greater insulin secretion in response to intestin-
ally delivered glucose over iv-glucose) were determined. Additionally, sensations
of satiety, fullness, gastric distension and nausea were recorded by a visual ana-
logue scale (VAS).
RESULTS: Change in BMI, absolute weight loss and %4weight loss was sig-
nificantly more pronounced in the VSG-group than after HD (18.91.0% vs.
8.80.5%, p50.001). While the relative reduction of fasting glucose was greater
in the VSG-group (15013 to 1008 mg/dl vs. 1326 to 1146 mg/dl, p50.05)
absolute values did not differ 3 months after the intervention. Similarly, insulin
resistance and insulin secretion in response to iv-glucose improved markedly in
both cohorts but were not significantly different after diet or VSG. However,
after the meal insulin secretion was significantly more pronounced (4.70.9 vs.
2.20.2-fold increase over fasting, p40.01) in the VSG group than after diet.
Furthermore, the incretin effect (717 vs. 486%, p50.05) was significantly
greater 3 months after VSG compared with diet alone. This was associated
with significantly higher postprandial levels of incretin hormones, more rapid
gastric emptying and greater satiety in the operated subjects.
CONCLUSION: These results suggest that HD in the short term results in a
number of beneficial effects on glucose metabolism similar to VSG, particularly
in the fasting state (insulin resistance, glucose stimulated insulin secretion, fasting
glucose). However, in the postprandial state VSG mediates additional metabolic
effects that cannot be mimicked by caloric restriction per se. Particularly the
faster rate of gastric emptying and the higher levels of anorexigenic gut hormones
as well as the more pronounced insulin response seem to be responsible for the
favorable and more durable effects of bariatric surgery compared to dietary
interventions.
Disclosure of Interest: None declared
OP074 IMPAIRED GLUCOSE REGULATION IN OBESE SUBJECTS:
THE LINK TO HYPERINSULINEMIA IN OBESIY?
A.C. Meyer-Gerspach1,*, D. Riva1, L. Cajacob1, R. Herzog1, T. Peters2,
R. Peterli2, C. Beglinger1, B. Wolnerhanssen1
1
University Hospital Basel, 2St. Claraspital, Basel, Switzerland
INTRODUCTION: An important clinical finding in obesity is insulin resistance.
The potential influence of gastric emptying on the incretin effect mediated by
GIP and GLP-1 has not been defined. In healthy subjects, the incretin effect
during an oral glucose tolerance test increases with the size of glucose load,
resulting in similar glucose excursions independently of the glucose loads.
Whether patients with obesity are able to regulate their incretin effect through
gastric emptying is unknown.
AIMS & METHODS: A total of 24 non-diabetic obese (12 male and 12 female,
BMI  30 kg/m2) and 24 lean control (12 male and 12 female, BMI between 18.5
and 25.0 kg/m2) subjects were included. The study was conducted as a rando-
mized, double-blind, parallel-group trial. Subjects received intragastric infusions
of different glucose concentrations (10g, 25g and 75g glucose). The test solutions
were labelled with 13C-sodium acetate for determination of gastric emptying
rates. Plasma samples were collected for insulin, glucose, glucagon, glucagon-
like peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP) and pep-
tide tyrosine tyrosine (PYY) analysis.
RESULTS: Obese subjects had significantly higher fasting insulin (P50.001) and
glucose (P0.005) levels resulting in a markedly higher HOMA index (P50.001).
Patients with obesity exhibited higher peak plasma glucose and insulin levels in
response to increasing oral glucose loads, whereas no differences in peak plasma
glucose values among control subjects were observed. Fasting as well as post-
prandial glucagon levels were significantly above the levels of the lean control
group (P50.001, respectively). In the obese group, a trend for decreased secre-
tion of GLP-1 and PYY was observed after 75g glucose. Equal and progressively
delayed gastric emptying due to the increasing loads was found in both groups,
but gastric emptying rates of the different glucose loads were significantly
delayed in obese subjects (P0.001, respectively) compared to healthy controls.
CONCLUSION: In healthy subjects, glucose metabolism is largely determined
by gastric emptying rates. Patients with obesity are characterized by impaired
gastric emptying with consecutive changes in glucose regulatory hormone secre-
tions, which may contribute to the exaggerated glucose excursions after oral
ingestion of glucose in these patients. We conclude that these changes are impor-
tant pathophysiological steps in the development of metabolic syndrome in
obesity.
Disclosure of Interest: None declared
OP075 BITTER TASTE RECEPTOR T2R38 EXPRESSION IN THE
COLON OF OVERWEIGHT/OBESE AND LEAN SUBJECTS
R. Latorre1,*, J. Huynh2, A. Gupta2, M. Mazzoni3, P. Clavenani3, L. Chang2,
E.A. Mayer2, R. De Giorgio1, C. Sternini2
1
Medical and Surgical Science, University of Bologna, Bologna, Italy, 2CURE,
Division of Digestive Disease, Dept. Of Medicine, UCLA, Los Angeles, United
States, 3Veterinary Medical Science, University of Bologna, Bologna, Italy
Contact E-mail Address: csternin@ucla.edu
INTRODUCTION: The sense of taste is important to evaluate the quality of
nutrients and distinguish between safe and dangerous food prior to ingestion. in
particular, bitter taste has evolved as a warning mechanism against toxic or
harmful chemicals. Transcripts for bitter taste receptors (T2Rs) and their signal-
ing molecules are distributed to the mucosa of the mammalian gastrointestinal
A25
(GI) tract including humans and are expressed by enteroendocrine cells (EECs).
Intraluminal bitter tastants actiate vagal afferent neurons, induce avoidance and
affect feeding behavior and gastric emptying. Bitter tastants also induce release of
cholecystokinin (CCK) and glucagon like peptide 1 (GLP1) from EECs, peptides
that are involved in GI chemosensing. We have shown that T2R subtypes are
differentially regulated in the mouse GI tract by diet manipulation and that
T2R138 expression is upregulated by long-term high fat diet, which is known
to alter the gut microflora and is associtated with chronic low grade
inflammation.
AIMS & METHODS: Test whether T2R38 expression is altered in the mucosa of
overweight or obese healthy subjects compared to lean subjects and to character-
ize the cell types expressing T2R38 in human colonic mucosa.
Methods: Colonic mucosal biopsies were obtained during screening sigmoido-
scopy from 30 volunteers: 15 overweight to obese (OW/OB) (8 males and 7
females; 20-55 year-old; mean BMI 320.7 kg/m2) and 15 normal weight
(NW) (7 males and 8 females; 22-55 year-old; mean BMI 200.5) subjects.
Biopsies were processed for quantitative qRT-PCR using Taqman Gene expres-
sion assays with hT2R38 and 18S RNA as the reference gene, and immunohis-
tochemistry. For double immunolabeling, the following antibodies were used:
rabbit anti-T2R38 (1:2,000), goat anti-chromogranin (CgA, 1:600, a generalized
marker for EECs), mouse anti- GLP-1 (1:1,000), mouse anti-CCK (1:1,000), and
guinea pig anti-peptide YY (PYY, 1:600).
RESULTS: The levels of hT2R38 mRNA in the mucosa of OW/OB subjects were
markedly increased compared to those in the mucosa of NW subjects (4.200.9
vs. 1.680.5, respectively, P50.05). T2R38 immunoreactivity (-IR) was localized
to EECs as shown by their labeling with CgA. T2R38-IR cells coexpressed CCK-,
GLP1- or PYY-IR. The number of T2R38/CgA cells in the OW/OB group was
significantly increased compared to lean controls (124.515.9 vs. 55.888.0 in
3.36 mm2, respectively) (P50.006). There was an increase in T2R38/GLP1 and
T2R38/CCK cells in OW/OB vs. NW subjects (5114.2 vs. 24.63.9, and
34.06.4 vs. 19.66.5, respectively) whereas there was no difference in the
number of T2R38/PYY cells in OW/OB vs. NW subjects (8.62.1 vs. 9.24.8).
CONCLUSION: T2R38 upregulation observed in overweight / obese subjects
might be due to changes in luminal content including alteration of microbiome
that has been associated with obesity. This is consistent with the proposal that
T2R38 is activated by food-born toxins and quorum-sensing molecules released
by bacteria to initiate a protective response, which could involve the release of
gut hormones such as GLP1, CCK and PYY.
Disclosure of Interest: None declared
OP076 STABLE GENOMIC INTEGRANT OF E. COLI NISSLE 1917 (ECN)
AS NATURAL ALTERNATIVE TO ALLEVIATE SUCROSE INDUCED
METABOLIC EFFECT
S.K. Pandey1,*, A.K. Singh1, P. Banarjee1, G.N. Kumar1
1
Biochemistry, The Maharaja Sayajirao University Of Baroda, Vadodara, India
Contact E-mail Address: sumitkumarpandey2@gmail.com
INTRODUCTION: Implementation of probiotics in the field of therapies is
sustaining in the market since decades. Against the various drug based treatments
available in the market, probiotics proves to be significantly safe and efficient
towards the most commonly prevailing clinical outcomes. Risk factors are rela-
tively high in metabolic diseases associated with sugar consumption. These meta-
bolic effects can be attributed to hypertension, hypertriglyceridemia oxidative
stress and many more. EcN has been promising probiotic with unique character-
istics i.e. antimicrobial activity, lack of endotoximia.
AIMS & METHODS: To achieve stable expression of Vitreoscilla Hemoglobin
(vgb), Green fluorescent protein (gfp), pyrroloquinoline quinone (pqq) and inu-
losucrase (inuJ) in EcN for alleviating metabolic effect induced by dietary
sucrose. Stable genomic integration was carried out by Tn7 mediated integration
system. Male Charles foster rat weighing 180-220 grams were fed with 20%
sucrose in drinking water for 70 days. Modified EcN was given 109CFU/per
week. Antioxidant enzyme activity, serum insulin, serum and hepatic lipid pro-
file, short chain fatty acid (SCFA) analysis and liver oil red O staining was used
to assess metabolic syndrome. Expression of FAS, ACOx and Mitochondrial to
nuclear DNA ratio was quantified in liver by real time PCR.
RESULTS: Genomic integrants of EcN:: vgb-gfp-pqq-inuJ were confirmed by
loss of ampicillin resistance and PCR. PQQ quantification, formation of red
colour in Tris buffered media and growth on sucrose was monitored to check
the functionality of inuj-pqq gene. Rat fed with 20% sucrose in drinking water
developed clinical characteristics of metabolic syndrome including increased
plasma glucose, triglycerides and oxidative stress (Blood and Hepatic) in com-
parison to control group. In addition, they showed increased liver lipid accumu-
lation, compared to chow fed controls. mRNA expression of FAS was found to
be significantly increased and ACOx was decreased in sucrose fed rats without
probiotic supplementation. EcN:: vgb-gfp-pqq-inuJ administration restored clin-
ical characteristics of metabolic syndrome to almost normal levels. In addition,
EcN:: vgb-gfp-pqq-inuJ showed significant increase in colonic SCFA (Acetic acid,
propionic acid and butyric acid) on comparison with all other groups.
CONCLUSION: Modified probiotic EcN:: vgb-gfp-pqq-inuJ can suppressed diet-
ary sucrose induced metabolic effects, therefore, may provide an natural alter-
native for dietary sucrose induced metabolic syndrome.
REFERENCES
Lim SJ, Mietus-Snyder M, Valente A, et al. the role of fructose in the pathogen-
esis of NAFlD and the metabolic syndrome. Nat Rev Gastroenterol Hepatol 2010;
5: 251-264.
McKenzie GJ and Craig NL. Fast, easy and efficient: site-specific insertion of
transgenes into Enterobacterial chromosomes using Tn7 without need for selec-
tion of the insertion event. BMC Microbiol 2006; 6: 39.
Rucker R, Chowanadisai W and Nakano M. Potential physiological importance
of pyrroloquinoline quinone. Altern Med Rev. 2009; 14: 268-277.
A26
Sonnenborn U and Schulze J. The non-pathogenic Escherichia coli strain Nissle
1917 features of a versatile probiotic. Microb Ecol Hlth Dis 2009; 21: 122-158.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
HOT TOPICS FROM LATIN AMERICA HALL F1_____________________
OP077 INTRAGASTRIC BALLOON IN PREPARATION FOR BARIATRIC
SURGERY PATIENTS
B.Q. Sander1,*, J., I. B. Scarparo2, G.C. Nunes3
1
Endoscopy, Clnica Sander, Belo Horizonte, 2Endoscopy, Clnica Balao BIB, successfully (100%) in retroflexed position in all attempted patients. Adverse
3
Nutrition, Clnica Ultranutri, Sao Paulo, Brazil
Contact E-mail Address: brunosander@hotmail.com
INTRODUCTION: It is well established that the loss of at least 10% of initial
weight or 25% of overweight in pre-bariatric surgery significantly improves the
comorbidities of morbid obese patients.
The use of pharmacotherapy can promote mild weight loss, but carries a greater
risk to the patient for possible side effects of many medications. High failure rates
(between 90 and 98%) have been reported in the literature.
With the high rates of failure of less invasive therapies using new techniques in
the preparation of these patients is necessary. A considerable option is the use of
the intragastric balloon (BIG).
AIMS & METHODS: The aim of this study is to evaluate the weight loss
induced by gastric balloon preoperative bariatric surgery.
Retrospective study of patients from clinics in Sao Paulo and Belo Horizonte. All
patients were evaluated with greater than 45 kg / m2 who chose to put the BIG
weight loss prior to bariatric surgery between January 2008 to December 2013
and remained with the BIG BMI at certain time (6 months). Of the 38 patients,
19 (76.32%) were female and 9 male (23.68%). All participants were over 18
years old.
RESULTS: The mean initial weight of these patients was 143kg (25.70), and
initial BMI was 50.52 kg / m2 (7.86). After removal of the BIG average final
weight was 111.2 kg (17.5), with the final BMI of 42.49 kg / m2 (6.68). The
weight loss during the treatment period, on average, was 25.3 kg (12.7), which
represented 17.4% (00,6) of initial weight. Thus we found a loss of 31.86%
(9.65) of the initial excess weight and a final BMI of 42.49 kg / m2 (6.68) after
six months of using BIG. The values in parentheses correspond to the standard
deviation.
CONCLUSION: We observed that there was an average weight loss of 25.3 kg
and 31.86% overweight, considerably reducing the BMI of the patients. The
reduction of at least 10% of the initial or 25% overweight weight was achieved
in 100% of patients. Thus we conclude that the BIG is an excellent therapeutic
option for weight loss for morbidly obese patients undergoing bariatric surgery.
REFERENCES
Gottig S, Daskalakis M, Weiner S, et al. Analysis of safety and efficacy
of intragastric balloon in extremely obese patients. Obesity surgery 2009; 19:
677-683. http://www.springerlink.com/content/h436w700l5480718/ (accessed 19
August 2011).
Favretti F, Luca M, Segato G, et al. 1n: Schauer PR, Schirmer BD and Brethauer
SA (eds) Minimally invasive bariatric surgery. New York, NY: Springer, 2007, pp.
389-394. http://www.springerlink.com/content/h76742mj81100t24/ (accessed 19
August 2011).
Disclosure of Interest: None declared
OP078 PENTAX RETROVIEWTM COLONOSCOPE FOR THE
EVALUATION OF COLON MUCOSA IN FORWARD AND
RETROVIEWING: A SAFETY AND FEASIBILITY PILOT STUDY
C. Robles-Medranda1,*, M. Soria1, A. Oropeza1, F. Abarca1, F. Abarca
Rendon1, J. Ospina1, G. Bravo1, C. Robles-Jara1, H. Pitanga Lukashok1
1
ENDOSCOPY, INSTITUTO ECUATORIANO DE ENFERMEDADES
DIGESTIVAS, UNIVERSITY HOSPITAL OMNI, ESPIRITU SANTO
UNIVERSITY, Guayaquil, Ecuador
Contact E-mail Address: carlosoakm@yahoo.es
INTRODUCTION: Colonoscopy is the gold standard for inspection of the
colon, but it offers incomplete visualization of the proximal aspects of colonic
haustral folds, flexures or valves. Recent studies indicate that retroflexing in the
right colon or the use of retrograde viewing devices can provide a more thorough
examination, with improvements in polyp detection reported. However, limita-
tions as: absence of high definition (HD) vision, use of a second equipment and
no therapeutic possibility is reported. A new colonoscope RetroView (RV)
(PENTAX Medical) with a 4 cm retroflexed radius and 3.2 mm working channel
may allow withdrawal from the cecum to rectum in segmental retroflexion and
provide therapeutic access.
AIMS & METHODS: To test the feasibility and safety of segmental retroflexion
with the RV colonoscope throughout the entire colon.
Methods: In this single centre, one operator, prospective study, the RV colono-
scope was advanced to the cecum in the forward view in all enrolled patients,
after approval by the ethics committee and signing of an informed consent.
Withdrawal colonoscopy was performed in retroflexion until the hepatic flexure,
at which point the distal tip was straightened and readvanced to the cecum and
withdrawn in forward view through the hepatic flexure. RV was again retroflexed
and the withdrawal pattern was repeated by segment (transverse, left, sigmoid
and rectum). Data was collected on cecal intubation rate, segmental retroflexion
success, total procedure time, time to cecum, total withdrawal time, lesions
detected in retroflexion, biopsy/therapeutics performed while retroflexed and
adverse events.
United European Gastroenterology Journal 2(5S)
RESULTS: Forty-eight consecutive screening, surveillance or diagnostic patients
underwent colonoscopy {64% (31/48) female with mean age of 55}. Cecal intu-
bution was achieved in 48/48 pts (100%). Retroflexed withdrawal success: right
colon 47/48 (98%), transverse colon 48/48 (100%), left colon 48/48 (100%),
sigmoid colon 39/48 (81%), rectum 48/48 (100%). Total mean procedure time
was 16.5 mins and mean withdrawal time was 9.81mins. 31% more lesions (3
ulcers, 12 polyps, 9 diverticules, 2 erosions, 6 vascular ectasia, 1 papiloma and 1
hemorrhoid) were seen in retroflexion that were not seen in forward view, includ-
ing 67% (6/9) more adenomas: 2 in right colon (10mm, 10mm) and 4 in trans-
verse colon (7mm,10mm,10mm, 15mm). Therapeutics, including biopsy,
endoscopic mucosal resection and argon plasma coagulation were performed
event post-procedure (abdominal pain) was observed in 1/48 cases (2%).
CONCLUSION: In this single centre, single operator study, segmental retroflex-
ion with the RetroView throughout the colon was safe, allowed performance of
retroflexed biospies/therapeutics, increased the number of lesions found by 31%
and the number of adenomas by 67% compared to forward view alone.
REFERENCES
Dik VK, Moons LM and Siersema P. Endoscopic innovations to increase the
adenoma detection rate during colonoscopy. World J Gastroenterol 2014; 20:
2200-2211.
Disclosure of Interest: C. Robles-Medranda Consultancy for: Pentax Medical,
MaunaKea technologies, M. Soria: None declared, A. Oropeza: None declared,
F. Abarca: None declared, F. Abarca Rendon: None declared, J. Ospina: None
declared, G. Bravo: None declared, C. Robles-Jara: None declared, H. Pitanga
Lukashok: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
NEW DIAGNOSTIC MODALITIES IN UPPER GI ENDOSCOPY HALL G/
H_____________________
OP079 NARROW-BAND IMAGING AND MAGNIFYING ENDOSCOPY
IN PATIENTS WITH DYSPHAGIA AND FOOD IMPACTION.
PREVALENCE OF EOSINOPHILIC ESOPHAGITIS/ESOPHAGEAL
EOSINOPHILIA AND LYMPHOCYTIC ESOPHAGITIS
T. Ichiya1,*, K. Tanaka1, C.A. Rubio2, P.T. Schmidt1
1
Department of Gastroenterology and Hepatology, 2Department of Pathology,
Karolinska University Hospital, Stockholm, Sweden
Contact E-mail Address: tamaki_ichiya@yahoo.co.jp
INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic inflammatory
dysfunction characterized by eosinophilic infiltration in the esophageal epithe-
lium. Lymphocytic esophagitis (LyE) is an independent entity expressing intrae-
pithelial lymphocytes infiltration. Endoscopy plays a vital role in the diagnostic
process since esophageal biopsies are required for diagnosis. Several conventional
endoscopic features in EoE have been reported, however they are not specific for
EoE and can be observed in other esophageal disorders. Very few studies report
on endoscopic findings in LyE. Magnifying NBI endoscopy (NBI-ME) is able to
highlight the esophageal mucosa and have widely used for esophageal early
neoplasm. This study aimed to clarify the prevalence of EoE including esopha-
geal eosinophilia(EEo) and LyE in the patient with dysphagia, and to assess
endoscopic and NBI-ME features.
AIMS & METHODS: Adult patients with dysphagia and/or food impaction in
the esophagus underwent EGD with magnifying NBI between August 2011 and
November 2013. Biopsies were collected in proximal, middle and distal esopha-
gus besides the antrum and duodenum. Based on previous reports, four endo-
scopic findings were identified as valuables of EoE/EEo (EoE group) and LyE
(LyE group): mucosal rings, linear furrows, white exudates, and narrow- caliber/
stenosis. Meanwhile NBI ME features used were: (1) beige color of the mucosa,
(2) increased and dot-shaped congested IPCLs, and (3) invisibility of submucosal
vessels which were established in our previous report (Tanaka, Endoscopy, 2013).
Endoscopic findings were compared with the histological diagnosis.
RESULTS: A total of 114 patients with dysphagia and/or food impaction under-
went gastroscopy with biopsies. Of these 95 patients were studied with NBI-ME.
Eighteen patients (19%) of 95 were histologically diagnosed as the EoE/EEo
(definite EoE; 6), nineteen as LyE (20%) and twenty (21%) as GERD. In con-
ventional endoscopy, mucosal rings, linear furrows, white exudates, and narrow-
caliber/stenosis were seen in 14, 14, 11, 8 patients in the EoE group; 8,9,4,5 in the
LyE group and 3,2,0,4 patients in the GERD groups. With NBI-ME, beige color,
increased IPCL, invisibility of submucosal vessels were observed in all 18 patients
in the EoE group, 12, 13,10 in the LyE group and 3,7 and none patients in the
GERD group. With conventional endoscopy, at least 1 finding was seen in 16
patients (89%) in the EoE group, 14 (74%) in the LyE group and in 8 (40%) in
the GERD group.Regarding NBI-ME, all patients in the EoE group, 13 (68%) in
the LyE group and none in the GERD group had all three findings. The EoE and
the LyE group patients with these all three findings are significantly higher than
the GERD group (p50.0001, p50.0001).
CONCLUSION: Esophageal biopsies showing eosinophilia or severe lymphocy-
tic infiltration(EoE/EEo or LyE) are common findings in patients with dysphagia
or food impaction. Conventional endoscopy might assist the diagnosis of EoE/
EEo and LyE when one of four findings is observed, however, they can be found
in GERD. A combination of three NBI features was found in all patients with
EoE/EEo and in the majority of LyE. NBI-ME was more reliable than conven-
tional endoscopy in predicting endoscopic EoE/Eeo/LyE diagnosis before patho-
logical assessment.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP080 WHITE GLOBE APPEARANCE: A NOVEL FINDING USEFUL
FOR CORRECT DIAGNOSIS OF EARLY GASTRIC CANCER BY
MAGNIFYING NARROW-BAND IMAGING
H. Doyama1,*, N. Yoshida1, S. Tsuyama2, R. Ota1, H. Nakanishi1, K. Tsuji1,
K. Tominaga1, S. Tsuji1, K. Takemura1, S. Yamada1, H. Kurumaya2, K. Yao3,
A. Iwashita4
1
Gastroenterology, 2Diagnostic Pathology, Ishikawa prefectural central hospital,
Kanazawa city, 3Endoscopy, 4Pathology, Fukuoka University Chikushi Hospital,
Chikushino, Japan
Contact E-mail Address: doyama.134@ipch.jp
INTRODUCTION: We previously reported that magnifying endoscopy with
narrow-band imaging (M-NBI) is useful for the correct diagnosis of gastric
mucosal lesions [1]. However, differential diagnosis between low-grade adenoma
(LGA) and high-grade dysplasia (HGD)/early cancer (EC) is sometimes difficult
even with M-NBI. We recently noticed the unique finding of a small white lesion
with a globular shape (51 mm), present underneath the gastric cancerous epithe-
lium, during M-NBI examination. Conversely, this finding was rarely detected in
noncancerous lesions. We termed this finding the white globe appearance
(WGA). However, the nature of this finding and its clinical significance were
unclear.
AIMS & METHODS: The aims of this study were to: (1) investigate the histo-
logical nature of the WGA, and (2) determine whether the WGA is a useful
marker in the differential diagnosis between LGA and HGD/EC. (1) Two EC
specimens in which the WGA was detected by M-NBI and that were resected by
endoscopic submucosal dissection (ESD) were prepared for histopathological
investigation. Before resection, we placed a marking beside the WGA using
electrocoagulation under M-NBI. We then resected the lesion by ESD. After
extending the specimen on a board, we placed two pins on the specimen with
reference to the electrocoagulation mark to create a section identical to the
WGA. (2) We retrospectively reviewed the M-NBI findings of 111 consecutive
patients with gastric LGA, HGD, and EC that were resected by ESD from July
2013 to January 2014. We determined the prevalence of the WGA in HGD/EC,
LGA, and non-neoplastic background mucosa (BM).
RESULTS: (1) By careful histological investigation, the WGA visualised by M-
NBI was proven to be identical to the histological presence of intraglandular
necrotic debris (IND) within markedly dilated neoplastic glands. (2) The preva-
lence of the WGA in HGD/EC, LGA, and BM was 21.7% (20/92), 0% (0/19),
and 0% (0/111), respectively. Accordingly, the WGA was evident in HGD/EC
lesions, but not in LGA or BM (P 5 0.001, Fishers exact test). The sensitivity,
specificity, positive predictive value, and negative predictive value for differential
diagnosis between HGD/EC and LGA according to the presence of the WGA
were 21.7%, 100%, 100%, and 20.9%, respectively.
CONCLUSION: Because IND with dilated neoplastic glands is a possible his-
tological marker specific for HGD/EC but not for LGA [2], we suggest that the
presence of the WGA could be a novel marker for differential diagnosis between
HGD/EC and LGA. We have started a prospective study to verify this hypoth-
esis (UMIN 000013650).
REFERENCES
1. Ezoe Y, Muto M, Uedo N, et al. Magnifying narrowband imaging is more
accurate than conventional white-light imaging in diagnosis of gastric mucosal
cancer. Gastroenterology 2011; 141: 20172025.
2. Watanabe Y, Shimizu M, Itoh T, et al. Intraglandular necrotic debris in gastric
biopsy and surgical specimens. Ann Diagn Pathol 2001; 5: 141-147.
Disclosure of Interest: None declared
OP081 A NOVEL SYSTEM OF HYPOXIA IMAGING ENDOSCOPY
EQUIPPED WITH LASER LIGHT SOURCE
K. Kaneko1,*, H. Yamaguchi2, Y. Oono1, H. Ikematsu1, T. Yano1, T. Odagaki1,
S. Ohsera1, H. Morimoto1, A. Sato3, M. Kojima4, A. Ochiai4
1
Department of Gastroenterology, Endoscopy Division, National Cancer Center
Hospital East, Kashiwa, 2Imaging Technology Center, FUJIFILM Corporation,
Fujisawa, 3Clinical Trial Section, 4Department of Pathology, National Cancer
Center Hospital East, Kashiwa, Japan
INTRODUCTION: Recent endoscopy has evolved into image-enhanced endo-
scopy (IEE), such as Narrow Band Imaging and Blue Laser Imaging. IEE
focused on increasing abnormal microvessels in the surface of early cancers. It
is difficult to recognize biological change, function, and metabolism in cancer by
observing the morphological features of the microvessels. In contrast, hypoxia is
one of the functional characteristics in cancer, with strong association to the
biological features. Therefore, hypoxia imaging was innovated to visualize
directly the biological and functional changes in cancer.
AIMS & METHODS: The aim of this prospective study is to evaluate the
visualization of human early cancers in hypoxia imaging endoscopy. In endo-
scopic equipment, we utilized a difference of absorption between oxy- and deoxy-
hemoglobin in visible light wavelength. The signals converted from laser light
were calculated in oxygen saturation (StO2) by processor. Hypoxia imaging was
obtained in real-time, displaying two types of StO2 images. One was a pseudo-
color image showing StO2 levels as different hues, and the other was an overlay
image that overlapped low StO2 levels in blue on a white light illumination image
of background mucosa. In the first in human clinical trial (UMIN: 000004983),
patients who had been confirmed to have pharyngeal, esophageal, gastric, or
colorectal neoplasia by previous endoscopy were enrolled. To compare histologic
findings to hypoxia imaging, all patients received endoscopic resection immedi-
ately after conventional and hypoxia imaging endoscopy. We determined the
corresponding areas of neoplasia and non-neoplasia in the endoscopic images
and obtained StO2 levels from the StO2 map.
RESULTS: Forty patients with neoplastic lesions in the pharynx, esophagus,
stomach and colorectum were analysed. The hypoxic area was completely
A27
corresponded to the portion of early cancer. Furthermore, 8 colorectal adenomas
with histological low-grade atypia were also detected as hypoxia, ranging from 3
to 10 mm in diameter. All esophageal cancers including 2 Barretts cancers were
detected in hypoxia images. Median StO2 differences between neoplastic and
non-neoplastic areas in the pharynx, esophagus, stomach and colorectum were
-15.4%, -14.5%, -5.1% and -21.5%, respectively. Significant differences of StO2
levels were seen in the esophagus (p0.0078, n8) and colorectum (p0.0001,
n14), but not in the stomach (p0.9341, n15) or pharynx (p0.2500, n3).
Furthermore, sensitivity of neoplasia, defined as the proportion having correctly
detected neoplasia, in the pharynx, esophagus, stomach, and colorectum was
67%, 100%, 33% and 86%, respectively.
CONCLUSION: Hypoxia imaging with the laser endoscope enables us to visua-
lize spatial and temporal information of hypoxic conditions in human tumors.
Hypoxia imaging illustrates a novel aspect of cancer biology as a potential bio-
marker and can be widely utilized in cancer diagnosis.
Disclosure of Interest: None declared
OP082 SMART ATLAS FOR SUPPORTING THE INTERPRETATION OF
PROBE-BASED CONFOCAL LASER ENDOMICROSCOPY (PCLE) OF
GASTRIC LESIONS: FIRST CLASSIFICATION RESULTS OF A
COMPUTER-AIDED DIAGNOSIS SOFTWARE BASED ON IMAGE
RECOGNITION
M. Kohandani Tafreshi1,*, Y.Q. Li2, R. Pittayanon3, D. Pleskow4, V. Joshi5,
P. Chiu6, N. Ayache1, B. Andre7
1
INRIA, Sophia Antipolis, France, 2Qilu hospital, Jinan, China, 3Chulalongkorn
University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand,
4
Harvard Medical School, Boston, 5Ochsner medical center, New Orleans, United
States, 6Prince of Wales hospital, Hong Kong, China, 7Mauna Kea Technologies,
Paris, France
Contact E-mail Address: marzieh.kohandani-tafreshi@inria.fr
INTRODUCTION: pCLE enables microscopic imaging of gastrointestinal
mucosal lesions, in vivo and in real time, during an endoscopy procedure.
Recent studies have demonstrated that pCLE enables accurate diagnosis of
superficial gastric neoplasia. In parallel, a computer-aided diagnosis software
called Smart Atlas has been developed to assist endoscopists with the interpreta-
tion of pCLE sequences. This study aims at evaluating the performance of this
software for the classification of gastric lesions into four pathological classes:
healthy stomach, gastric intestinal metaplasia (GIM), dysplasia, and cancer.
AIMS & METHODS: Several pCLE video sequences were retrospectively col-
lected from pCLE procedures performed in multiple clinical centers. These
sequences, along with their annotated final diagnosis, were used to train a clas-
sification software that uses a content-based image retrieval algorithm to predict
the diagnosis of a query video based on the diagnoses of the most visually similar
atlas videos. For all cases, final diagnosis was based on histological analysis of
corresponding tissue sampling. All evaluations were performed using leave-one-
patient-out cross-validation to avoid bias. A confusion matrix was established to
evaluate 4-class classification, and a receiver operating curve was generated to
evaluate the binary classification between non-neoplasia (healthy stomach, GIM)
and neoplasia (dysplasia, cancer).
RESULTS: Among the 40 pCLE video sequences collected from 30 patients, 14
were annotated with healthy stomach, 13 with GIM, 6 with dysplasia, and 7 with
cancer. For the differentiation of non-neoplasia and neoplasia, the results max-
imizing the accuracy show an accuracy of 92.5%, a sensitivity of 92.3%, a spe-
cificity of 92.6%, a PPV of 85.7% and a NPV of 96.2%. The 4-class classification
results show an average accuracy of 75% and per-class accuracies of 90% for
healthy stomach, 82.5% for gastric intestinal metaplasia, 85% for dysplasia and
92.5% for cancer. In comparison, Bok at al. reported in GIE 2013 that, for real-
time in vivo pCLE diagnosis of superficial gastric neoplasia, endoscopists achieve
overall accuracy, sensitivity and specificity of 90.7%, 90.6% and 90.9%,
respectively.
CONCLUSION: These first results demonstrate that gastric lesions can be auto-
matically classified into four pathological classes by the Smart Atlas software
based on the image content of pCLE video sequences only. The high accuracy,
sensitivity and specificity results achieved by the software for differentiating non-
neoplasia and neoplasia are comparable to those achieved by endoscopists. The
case-based reasoning software could thus be used as an educational tool to train
non-expert endoscopists, but also as a second-reader tool to assist any endosco-
pist in real-time diagnosis of gastric diseases using pCLE.
Disclosure of Interest: None declared
OP083 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY
(NCLE) FOR THE DIAGNOSIS OF LYMPH NODES:
CORRELATION BETWEEN PCLE AND HISTOLOGICAL CRITERIA
(CONTACT STUDY)
F. Caillol1,*, M. Giovannini2, D. Lucidarme3, B. Pujol4, F. Poizat2, G. Monges2,
B. Filoche3, A., I. Lemaistre5, B. Napoleon4
1
Gastro enterology, 2Institut Paoli Calmettes, Marseille, 3GHICL, Lille, 4Hopital
Jean Mermoz, 5Centre Leon Berard, Lyon, France
Contact E-mail Address: giovanninim@wanadoo.fr
INTRODUCTION: Needle-based Confocal Laser Endomicroscopy (nCLE) is an
imaging technique, which enables microscopic observation of solid organs, in vivo
and in real-time, during an EUS-FNA procedure. The CONTACT study
(Clinical evaluation Of NCLE in The lymph nodes Along with masses and
Cystic Tumors of the pancreas) aims at building an image atlas, and define
interpretation criteria for nCLE images in the lymph nodes, within the frame
of cancer staging.
A28
AIMS & METHODS: 3 centres in France (7 investigators) took part in this
prospective study. Patients with a suspicious lymph node  1 cm proposed for
a EUSFNA, were included. In case of multiple lymph nodes, only one of them
could be imaged. The puncture was done with a 19G puncture needle with the
nCLE probe preloaded. After examination of the track of the puncture by nCLE,
aspiration was done in the same track to compare images and histological results.
17 patients with suspicious lymph node were included over 8 months (August
2012 to March 2013). There were 14 men, and 3 women, mean age 59 years old,
(extreme: 35-69 years old). The localization of the lymph nodes were: mediastinal
(6 cases), celiac (6 cases), intra-abdominal (3 cases), hepatic hilum (1 case) and
hepatic pedicule (n1). All had a size superior to 10mm.
No complication occured during the nCLE procedure or the puncture. A defini-
tive histological diagnosis was obtained in 14/17 patients. It was the following: 7
malignant (metastasis of primary cancer: pancreas, stomach, lung, kidney, pros-
tate and lymphoma), 7 benign (according to a one year follow-up).
Preliminary characteristic descriptive criteria were previously described [1]. To go
further, nCLE sequences were re-visualized by two gastro-enterologists and two
pathologists in order to compare, for each type of lesion, their findings to the
pathology specimen.
RESULTS: During this review, all benign or inflammatory lymph nodes showed
one sign: a reticular background, which corresponds to the histological structure
of lymphocytes.
Tumoral lymph nodes presented dark clumps or aggregates of dark cells, tumoral
glands and some times only a grey background which could histologically corre-
ponds to necrosis.
Finally, all a few criteria could be observed in all cases: white bands (blood
vessels), macrophages, fat cells (bubbles), and thin straight bands over a regular
dark aggregate which corresponds to fibrosis in the capsula of the lymph node.
CONCLUSION: This preliminary classification of nCLE images obtained in
lymph nodes could help in the differentiation of malignant and benign lymph
nodes. nCLE could therefore facilitate the diagnosis of these lesions, by bringing
in vivo microscopic information, in real-time.
REFERENCES
[1] Caillol F. Needle-based confocal laser endomicroscopy for the diagnosis of
lymph nodes: preliminary criteria (CONTACT study). Oral presentation at
UEGW 2013 (OP 338).
Disclosure of Interest: None declared
OP084 A RETROSPECTIVE AUDIT OF THE EFFECTIVE USE OF
ENDOSCOPIC UPPER GASTROINTESTINAL HISTOPATHOLOGY
S. Murray1,*, M. Farrant1, K. Laycock1, N. Halliday1, N. Thoua1, R. Shidrawi1
1
Gastroenterology, Homerton University Hospital, London, United Kingdom
Contact E-mail Address: murray.sam@gmail.com
INTRODUCTION: Histological assessment is an important tool for the endos-
copist and remains the gold standard for the diagnosis of many conditions affect-
ing the gastrointestinal (GI) tract. GI biopsies cost approximately 601 (E73) to
process and create considerable histopathology workload. With the growing
demand for diagnostic oesophagogastroduodenoscopy (OGD), recently pub-
lished guidance to clarify the appropriate indications for endoscopic biopsy
and histological evaluation is welcomed2.
AIMS & METHODS: We retrospectively audited our units use of endoscopic
biopsy against the new guidelines2. Our aim was to highlight methods of reducing
the histopathology workload and validate the guideline against local UK hospital
practice. Using an endoscopy auditing tool (Unisoft) we identified all OGDs
where a biopsy was taken over a 6 month period (1st July 31st Dec 2013).
Reviewing the endoscopy report we compared the stated indication for biopsy
to the guideline. The procedural details were cross-referenced with the pathology
database to identify relevant histology results.
RESULTS: During the study period 1439 OGDs were performed and a biopsy
was taken during 655 (45.5%) procedures. Nurse endoscopists performed 190
OGDs, trainees 137 and consultants 328. In the study population 53.9% of
patients were female with a median age of 55 (IQR 40-68).
Approximately two thirds (435/655) of OGDs had biopsies taken in accordance
within the stated criteria. The most common indications for biopsy were identi-
fication of coeliac disease (46.4%) and mucosal lesions suspicious of neoplasia
(23.6%). Indications for biopsy were missing in 12.2% (80/655) of endoscopy
reports. In 21.4% (140/655) of OGDs biopsies were taken outside criteria.
Indications in this group included uncomplicated inflammation (100/140), check-
ing Helicobacter pylori status in patients on proton pump inhibitors, surveillance
of premalignant conditions e.g. intestinal metaplasia (IM) and abnormal imaging
findings with normal endoscopic appearance.
Histopathologic assessment of biopsies taken outside guideline criteria demon-
strated pathology that could potentially change management in 25.7% of cases
(36/140): 20 cases of H. pylori; 14 of IM; 1 of possible inflammatory bowel
disease; 1 new neuroendocrine nodule.
In total 3531 individual biopsies were taken, which equates to approximately
211,860. The estimated number of biopsies taken without a stated indication
or indications outside the criteria is 954, generating a cost of 57,240 over 6
months. There were no recorded complications related to biopsy retrieval
during the study period.
CONCLUSION: The new guidelines give a timely reminder of the financial
implications of routine histology. By adopting biopsy policies, endoscopy depart-
ments can make significant savings of time and money to ensure effective use of
healthcare resources. We have demonstrated that stringent application of the
guidelines may miss certain pathology. However the uncertain implications of
IM and the availability of other methods of identifying H. pylori mean their
identification by biopsy are of debatable clinical importance1. We would recom-
mend adapting the current guidance to develop unit specific policies applicable to
local practice.
United European Gastroenterology Journal 2(5S)
REFERENCES
1. Shepherd NA, et al. Frontline Gastroenterol 2014; 5: 84-87.
2. Loughrey MB, et al. Frontline Gastroenterol 2014; 5: 88-95.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
LATE BREAKING CLINICAL TRIALS IN DIGESTIVE DISEASES HALL I/K_____________________
OP084-LB1 TIMING OF CHOLECYSTECTOMY AFTER MILD BILIARY
PANCREATITIS: A RANDOMISED CONTROLLED MULTICENTER
TRIAL
D. da Costa1,* on behalf of Dutch Pancreatitis Study Group
1
St. Antonius Hospital, Nieuwegein, Netherlands
Contact E-mail Address: d.dacosta@pancreatitis.nl
INTRODUCTION: In mild biliary pancreatitis, international guidelines advise
cholecystectomy during index-admission or within four weeks after discharge to
prevent recurrent biliary disease. However, high quality evidence for the optimal
timing of cholecystectomy is limited and in daily practice the waiting period for
cholecystectomy often exceeds 6 weeks.
AIMS & METHODS: We conducted a randomised trial to investigate whether
cholecystectomy during primary admission can reduce the number of readmissions
for biliary events compared to postponed cholecystectomy. All adult patients
admitted with a first episode of mild biliary pancreatitis (i.e. the absence of necro-
tizing pancreatitis, fluid collections or organ failure) were assessed for eligibility.
Patients were randomised before discharge for either laparoscopic cholecystect-
omy within 72 hours (early) or after 25 to 30 days (interval). Primary endpoint
was a composite of mortality or readmission for biliary events (i.e. recurrent
pancreatitis, biliary colics, cholecystitis or choledocholithiasis needing endoscopic
retrograde cholangiopancreatography [ERCP]). Secondary endpoints included
patient reported biliary colics at home, safety of cholecystectomy expressed by
technical difficulty, need for conversion, perioperative complications and length of
hospital stay. The trial protocol has been published1.
RESULTS: In 23 Dutch hospitals 265 patients with mild biliary pancreatitis were
enrolled. 129 Patients were randomised for early cholecystectomy and 136 for
interval cholecystectomy. Baseline characteristics were similar between groups.
Median time from randomisation to cholecystectomy was 1 day (interquartile
range [IQR] 1 to 2) in the early vs. 27 days (IQR 26 to 29) in the interval group.
The primary endpoint occurred less often in the early group (5% vs. 17%; risk
ratio 0.28; 95% confidence interval [CI] 0.12-0.66; p 0.002). The incidence of
recurrent biliary pancreatitis was lower in the early group (2% vs. 9%; RR 0.27;
95% CI 0.08-0.92; p 0.03). 51% of the patients in the interval group reported
colics during the waiting period. Need for ERCP, readmissions for colics, diffi-
culty of cholecystectomy, number of conversions, perioperative complications,
and length of hospital stay did not differ between groups.
CONCLUSION: This trial provides solid evidence that cholecystectomy should
be performed during the initial admission for mild biliary pancreatitis, as this
prevents readmissions for recurrent biliary events, including recurrent biliary
pancreatitis, without increased risk of complications.
REFERENCES
1. Bouwense SA, Besselink MG, et al. Pancreatitis of biliary origin, optimal
timing of cholecystectomy (PONCHO trial): study protocol for a randomized
controlled trial. Trials 2012; 13: 225.
Disclosure of Interest: None declared
OP084-LB2 COMPARATIVE CLINICAL EFFECTIVENESS OF
INFLIXIMAB AND CICLOSPORIN FOR ACUTE SEVERE
ULCERATIVE COLITIS: EARLY RESULTS FROM THE CONSTRUCT
TRIAL
J.G. Williams1,*, M.F. Alam2, L. Alrubaiy1, C. Clement1, D. Cohen2,
G.P. Croft1, M. Grey1, H.A. Hutchings1, J.M. Morgan1, F. Rapport1, I.
T. Russell1, A.C. Seagrove1, A. Watkins1
1
College of Medicine, Swansea University, Swansea, 2Health Economics & Policy
Research Unit, University of South Wales, Pontypridd, United Kingdom
Contact E-mail Address: j.g.williams@swansea.ac.uk
INTRODUCTION: The relative clinical effectiveness and cost-effectiveness of
infliximab (IFX) and ciclosporin (CsA) in the treatment of steroid-resistant,
acute severe ulcerative colitis are not known. In 2012 GETAID reported no
significant difference in efficacy, colectomy rates or adverse events in 115 patients
3 months after treatment.
AIMS & METHODS: Between May 2010 and March 2014, we conducted a
multi-centre, pragmatic, randomised trial in 52 sites across the United
Kingdom. This mixed methods study addressed clinical and cost-effectiveness,
patient and professional views, and will monitor long-term outcomes using rou-
tinely collected data. Two hundred and seventy patients with acute severe colitis
who failed to respond to intravenous (iv) hydrocortisone over 2 to 5 days con-
sented to randomised treatment with IFX or CsA. IFX was given as Remicade
in 5mg/kg iv infusions over two hours, at baseline and 2 and 6 weeks after the
first infusion, in accordance with local prescribing guidelines. Participants ran-
domised to CsA received it as Sandimmun by continuous infusion of 2 mg/kg/
day. Intravenous treatment continued for up to 7 days if successful. Participants
responding to iv CsA were changed to twice-daily oral doses delivering 5.5 mg/
kg/day, adjusted to achieve trough CsA concentrations of 100200 ng/ml.
Depending upon recruitment date, participants were followed up for 1 to 3
years. The primary outcome was quality-adjusted survival (QAS), measured by
the area under the curve of scores from the Crohns & Colitis Questionnaire
(CCQ), a modification of the UKIBDQ validated for use by patients in both
United European Gastroenterology Journal 2(5S)
acute and community settings. It was completed by patients at baseline, 3 and 6
months after randomisation, and then at 6-monthly intervals.
RESULTS: There was no significant difference between age, gender, ethnicity,
family history, smoking status, Mayo score on sigmoidoscopy, or quality of life
scores of the 135 patients in each group at baseline. No difference in QAS (IFX
mean 614.6 days; sd 229.8; CsA 626.0 days; sd 226.8), or QAS per day, was found
between the two groups. There was no significant difference in mean CCQ or EQ-
5D scores over time; colectomy rates (IFX 53; CsA 63); time to colectomy;
mortality (IFX 3; CsA nil); or serious adverse reactions (IFX 12; CsA 11, includ-
ing 3 and 1 malignancies respectively).
CONCLUSION: There is no difference between the two drugs in clinical effec-
tiveness. This conclusion highlights the importance of the other elements of this
mixed methods study.
Disclosure of Interest: None declared
OP084-LB3 BETTER LIVING THROUGH ALGORITHMS: MACHINE
LEARNING ALGORITHMS TO IDENTIFY ADEQUATE
IMMUNOSUPPRESSION AND PREDICT IMPORTANT CLINICAL
OUTCOMES ARE SUPERIOR TO THIOPURINE METABOLITE
CHEMISTRY
P.D. Higgins1,*, K. Sauder1, A. Patel1, Y. Zhang2, J. Zhu2, U. Balis3,
A.K. Waljee1
1
Internal Medicine, 2Statistics, 3Pathology, UNIVERSITY OF MICHIGAN, Ann
Arbor, United States
Contact E-mail Address: phiggins@umich.edu
INTRODUCTION: Optimizing thiopurine therapy for IBD has proven difficult.
Current methods using 6-thioguanine nucleotide (6-TGN) metabolites have
failed in two published RCTs, and have never been used to predict biologic
remission (BR).
AIMS & METHODS: (1) Develop a machine learning algorithm (MLA) using
lab values and age to identify patients in biologic remission (thus adequate
immunosuppression [IS]) on thiopurines, and (2) determine whether achieving
lab patterns predictive of IS resulted in fewer clinical events (steroid prescrip-
tions, hospitalizations, and surgeries) per year. Data from 1082 IBD patients
(3269 observations) on thiopurines were used to build the MLA with lab
values from the CBC and chemistry panel as predictors. Biologic Remission
was defined by the absence of objective measures of inflammation on scan,
scope, biopsy, or serum/fecal tests. The MLA was built in a 70% training set
and tested on a 30% test set. IS was defined as a lab pattern predictive of BR as
identified by the MLA. Clinical event rates per year of follow-up were compared
in those with sustained predicted IS vs. those without predicted IS.
RESULTS: A MLA to differentiate patients with BR from non-responders pro-
duced an AuROC curve of 0.79 (95% CI, 0.78-0.81) in the 30% test set. This is
dramatically superior to 6-TGN measurement, which had an AuROC of 0.49 for
BR (95% CI, 0.44-0.54). In patients with sustained predicted IS, the mean total
number of clinical events per year was 1.52 compared to 4.69 in those who did not
achieve predicted IS (p0.0000000002). Reductions in the individual endpoints of
steroid prescriptions/year (-1.63, p1.2E-9) hospitalizations/year (-1.05, p2.0E-
6), and surgeries /year (-0.19, p0.065) were seen with sustained predicted IS.
Therapeutic interventions changed 32 subjects from sustained lack of IS to sus-
tained predicted IS, largely through dose increases and splitting dosing to bid. In
these subjects, the mean number of steroid prescriptions decreased by 2.4/year,
hospitalizations by 1.5/year, and surgeries by 0.5/year. Total events decreased by a
mean of 4.3/year after achieving sustained predicted IS.
CONCLUSION: This MLA can predict adequate IS in IBD patients on thiopur-
ines. Sustained predicted IS is associated with significant clinical benefits, includ-
ing decreased steroid prescriptions, hospitalizations, and surgeries. Therapeutic
interventions can induce sustained predicted IS and clinical benefits in patients
on inadequate thiopurine monotherapy.
Disclosure of Interest: P. Higgins Other: My employer, the University of
Michigan, holds the patent on this algorithm, K. Sauder: None declared, A.
Patel: None declared, Y. Zhang: None declared, J. Zhu: None declared, U.
Balis: None declared, A. Waljee: None declared
OP084-LB4 OBJECTIVE EFFECTIVENESS, SATISFACTORY RELIEF,
AND COMPLIANCE DURING LOW-FODMAP AND GLUTEN-FREE
DIETS IN IBS PATIENTS ARE NOT RELATED TO
PSYCHOPATHOLOGICAL STATUS. A DOUBLE-BLIND
RANDOMIZED CONTROLLED CLINICAL STUDY
D. Piacentino1, S. Rossi2, V. Alvino2, R. Cantarini2, L. Piretta2, D. Badiali2,
N. Pallotta2, E.S. Corazziari2,*
1
NESMOS (Neuroscience, Mental Health and Sensory Organs), 2Internal
Medicine and Medical Specialties, Sapienza - University of Rome, Rome, Italy
Contact E-mail Address: enrico.corazziari@uniroma1.it
INTRODUCTION: Low-FODMAP diets are suggested as effective interventions
for IBS. Many IBS patients eliminate gluten from their diet, reporting benefit.
Some IBS patients are affected by non-celiac gluten sensitivity. Gluten amount is
undeniably reduced in low-FODMAP diets. It is not known to what extent the
benefits of low-FODMAP diets are due to low FODMAPs per se or gluten
reduction. It is also unclear whether patients psychopathology modulates
these benefits.
AIMS & METHODS: The aims were to: 1) assess in 60 IBS patients (F37, age
range21-67 yrs), the effectiveness on abdominal bloating and pain of 3 diets,
low FODMAP and gluten-free (FOD-GF), low-FODMAP and normal-gluten
(FOD-NG), normal-FODMAP and normal-gluten (balanced control diet); eval-
uate if satisfactory relief and compliance differed between the 3 groups and were
influenced by psychopathology. At enrollment, patients filled out the Symptom
A29
Checklist-90-Revised (SCL-90-R) to assess psychological features, a visual ana-
logue scale (VAS), ranging 0-100, to rate the subjective intensity of bloating, and
a 2-week diary card registering their habitual diet to calculate the objective
frequency of abdominal bloating/pain. After diary completion, they were blindly
assigned to one of the three 4-week diets. During the last 2 weeks they filled out a
2nd diary card and then rerated the intensity of bloating, plus satisfactory relief
and compliance, by using a VAS. Paired t-test measured intragroup differences of
IBS symptoms, pre- and post-diet, one-way ANOVA with Tukey post-hoc test
intergroup differences. Pearsons r was used for correlations.
RESULTS: Age, gender, IBS subtype, SCL-90-R scores, and satisfactory relief
did not differ between the 3 groups, compliance was lower in the FOD-GF group
(p0.041). After the diets, FOD-GF and FOD-NG groups showed improved
intensity of abdominal bloating and frequency of abdominal bloating/pain (p-
values from 0.001 to 0.008 in the former group and equal to 0.000 in the latter),
while controls only slightly improved. Intensity of bloating and frequency of
abdominal bloating/pain were comparable in the 3 groups pre-diet (p0.217),
but differed post-diet (p0.000). A greater improvement of IBS symptoms in the
2 test diet groups vs. the control group, and a trend favoring the FOD-NG group
vs. the FOD-GF group were found. No correlation was found between SCL-90-
R scores, objective benefits, satisfactory relief, and compliance.
CONCLUSION: IBS patients have considerable benefit from restricting
FODMAPs in the diet. Gluten avoidance in addition to a FODMAP restricted
diet does not seem to add any significant benefit and affects negatively compli-
ance. A modified balanced diet benefits patients in terms of satisfactory relief,
irrespectively of FODMAP or gluten content. Psychopathology does not influ-
ence clinical improvement, satisfactory relief, or compliance during the diets.
Disclosure of Interest: None declared
OP084-LB5 EFFECTS OF THE GLUCAGON-LIKE PEPTIDE-1 (GLP-1)
RECEPTOR AGONIST, EXENATIDE, ON SMALL INTESTINAL
MOTILITY, FLOW, AND GLUCOSE ABSORPTION IN HEALTHY
SUBJECTS AND IN TYPE 2 DIABETES
S.S. Thazhath1,*, C. Marathe1, T. Wu1, J. Chang1, J. Khoo1, P. Kuo1,
H. Checklin1, M. Bound1, A. Russo1, R.S. Rigda1, K.L. Jones1, M. Horowitz1,
C.K. Rayner1
1
Discipline of Medicine, University of Adelaide, Adelaide, Australia
Contact E-mail Address: chris.rayner@adelaide.edu.au
INTRODUCTION: The GLP-1 receptor agonist, exenatide (Ex) reduces post-
prandial blood glucose in type 2 diabetes in part by slowing gastric emptying.
However, its impact on small intestinal function is unknown.
AIMS & METHODS: Our aim was to determine the acute effects of intravenous
(IV) Ex on duodenal motility, flow events, and glucose absorption, following
intraduodenal (ID) glucose infusion. 10 healthy subjects (HS) (mean age (SE)
375yrs; BMI 27.41.7 kg/m2) and 10 patients with diet-controlled type 2 dia-
betes (DM) (60.42.3 yrs; BMI 29.11.5 kg/m2) were studied twice in random
order. After an overnight fast, a catheter was positioned with 6 manometry side-
holes, 7 impedance electrode pairs, and an infusion port in the duodenum. Ex
(7.5mg) or saline control was given IV from T -30 to 240min. ID glucose was
infused from T0 to 60min at 3kcal/min, together with 5g 3-O-methylglucose (3-
OMG). Blood was sampled frequently for blood glucose and serum 3-OMG
concentrations (an index of glucose absorption). Symptoms were monitored
using 100mm visual analogue scales.
RESULTS:
T 0 to 240 min Exenatide Control P
HS - Peak blood glucose (mmol/L) 7.9  4 10.7  0.5 50.001
DM- Peak blood glucose (mmol/L) 11.5  0.7 13.4  0.7 50.05
HS Number of duodenal pressure waves 577  98 2088  282 50.001
DM - Number of duodenal pressure waves 781149 1976  446 50.05
HS Number of antegrade flow events 55  12 114  15 50.05
DM Number of antegrade flow events 36  8 105  10 50.001
HS - Serum 3-OMG AUC (mmolL-1.min) 68.3 3.4 101.56.7 50.005
DM - Serum 3-OMG AUC (mmolL-1.min) 81.0  6.1 128.7  10.3 50.001
HS DM Peak nausea score (%) 32.37.7 72.5 50.005
Blood glucose (T0 to 240min) was lower during Ex than control in both HS and
DM. During the same period, there were fewer duodenal pressure waves with Ex
than control in both groups, as well as fewer antegrade flow events. 3-OMG
absorption (area under the curve) was markedly less with Ex than control, in
HS and DM. Peak nausea scores were higher with Ex than control in both
groups. However, 10 subjects without any nausea still had suppression of duo-
denal pressure waves (678  137 vs 1963 467; P50.05) and flow (58  9 vs
106 6; P50.001).
CONCLUSION: IV Ex acutely suppresses duodenal motility and flow events,
and slows small intestinal absorption of glucose, in both health and type 2
diabetes, suggesting that changes in small intestinal motor function, and thereby
glucose absorption, contribute to the lowering of postprandial glycaemia by
GLP-1 receptor agonists.
Disclosure of Interest: S. S. Thazhath: None declared, C. Marathe: None
declared, T. Wu: None declared, J. Chang: None declared, J. Khoo: None
declared, P. Kuo: None declared, H. Checklin: None declared, M. Bound:
None declared, A. Russo: None declared, R. S. Rigda: None declared, K. L.
Jones: None declared, M. Horowitz: None declared, C. K. Rayner Financial
Support from: This research was conducted with support from the
Investigator-Sponsored Study Program of AstraZeneca
A30
OP084-LB6 THE COMPARATIVE STUDY OF SPLIT-DOSE OF
POLYETHYLENE GLYCOL (PEG) BETWEEN LOW VOLUME PEG
PLUS ASCORBIC ACID FOCUSING ON THE BOWEL CLEANSING
EFFICACY, PATIENTS AFFINITY TO PREPARATION SOLUTION
AND MUCOSAL INJURY: A PROSPECTIVE RANDOMIZED TRIAL
J. Park1,*
1
Department of Internal Medicine, Inje University, College of Medicine, Haeundae
Paik Hospital, Busan, Korea, Republic Of
INTRODUCTION: Adequate bowel cleansing is essential for a high-quality,
effective, and safe colonoscopy. The aims of this study were to compare the
efficacy and patients affinity to preparation solution and mucosal injury of
split dose of polyethylene glycol (PEG) solution with low volume PEG plus
ascorbic acid for outpatients who underwent scheduled colonoscopy.
AIMS & METHODS: Overall, 160 patients were enrolled for split-dose of PEG
and 159 for the low volume PEG plus ascorbic acid, respectively. The bowel
cleansing efficacy of preparation was rated according to the Ottawa bowel pre-
paration scale and patients affinity to preparation solution was assessed using a
questionnaire. All mucosal abnormalities observed during colonoscopy were
noted and biopsied. These biopsy specimens were reviewed by pathologists.
RESULTS: Of the 319 patients, 308(96%) ingested more than 75% of the bowel
preparation. There was no significant difference between the two groups for the
mean total score using the Ottawa bowel preparation scale (P 0.376).
Significantly greater residual colonic fluid was observed in the low volume
PEG plus ascorbic acid group (0.81  0.54) than in the split-dose PEG group
(0.66  0.62) (P 0.023). There was significant difference in the Ottawa bowel
preparation score for the middle colon (split-dose PEG vs. low volume PEG plus
ascorbic acid: 1.19  0.94 vs. 1.42  0.73; P 0.014). In patients preference and
acceptance, low volume PEG plus ascorbic acid group showed better results (P
0.001). The overall incidence of adverse events was not significantly different
between the two groups (69/160 [43.1%], 69/159 [43.4%], P 0.972); however,
the split-dose PEG group tended to have less headache and dizziness (P 0.056).
Endoscopically, mucosal lesions, possibly associated with two preparation regi-
men, were observed in total 11 patients (split-dose PEG: 5, low volume PEG plus
ascorbic acid: 6, respectively). Mucosal ulceration occurred in 1 patient taking
split-dose PEG compared with 2 patients receiving low volume PEG plus ascor-
bic acid.
CONCLUSION: Low volume PEG solution plus ascorbic acid, compared with
split-dose PEG, was associated with more residual fluid, but showed equivalent
colon cleansing efficacy and resulted in more patient preference, and acceptance.
There was no significant difference in mucosal injury.
REFERENCES
1) Corporaal S, Kleibeuker JH and Koornstra JJ. Low-volume PEG plus ascor-
bic acid versus high-volume PEG as bowel preparation for colonoscopy. Scand J
Gastroenterol 2010; 45: 1380-1386.
Disclosure of Interest: None declared
OP084-LB7 EFFICACY AND TOLERABILITY OF LOW VOLUME
POLYETHYLENE GLYCOL PLUS ASCORBIC ACID VERSUS
SODIUM PICOSULFATE MAGNESIUM CITRATE: A
PROSPECTIVE RANDOMIZED TRIAL
B. Choi1,*, K. Kim1, S. Seo1, J. Kang1, B. Yang1
1
Kangdong sacred heart hospital, Seoul, Korea, Republic Of
Contact E-mail Address: bygging@hanmail.net minsoksumin@hallym.or.kr
INTRODUCTION: Colonoscopy is the standard method for the evaluation of
mucosa of large intestine. High quality bowel preparation is essential for improv-
ing patients compliance and the detection rate of colorectal lesions in screening
colonoscopy. Recently, a new Polyethylene glycol (PEG)-based solution has
became available. It combines PEG with a high dose of ascorbic acid (PEG
Asc, Coolprep, Taejoon, Korea). Also, sodium picosulfate with magnesium
oxide and citric acid (MC-SP, Picolight, Pharmbio, Korea) is a commonly
prescribed hyperosmolar bowel preparation in Korea.
AIMS & METHODS: The aim of this study is to compare the efficacy, toler-
ability, and safety of this new 2L PEG Asc with MC-SP. Patients were enrolled
from the endoscopy unit at the Kangdong sacred heart hospital, Seoul, Korea,
between Feb 2014 and June 2014. Adult ambulatory outpatients scheduled for
elective colonoscopy were randomized to receive 2L PEG Asc (Coolprep), or
MC-SP (Picolight). Before colonoscopy, patients were asked to complete a
questionnaire regarding the acceptability, the tolerability, and side effects of
the preparation. Six experienced endoscopists, who were blinded to the rando-
mization and the study group of the patients, rated the quality of bowel cleansing
by using Ottawa bowel preparation scale immediately after colonoscopy.
RESULTS: A total number of 223 consecutive individuals were randomly assigned
to receive either 2L PEG Asc solution (n109) or MC-SP solution (n114). Baseline
and demographic characteristics were not different between both groups. Comparing
PEG Asc and MC-SP, there were no differences in overall quality of bowel cleansing
(p0.806). However, when dividing individual bowel segments, MC-SP was superior
to the PEG Asc in right colon segment (p0.03). Side effects during preparation,
such as nausea, vomiting, abdominal pain, abdominal bloating and dizziness, were less
frequent in MC-SP group (p0.031). Overall satisfaction of patients was superior in
MC-SP group (p50.001) and more patients had an intention to do next colonoscopy
with same bowel preparation method in MC-SP group (p0.001).
CONCLUSION: Our study suggest that MC-SP provided significantly better
cleansing in the right colon, and showed better acceptability and tolerability
profile to that achieved with 2L PEG Asc solution. However, for overall
quality of bowel cleansing, both solutions showed similar level of effectiveness.
REFERENCES
1) Moon W. Optimal and safe bowel preparation for colonoscopy. Clin Endosc
2013; 46: 219-223.
United European Gastroenterology Journal 2(5S)
2) Seo HW, Han KH, Kim S, et al. The efficacy and tolerability of sugared
polyethylene glycol for colonoscopy. Korean J Gastroenterol 2013; 61: 88-92.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
IBD: NEW THERAPEUTICS FOR SPECIFIC TARGETS HALL L/M_____________________
OP085 INDUCTION OF MUCOSAL LIPOCALIN 2 IS A KEY
REGULATORY EVENT IN IBD THAT SHAPES MICROBIAL
COMMUNITIES TO CURB INFLAMMATION AND PREVENT
COLITIS-ASSOCIATED CANCER
A.R. Moschen1,*, R.R. Gerner1, J. Wang2, P. Moser3, S. Alexander4, D. Orth5,
G. Weiss1, J. Baines2, A. Kaser6, H. Tilg1
1
Department of Medicine, Medical University Innsbruck, Innsbruck, Austria, 2Max
Planck Institute for Evolutionary Biology, Plon, Germany, 3Department of
Pathology, Medical University Innsbruck, Innsbruck, Austria, 4Department of
Medicine, Gastroenterology, Universitatsmedizin Berlin, Berlin, Germany,
5
Division of Hygiene and Medical Microbiology, Medical University Innsbruck,
Innsbruck, Austria, 6Department of Medicine, University of Cambridge,
Cambridge, United Kingdom
INTRODUCTION: Lipocalin2 (Lcn2), a member of the lipocalin family, con-
stitutes an innate immune molecule involved in antimicrobial immunity and iron
metabolism. Lcn2 is upregulated during inflammatory bowel diseases (IBD). Its
functional contribution to mucosal immunity remains unknown.
AIMS & METHODS: Aim of this study was to decipher the functional role of
Lcn2 in IBD. For this purpose we generated mice doubledeficient in IL10 and
Lcn2. Severity and course of colitis were measured by clinical, histological, and
biochemical parameters. Microbial communities were assessed by culture-
independent analyses of bacterial 16S rRNA genes in fecal samples and comple-
mented by bacterial FISH. Relevant findings were amended by additional
functional experiments in vitro and in vivo.
RESULTS: We show that deficiency of Lcn2 resulted in exacerbated colitis and
spontaneous emergence of proximal colonic tumours in IL-10deficient mice.
Colitis and tumourigenesis were dependent on microbial signals and responsive
to antibiotics and IL-6deletion. Lcn2deficiency was associated with altera-
tions in the composition of gut microbial communities and loss of spatial segre-
gation. Colito and tumourigenic properties were transmissible by
crossfostering and cohousing. Lcn2induced dysbiosis fostered the bloom
of pathobionts such as Alistipes and Robinsoniella species able to mimic
observed changes when gavaged.
CONCLUSION: Our results suggest a pivotal role of inflammation-induced
Lcn2 as a key guard against colonic inflammation and carcinogenicity in IBD
through its microbiotamodulating properties.
Disclosure of Interest: None declared
OP086 EPITHELIAL IL-23R SIGNALING LICENSES PROTECTIVE IL-22
RESPONSES IN INTESTINAL INFLAMMATION
K. Aden1,2,*, A. Rehman1, R. Hasler1, S. Lipinski1, M. Paulsen1, A. Kaser3,
S. Schreiber2, P. Rosenstiel1
1
Institut of clinical molecular biology, 2I. Medical Department, Kiel, Kiel
University, Kiel, Germany, 3Department of Medicine, Addenbrookes Hospital,
University of Cambridge, Cambridge, United Kingdom
Contact E-mail Address: k.aden@ikmb.uni-kiel.de
INTRODUCTION: The identification of the IL23R as a genetic risk factor in
inflammatory bowel disease (IBD) has highlighted the role of IL-23 signaling in
the intestinal immune response. However, the impact of IL-23 on the immune reg-
ulation is ambigious. Whereas IL-23 induced Th-17 polarization contributes to
pathogenesis of IBD5, IL-23 induced IL-22 in Thy-1 innate lymphoid cells is indis-
pensable in the innate immune response to bacterial pathogens and experimental
colitis. This study aimed to describe the role of the Il23R in the intestinal epithelium.
AIMS & METHODS: Conditional knockout of the Il23R in the intestinal
epithelium was established by crossing VillinCre mice with Il23Rfl/fl mice, result-
ing in IL23RIEC-KO or IL23Rfl.
For chronic colitis induction, mice were supplied with 2% of DSS dissolved in
drinking water for 5 days followed by 5 days of regular drinking water with total
3 cycle repetitions.
Diseased intestines were subjected to gene expression analysis was performed
using custom made TaqMan probes and post-mortem histopathological analysis.
Lumina faeces were subjected to pyrosequencing of bacterial DNA and
sequences with at least 97% similarity were clustered in to species level opera-
tional taxonomical units (OTUs).
RESULTS: Here we show that IL23R is expressed in intestinal epithelial cells
and profoundly affects the intestinal immune defense. IL23RIEC-KO mice produce
less antimicrobial peptides, have a disturbed colonic microflora and succumb to
experimental colitis. IL23RIEC-KO intestinal lamina propria cells contain less
immune cells and produce less IL-22 in response to IL-23 or Flagellin stimula-
tion. Lastly, we could show, that IL-22 therapy fully restores epithelial immune
defense in IL23RIEC-KO.
CONCLUSION: These data contribute to the understanding of the IL-23 axis in
primary immune response and describes a so far unknown role of IL23R signal-
ing in the intestinal epithelium.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 15:4517:15
IMMUNOPATHOGENESIS OF PANCREATITIS AND HEPATITIS HALL
R_____________________
OP087 AUTOIMMUNE PANCREATITIS EXPLORING DISEASE
PATHOPHYSIOLOGY AND NOVEL, STEROID SPARING
THERAPEUTIC INTERVENTIONS
G.M. Seleznik1,*, T. Reding1, J. Browning2, S. Segerer3, M. Heikenwaelder4,
R. Graf1
1
Swiss HPB Center, Visceral & Transplantation Surgery, University Hospital
Zurich, Zurich, Switzerland, 2Department of Microbiology, Boston University
School of Medicine, Boston, United States, 3Division of Nephrology, University
Hospital Zurich, Zurich, Switzerland, 4Institute of Virology, Technische
Universitat MunchenHelmholtz Zentrum Munchen, Munich, Germany
INTRODUCTION: Autoimmune pancreatitis (AIP) is a recently identified, rare
form of chronic pancreatitis, which has become a new evolving field in gastro-
enterology. Currently, the treatment options, especially the long-term manage-
ment for AIP are limited. The only therapy that has been established and
accepted so far is corticosteroids, but the relapse rate is significant (15-60%).
We previously demonstrated that acinar specific Lymphotoxin expression in mice
(Tg(Ela1-Lta, b)) induces autoimmunity with features reminiscent of human
AIP. This includes formation of tertiary lymphoid organs, increased serum
IgGs, anti-nuclear antibodies and immune-complex glomerulonephritis. In this
model we have previously shown that in contrast to corticosteroids, which only
diminished inflammation, inhibition of Lymphotoxin beta receptor signaling
A31
CONCLUSION: This study demonstrates for the first time wide-spread NET
formation in AP. We found that NET formation regulates local and remote
organ inflammation and damage in AP. These novel findings provide new
insights in the pathophysiology of pancreatitis and indicate that targeting
NETs might be an effective way to ameliorate tissue damage severe AP.
Disclosure of Interest: None declared
OP089 EARLY INTRAACINAR EVENTS AND IMMUNE RESPONSE IN
ALCOHOLIC ACUTE PANCREATITIS IN HUMANS
R. Talukdar1,*, A. Jakampudi2, R. Jangala2, P.U. Pelluri2, C. Ramji1, M. S2, G.,
V. Rao1, D.N. Reddy1
1
Asian Institute Of Gastroenterology, 2Asian Healthcare Foundation, Hyderabad,
India
Contact E-mail Address: rup_talukdar@yahoo.com
INTRODUCTION: Acute pancreatitis (AP) continues to be a challenging pro-
blem without specific solution. 20-25% of patients with AP develop severe dis-
ease. Systemic inflammatory response syndrome (SIRS) and associated
multiorgan dysfunction (MODS) is responsible for early mortality. It is prudent
to understand the early pathogenesis of AP and the associated immune
responses, so that effective focused treatment modalities can be developed.
Even though pathogenesis of AP has been studied extensively in murine experi-
mental models, data are lacking for AP in humans.
AIMS & METHODS: In this study we evaluate the early intraacinar events and
acinar-immune interactions in alcoholic AP in humans.
(LTR-Ig) also abrogated autoimmunity. Normal pancreatic tissues were obtained from samples of Whipples surgery for
AIMS & METHODS: The aim of the study is to investigate the effectiveness of symptomatic benign biliary and periampullary pathology and pancreatic resec-
LTR pathway inhibition compared to the depletion of specific subset of tion for pancreatic cystic lesions. Pancreatic slices and acini were prepared, trea-
immune cells (B-cells and CD4 T-cells), which are suggested to play a patho- ted with 50mM fatty acid ethyl esters/FAEE (alcohol metabolites) and incubated
logical role in AIP development. Therefore, Tg(Ela1-Lta, b) mice with estab- for different time intervals. Acinar injury was evaluated by trypsin and cathepsin
lished AIP were treated with anti-CD20 mAb (Rituximab), anti-CD4 mAb in B activation, H&E staining and transmission electron microscopy. McDonald &
order to deplete B- and CD4 T-cells respectively and with LTR-Ig fusion Ellis and Kawabata methods were used to evaluate for trypsin and cathepsin B
protein. Histology, autoantibody production, cytokine and chemokine expres- activity respectively. Subcellular fractionation was performed to evaluate intraa-
sion, TLO integrity and other organ involvement (in kidneys) were tested, and cinar redistribution of zymogen and lysosomal compartments. IHC and western
compared to LTR-Ig treatment. Furthermore, macrophage and T helper cell blotting was used to evaluate the type of cell injury. Flow cytometry was per-
polarization was evaluated upon different treatments. formed to evaluate cytokine release by stimulated acinar cells and peripheral
RESULTS: LTR-Ig and anti-CD20 treatment led to a significant decrease in
autoantibody production, inflammatory cell infiltration in the pancreas and
reduced extrapancreatic manifestation in the kidneys. The molecular mechanism
of this beneficial effect possibly involves the down regulation of Stat3 and non-
canonical NF-b activation. Additionally, in contrast to anti-CD20 and anti-
blood mononuclear cells (PBMCs) exposed to conditioned medium from stimu-
lated acinar cells.
In order to validate our experimental findings, we evaluated cytokine expression
from PBMCs isolated from patients with AP (n43) at different time points and
studied the association with clinical severity.
CD4 treatments, blocking LTR-signaling reverted acinar cell proliferation
and acinar-to-ductal metaplasia formation and also disrupted the formation of
TLOs. Anti-CD4 treatment resulted in reduced Th1 and Th2 polarization; how-
ever this did not ameliorate AIP.
CONCLUSION: In this unique genetic mouse model of AIP, we demonstrate
RESULTS: FAEE induced acinar injury was evidenced by a 15- and 10-fold
elevation of trypsin and cathepsin B activity within 30mins of exposure. This
was corroborated with histologic evidence of acinar injury. Subcellular fractiona-
tion demonstrated redistribution of cathepsin to zymogen-enriched compartment
after 30mins exposure. There was a time dependent secretion of predominantly
that therapy with LTR-Ig and anti-CD20 antibody is superior to CD4 T-cell IL-6 and IL-8 by the FAEE treated acini from 2hrs onwards which peaked at
depletion. With these targeted therapies we reveal novel anti-inflammatory and 18hrs (median values of 1052.18 pg/mL and 3933.99pg/mL respectively). A
anti-autoimmune mechanisms. Assessing numerous parameters associated with robust secretion of the cytokines IL-6, IL-8, IL-1b, IL-10 and TNF-a (median
AIP pathogenesis, LTR-Ig achieved the greatest improvements. Therefore, inhi- values of 13583.77 pg/mL, 1462.97 pg/mL, 4875.32 pg/mL, 1858 pg/mL and
bition of the LTR-signaling pathway could become an alternative or supple-
mentary approach for AIP treatment.
Disclosure of Interest: None declared
OP088 NEUTROPHIL EXTRACELLULAR TRAPS TRIGGER TRYPSIN
ACTIVATION, PATHOLOGICAL INFLAMMATION AND TISSUE
DAMAGE IN SEVERE ACUTE PANCREATITIS
H. Throlacius1,*, H. Hartmen1, M. Merza1, M. Rahman1, R. Hwaiz1, S. Regner1
1
Surgery, Lund University, Malmo, Sweden
Contact E-mail Address: henrik.thorlacius@med.lu.se
INTRODUCTION: Neutrophils play a pivotal role in local and systemic com-
plications of acute pancreatitis (AP), but the mechanisms regulating neutrophil-
induced tissue damage in the inflamed pancreas is not fully understood. Recently,
neutrophil extracellular traps (NETs) have been demonstrated to contribute to
organ dysfunction in both infective and non-infective diseases. In the present
study, we investigated for the first time the potential role of NETs in AP.
AIMS & METHODS: AP was induced in male C57BL/6 mice by infusion of
taurocholate into the pancreatic duct. Extracellular DNA was stained by Sytox
green and NET formation was quantified by confocal microscopy and cell-free
DNA in plasma. Pancreatic levels of chemokines and histone 3 and 4 as well as
cytokines and chemokines in plasma were determined by ELISA. Neutrophil
expression of Mac-1 was determined by flow cytometry. To analyze the impact
of NET formation in AP, NET depletion was induced by DNAse I administra-
tion. In separate experiments, signal transducer and activator of transcription-3
(STAT-3) phophorylation and trypsin activation were analysed in isolated acinar
cells exposed to NETs and histone 3 and 4.
RESULTS: Taurocholate challenge evoked formation of NET in the pancreas
and increased cell-free DNA in plasma. Formation of macrophage inflammatory
protein-2 (CXCL2), neutrophil infiltration and tissue damage in the inflamed
pancreas and lung were significantly attenuated by DNAse I treatment.
Moreover, DNAse I administration markedly reduced levels of blood amylase,
CXCL2, interleukin-6 and high-mobility groups protein 1 as well as macrophage-
1 antigen expression on circulating neutrophils in mice with pancreatitis. NETs
and histones triggered trypsin formation and activation of STAT-3 in isolated
acinar cells. Pre-incubation of NETs with polysialic acid abolished NET-induced
activation of trypsin in acinar cells, suggesting that histones are responsible for a
great part of NET-induced trypsin activation.
1121.71 pg/mL respectively) was observed from PBMCs exposed to conditioned
media from FAEE treated acini. Interestingly, there was no secretion of IL-10
and TNF-a by the FAEE treated acinar tissue.
PBMCs from patients with alcoholic AP showed a significant increase in IL-6
and IL-8 secretion from the first week to the second week compared to non-
alcoholic AP. This was significantly associated with disease severity (persistent
organ failure).
CONCLUSION: Alcoholic AP in humans is characterized by early autophagy
and redistribution of cathepsin B, which possibly causes intraacinar trypsinogen
activation to active trypsin. There is also early secretion of pro-inflammatory
cytokines by the treated acini that causes activation of circulating monocytes to
further produce cytokines and initiate SIRS.
Disclosure of Interest: R. Talukdar Financial support for research from:
Wellcome-DBT India Alliance, A. Jakampudi: None declared, R. Jangala:
None declared, P. Pelluri: None declared, C. Ramji: None declared, M. S:
None declared, G. Rao: None declared, D. Reddy: None declared
OP090 RESVERATROL IMPROVES THE PATHOGENESIS OF
NONALCOHOLIC STEATOHEPATITIS THROUGH INHIBITION OF
ENDOTOXIN-INDUCED LIVER INFLAMATION AND FIBROSIS
T. Kessoku1,1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, A. Nakajima1
1
gastroenterology and hepatology, Yokohama city university, yokohama, Japan
INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in
Asia Pacific region is close to 1224%, while in Western countries is about 20
30% and NAFLD can progress to nonalcoholic steatohepatitis (NASH), cirrho-
sis and hepatocellular carcinoma. In spite of its high prevalence, up till now here
is no proven effective treatment for NAFLD. Although gut-derived endotoxin
(ET), such as lipopolysaccharide (LPS), plays a key role in the pathogenesis of
nonalcoholic steatohepatitis (NASH), detailed mechanisms of this pathogenesis
becomes clear. We previously reported that overexpression of CD14 via activa-
tion of leptin-STAT3 signaling in Kupffer cells induced hyper-inflammatory
response to low-dose ET, resulting in progression from simple steatosis to stea-
tohepatitis with liver fibrosis. Therefore, we hypothesized that inhibition of
leptin-STAT3 signaling in Kupffer cells may lead to attenuate the progression
of steatohepatitis via inhibition of CD14 expression.
AIMS & METHODS: The aim of this study was to investigate whether the
resveratrol which is known to inhibit activation of STAT3, improves the patho-
genesis of steatosis or steatohepatitis in murine model. Eight-week-old male
A32
C57BL/6J mice were randomly distributed into 3 groups of 10 animals each: a
high fat diet group (HF), HF supplemented with 2mg/kg resveratrol daily
(HFR2), and HF supplemented with 20mg/kg resveratrol daily (HFR20). After
12 weeks of dietary treatment, the rats were euthanized and relevant tissues were
prepared for subsequent analysis. In this study, E. coli-derived LPS (0.25 mg/kg)
was used.
A) We investigated whether the resveratrol attenuates HFD-induced steatosis.
B) We investigated whether the resveratrol attenuates ET-induced liver damage
via inhibition of response to ET.
C) We investigated whether the resveratrol improves the pathogenesis of long-
term exposed ET-induced steatohepatitis with liver fibrosis.
RESULTS: Resveratrol prevented the high fatinduced steatosis assessed by
semiquantitative grading, which furthermore corresponded with a complete nor-
malization of the hepatic triglyceride content (P 5 .001), despite no change in
total body fat, and hepatic SREBP1c expression was significantly decreased as
compared with HF. HFR showed significant inhibition of hepatic CD14 expres-
sion through suppression of STAT3 activity in Kupffer cells, following inhibition
of a single low-dose LPS-induced liver damage. Moreover, long-term low-dose
LPS-induced liver fibrosis in HFR is significantly decreased as compared with
HF.
CONCLUSION: These data indicated that the resveratrol improves not only the
pathogenesis of steatosis thorough inhibition of lipogenesis but also steatohepa-
titis through inhibition of endotoxin-induced liver damage via suppression of
STAT3-CD14 signaling in Kupffer cells. The resveratrol may have application
for the treatment of NAFLD
REFERENCES
1) Imajo K, Fujita K, Yoneda M, et al. Hyperresponsivity to low-dose endotoxin
during progression to nonalcoholic steatohepatitis is regulated by leptin-
mediated signaling. Cell Metab 2012; 16:44-54.
Disclosure of Interest: None declared
OP091 GUT-DERIVED LYMPHOCYTES MIGRATE TO THE LIVER IN A
MOUSE MODEL OF NON-ALCOHOLIC FATTY LIVER DISEASE
Y. Hu1, H. Zhang2, J. Li1, X. Cong2, Y. Chen2, G. He2, Y. Chi3, Y. Liu1,*
1
Department of Gastroenterology, 2Peking University Hepatology Institute, Beijing
Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Peking
University Peoples Hospital, 3 Institute of Clinical Molecular Biology, Peking
University Peoples Hospital, Beijing, China
INTRODUCTION: An intimate immunological relationship between the gut
and liver has been demonstrated, but the role of gut-derived lymphocytes in
the progression of non-alcoholic fatty liver disease (NAFLD) remains unknown.
We investigated the migration of gut-derived lymphocytes to the liver in a mouse
model of NAFLD.
AIMS & METHODS: The mice were fed a high-fat diet for 12 weeks to induce
NAFLD model. Control mice were fed a normal-fat diet. Lymphocytes from the
spleen, bone marrow, thymus and mesenteric lymph nodes (MLN) of NAFLD
mice were intravenously injected into NAFLD and control mice for near-infrared
scanning. The percent of the lymphocyte subsets were analysised by flow cyto-
metry. The chemotactic index of MLN cells of NAFLD and control mice was
analyzed by chemotaxis assays.
RESULTS: The fraction of activated CD4T cell(CD4CD44highCD62low) in
MLN was significantly increased in NAFLD mice. Meanwhile, the control
memory CD4T cells and CD8T cells(CD4CD44highCD62Lhigh and INTERLEUKIN-8 RECEPTORS
CD8CD44highCD62Lhigh), B cells increased in liver of NAFLD mice.
Additionally, the fraction of CD4 effector T cells (Th1 and Th17) increased
significantly in the liver, MLN and blood of NAFLD mice. The adoptive transfer
model showed that MLN cells from the NAFLD donor mice predominately
accumulated in the liver in both NAFLD and control recipient mice.
Compared to control recipient mice, NAFLD recipient mice accumulated
much more MLN cells from NAFLD donor mice in their livers. Whereas only
a few lymphocytes from the spleen, bone marrow and thymus of the NAFLD
donor mice migrated to the liver. Moreover, MLN cells from NAFLD mice
induced liver injury in both NAFLD and control recipient mice, as reflected
by elevated levels of serum ALT and AST after adoptive transfer. After the
injection of MLN cells from NAFLD donor mice, the percent of activted
CD4T cells, activated CD8T cells and B cells increased in liver. The CCL5
mRNA expression increased significantly in liver of NAFLD mice. Meanwhile,
the CCL5 receptor CCR3 expression increased in CD4T cell subsets, CD8T
cell subsets and CD19B cells in the MLN cells of NAFLD mice. Blocking the
CCL5 with the CCL5 antibody inhibited the migration of the MLN cells of
NAFLD mice migration to liver.
CONCLUSION: Our study provides evidence that gut-derived lymphocytes
from NAFLD mice have a strong propensity to migrate to the liver and
induce liver injury and that fatty liver promotes the migration of gut-derived
lymphocytes. Meanwhile, the gut-derived lymphocytes promoted CD4T cells
and CD8T cells activation in liver of NAFLD mice. The propensity for the
migration of gut-derived lymphocytes to the liver was associated with the
mechanism of the upregulation of CCL5 in liver and CCL5 receptor CCR3 in
gut-derived lymphocytes.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP092 SIGNIFICANCE OF SELECTED BIOMARKERS OF
INFLAMMATION, ANGIOGENESIS AND ADIPOKINES IN THE
NON-INVASIVE ASSESSMENT OF PATIENTS WITH ALCOHOLIC
LIVER DISEASE
B. Kasztelan-Szczerbinska1,*, A. Surdacka2, M. Slomka1, J. Rolinski2,
K. Celinski1, H. Cichoz_ -Lach1, M. Szczerbinski1
1
Dept. of Gastroenterology with Endoscopy Unit, 2Dept. of Clinical Immunology,
Medical University of Lublin, Poland, Lublin, Poland
Contact E-mail Address: beata.szczerbinska@op.pl
INTRODUCTION: Alcohol abuse is a major cause of liver disease in Europe.
The idea of using serum biomarkers for early risk stratification and decision
making in patients with alcoholic liver disease (ALD) seems an attractive alter-
native to invasive diagnostic methods (eg. liver biopsy, endoscopy) used in the
current clinical practice.
AIMS & METHODS: Determination of serum profile of selected biomarkers of
three different processes showing synergism in the pathogenesis of ALD i.e.
inflammation, angiogenesis and adipose tissue secretion (adipokines). Two new
subsets of T helper cells: Th17 and Treg, vascular endothelial growth factor
(VEGF), angiopoietin 1, 2 (Ang1, Ang2), as well as total adiponectin (Acrp30),
leptin and resistin were investigated. 147 pts (40 females, 107 males) with ALD
were prospectively recruited and compared with 30 healthy controls (HC). They
were divided into subgroups based on their: 1. gender, 2. severity of liver dysfunc-
tion according to the Child-Turcotte-Pugh and MELD scores; and 3. the presence
of ALD complications at the time of hospital admission (i.e. ascites, hepatic ence-
phalopathy, esophageal varices, cholestasis, renal dysfunction and death). In order
to confirm alcohol misuse the AUDIT-C questionnaire was used. A FACSCalibur
flow cytometer (Becton Dickinson, USA) with CellQuest software was used to
identify T cell phenotype. CD3CD4IL17 cells were considered Th17 and
CD4CD25FOXP3 Tregs. They were expressed as the percentage of all
CD3CD4 and CD4CD25 lymphocytes, respectively. Serum levels of angio-
genic biomarkers and adipokines were assessed using immunoenzymatic ELISA
tests. Multivariable logistic regression was applied in order to select independent
predictors of advanced liver dysfunction and the disease complications.
RESULTS: Twelve of 147 pts died within the 90-day follow up. The alteration of
the Th17/Treg balance was observed in the most severely ill patients. Frequency
of Th17 cells was an independent predictor of mortality in the study group.
Significantly higher plasma concentrations of Ang2 and VEGF, as well as
Acrp30 and resistin in comparison with HC were found. Increased Ang2 con-
centrations turned out to be an independent predictor of severe liver dysfunction
(MELD score  20) and the development of ascites, encephalopathy, renal dys-
function, and death. Also Acrp30 concentrations revealed an independent asso-
ciation with the severity of liver dysfunction and the development of ascites and
hepatic encephalopathy.
CONCLUSION: High frequency of Th17 cells, as well as Ang2 and Acrp30
concentrations revealed the best individual predictive value for ALD complica-
tions. The predictive power of complex statistical models which included several
parameters from different pathways in the pathogenesis of ALD occurred to be
superior to either biomarker alone.
Disclosure of Interest: None declared
OP093 RESCUE FROM EXPERIMENTAL ALCOHOLIC
STEATOHEPATITIS BY A PEPDUCIN-BASED BLOCKADE OF
V. Wieser1, A. Kaser2, H. Tilg1, N.C. Kaneider2,*
1
Abteilung fur Innere Medizin 1, Medizinische Universitat Innsbruck, Innsbruck,
Austria, 2Div. of Gastroenterology and Hepatology, Dept. of Medicine, University
of Cambridge, Cambridge, United Kingdom
Contact E-mail Address: nk428@cam.ac.uk
INTRODUCTION: Alcoholic steatohepatitis (ASH), exhibiting short-term mor-
tality rates as high as 40%, is characterised by hepatic neutrophil infiltration and
peripheral blood neutrophilia. It is thought to evolve from an initial inflammatory
response to end products of ethanol catabolism and ethanol-induced break-down of
the enteric barrier with consecutive bacteraemia and entotoxinaemia. Interleukin-8-
induced signalling through CXCR1/2 G protein coupled receptors (GPCRs) is
critical for the recruitment and activation of neutrophils at sites of inflammation.
We have previously shown that pepducins, short consciously designed lipopeptides,
modulate GPCRs by interfering with the receptors activation of G-proteins.
AIMS & METHODS: Pepducins were synthesised by standard fMOC and tested
in a murine model of ASH. Mice were fed a liquid high fat (Lieber DeCarli) diet
for 5 weeks, followed by parenteral administration of endotoxin. Liver/body
weight ratio, histological hepatic inflammation, and neutrophil myeloperoxidase
were measured.
RESULTS: We demonstrate that experimental ASH is driven by CXCR1/2-
dependent activation of neutrophils. CXCR1/2-specific pepducins protected
from histological inflammation, weight loss and mortality associated with experi-
mental ASH. Importantly, pepducins were effective even when administration
was commenced late in established experimental ASH. Neutrophil infiltration
and lipid accumulation in hepatocytes were significantly reduced by CXCR1/2
pepducin treatment. Hepatocyte cell lines were shown to secrete interleukin-8
upon ethanol stimulation, and CXCR1/2 pepducins blocked chemoattraction
of neutrophils toward hepatocyte supernatants.
CONCLUSION: Experimental ASH remarkably closely phenocopies human
ASH, which represents a major unmet therapeutic need. These data establish a
key role for CXCR1/2 signalling and hepatic neutrophil recruitment in the patho-
genesis of ASH. CXCR1/2 pepducins might therefore represent a pharmacolo-
gical approach that merits exploration in a clinical trial in ASH. Pepducins
directed against another GPCR are currently studied in a phase I clinical trial.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 15:4517:15
PROGRESS IN GASTRIC AND DUODENAL ENDOTHERAPY HALL
N_____________________
OP094 LONG TERM FOLLOW-UP OF UPPER GI NEOPLASIA
TREATED BY ENDOSCOPIC RESECTION
C. Teixeira1, M. Maia1, R. Jobim1, N. Coelho1,*, L. Figueiredo1
1
END0SCOPY, FUGAST, Porto Alegre, Brazil
Contact E-mail Address: nelsoncoelho@urgegastro.com.br
INTRODUCTION: Endoscopic mucosal resection (EMR), or mucosectomy
technique, developed by Japanese endoscopists consists of resecting flat and
polypoid neoplasms of the mucosa. Its a relatively simple technique and carries
a low morbidity. It represents an important advance for endoscopists in both
technical and cancer areas. Is based on the concept that endoscopy provides
visualization and acess to the mucosa, the innermost lining of the gastrointestinal
tract. EMR presents also the advantage of obtaining a complete specimen for
histologic analysis, allowing to know whether the resection has been complete
laterally, in depth and the level of tumor invasion. Provides the opportunity to
preserve organs anatomy and physiology avoiding surgery and long term hospi-
tal stay.
AIMS & METHODS: The aims of the study were to measure the success rate of
achiving complete resection and the complication rate of EMR in a single center.
A retrospective analysis was done among 137 EMRs procedures conducted in
our endoscopic department between December 1997 and March 2014. The pro-
cedure was done either with dual-channel gastroscope Fujinom and cap or band-
ligation with regular scope. EUS was performed in the majority of patients with
high frequence miniprobes or radial Fujinom System scope. In patients with
high-grade dysplasia (HGD) and intramucosal cancer who were treated by
EMR, careful follow-up and additional therapy to treat residual or recurrent
cancer was done.
RESULTS: 81 of 137 patientes were men. The average age was 68 /- 9
years.EMR was done in outpatient basis and the patients were discharged after
4 hours in the recovering area. Twenty-five of 137 lesions were esophageal squa-
mous cell carcinoma (18.2%), nineteen HGD and esophageal adenocarcinoma
(13.8%), forty-eight gastric adenocarcinoma (35%), thirteen duodenal adenocar-
cinoma (9.4%) and the remaining thirty-two (23%) benign lesions. Of the 137
patients treated by EMR during a mean follow-up of 49.8 months, only 6
patients with HGD and intramucosal cancer presented recurrent lesions
(5.7%). 95.1% curative resection was achieved in patients with m1, m2 and
reaching m3 disease. En-bloc resection was possible initially in 91.2%. Minor
bleeding was present in 17 patients (12.4%), controlled endoscopically with
clips. Prophylatic clips were used in 22 patients (16%). One large perforation
was treated by surgical repair.
CONCLUSION: EMR is well suited for superficial esophageal, gastric and duo-
denal cancer treatment with very little risk of complication and low recurrence
rate, as shown in our long-term retrospective study. However in cases when
lateral margins and depth of invasion of the specimen are not clear of neoplastic
changes (mainly in peace-meal resections), the patients should have careful
follow-up.
REFERENCES
1. Yamamoto H, Yube T, Isoda N, et al. A novel method of endoscopic mucosal
resection using using sodium hyaluronate. Gastrointestinal Endosc 1999; 50:
251-256.
2. Takekoshi T, Baba Y, Ota H, et al.Endoscopic mucosal resection of early
gastric carcinoma:results of a retrospective analysis of 308 cases. Endoscopy
1994; 26: 352-358.
3. Lambert R. Endoscopic treatment of esophageal and gastric tumors.
Endoscopy 1998; 30: 80-93.
4. Inoue H, Tani M, Nagai K, et al Treatment of esophageal and gastric tumors.
Endoscopy 199; 31: 47-55.
Disclosure of Interest: None declared
OP095 FEASIBILITY AND SAFETY OF ENDOSCOPY-ASSISTED
LAPAROSCOPIC FULL-THICKNESS RESECTION FOR
SUPERFICIAL DUODENAL NEOPLASMS
Y. Minato1,*, K. Ohata1, M. Murakami2, K. Yamazaki2, M. Takita1,
Y. Matsuyama1, T. Tashima1, K. Nonaka1, N. Matsuhashi1
1
Gastroenterology, NTT Medical Center Tokyo, 2Gastroenterological and General
Surgery, Showa University Hospital, Tokyo, Japan
Contact E-mail Address: yoheiminato55925@gmail.com
INTRODUCTION: Superficial duodenal neoplasms (SDNs) are a challenging
target in the digestive tract. Endoscopic resection is technically difficult and
surgical approach is difficult to decide the borderline of the lesion precisely.
We invent the new approach to remove SDNs that involves a combination of
endoscopic and laparascopic technics: endoscopy-assisted laparoscopic full-
thickness resection (EALFTR).
AIMS & METHODS: The aim of this study was to investigate the results of a
single center experience and assess the validity of EALFTR for SDNs. Between
January 2011 and March 2014, 64 patients with nonamupllary duodenal neo-
plasm without familial polyposis syndrome were included in this study. All cases
were assessed for their age, sex, location, en-bloc resection rate, R0 resection rate,
lesion size, sample size, procedure time, length of hospital stay after EALFTR,
complication, and histopathological report. EALFTR procedure: Under general
anesthesia, the duodenum was first mobilized laparoscopically under endoscopic
guidance. Then the tumor location was confirmed by endoscopy. The peripheral
margin was marked around the tumor endoscopically and each marking was
perforated intentionally using a needle knife in the coagulation mode under
A33
laparoscopic observation. Subsequently, the sero-muscular layer was laparosco-
pically dissected along the marking circumferentially using an ultrasonically acti-
vated device. After sero-muscular layer incision, submucosa-mucosal layer was
dissected along sero-muscular layer incision with ultrasonically activated device.
The closure of the defect in the duodenal wall was performed by the laparoscopic
hand-suturing technique.
RESULTS: 64 patients (50 males and 14 females, mean age 62.7) were treated by
EALFTR. In 2 patients, because 2 lesions were located quite closely, we resected
them at the same time. 37 lesions were located at the second portion, 24 at the
bulb and 5 at the third portion of the duodenum. En-bloc and R0 resection was
achieved for 97.0 % (64/66), too. The mean resected lesion size was 12.0 mm, and
the mean resected specimen size was 26.0 mm. The mean procedure time was 136
minutes. The mean length of hospital stay after EALFTR was 13.1 days.
Anastomotic leakage occurred in three patients and anastomotic stenosis
occurred in three patients postoperatively, but all cases recovered conservatively.
Histopathological examination confirmed that 31 were adenomas, 17 adenocar-
cinomas, 13 neuroendcrine tumors and 5 hyperplastic polyps.
CONCLUSION: EALFTR enables successful en bloc, R0 resection, and full-
thickness excision was achieved with an adequate surgical margin in all patients
without severe complications. We believe that in treatment of SDNs this method
can be a feasible, safe, and minimally invasive treatment option for superficial
nonampullary duodenum tumors.
Disclosure of Interest: None declared
OP096 HEMOSTATIC SECOND-LOOK ENDOSCOPY IS USEFUL FOR
PREVENTING DELAYED BLEEDING AFTER ENDOSCOPIC
SUBMUCOSAL DISSECTION (ESD) IN EARLY GASTRIC CANCERS
K. Nagao1,*, H. Noda1, N. Ogasawara1, Y. Hijikata1, S. Izawa1, Y. Kondo1,
Y. Ito1, A. Tanabe1, Y. Tamura1, M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University School of Medicine, Nagakute, Japan
Contact E-mail Address: nagao.kazuhiro.621@mail.aichi-med-u.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been now
standard therapy for early gastric cancers. Although safety of the ESD procedure
has been substantiated, complications such as perforation and bleeding are still
serious problems. Second-look endoscopy for the purpose of hemostasis is rou-
tinely performed to prevent post-ESD bleeding in most hospitals, though there is
little solid evidence to support this practice. A few reports suggested that second-
look endoscopy after gastric ESD contributed little to preventing delayed bleed-
ing. However, these results contradicted our experience. Hemostatic second-look
endoscopy is considered to reduce delayed bleeding when it would be appropri-
ately performed according to Forrest classification. The aim of the present study
was to verify whether a second-look endoscopy after ESD is effective for the
prevention of delayed bleeding and to investigate the clinicopathological features
of delayed bleeding after hemostatic second-look endoscopy to identify specific
lesions that may require third-look endoscopy.
AIMS & METHODS: Subjects were 186 consecutive patients (142 males and44
females; mean age, 71.0 years) who underwent ESD for gastric cancers between
January 2006 and December 2013. Properly preventative coagulation for all
exposed vessels on the artificial ulcer with hemostatic forceps was performed
routinely at the end of ESD procedure. The vessel types on artificial post-ESD
ulcers were evaluated by Forrest classification at the next day after ESD. Ia, Ib or
IIa of Forrest classification were essentially required with endoscopic hemostasis.
On the other hand IIb or III of Forrest classification were not performed with
endoscopic hemostasis.
RESULTS: Patients with hemodialysis significantly harbored Ia, Ib or IIa of
Forrest classification at second-look endoscopy. However, there were no signifi-
cant differences in patient-related factors (age, gender, and use of anticoagulants
and antiplatelet drugs) and tumor related factors (tumor location, histological
type, depth, size of the resected specimen, and operation time) between Ia, Ib or
IIa and IIb or III of Forrest classification. None of 136 patients with IIb or III of
Forrest classification at second-look endoscopy had delayed bleeding during
hospitalization. In 50 patients with Ia, Ib or IIa of Forrest classification at
second-look endoscopy, there was only one patient (2%) with delayed bleeding
which required hemostatic third-look endoscopy. The patient underwent hemo-
dialysis and took an antiplatelet drug. The rate of bleeding after appropriately
hemostatic second-look endoscopy was 0.5% (1 of 186 patients). The rate in our
study was extremely low compared with previous reports in which second-look
endoscopy was not performed.
CONCLUSION: Appropriately hemostatic second-look endoscopy for early gas-
tric cancers removed by ESD was useful for preventing delayed bleeding. Precise
hemostasis based on Forrest classification at second-look endoscopy may exceed-
ingly reduce delayed bleeding. Third-look endoscopy was not required when
appropriate hemostasis at second-look endoscopy was performed.
Disclosure of Interest: None declared
A34
OP097 ENDOSCOPIC TISSUE SHIELDING METHOD WITH
POLYGLYCOLIC ACID SHEETS AND FIBRIN GLUE DECREASES
THE RISK OF BLEEDING AFTER ENDOSCOPIC SUBMUCOSAL
DISSECTION OF GASTRIC NEOPLASMS
Y. Tsuji1,*, M. Fujishiro2, Y. Sakaguchi3, C. Minatsuki3, I. Asada-Hirayama3,
K. Niimi4, S. Mochizuki3, S. Ono3, S. Kosdashima3, N. Yamamichi3, K. Koike3
1
Department of Endoscopy and Endoscopic Surgery, Graduate School of Medicine,
The University of Tokyo, 2Department of Endoscopy and Endoscopic Surgery,
Graduate School of Medicine, 3Department of Gastroenterology, 4Center for
Epidemiology and Preventive Medicine, Graduate School of Medicine, The
University of Tokyo, Bunkyo-ku, Tokyo, Japan
Contact E-mail Address: ytsuji-tky@umin.ac.jp
INTRODUCTION: Prevention of bleeding after endoscopic submucosal dissec-
tion (ESD) for gastric neoplasms is still an important problem, but there have
been no preventive measures other than proton pump inhibitor use and preven-
tive coagulation of visible vessels on the artificial ulcer after ESD.
AIMS & METHODS: We aimed to evaluate the efficacy and safety of the tissue
shielding method with polyglycolic acid (PGA) sheets and fibrin glue for pre-
venting bleeding after gastric ESD. This is a non-randomized historical con-
trolled study. We defined high-risk patients for post-ESD bleeding as follows:
1) those who took antithrombotic drugs regularly; or 2) those who were expected
to undergo large mucosal resection ( 40mm). We enrolled patients who were
scheduled to undergo gastric ESD and had above-mentioned risk factors from
July 2013 as the study group (Group A). We placed PGA sheets on the mucosal
defect and fixed with fibrin glue in the study group. Between January and July
2013, before the first enrolment of a study patient, 126 gastric neoplasms in
101 consecutive patients were treated with ESD. From this cohort, we extracted
high-risk patients as the historical control group (Group B). We set the post-ESD
bleeding rate as the primary endpoint to compare both groups.
RESULTS: From July 2013 to February 2014, 45 ESD-induced ulcers in 41 high-
risk patients for bleeding were enrolled in the study group. In the historical
control group, 41 ESD-induced ulcers in 37 patients were extracted. The baseline
characteristics were not significantly different between the two groups: sex
(A: male 41/female 4, B: male 34/female 7; P 0.256); age (A: 73.6  7.5 yrs,
B: 74.8  7.0 yrs; P 0.482); antithrombotic drug use (A: 29 lesions, 66.4%, B:
23 lesions, 56.1%; P 0.429); Heparin bridging therapy (A: 7 lesions, 15.6%, B:
3 lesions, 7.3%; P 0.319); and the diameter of resected specimens (A: 40.1 
12.4 mm, B: 43.9  15.1 mm; P 0.206). Neither intraoperative perforation or
delayed perforation occurred in the two groups. Post-ESD bleeding occurred at a
rate of 6.7% in the study group (3 lesions), and 22.0% in the historical control
group (9 lesions). There was a significant difference in the post-ESD bleeding rate
between the two groups (P 0.041). In the study group, post-ESD bleeding
occurred only in heparin bridging therapy. In the study group, the procedural
time for applying PGA sheets and fibrin glue was 20.4  9.5 min.
CONCLUSION: The endoscopic tissue shielding method with PGA sheets and
fibrin glue appears to be promising for the prevention of post-ESD bleeding.
Disclosure of Interest: Y. Tsuji: none, M. Fujishiro Financial support for research
from: Astellas Pharmaceutical, Takeda Pharmaceutical, Zeria Pharmaceutical,
Otsuka Pharmaceutical, Astrazeneca Pharmaceutical, Dainihon-Sumitomo
Pharmaceutical, Taiho Pharmaceutical, Ajinomoto Pharmaceutical, and, Eisai
for his department outside the submitted work, Lecture fee(s) from: Olympus
Medical Systems, HOYA Pentax, Eisai, MSD, Daiichi-Sankyo Pharmaceutical,
Astrazeneca Pharmaceutical, Aska Pharmaceutical, Taisho-Toyama
Pharmaceutical, Otsuka Pharmaceutical, Zeria Pharmaceutical, Takeda
Pharmaceutical, Astellas Pharmaceutical, Seikagaku Corp., Johnson &
Johnson, Ajinomoto Pharmaceutical, Amco, Novartis Pharmaceutical, Boston
Scientific, and, Boehringer-Ingelheim, outside the submitted work, Other: non-
financial support from HOYA Pentax, Olympus Medical Systems, and, Fujifilm
for his department, Y. Sakaguchi: none, C. Minatsuki: none, I. Asada-Hirayama:
none, K. Niimi: none, S. Mochizuki: none, S. Ono: none, S. Kosdashima: none,
N. Yamamichi: none, K. Koike: none
OP098 LONG-TERM SURVEILLANCE AND TREATMENT OUTCOMES
OF METACHRONOUS GASTRIC CANCER AFTER CURATIVE
ENDOSCOPIC SUBMUCOSAL DISSECTION
S. Abe1,*, I. Oda1, H. Suzuki1, S. Nonaka1, S. Yoshinaga1, M. Sekiguchi1,
G. Mori1, H. Taniguchi2, S. Sekine2, H. Katai3, Y. Saito1
1
Endoscopy Division, 2Pathology Division, 3Gastric Surgery Division, National
Cancer Center Hospital, Tokyo, Japan
Contact E-mail Address: seabe@ncc.go.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) allows patients
with early gastric cancer (EGC) to preserve their stomach and contributes to
better quality of life compared with surgery. However, the incidence of meta-
chronous gastric cancer (MGC) after ESD is higher than that after gastrectomy.
The long-term treatment outcomes of MGC after curative ESD are poorly
understood.
AIMS & METHODS: This study aimed to evaluate long-term surveillance and
treatment outcomes of MGC after curative ESD. Among 1537 consecutive
patients with initial EGC who achieved curative resection by ESD between
1999 and 2006, 1526 patients who were followed up were included in this
study. 11 patients who underwent scheduled surgery for synchronous esophageal
or gastric cancer just after ESD were excluded. They were generally followed up
by annual or biannual upper gastrointestinal endoscopy to check for MGC. This
study assessed treatment outcomes of MGC, 5-year and 10-year disease specific
survival (DFS). Curability of ESD was assessed based on Japanese Gastric
Cancer Treatment Guideline 20101).
RESULTS: Of 1526 patients, 334 MGCs were found in 238 patients during a
median follow up period of 82.2 months (5 year follow-up: 90.6%). 5- and 7-year
United European Gastroenterology Journal 2(5S)
cumulative incidence of MGC on surveillance endoscopy were 10.0% and 16.4%,
respectively. 296 MGCs in 215 patients were treated with endoscopic resection
(Upper/Middle/Lower62/125/109, Differentiated (D)-type/Undifferentiated
(UD)-type/Special/13/2, median tumor size 10 mm (1-50), intramucosa: M/
minute submucosa (5500m): SM1/deeper submucosa (500m): SM2270/
15/11, ESD/strip biopsy294/2). En bloc resection, R0 resection and curative
resection were 99.3% (294), 94.3% (279) and 88.8% (263), respectively. 183
patients were determined to have curative resection and 32 patients had non-
curative resection. Of 183 patients with curative resection, one died of initial
EGC with local recurrence and distant metastasis (9.1 years after initial ESD)
but none died of MGC. 14 of 32 patients with non-curative resection underwent
additional surgery and 18 patients were followed up (the cause of non-curative
resection in 10 patients was only positive margin). Of 32 patients with non-
curative resection, one patient who underwent additional surgery and one who
was followed up died of MGC (2.7 and 4.6 years after initial ESD). 25 MGCs in
14 patients were treated surgically (Upper/Middle/Lower8/7/10, D-type/UD-
type17/8, median tumor size: 25.0 mm (1-108), M/SM1/SM2/advanced16/0/
4/5). Two of 14 patients died of MGC (6.2 and 7.2 years after initial ESD). 3
patients with 3 clinically unresectable MGCs received palliative chemotherapy
and died of MGC (over 5 years after initial ESD). The remaining 10 lesions in 6
patients were observed without any intervention due to high age or co-morbidity
but none died of MGC. 5-year and 10-year DFS in 238 patients with MGC was
99.2% and 92.5%, respectively. Both of 5-year and 10-year DFS in 1288 patients
without MGC were 100%.
CONCLUSION: Careful surveillance should be utilized for early detection of
MGC not only for 5 years but also beyond 5 years after curative gastric ESD.
REFERENCES
1) Japanese gastric cancer treatment guidelines 2010 (ver. 3). Gastric Cancer 2011;
14: 113123.
Disclosure of Interest: None declared
OP099 INTERIM RESULTS OF A MULTI-CENTER, PROSPECTIVE,
CONTROLLED TRIAL OF THE DUODENAL-JEJUNAL BYPASS
LINER FOR THE TREATMENT OF TYPE 2 DIABETES IN OBESE
PATIENTS: ARE THERE ANY FACTORS PREDICTING A SUB-
OPTIMAL EFFECT?
M. Benes1,*, T. Hucl1, P. Drastich1, J. Spicak1
1
Hepatology and Gastroenterology, IKEM, Prague, Czech Republic
INTRODUCTION: The global increase in obesity incidence results in an increase
of type 2 diabetes mellitus (T2DM) incidence. Surgical treatment has proven to
be effective, however it carries a high risk of complications. The duodenal-jejunal
bypass liner (Endobarrier, GI Dynamics, DJBL) is an endoscopic implant that
mimics the intestinal bypass portion of the Roux-en-Y gastric bypass. It results in
weight loss and improvements in glucose control in obese patients with T2DM.
AIMS & METHODS: This is an interim report of an ongoing three years study.
The aim of this prospective, controlled, multicentre study is to determine the
effectiveness of DJBL and to identify clinical factors associated with a subopti-
mal outcome of DJBL.
RESULTS: Forty four subjects (24 with an implant, 20 controls) were included in
the study. The groups were comparable with respect to age, gender, BMI (mean
37.7 vs. 38.1 kg/m2), T2DM duration (7.2 vs. 8.3 years), HbA1c level (8.8 % vs
8.1 %) and T2DM treatment. In the stent group, all devices were successfully
implanted. Only three devices had to be explanted prior to the end of the 6
months study period (bleeding, dislocation and need for ERCP because of cho-
ledocholithiasis). The mean procedure time was 21.2 minutes for an implantation
and 35.5 minutes for an explantation. At six months there was significantly
greater weight loss (27% vs. 9%) and significantly improved HbA1c % (2.3 vs.
1.1) in the device group. T2DM medicinal treatment could be reduced in more
device subjects than controls. There was no serious adverse event. Mild abdom-
inal pain and nausea after implantation were experienced by 75% of patients
during first 14 days after implantation, 40% of patients during the first month
and 11% of patients after one month. Lower initial BMI, distal position of the
anchor and lower body height were identified as negative prognostic factors for
pain.
CONCLUSION: The DJBL is safe when implanted for 6 months, and results in
significant weight loss and HbA1c reduction. This suggests that this novel device
is a candidate for the primary therapy of morbid obesity and type 2 diabetes.
Lower initial BMI, distal position of the anchor and lower body height could be
negative prognostic factor for pain.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 15:4517:15
CHANGING LANDSCAPE OF H. PYLORI INFECTION HALL O_____________________
OP100 INTERGENERATIONAL CHANGE IN HELICOBACTER PYLORI
COLONIZATION IN CHILDREN LIVING IN A MULTI-ETHNIC
WESTERN POPULATION
W.J. Den Hollander1,2,*, I. L. Holster1, A. J. van Vuuren1, V. W. Jaddoe2, G.,
I. Perez-Perez3, E.J. Kuipers1, H.A. Moll4, M. Blaser3
1
Gastroenterology and Hepatology, 2The Generation R Study Group, Erasmus
MC, Rotterdam, Netherlands, 3Medicine and Microbiology, New York University
Langone Medical Centre, New York, United States, 4Paediatrics, Erasmus MC,
Rotterdam, Netherlands
Contact E-mail Address: w.denhollander@erasmusmc.nl
INTRODUCTION: Helicobacter pylori (H. pylori) colonization rates in child-
hood have declined in Western populations, but it is unknown whether this trend
is similar in children of non-Western ethnic backgrounds, who are born in a
Western country. Insight into colonization and transmission of H. pylori could
improve approaches to assessing H. pylori-related diseases.
AIMS & METHODS: We aimed to identify H. pylori status in mothers and their
children, and to determine both mother-to-child transmission and factors asso-
ciated with loss of H. pylori in one generation. Antibodies against H. pylori and
cytotoxin-associated gene A (CagA) were measured in mothers and children
participating in a population-based prospective cohort study in Rotterdam, the
Netherlands. Information on demographics, maternal and childs characteristics
was collected using questionnaires. Logistic regression analysis was used to assess
factors associated with loss of H. pylori, including the following: gender, ethni-
city, mothers educational level, delivery mode, breastfeeding, number of older
siblings, day-care attendance, and cumulative antibiotic exposures.
RESULTS: H. pylori and CagA status were determined in 3,185 mothers and
their children. In mothers (mean age of 30.5 5.0 years), the overall H. pylori
colonization rate was 42%, compared to 10% (p50.001) in their children
(mean age of 6.2 0.5 years). An H. pylori-positive mother was associated
with an H. pylori-positive child (OR 3.22; 95% CI 2.52-4.12). Overall, the H.
pylori prevalence decreased 76% comparing mothers and their children. A sig-
nificant and consistent decline in both H. pyloriCagA- and H. pyloriCagA-
strains was observed across all nine ethnic groups studied. Multivariate analysis
of the loss of H. pylori in children with an H. pylori-positive mother (n 1,328)
revealed male gender (OR 1.64; 95% CI 1.21-2.23), higher maternal education
level (OR 1.78; 95% CI 1.15-2.76), and no older siblings (OR 1.37; 95% CI 1.01-
1.88) independently associated with an H. pylori-negative child.
CONCLUSION: We identified a large decline in H. pylori colonization rate in
children living in a European city. The observed drop was uniform across all
ethnic groups, implying the importance of environmental factors in H. pylori
transmission in modern cities, independent of ethnicity.
Disclosure of Interest: None declared
OP101 HELICOBACTER PYLORI COLONIZATION, RESPIRATORY
OUTCOMES AND ECZEMA IN SCHOOL-AGE CHILDREN
W.J. den Hollander1,2,*, A. M. M. Sonnenschein-van der Voort2, I. L. Holster1, J.
C. de Jongste3, V. W. Jaddoe2, G., I. Perez-Perez4, H.A. Moll3, M. Blaser4,
L. Duijts3, E.J. Kuipers1
1
Gastroenterology and Hepatology, 2The Generation R Study Group, 3Paediatrics,
Erasmus MC, Rotterdam, Netherlands, 4Medicine and Microbiology, New York
University Langone Medical Centre, New York, United States
Contact E-mail Address: w.denhollander@erasmusmc.nl
INTRODUCTION: The declined Helicobacter pylori (H. pylori) prevalence in
Western countries is suggested to be associated with the simultaneous increases in
childhood asthma and allergic diseases. Bacterial exposure during childhood may
be protective for asthma and atopy.
AIMS & METHODS: We aimed to examine the association between childrens
H. pylori colonization and asthma or related diseases. This study was embedded
in The Generation R Study, a population-based prospective multi-ethnic cohort
study among children, followed from early pregnancy onwards. We measured
anti-H. pylori and anti-CagA-IgG antibodies in serum of children obtained at age
of 6 years. Also at age 6 years, asthma-related outcomes including ever wheezing,
physician-diagnosed asthma, and eczema were obtained by questionnaires. Data
analyses were performed in the total cohort as well as in different ethnic groups
(Western vs. non-Western). Multivariate logistic regression analyses were
adjusted for maternal educational level, history of asthma and atopy, smoking
during pregnancy, and parity, and for childs gender, ethnicity, gestational age at
birth, birth weight, breastfeeding habits, day-care attendance, pet keeping, and
lower respiratory tract infections.
RESULTS: In total 3,838 children (mean age 6.1  SD 0.5) were available for
these analyses. Of those, 328 (9%) were H. pylori-positive, of whom 100 (30%)
were CagA-positive. Univariate analyses revealed the following results of com-
parison between H. pylori-positive versus negative children: ever wheezing
[63.3% vs. 56.0% (p0.07)], physician-diagnosed asthma [11.2% vs. 6.6%
(p0.01)], and eczema [27.0% vs. 22.2% (p0.07)]. In multivariate analyses H.
pylori-positivity was associated with physician-diagnosed asthma (odds ratio
(OR) 1.63; 95% CI 1.02-2.61), but not with ever wheezing (OR 1.02; 95% CI
0.85-1.23) or eczema (OR 1.06; 95% CI 0.79-1.41). A significant interaction
between H. pylori and ethnicity was found for wheezing (p50.001) and eczema
(p0.006). Analyses stratified according to ethnicity showed that H. pylori-posi-
tivity was inversely associated with ever wheezing (OR 0.66; 95% CI 0.48-0.91),
and eczema (OR 0.64; 95% CI 0.41-1.00) in children of non-Western ethnicity
(n 1,155), but not in children of Western ethnicity (n 2,683). This negative
association was mainly explained by the CagA-positive strains.
A35
CONCLUSION: H. pylori colonization is negatively associated with both wheez-
ing and eczema in children of non-Western ethnicity, with the strongest inverse
effect found for CagA-positive strains. In contrast, in all children H. pylori-
colonization was positively associated with physician-diagnosed asthma to the
age of 6 years. Trends in the Western and non-Western children appear opposite.
Disclosure of Interest: None declared
OP103 META-ANALYSIS OF SEQUENTIAL VS. STANDARD TRIPLE
THERAPY FOR HELICOBACTER PYLORI ERADICATION: FINAL
RESULTS OF A COCHRANE SYSTEMATIC REVIEW
O.P. Nyssen1,*, A.G. McNicholl2, F. Megraud3, V. Savarino4, G. Oderda5,
C. Fallone6, L. Fischbach7, F. Bazzoli8, J.P. Gisbert2
1
Centre For Primary Care and Public Health, Barts and The London School of
Medicine and Dentistry, London, United Kingdom, 2H. La Princesa and IP,
CIBERehd, Madrid, Spain, 3Bacteriologie-Enfants, Hopital Pellegrin, Bordeaux,
France, 4Dipartimento di Medicina Interna e Specialita Mediche, Universita di
Genova, Genova, 5Paediatric Endoscopy Units, Universita del Piemonte Orientale,
Novara, Italy, 6carlo.fallone@muhc.mcgill.ca, McGill University Health Centre,
Montreal, Canada, 7Epidemiology, University of North Texas Health Science
Center, Fort Worth, Texas, United States, 8Medicina Interna e Gastroenterologia,
Universit degli Studi di Bologna, Bologna, Italy
Contact E-mail Address: olgapnyssen@yahoo.es
INTRODUCTION: Sequential therapy (SEQ) has been suggested as a new first-
line treatment option to replace the standard triple therapy (STT), where eradi-
cation rates have declined to unacceptable levels.
AIMS & METHODS: To conduct a meta-analysis of studies comparing SEQ vs.
STT for H. pylori eradication.
Selection of studies: randomized controlled trials comparing SEQ (10 days) and
STT (at least 7 days) for the eradication of H. pylori. Search strategy: bibliogra-
phical searches in electronic databases, and manual search of abstracts from
Congresses, were conducted up to November 2013. Data synthesis: intention-
to-treat eradication rate.
RESULTS: We included 33 randomized controlled studies with a total of 9,750
patients (4,542 in SEQ and 5,208 in STT). The overall analysis showed that SEQ
was significantly more effective than STT (84% vs. 74% in the intention-to-treat
analysis; OR2.07; 95%C.I.1.64-2.61; p50.001). Results were highly hetero-
geneous (I277%) and 11 studies were unable to demonstrate differences
between therapies. Subgroup analyses suggested that patients with clarithromy-
cin resistance and/or taking esomeprazole-rabeprazole could benefit more from
the SEQ. However there were no differences when STT lasted 14 days. Although,
overall, mean eradication rate with SEQ was over 80%, a tendency towards
lower efficacy with this regimen was observed in the more recent studies
[weighted linear regression per year -0.02 (-2% per year) in SEQ vs. -0.005 (-
0.5% per year) in STT], and in studies performed outside Italy (OR 1.57 vs. 4.09).
CONCLUSION: The meta-analysis demonstrated that SEQ is more effective
than STT lasting less than 14 days. Nevertheless, the apparent advantage of
sequential treatment seems to be decreasing over time; therefore further and
continuous assessment is needed before a generalized change in all settings is
recommended for first line H. pylori treatment.
Disclosure of Interest: None declared
OP104 THE EFFICACY OF PROBIOTICS AS ADJUVANT TREATMENT
IN ERADICATING HELICOBACTER PYLORI BY STANDARD
TRIPLE THERAPY: A RANDOMIZED CONTROLLED TRIAL
G. Hauser1,*, N. Salkic2, K. Vukelic3, V. K. Vrbanovic3, D. Stimac1
1
Department of Internal Med., Division of Gastroent, CLINICAL HOSPITAL
CENTRE, RIJEKA, CROATIA, Rijeka, Croatia, 2Gastroenterology, University
Clinical Centre, Tuzla, Tuzla, Bosnia and Herzegovina, 3JGL d.d., Rijeka, Croatia
Contact E-mail Address: goran.hauser@medri.uniri.hr
INTRODUCTION: The current report of the European Helicobacter Study
Group considers probiotics as an adjuvant treatment in reducing side effects
during the standard Helicobacter pylori eradication therapy. The primary objec-
tive in the study is determination of efficacy of probiotic preparation as a sup-
portive therapy in eradication of H. pylori.
AIMS & METHODS: The study was multicenter, prospective, randomized, pla-
cebo controlled, and double-blind. The enrolment of subjects into the trial was
conducted in 121 general practitioners offices, in different regions in Croatia
from September 2009 until June 2012. The study was reported according to the
CONSORT guidelines and was registered at www.clinicaltrials.gov
(NCT01969331).The initial diagnosis of H. pylori infection was established
using rapid urease test, stool antigen, or urea breath test. The subjects first
filled out a specially designed questionnaire in order to assess the severity of
the 10 symptoms which can be related to eradication therapy to be monitored
during the trial. Each subject then received 28 capsules of probiotic preparation
or matching placebo capsules, which they were supposed to take over the follow-
ing 14 days, twice a day, at least two hours prior to or after the antibiotic therapy
administration.
RESULTS: A total of 804 patients were enrolled in the trial, of which
650(80.85%) were included in the analysis. The results show a significantly
larger share of cured subjects in the probiotic arm versus the placebo arm
(87.38% vs. 72.55%; p50.001). Additionally, odds ratio, absolute and relative
risk reductions as well as number needed to treat all point strongly in favour of
probiotic arm. Overall, at baseline the average value of intensity for all 10 symp-
toms was 1.17 for subjects on probiotic and 1.07 for subjects on placebo
(p50.001). At follow-up visit 15 days after the start of the trial, the intensity
of the same symptoms that were monitored at enrolment was again evaluated.
A36 United European Gastroenterology Journal 2(5S)

OP106

Procore FNA
ProCore FNA Pooled Estimate: Pooled Estimate: Pooled RR
Outcome Measure (n) (n) mean % (95% CI) mean % (95% CI) (95%CI) p-value

Diagnostic Adequacy: 742 745 82.7 (74.2-89.8) 79.3 (70.4-87.0) 1.06 (0.97-1.16) 0.221
All Masses
Diagnostic Adequacy: 317 324 84.8 (70.4-95.0) 88.5 (80.1-94.9) 0.98 (0.85-1.12) 0.721
Pancreatic Masses
Diagnostic Accuracy: 421 474 84.9 (76.1-92.0) 79.3 (71.8-85.9) 1.06 (0.99-1.14) 0.083
All Masses
Diagnostic Accuracy: 225 277 88.4 (82.4-93.3) 79.9 (73.6-85.5) 1.12 (0.99-1.26) 0.067
Pancreatic Masses
Histology: 104 108 66.8 (49.7-81.9) 68.7 (54.5-81.3) 1.02 (0.85-1.22) 0.864
All Masses
Histology: 66 70 75.4 (60.2-87.8) 75.2 (63.2-85.5) 1.03 (0.84-1.26) 0.756
Pancreatic Masses
Mean no. of passes 209 209 - - SMD -0.90 (-1.80 - 0.051
for diagnosis: 0.005)
All Masses

Overall, the average intensity value for all 10 symptoms was 0.55 for subjects on CONCLUSION: H. pylori management by gastroenterologists in Europe is
probiotic and 0.76 for subjects on placebo (p50.001). extremely diverse. It is important to notice that the achieved eradication rates
CONCLUSION: Adding probiotics to the standard triple therapy for H. pylori are clearly suboptimal, especially with the use of the commonly recommended
eradication significantly contributes to treatment efficacy and distinctly decreases standard triple therapy (76%). Continuation of this registry and deeper evalua-
the adverse effects of therapy and the symptoms of the underlying disease. tion of its data may offer valuable information to improve H. pylori
Disclosure of Interest: G. Hauser Financial support for research from: Company management.
sponsored trial, Consultancy for: principal investigator served as consultant, N. Disclosure of Interest: None declared
Salkic: None declared, K. Vukelic Other: emploee of the company, V. Vrbanovic
Other: emploee of the company, D. Stimac: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
MINIMALLY INVASIVE INTERVENTIONS IN THE PANCREAS LOUNGE
OP105 PAN-EUROPEAN REGISTRY ON H. PYLORI MANAGEMENT: 5_____________________
INTERIM ANALYSIS OF 5,000 PATIENTS
A.G. Mcnicholl1,*, A. Gasbarrini2, B. Tepes3, F. Lerang4, D.S. Bordin5, OP106 ENDOSCOPIC ULTRASOUND-GUIDED TISSUE ACQUISITION:
O. Shvets6, T. Rokkas7, L. Kupcinskas8, M. Leja9, M. Katicic10, J.C. Machado11, META-ANALYSIS COMPARING THE PROCORE AND STANDARD
L. Boyanova12, K. Przytulski13, I. Simsek14, G.M. Buzas15, T. Axon16, FINE NEEDLE ASPIRATION NEEDLES
C. Beglinger17, P. Bytzer18, V. Lamy19, A. Goldis20, L.G. Cappelle21, L. Veijola22, J.Y. Bang1,*, M. Hasan1, R. Hawes1, S. Varadarajulu1
M. Caldas1, M. Ramas1, F. Megraud23, C.A. OMorain24, J.P. Gisbert1 on behalf 1
Center for Interventional Endoscopy, Florida Hospital, Orlando, United States
of On Behalf of the Hp-EuReg investigators and, the European Helicobacter Contact E-mail Address: jybang213@gmail.com
Study Group
1
H. La Princesa and IP, CIBERehd, Madrid, Spain, 2U.Sacro Cuore, Italy, Rome, INTRODUCTION: To overcome the limitations associated with cytology, a
Italy, 3AM DC Rogaska, Ljubliana, Slovenia, 4Central Hospital, stfold, Norway, ProCore biopsy platform has been developed in 19, 22 and 25G sizes.
5
Clinical Sci. Centre, Moscow, Russian Federation, 6Medical University, Kyiv, However, individual studies comparing the ProCore and FNA needles have
Ukraine, 7H. Henry Dunant, Athens, Greece, 8U. of Health Sciences, Kaunas, yielded varying conclusions.
Lithuania, 9University of Latvia, Riga, Latvia, 10Clinical Hospital, Zagreb, AIMS & METHODS: This meta-analysis was conducted to compare the perfor-
Croatia, 11IPATIMUP, Porto, Portugal, 12Medical University of Sofia, Sofia, mance of the ProCore and standard FNA needles when performing EUS-guided
Bulgaria, 13Medical C. Postgraduate Education, Warsaw, Poland, 14Dokuz Eylul tissue acquisition. All published manuscripts and presented abstracts
University, Izmir, Turkey, 15Ferencvaros Health Centre, Budapest, Hungary, (International Scientific Meetings) that compared the ProCore and FNA needles
16
University, Leeds, United Kingdom, 17U. Hospital, Basel, Switzerland, 18U. were analyzed. Excluded were non-comparative and technical feasibility studies.
Hospital, Koge, Denmark, 19CHU, Charleroi, Belgium, 20CECH, Timisoara, Main outcome measures: Compare the rates of diagnostic adequacy, diagnostic
Romania, 21Erasmus MC, Rotterdam, Netherlands, 22Hospital, Herttoniemi, accuracy, histological core tissue procurement and mean number of passes to
Finland, 23Bacteriologie-Enfants, Hopital Pellegrin, Bordeaux, France, 24Trinity diagnosis when sampling all solid organ lesions and solid pancreatic masses.
College Dublin, Dublin, Ireland RESULTS: A total of 21 studies involving 1617 patients met inclusion criteria.
Contact E-mail Address: adrian.mcn@gmail.com There was significant heterogeneity in study design and end points. Study out-
comes are shown in the Table. There was no significant difference in diagnostic
INTRODUCTION: Due to the diversity of H. pylori strains, resistances and adequacy/accuracy, histological core tissue procurement or mean number of
geographical particularities, the most efficient management strategy is still to passes to diagnosis between both cohorts. Subgroup analysis did not reveal
be found. any difference between the 19, 22/25G needles for any of the outcome measures.
AIMS & METHODS: To systematically register the clinical practice of CONCLUSION: Current data does not demonstrate a significant difference in
European gastroenterologists regarding H. pylori infection and treatment (31 performance between the ProCore and standard FNA needles for establishing a
countries and 250 recruiting investigators) diagnosis with fewer no. of passes, for yielding a better cytological aspirate or
A Local Coordinator was selected from each Country with more than 10 H. histological core tissue. Therefore, the choice of a needle should be based on
pylori REFERENCES on PubMed. Each Coordinator selected a representative endosonographer preference and needle costs.
group of recruiting investigators from its country (250 so far). An electronic Disclosure of Interest: None declared
clinical research file was created to systematically register all adult patients
infected with H. pylori. Variables included: Patients demographics, previous
eradication attempts, prescribed eradication treatment, adverse events, and out-
comes (cure rates, compliance, follow up, etc.).
RESULTS: Up to now, 5,000 patients have been included, and 3,333 have fin-
ished follow up. 58% females. 87% Caucasian. Mean age was 57 years. 4.3% had
drug allergies (77% to penicillin). 53% of indications were dyspepsia. 23% had
gastroduodenal ulcer. 70% were diagnosed using endoscopy based methods.
78% were na ve, 16% second-line, 4.8% third-line, 1.2% fourth-line, and 0.5%
fifth-line. Culture was performed in 15%, of which 57% showed antibacterial
resistance (40% to nitroimidazoles, 32% clarithromycin, 17% quinolones, 0.8%
amoxicillin and 0.9% tetracycline). 63% of prescriptions were triple regimens
(PPI 2 antibiotics), 12% non-bismuth concomitant quadruple, 14% sequential,
and 6.9% bismuth quadruple. 53% of patients had adverse events (13% metallic
taste, 12% diarrhea, and 11% nausea) although they were mostly mild (65%) and
lasted an average of 6.8 days, causing treatment discontinuation in 4.2% of cases.
Overall eradication rate was 80%, and only 64% of eradication failures were
retreated. The most common prescribed treatments for first (triple therapy with
clarithromycin and amoxicillin) and second line (triple therapy with amoxicillin
and levofloxacin) achieved suboptimal eradication rates: 76% and 78%
respectively.
United European Gastroenterology Journal 2(5S)
OP107 SMART ATLAS FOR SUPPORTING THE INTERPRETATION OF
NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY (NCLE)
OF PANCREATIC CYSTS: FIRST CLASSIFICATION RESULTS OF A
COMPUTER-AIDED DIAGNOSIS SOFTWARE BASED ON IMAGE
RECOGNITION
M. Kohandani Tafreshi1,*, B. Napoleon2, A.-I. Lemaistre3, M. Giovannini4,
V. Joshi5, N. Ayache1, B. Andre6
1
INRIA, Sophia Antipolis, 2Hopital prive Jean Mermoz, 3Centre Regional Leon
Berard, Lyon, 4Institut Paoli Calmette, Marseille, France, 5Ochsner Clinic
Foundation, New Orleans, United States, 6Mauna Kea Technologies, Paris, France
Contact E-mail Address: marzieh.kohandani-tafreshi@inria.fr
INTRODUCTION: nCLE enables microscopic imaging of pancreatic cysts,
in vivo and in real time, during an EUS-FNA procedure. Differentiating
branch duct-type Intraductal Papillary Mucinous Neoplasm (IPMN) and
Serous Cystadenoma (SCA) of the pancreas can be difficult, especially in case
of a solitary lesion without clear communication with the pancreatic duct. Recent
studies (Konda et al., Endoscopy 2013; Napoleon et al., DDW 2013) have iden-
tified reliable nCLE descriptive features (superficial vascular network in SCA;
finger- like projections in IPMN), allowing endoscopists to discriminate between
SCA and IPMN. In parallel, a computer-aided diagnosis software called Smart
Atlas has been developed to assist endoscopists with the interpretation of nCLE
video sequences. This study aims at evaluating the performance of this software
for the differentiation of SCA and IPMN cases.
AIMS & METHODS: Several nCLE sequences, of proven SCA or IPMN, were
retrospectively collected from nCLE procedures performed in multiple clinical
centers. These video sequences, along with their annotated final diagnosis, were
used to train a classification software that uses a content-based image retrieval
algorithm to predict the diagnosis of a query video based on the diagnoses of the
most visually similar atlas videos. All evaluations were performed using leave-
one-patient-out cross-validation to avoid bias. To reduce the number of unne-
cessary surgeries with high morbidity rates, false positives were minimized on a
receiver operating curve.
RESULTS: 29 nCLE video sequences were collected from 18 patients, with one
lesion per patient (12 SCA, 6 IMPN), leading to 22 sequences annotated with
SCA and 7 sequences annotated with IPMN. The classification results maximiz-
ing the specificity for an acceptable sensitivity show a specificity of 95.5% for a
sensitivity of 85.7%, an accuracy of 93.1%, a PPV of 85.7% and a NPV of
95.5%, with only one false positive and one false negative. In comparison,
Napoleon et al. reported that the performance achieved by a consensus of inves-
tigators on retrospective data to differentiate SCA from all other types of lesions
reaches a specificity of 100% for a sensitivity of 62.5%.
CONCLUSION: These first results demonstrate that the Smart Atlas software is
able to differentiate SCA and IPMN cases using only the image content of nCLE
sequences, with very high specificity and rather high sensitivity. Besides, the case-
based reasoning software can detect relevant video content and provide diagnos-
tic confidence levels. It could thus be used as an educational tool to train non-
expert endoscopists, but also as a second-reader tool to assist any user in real-
time diagnosis of pancreatic cysts using nCLE. Future software improvements
will leverage a larger sample size, various types of cysts and clinical metadata.
Disclosure of Interest: None declared
OP108 A PROSPECTIVE RANDOMIZED CROSS-OVER STUDY OF THE
DIFFERENCE IN DIAGNOSTIC YIELD BETWEEN EUSFNA
NEEDLES WITH AND WITHOUT A SIDE PORT IN PANCREATIC
MASSES
T.L. Ang1,*, A. Kwek1, D.W. Seo2, W.H. Paik2, H.-P. Wang3, T.-Y. Cheng3
1
Gastroenterology and Hepatology, Changi General Hospital, Singapore,
Singapore, 2Gastroenterology, Asan Medical Centre, Seoul, Korea, Republic Of,
3
Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan,
Province of China
Contact E-mail Address: tiing_leong_ang@cgh.com.sg
INTRODUCTION: Currently two needles with similar designs, apart from
absence and presence of side port, are available from Olympus Corporation
(Tokyo, Japan) for EUS-guided fine needle aspiration (FNA). These are EZ-
Shot 2 and EZ-Shot 2 with side port. The theoretical basis for introduction of
the side port was to facilitate the process of FNA and increase diagnostic yield
but this advantage remained unproven.
AIMS & METHODS: This pilot study aimed to determine the difference in
diagnostic yield between EZ-Shot 2 and EZ-Shot 2 with side port in patients
with pancreatic masses. This was a pilot multicenter prospective randomized
cross-over study involving 3 referral centers in Korea, Singapore and Taiwan.
Patients referred for EUSFNA of pancreatic masses were recruited. Four
EUSFNA passes were performed per patient. Patients were randomized to one
needle for the first 2 passes, followed by the other needle for the next 2 passes.
Rapid on-site cytopathological assessment was not performed. A pathologist
blinded to the needle that was used assessed each individual needle pass for
cellularity and morphology. The diagnostic yield between both needles was com-
pared. The reference standard was based on composite of cytology, histology and
clinical course.
RESULTS: A total of 30 patients were recruited (mean age 66 year; 53% female)
with total of 120 needle passes. The sites of lesions were 15/30 at pancreatic head,
7/30 at pancreatic neck/body and 8/30 at pancreatic tail. The final diagnoses were
pancreatic adenocarcinoma (24/30), neuroendocrine tumor (2/30), cholangiocar-
cinoma (1/30), pancreatitis related pseudotumour (2/30) and serous cystadenoma
(1/30). Mean size of mass was 3.5 cm (range: 1.2 6.3). Comparison of the 2
needles for cellularity adequacy: first pass: EZ Shot 2 vs. EZ Shot 2 with side
port: 26/30 (86.7%) vs. 25/3 (83.3%) (p 0.718): 2nd pass: EZ Shot 2 vs. EZ Shot
2 with side port: 25/30 (3.3%) vs. 26/30 (86.7%) (p 0.718). Comparison of the 2
A37
needles for diagnostic accuracy: first pass: EZ Shot 2 vs. EZ Shot 2 with side port:
22/30 (73.3%) vs. 23/30 (76.7%) (p 0.766); combined 2 passes: EZ Shot 2 vs.
EZ Shot 2 with side port: 26/30 (86.7%) vs. 26/30 (86.7%) (p 1.0). When the 4
passes for each lesion were assessed together adequate cellularity was obtained in
all cases and the correct diagnosis was obtained in 24/24 cases of pancreatic
adenocarcinoma, 2/2 neuroendocrine tumor, 2/2 pseudotumor, 1/1 serous cysta-
denoma and 0/1 case of cholangiocarcinoma. There were no EUSFNA related
complications.
CONCLUSION: For EUSFNA of pancreatic masses, there were no statistically
significant differences in adequacy of cellularity or diagnostic accuracy between
FNA needles with or without side port. After 4 passes, adequate cellularity was
obtained in all cases and the correct diagnosis was achieved in 96% of cases.
Disclosure of Interest: None declared
OP109 CRITICAL ASSESSMENT OF THE CHOICE OF
ENDOPROSTHESIS FOR TRANSMURAL DRAINAGE OF
PANCREATIC FLUID COLLECTIONS
J.Y. Bang1,*, R. Hawes1, S. Varadarajulu1
1
Florida Hospital, Orlando, United States
Contact E-mail Address: jybang213@gmail.com
INTRODUCTION: With increased application of endoscopic techniques for the
management of pancreatic fluid collections (PFCs), metal stents are being used
more frequently for transmural drainage despite the lack of data.
AIMS & METHODS: A systematic review and meta-analysis were conducted to
compare the performance of metal and plastic stents when undertaking endo-
scopic transmural drainage of PFCs.
MEDLINE and EMBASE were searched to identify all published manuscripts
that evaluated metal stents for endoscopic transmural drainage of PFCs.
Additionally, all published studies from the same period involving plastic stent
placement for the same indication that included 450 patients were also identi-
fied. A random effects model was used. Main Outcome Measures: Compare the
rates of treatment success, complications and recurrence between patients under-
going metal versus plastic stent placement for endoscopic transmural drainage of
PFCs.
RESULTS: A total of 12 studies consisting of 725 patients met inclusion criteria.
The overall treatment success was marginally higher for patients treated with
plastic than metal stents (Table) as the proportion of success for plastic stents
(89.7%) was more than the 95% confidence interval (CI) for metal stents (72.6-
88.7%). Also, subgroup analysis revealed that the treatment success rates were
higher when pseudocysts were drained using plastic (96.3% [95% CI 91.8-
98.4%]) than metal stents (82.0% [95% CI 71.8-89.1%]) as there was no overlap
of 95% CI between the cohorts. There was however, no difference in the rates of
treatment success for walled-off pancreatic necrosis (WOPN). Additionally, there
was no difference in the rates of complications or recurrence between plastic and
metal stents as evident by the considerable overlap of 95% CIs.
Metal stents (n94) Plastic stents (n631)
Treatment success: % (95% CI)
All PFC types 82.1 (72.6 - 88.7) 89.7 (78.9 - 95.3)
Pseudocysts only 82.0 (71.8 - 89.1) 96.3 (91.8 - 98.4)
WOPN only 75.1 (39.2 - 93.4) 74.9 (56.9 - 87.1)
Complications: % (95% CI)
All PFC types 17.9 (10.7 - 28.3) 15.7 (9.4 - 25.1)
Pseudocysts only 17.1 (9.6 - 28.5) 9.8 (2.9 - 27.9)
WOPN only 20.6 (6.0 - 51.3) 17.0 (12.0 - 23.6)
Recurrence: % (95% CI)
All PFC types 9.3 (4.1 - 15.9) 9.1 (5.1 15.6)
Pseudocysts only 9.2 (3.9 - 20.5) 9.7 (3.7 - 23.0)
WOPN only 10.0 (0.6 - 67.4) 8.3 (3.3 - 19.5)
CONCLUSION: Current evidence does NOT support the routine placement of
metal stents for transmural drainage of PFCs, particularly pseudocysts. Large,
multicenter, randomized trials are needed to justify the use of metal stents for
PFC drainage.
Disclosure of Interest: None declared
OP110 LAPAROSCOPIC VERSUS OPEN DISTAL PANCREATECTOMY
FOR BENIGN AND MALIGNANT DISEASE: A MULTICENTER
RETROSPECTIVE MATCHED-COHORT STUDY
T. de Rooij1,*, A. Jilesen1, G. Kazemier2, D. Boerma3, B. Bonsing4, K. Bosscha5,
R. van Dam6, C. van Eijck7, M. Gerhards8, H. van Goor9, E. van der Harst10,
I. de Hingh11, J. Klaase12, Q. Molenaar13, E. Nieveen van Dijkum1, G. Patijn14,
H. van Santvoort13, J. Scheepers15, G. van der Schelling16, J. Vogel1, E. Sieders17,
O. Busch1, M. Besselink1
1
Surgery, Academic Medical Center, 2Surgery, VU Medical Center, Amsterdam,
3
Surgery, Antonius Hospital, Nieuwegein, 4Surgery, Leiden University Medical
Center, Leiden, 5Surgery, Jeroen Bosch Hospital, Den Bosch, 6Surgery, Maastricht
University Medical Center, Maastricht, 7Surgery, Erasmus University Medical
Center, Rotterdam, 8Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, 9Surgery,
St Radboud University Medical Center, Nijmegen, 10Surgery, Maasstad Hospital,
Rotterdam, 11Surgery, Catharina Hospital, Eindhoven, 12Surgery, Medisch
Spectrum Twente, Enschede, 13Surgery, University Medical Center Utrecht,
Utrecht, 14Surgery, Isala Clinics, Zwolle, 15Surgery, Reinier de Graaf Groep, Delft,
A38
16
Surgery, Amphia Hospital, Breda, 17Surgery, University Medical Center
Groningen, Groningen, Netherlands
Contact E-mail Address: t.derooij@amc.nl
INTRODUCTION: Recent cohort studies from expert centers suggest that
laparoscopic distal pancreatectomy (LDP) is superior to open distal pancreatect-
omy (ODP). Introduction of LDP, however, has been slow, possibly because of
unclear external validity of these data. Data on the use, outcomes and attitude
regarding LDP on a national level are lacking.
AIMS & METHODS: This study aimed to determine the extent of LDP in the
Netherlands and to assess the attitude of Dutch pancreatic surgeons regarding
this procedure. Adults who underwent LDP or ODP in one of the 17 Dutch
medium-high volume centers between January 2005 and September 2013 were
analyzed retrospectively. Patients were excluded if DP was not the primary pro-
cedure or if too little data were available. Every LDP patient was matched to an
ODP patient based on sex, age, ASA score, indication for surgery and tumor size.
Primary endpoint were clinically relevant complications (Clavien-Dindo score
42). Analyses were by intention-to-treat. A questionnaire regarding attitudes
towards LDP was sent to all 30 Dutch pancreatic surgeons.
RESULTS: Of 633 included patients, 64 (10%) underwent LDP and 569 (90%)
ODP. 128 patients were excluded, 124 because DP was not the primary procedure
and 4 because too little data were available. 63 LDP patients were matched
adequately to 63 ODP patients, such that baseline characteristics were compar-
able. Clinically relevant complications occurred less after LDP than after ODP
(14% vs. 30%, P0.03). Conversion occurred in 33% of LDPs. LDP was asso-
ciated with 375ml less intra-operative blood loss (P0.04) and 2 days shorter
postoperative stay (P0.01). No significant differences were seen regarding oper-
ating time, fistula, gastroparesis, bleeding, infection, ICU admittance and total
duration of hospitalization. The questionnaire (90% response) showed that 85%
of Dutch pancreatic surgeons wanted to participate in LDP-training and 96% in
a randomized trial.
CONCLUSION: LDP seems to be safe in the Netherlands in this relative small
group of selected patients despite the high conversion rate. A nationwide training
scheme for LDP (LAELAPS) has been developed.
Disclosure of Interest: None declared
OP111 ENDOSCOPIC TREATMENT OF CHRONIC PANCREATITIS IN
CHILDREN: LONG TERM FOLLOW UP
M. Napoleone1, I. Boskoski1,*, P. Familiari1, I. Costamagna2, A. Tringali1,
V. Perri1, M. Mutignani3, G. Costamagna4
1
DIGESTIVE ENDOSCOPY UNIT, 2Department of Anestesiology, CATHOLIC
UNIVERSITY OF ROME, Rome, 3Digestive Endoscopy, Niguarda Hospital,
Milan, 4Digestive Endoscopy, CATHOLIC UNIVERSITY OF ROME, Rome,
Italy
Contact E-mail Address: ivoboskoski@yahoo.com
INTRODUCTION: Chronic pancreatitis (CP) in children is a rare disease and
experience of ERCP in children with CP is limited.
AIMS & METHODS: All pediatric patients (518 yrs) with CP who underwent
ERCP from Oct 1992 to Feb 2013 were retrospectively identified from a pro-
spective database at a tertiary care referral center. Indications, findings, treat-
ment modalities, adverse events/outcomes were recorded. Data on long term
follow-up were analyzed. Safety and efficacy on treatment were also evaluated.
RESULTS: During the study period 125 children underwent ERCP for bilio-
pancreatic disorders. Of these, 35 (28%) children (16 boys, mean age 11.6 yrs
[range 2.5-17]) underwent ERCP for painful CP and were included in the study.
Indications to ERCP were recurrent bouts of pancreatitis and pain. Mean symp-
toms duration before ERCP was 2.4 yrs (range 0.1 to 14 yrs). Gene mutations for
CP had 17 (48.5%) children while 8 (22.8%) had pancreatic calcifications (X-ray/
CT/US). Data were missing regarding the number of patients that underwent
MRCP before ERCP. On ERCP, normal main pancreatic duct (MPD) anatomy
was found in 19 (54.3%) children, while pancreas divisum and dominant dorsal
duct anatomy had 10 (28.6%) and 6 (17.1%) respectively. On first ERCP, 21
children had major papilla pancreatic endoscopic sphincterotomy (ES), while
minor papilla ES was done in 9 (5 had both major and minor papilla ES). Of
these, 3 underwent also Extracorporeal Shock-Wave Lithotripsy on pancreatic
stones. Stones and plugs were extracted and in 17 cases. Dominant MPD stric-
ture was found in 5 children, and plastic stents were placed. ERCP-related com-
plications during the first treatment (bleeding/pancreatitis) occurred in 2 children
(5.7%) and were managed conservatively. Mean follow-up of the 35 patients was
8 yrs (range 0.7-21). Fourteen (40%) children had only one ERCP and were pain-
free during 7.3 yrs (range 0.7-17) of follow-up, while 21 (60%) had recurrence of
pain after a mean of 3.8 yrs (range 0.1-20.4) and underwent additional ERCPs
(total of 68 re-interventions [range 1-13; 3.2/patient]). On re-interventions, 9
patients had dominant MPD stricture and were treated with plastic stents place-
ment. These were pain-free on last follow-up (5.8 yrs [range 0.3-14.8]) after stent
removal. Sixteen children had stricture on the site of ES and had re-ES and/or
pneumatic dilation. Plugs were extracted in 17 children during re-interventions.
One boy had post re-ES bleeding that was managed endoscopically and there
were two cholecystitis managed conservatively. After the last re-intervention
these children were pain-free for mean 3.6 yrs [range 0.3-5.6]). The number of
re-interventions was higher in female children (p 5 0.01), and in those with less
than 8 yrs of age (p50.01). Pain recurrences were not related to MPD anatomy
or the presence of gene mutations (p0.2 and p0.3 respectively).
CONCLUSION: ERCP in pediatric patients with chronic pancreatitis is a safe
and effective procedure. In more than one third of cases only one ERCP can be
resolutive. Like already described (1), our series confirms the need for repeated
ERCPs for pain recurrences, that can be managed endoscopically without major
complications.
United European Gastroenterology Journal 2(5S)
REFERENCES
(1) Agarwal J et al. ERCP in the management of pancreatic diseases in children.
Gastrointest Endosc 2014; 79: 271-278.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 15:4517:15
CIRRHOSIS AND NON-INVASIVE DIAGNOSIS OF FIBROSIS LOUNGE
6_____________________
OP112 PROTON PUMP INHIBITOR INTAKE IS NEITHER
ASSOCIATED WITH THE DEVELOPMENT OF SPONTANEOUS
BACTERIAL PERITONITIS OR OTHER INFECTIONS NOR WITH
MORTALITY IN PATIENTS WITH CIRRHOSIS AND ASCITES
M. Mandorfer1,*, S. Bota1, P. Schwabl1, T. Bucsics1, N. Pfisterer1,
C. Summereder1, A. Blacky2, A. Ferlitsch1, W. Sieghart1, M. Trauner1, M. Peck-
Radosavljevic1, T. Reiberger1 on behalf of Vienna Hepatic Hemodynamic Lab
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, 2Clinical Institute of Hospital Hygiene, Vienna
General Hospital, Vienna, Austria
Contact E-mail Address: thomas.reiberger@meduniwien.ac.at
INTRODUCTION: Conflicting results have been reported on the association
between proton pump inhibitor (PPI) intake and spontaneous bacterial perito-
nitis (SBP) development in patients with cirrhosis and ascites.
AIMS & METHODS: The aim of this study was to assess the impact of PPI
intake on the development of SBP or other infections, as well as mortality, in a
thoroughly documented cohort with a particularly high prevalence of PPI intake.
We performed a retrospective analysis of data from 607 consecutive patients with
cirrhosis who had their first paracentesis at the Medical University of Vienna
from 2006 through 2011. Cox models were calculated to investigate the effect of
PPI intake on the incidence of SBP or other infections, as well as transplant-free
survival. All models were adjusted for age, hepatocellular carcinoma (HCC),
previous variceal bleeding, varices and model of end-stage liver disease
(MELD) score.
RESULTS: PPI intake was very common (86%). At the first paracentesis, mean
age was lower (PPI:57.1 11.7 vs. no-PPI:60.2 12.1; P0.02), while median
MELD score was higher (PPI:18 (10.3) vs. no-PPI:15.2 (7.7); P0.037) among
patients with PPI intake. While the proportion of patients with HCC was higher
among patients without PPI intake (PPI:22% vs. no-PPI:37%; P0.003), pre-
vious variceal bleeding (PPI:20% vs. no-PPI:10%; P0.038) and varices
(PPI:75% vs. no-PPI:60%; P0.003) were more frequently observed in the PPI
group. Similar differences were observed in the subgroups of patients without
SBP and patients without SBP or other infections at the first paracentesis.
The proportion of patients with SBP at the first paracentesis was comparable
between PPI (19%) and no-PPI (17%; P0.691) patients. After adjusting for
potential confounding factors, PPI intake was not associated with SBP incidence
(HR:1.33; 95%CI:0.6-2.96; P0.486), or incidence of SBP or other infections
(HR:1.36; 95%CI:0.67-2.77; P0.389).
Moreover, PPI intake had no impact on transplant-free survival, neither in the
overall cohort (HR:0.973, 95%CI:0.719-1.317; P0.859), nor in the subgroups of
patients without SBP (HR:1.01, 95%CI:0.72-1.42; P0.971) and without SBP or
other infections at the first paracentesis (HR:0.944, 95%CI:0.668-1.334;
P0.742).
CONCLUSION: Previous studies reporting an association between PPI intake
and SBP incidence were based on cohorts with a substantially lower proportion
of patients on PPI treatment, suggesting indications for PPI administration were
followed more rigorously. In our cohort with a particularly high prevalence of
PPI intake, we observed no association between PPI intake and SBP or other
infections, as well as mortality. Thus, the underlying disease and other unknown
factors, rather than PPI treatment per se may predispose for complications in
patients with cirrhosis and ascites.
Disclosure of Interest: None declared
OP113 PORTAL VEIN THROMBOSIS NATURAL COURSE AND
SURVIVAL IN CIRRHOTIC PATIENTS
I. Girleanu1,*, A. Trifan1, C. Cojocariu1, A.M. Singeap1, O.C. Stoica1,
C. Stanciu1
1
Gastroenterology, University of Medicine and Pharmacy Iasi, Romania, Iasi,
Romania
Contact E-mail Address: gilda_iri25@yahoo.com
INTRODUCTION: Portal vein thrombosis (PVT) has a high incidence in
patients with liver cirrhosis, frequently in its advanced stages, and determines a
poor prognosis of hepatic disease.
AIMS & METHODS: The aim of this study was to evaluate long-term outcome
of patients with portal vein thrombosis and liver cirrhosis. We conducted a
prospective cohort study including all adult patients referred to a tertiary
center between January 2011 and December 2013 with non-malignant PVT
and liver cirrhosis. We excluded patients who received anticoagulant treatment,
patients with malignant disease including hepatocellular carcinoma, known
thrombofilia, those with portal cavernoma. All patients were evaluated by
Doppler abdominal ultrasound and computed tomography. Portal vein throm-
bosis group was compared with a control group consisting in cirrhotic patients
comparable in terms of liver disease severity.
RESULTS: A total of 62 patients (51.6 % female) were included, with a median
age at PVT-diagnosis of 59.02 years (range 2980). Study group included 32
patients diagnosed with PVT, 22 of them with partial PVT. The control group
consisted in 30 cirrhotic patients with comparable baseline characteristics as the
study group. Median follow-up was 21.69 months (range 431). There was no
United European Gastroenterology Journal 2(5S)
difference regarding hepatic decompensation rate at 6 and 18 months between
patients with PVT and control group groups (19% vs. 20%, P0.821 and 54%
vs. 51%, P0.755, respectively). The survival rate at 6 months was 81.3% in PVT
group vs. 84.7% (P0.067) in control group, and 63.1% vs. 61.7% (P0.122) at
18 months, respectively. Multivariate analysis showed that total PVT was the
independent predictor of hepatic decompensation [hazard ratio (HR) 1.56; 95%
confidence interval (CI): 1.14-6.67, P0,032] with no influence on survival rate.
CONCLUSION: There was no difference regarding decompensation and survi-
val rates between cirrhotic patients with or without PVT and similar stage of liver
disease. Total portal vein thrombosis negatively influence hepatic decompensa-
tion rate.
Disclosure of Interest: None declared
OP114 PATIENT UNDERSTANDING OF LIVER CIRRHOSIS:
IMPROVEMENT THROUGH USE OF AN EDUCATIONAL
SCREENCAST
W. Fateen1,2,*, M. Goldsworthy1, M. Aldersley2, R. Jones2
1
University of Leeds, 2Department of Hepatology, Leeds Teaching Hospitals NHS
Trust, Leeds, United Kingdom
Contact E-mail Address: umwaf@leeds.ac.uk
INTRODUCTION: Working in partnership with patients and their families is
essential in modern healthcare. For this partnership to be effective, patients must
have sufficient understanding of their condition. Patient understanding may be
limited due to restricted time for counselling in clinic and the variable quality of
available educational resources. To our knowledge, patient understanding of
cirrhosis and its complications has not been previously studied.
AIMS & METHODS: We aim to assess the baseline knowledge of a cohort of
patients with liver cirrhosis and to test the effectiveness of a condition-specific
screencast. This is a narrated video that presents relevant and evidence-based
information about liver cirrhosis, supported by on-screen text, diagrams and
animations.
The study has been approved by our local research and development department
as a study designed for service quality improvement. Patients attending the out-
patient clinic aged 18 years or over with liver cirrhosis and on a surveillance
programme for hepatocellular carcinoma were eligible to participate. Those
who were not aware they had liver cirrhosis and patients who had hepatic ence-
phalopathy were not eligible to participate.
Participants completed a baseline questionnaire assessing their knowledge of the
management and complications of cirrhosis. They were then invited to watch a
12-minute-long screencast, which was developed in collaboration with patient
groups and liver specialists. The screen-cast describes the definition, causes,
management and complications of cirrhosis. Patients were invited to complete
a new copy of the original questionnaire immediately after watching and once
again at least one month (range 1-6 months) after watching the screen-cast.
Participants completed the interval questionnaire and submitted it by post or
online.
RESULTS: Sixty-three patients were approached. Eight were not eligible to
participate and six declined. Forty-nine patients were assessed (M31, F 18)
with a median age of 56 and median follow-up period of three years. Participants
achieved a total score of 29.1% on the baseline questionnaire. This increased to
67.9% after watching the screencast (P50.001). Thirty-four patients completed
the follow-up questionnaire after an interval period. They achieved a total score
of 64.7%, an increase of 35.6% compared to baseline (P50.001). Between base-
line and interval follow-up, knowledge of the reason for having regular ultra-
sounds improved by 22.2%, regular endoscopies by 41.3%, bone-density scans
by 53.3%, being prescribed laxatives by 73.3%, risk of bleeding by 51.1%, lia-
bility to develop encephalopathy by 66.1%, knowledge of complications (e.g.
muscle wasting and impaired clotting) by 12.9% and knowledge of liver functions
by 27.2%.
CONCLUSION: Participating patients had been seen previously in a liver clinic
where information about cirrhosis is regularly delivered by healthcare profes-
sionals and where information leaflets are readily available. Despite this, baseline
understanding was poor. Delivering information by video led to a significant
increase in patients knowledge about their condition. This was present both
immediately and following an interval period. We therefore present an effective
way to empower patients with accurate, up-to-date and retainable information,
which could be easily translated to several other chronic disease conditions.
Disclosure of Interest: None declared
OP115 ASSESSMENT OF PORTAL HYPERTENSION USING PROBE-
BASED CONFOCAL LASER ENDOMICROSCOPY (P-CLE)
S.K. Singh1,*, E. Rodriguez-Diaz1, G. Baffy2
1
Medicine, Gastroenterology / Endoscopy, Boston University / VA Boston
Healthcare System, 2Medicine, Gastroenterology / Endoscopy, VA Boston
Healthcare System, Boston, United States
Contact E-mail Address: singhsk@bu.edu
INTRODUCTION: There has been recent increasing interest in the early detec-
tion of portal hypertension (PHT) in an attempt to prevent the morbidity of late-
stage cirrhosis, stratify disease severity and modify outcomes in potentially-rever-
sible conditions like NAFLD and alcoholic hepatitis.
AIMS & METHODS: To evaluate as a proof-of-concept the relationship of
novel quantitative endomicroscopic microvascular and morphological features
to clinical markers of PHT.
Methods: In an IRB-sanctioned study, we enrolled subjects with and without
PHT scheduled for a medically-indicated upper endoscopy at VA Boston.
Upon IV injection of 300 mg sodium fluorescein, real-time pCLE and video
microangiography were performed. The microvasculature was best visualized
A39
in the duodenum where villi were imaged using a GastroFlex-UHDTM mini-
probe (Mauna Kea Technologies, Atlanta, GA), providing 1000x magnification,
a 20 mm optical slice thickness, 1mm lateral resolution, and a 240mm field of view.
Digital videos were then analyzed off-line in a blinded manner for vessel and
epithelial morphometry using image processing algorithms.
RESULTS: To date, pCLE images have been analyzed from 15 control and 16
PHT patients. Average vessel diameter (AVD) and branching (AVB) were mea-
sured in 249 regions of interest from control vs. 301 regions from PHT subjects.
Average columnar cell height (ACCH) within the villus epithelial stripe was
measured in 219 control vs. 197 PHT regions. Spearman correlations of 0.87
(95%CI, 0.74,0.93; p8.3x10-11), 0.42 (95%CI, 0.09,0.67; p0.01), and 0.71
(95%CI, 0.48,0.85; p3.8x10-6) were obtained for AVD, AVB, and ACCH,
respectively, when compared to the severity of portal gastropathy, and of 0.88
(95%CI, 0.76,0.94; p1.99x10-11), 0.41 (95%CI, 0.07,0.66; p0.02), and of 0.66
(95%CI, 0.41,0.82; p3.1x10-5), respectively, when compared to the grade of
esophageal varices. In addition, AVD, AVB, and ACCH correlated with spleen
size with a Pearson correlation of 0.72 (95%CI, 0.49,0.85; p2.6x10-6), 0.20
(95%CI, -0.15,0.51; p0.26), and 0.56 (95%CI, 0.27,0.76; p6.2x10-4), respec-
tively, and correlated with platelet count with a correlation of -0.69 (95%CI, -
0.84,-0.45; p8.7x10-6), -0.30 (95%CI, -0.58,0.05; p0.09), and -0.40 (95%CI, -
0.65,-0.07; p0.02), respectively.
CONCLUSION: PHT is associated with endoscopically-inapparent microvascu-
lar dilatation and altered epithelial cell volume/morphology revealed in vivo by
pCLE. Analysis shows that quantitative pCLE markers correlate with surrogate
clinical markers of PHT. Additional studies will seek to define the correlation
between microscopic portal hypertensive vascular patterns, epithelial cell volume,
and the hepatic venous pressure gradient. Quantitative pCLE of the duodenum
may reveal subclinical PHT and serve as a novel and early biomarker of liver
disease and its complications.
Disclosure of Interest: None declared
OP116 LIVER STIFFNESS AND CONTROLLED ATTENUATION
PARAMETER FOR ASSESSMENT OF FIBROSIS AND STEATOSIS
IN CHILDREN WITH NON-ALCOHOLIC FATTY LIVER DISEASE
W. Janczyk1,*, E. Jurkiewicz2, A. Wierzbicka-Rucinska3, P. Socha1
1
Gastroenterology, Hepatology and Eating Disorders, Childrens Health Memorial
Institute, 2Radiology, Childrens Health Memorial Institute, 3Biochemistry and
Experimental Medicine, Childrens Health Memorial Institute, Warsaw, Poland
Contact E-mail Address: w.janczyk@czd.pl
INTRODUCTION: Liver stiffness measurement (LSM) by FibroScan (FS) was
previously shown to be a valuable method in detection of liver fibrosis in adults
with chronic liver diseases as HCV and non-alcoholic fatty liver disease
(NAFLD). The Controlled Attenuation Parameter (CAP) available on FS
allows simultaneous assessment of the degree of liver steatosis. This method
seems especially promising for children with liver diseases in whom indications
to perform liver biopsy are limited.
AIMS & METHODS: Aim of the study was to evaluate LSM and CAP in
children with NAFLD and compare these results to healthy controls. We also
assessed their relationship to non-invasive parameters describing the degree of
obesity, liver function and lipid metabolism.
We investigated 38 overweight/obese children aged 14y (11.4-15.8) [median (Q1-
Q3)] with NAFLD diagnosed by presence of liver steatosis on ultrasound and
increased ALT activity and 18 healthy controls aged 12y (6.7-15.2). NAFLD
patients underwent detailed investigation including risk factors associated with
metabolic syndrome. In children with NAFLD we performed MRI of the lumbar
region to assess subcutaneous (SAT) and visceral adipose tissue (VAT). VAT
area and SAT area at the L2-L3 and L4-L5 interspaces and total VAT and SAT
volumes were determined by manual examination using image analysis software.
Correlations were tested by Spearman rank test.
RESULTS: NAFLD patients had significantly increased LSM compared to con-
trols [5.35 (4.70-6.4) vs. 4.2 (3.6-4.4) kPa] and there was a marked difference in
CAP [264.5 (243-304) vs 187 (112-217) dB/m]; p50.05.
LSM correlated with all fat tissue compartments measured by MRI and HDL
cholesterol (r(-0.4)). CAP significantly correlated with waist circumference
(r0.51), extraperitoneal visceral adipose tissue (r0.37), subcutaneous subfas-
cial fat tissue (r0.38) and serum levels of ALT (r0.57), AST (r0.42) and
GGTP (r0.5).
CONCLUSION: 1. LSM and CAP using Fibroscan are easily applicable to
children with NAFLD.
2. Liver stiffness and steatosis using LSM and CAP are significantly higher in
NAFLD patients when compared to healthy controls.
3. Liver fat content measured by CAP correlates significantly with liver function
tests and adipose visceral tissue in the extraperitoneal compartment as well as
subcutaneous adipose tissue. LSM is correlated to fat tissue in all compartments
but does not correlate with liver function tests.
Disclosure of Interest: None declared
A40
OP117 ELASTOGRAPHIC ASSESSMENT OF LIVER STIFFNESS IN
CHILDREN
O. Belei1,*, L. Olariu1, O. Gradinaru2, O. Marginean1
1
First Pediatric Clinic, UNIVERSITY OF MEDICINE AND PHARMACY
VICTOR BABES, 2Gastroenterology Department, Emergency County Hospital,
Timisoara, Romania
Contact E-mail Address: oana22_99@yahoo.com
INTRODUCTION: Non-invasive techniques for liver fibrosis assessment were
developed for adult patients and recent researches tested their accuracy in chil-
dren. There is a trend towards elastography replacing liver biopsy in the evalua-
tion of liver fibrosis among children with chronic diffuse liver diseases.
AIMS & METHODS: To investigate the feasibility of liver stiffness (LS) mea-
surement in children with chronic diffuse hepatopathies by means of Acoustic
Radiation Force Impulse Elastography (ARFI) and Shear Wave Elastography
(SWE), compared to transient elastography (TE) as reference method. 54 chil-
dren aged 4-18 years with different chronic hepatopathies (HBV, HCV infections,
autoimmune hepatitis, nonalcoholic steato-hepatitis, Wilson disease) were
enrolled. All children were examined by means of TE using FibroScan.10 valid
TE measurements were performed under fasting conditions and the median value
was calculated. ARFI was performed with Siemens Acuson S2000 Virtual Touch
ultrasound system. We calculated the mean value of 10 valid measurements for
each patient. SWE was performed with an Aixplorer ultrasound system
(SuperSonic Imagine). We calculated the mean value of 5 valid measurements
for each patient. All measurements were performed in the right liver lobe, in the
same session. In all patients, transaminases levels didnt overcome 3 times upper
normal limit values.
RESULTS: 54 children with an average age of 8.4 years ( 2.5) were included
and had a successful measurement rate of 94,4%(51/54). Valid measurements
were defined as a median value of LS measurements with a success rate(SR)
60% and an interquartile range interval(IQR)530%. Mean values were as
follows: FibroScan: 7.36 1.3 kPa; ARFI: 1.46  0.12 m/s; SWE: 6.33  2.1
kPa. Accuracy of ARFI for detecting F1 was 85.71%, for F2 was 90.47 %,
for F3 was 80.95% and for F4 was 88%. Accuracy of SWE for detecting F1
was 88%, for F2 was 92.85%, for F3 was 91% and for F4 was 95.23%. We
found a significant correlation between FibroScan and SWE (r0.64, p0.001).
Analysis of the whole lot of patients with valid measurements didnt show sig-
nificant correlation between FibroScan and ARFI (r0.24, p0.14). SWE didnt
correlate with ARFI values (r0.18, p0.28). We analyzed separately the sub-
group of patients with valid measurements but less satisfactory technical para-
meters (SR between 60%470% and/or IQR30%). There was no significant
correlation between LS measurements by means of FibroScan and ARFI (r-
0.26, p0.52). However, in the same subgroup FibroScan correlated significantly
with SWE (r 0.67, p0.05). In the subgroup of children in whom the quality
parameters for LS measurements were fulfilled with SR between 70% and 100%
and IQR530%, there was a significant correlation between FibroScan and
ARFI (r0.58, p0.01) and FibroScan and SWE (r0.90, p0.01). 0.55, 0.54, p0.36) and length of hospital stay (Somers D, 0.27, 0.26, 0.23,
CONCLUSION: SWE based on supersonic share imaging is a new technique
designed to overcome some of the disadvantages of other elastographic techni-
ques. Overall, it seems to correlate better with FibroScan compared to ARFI in
children. Excluding patients with less satisfactory technical parameters
(SR60%470% and/or IQR30%), we obtained significant correlations
between all 3 elastographic techniques. Both SWE and ARFI are non-invasive
techniques feasible to perform in children along with FibroScan.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
THERAPY UPDATE: GORD HALL D_____________________
OP118 RANDOMIZED, PLACEBO-CONTROLLED TRIAL OF
BIOFEEDBACK FOR THE TREATMENT OF RUMINATION
F. Azpiroz1,2, E. Barba3,*, M. Mego3, A. Accarino3, J.R. Malagelada4
1
Medicina, Universitat Auto`noma Barcelona, Barcelona, 2Digestive System
Research Unit, University Hospital Vall dHebron, Barcelolna, 3Digestive System
Research Unit, University Hospital Vall dHebron, 4Digestive System Research
Unit, University Hospital Vall d?Hebron, Barcelona, Spain
Contact E-mail Address: azpiroz.fernando@gmail.com
INTRODUCTION: In a previous study we showed that rumination is produced
by an unperceived, somatic response to food ingestion and developed an original
biofeedback technique for the treatment of rumination based on EMG-guided
control of abdomino-thoracic muscular activity.
AIMS & METHODS: Our aim was to demonstrate the superiority of biofeed-
back versus placebo for the treatment of rumination. Twenty-four patients (16
women, 8 men; 16-82 yrs age range) who fulfilled the Rome criteria for rumina-
tion were recruited and randomly allocated to biofeedback and placebo treat-
ment. Abdomino-thoracic muscle activity after a challenge meal was recorded by
EMG and the signal was displayed on a monitor and front in the patients: in the
biofeedback group, patients were instructed to control muscle activity, whereas in
the placebo group patients were administered 120 mg symethicone. In each
patient 3 sessions were performed over a 10-day period. Physiological (muscular
activity by EMG) and clinical outcomes (number of rumination events by ques-
tionnaires administered daily for 10 days) were measured before and after treat-
ment. Data of 16 patients who already completely the study (8 per group) were
analyzed and mean SE calculated.
RESULTS: Patients on biofeedback, but not on placebo, effectively learned to
reduce intercostal activity (by 467 % vs 17 % on placebo; P5.001) and
anterior wall muscle activity (by 504 % vs 14 % on placebo; P5.001).
Biofeedback was followed by a reduction of rumination activity (738 %
decrease of regurgitation episodes/day vs -218 % on placebo; P015).
United European Gastroenterology Journal 2(5S)
CONCLUSION: Rumination can be effectively corrected by biofeedback-guided
control of abdomino-thoracic muscular activity
Disclosure of Interest: F. Azpiroz Financial support for research from: Danone,
Given, Beneo, Shire, Consultancy for: Danone, E. Barba: None declared, M.
Mego: None declared, A. Accarino: None declared, J. Malagelada: None
declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
UPDATE ON THE MANAGEMENT OF ACUTE PANCREATITIS HALL
B_____________________
OP119 VALIDATION AND COMPARISON OF THE NEW SEVERITY
CLASSIFICATION SYSTEMS FOR SEVERITY OF ACUTE
PANCREATITIS WITH OLD ATLANTA CLASSIFICATION
R.B. Thandassery1,*, M. Manrai1, J. Medarapalem1, P. Siddappa1, S. Appasani 1,
S.K. Sinha1, T.D. Yadav2, R. Kochhar1
1
Gastroenterology, 2General Surgery, Postgraduate Institute of Medical Education
and Research, Chandigarh, India
Contact E-mail Address: doc.ragesh@gail.com
INTRODUCTION: Two new classification systems for the severity of acute
pancreatitis (AP) have been proposed recently, the determinant based classifica-
tion (DBC) and revised Atlanta classification (RAC). We aimed to validate and
compare these classification systems with original Atlanta classification (OAC).
AIMS & METHODS: Our aim was to validate and compare the DBC and RAC
with original Atlanta classification (OAC).
469 adult patients with AP admitted to a tertiary care center from January 2009-
June 2013 were included in the study. The new classification systems were vali-
dated and compared in terms of outcomes (need for interventions, total hospital
and intensive care unit (ICU) stay and mortality).
RESULTS: The mean age of patients was 39.913.4 years (331 males) with the
commonest etiology being alcohol (161, 34.3%) followed by gall stones (125,
26.6%). There were 119 (25.4%) patients with mild and 250 (74.6%) patients with
severe AP as per OAC. Pancreatic necrosis was present in 66.1% and infected
pancreatic necrosis in 23.1% patients. 126 (26.9%) patients underwent interventions
(endoscopic n 49, 10.4%, radiological n95, 20.2% and surgical n47, 10%). 93
(19.8%) patients died. As per DBC, 97(20.7%), 172 (36.7%), 152 (32.4%), and
48(10.2%) patients were determined to have mild, moderate, severe, and critical
AP, respectively. As per RAC, 119 (25.4%), 160 (34.1%), and 190 patients
(40.3%) were determined to have mild, moderately severe, and severe AP, respec-
tively. Higher grades of severity were associated with worse outcomes in DBC, RAC
and OAC.
Predictive accuracies were evaluated using area under the receiver operator char-
acteristics curve (AUROC) and Somers D co-efficient. The DBC, RAC and
OAC were comparable in predicting the need for interventions (AUROC 0.53,
p0.41). However, both DBC and RAC had comparable but better accuracy
than OAC in predicting need for ICU admission (AUROC 0.73 for both vs. 0.62
for OAC, P50.001), length of ICU stay (Somers D, 0.35 for both vs. 0.24 for
OAC, p50.001) and mortality (AUROC 0.78 for both vs. 0.61 for OAC,
p50.001).
CONCLUSION: Determinant based classification and revised Atlanta classifica-
tion categorize patients into subgroups that reflect clinical outcomes. Both have
comparable and higher predictive accuracy than old Atlanta classification for
need for ICU admission, length of ICU stay and mortality.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
COLORECTAL CANCER SCREENING: THE FUTURE HALL C_____________________
OP120 POSITIVE PREDICTIVE VALUE OF FLEXIBLE
SIGMOIDOSCOPY SCREENING FOR PROXIMALLY LOCATED
COLON LESIONS
S. C. Van Doorn1,*, R. Bevan2, E.J. Kuipers3, C. Rees2, E. Dekker1
1
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
Netherlands, 2Gastroenterology and Hepatology, South Tyneside General Hospital,
South Shields, United Kingdom, 3Gastroenterology and Hepatology, Erasmus
Medical Center, Rotterdam, Netherlands
Contact E-mail Address: s.c.vandoorn@amc.uva.nl
INTRODUCTION: In the UK flexible sigmoidoscopy screening (FSS) is offered
at the age of 55. During sigmoidoscopy, if one of the following criteria is met, the
participant is referred for colonoscopy: detection of a polyp in left colon
410mm; 3 or more adenomas; adenoma with villous or tubulovillous compo-
nent; adenoma with high-grade neoplasia (dysplasia); or 20 or more hyperplastic
polyps 4 3 mm above the distal rectum. It is of importance to estimate which
lesions in the proximal colon (proximal to the splenic flexure) are left undetected
by FSS.
AIMS & METHODS: We aimed to evaluate the positive and negative predictive
value (PPV & NPV) of FSS for proximally located colorectal lesions using a
model screening population.
In a previous Dutch screening colonoscopy trial (COCOS-trial), 1426 asympto-
matic persons between 50-75 years of age underwent primary colonoscopy. We
evaluated which participants (based on the distally located findings that would
have been identified during a screening sigmoidoscopy) would have met the
criteria for referral for colonoscopy. We also evaluated which participants had
relevant lesions in the proximal colon (defined as carcinoma, any adenoma, any
sessile serrated adenoma/polyp, or a hyperplastic polyp 4 10 mm). We calcu-
lated the PPV and the NPV of FSS for lesions in the proximal colon.
United European Gastroenterology Journal 2(5S)
RESULTS: If participants of the Dutch primary colonoscopy screening trial had
been screened by sigmoidoscopy, 117 of 1426 (8.2%) would have been referred
for colonoscopy. In 59% of the referred participants, no relevant lesions would
have been detected in the proximal colon (Table 1). In 81.3% of 1309 participants
that would not have been referred, no relevant lesions would have been missed in
the proximal colon. However, in 18.7% a relevant lesion would have been
missed; 1.5%advanced neoplasia, and 16.6% tubular adenomas with low-grade
dysplasia. The PPV of FSS for the detection of relevant lesions in the proximal
colon is 41% and the NPV is 81%, with an accuracy of 78%.
Table 1.Lesions detected in the proximal colon
Would not have
been referred Would have
for colonoscopy been referred
Total number of 1309 for colonoscopy
colonoscopies 1426 (91.8%) 117 (8.2%)
Findings proximal colon 2 (0.1%) 2 (0.2%) 0
Carcinoma
Tubular & tubulovillous 8 (0.6%) 4 (0.3%) 4 (3.4%)
adenomas HGD any size
Tubulovillous adenoma 11 (0.7%) 8 (0.6%) 3 (2.6%)
LGD any size
Tubular adenomas 224 (15.8%) 189 (14.4%) 35 (29.9%)
LGD any size
Sessile serrated lesions 48 (3.4%) 42 (3.2%) 6 (5.1%)
any size and/or hyperplastic
polyps 4 10 mm
No findings 1133 (79.4%) 1064 (81.3%) 69 (59%)
CONCLUSION: This descriptive study evaluating the accuracy of FSS for pre-
dicting proximal lesions showed a PPV of 41% and a NPV of 81%. However, of
the missed relevant lesions only 1.5% had advanced dysplasia. A limitation of
our study is that the age of the participants in the primary colonoscopy screening
trial was 50-75 years old, whereas FSS participants are invited at the age of 55.
Larger studies are needed to further describe the yield of FSS.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
CHALLENGES IN COELIAC DISEASE AND GLUTEN-RELATED DISORDERS HALL
F1_____________________
OP121 BIOMARKER DISCOVERY THROUGH A PEPTIDE
MICROARRAY MASS MANUFACTURING IN THE CELIAC DISEASE
R.S. Choung1, C. Van Dyke2, T. Brantner2, V. Jayaraman3, J. Rajasekaran3,
K. Bei3, T. Wang3, H.K. Krishnamurthy3, J.A. Murray1,*
1
Gastroenterology and Hepatology, 2Mayo Clinic, Rochester, 3Vibrant Sciences,
LLC, Belmont, United States
Contact E-mail Address: choung.rokson@mayo.edu
INTRODUCTION: Celiac disease (CD) while triggered by a reaction to
gluten has features of an autoimmune disease with antibodies directed
against tissue transglutaminase (TTg). The B-cell reaction is directed at
both the autoantigen tTG and gliadin peptides especially those that have
been deamidated by TTg. However, the precise epitopes recognized by indi-
vidual patients varies and little is known about antibody recognition of the
TTg-gliadin complexes.
AIMS & METHODS: Our aims were to identify the optimal peptide sequences
of deamidated gliadin peptides (DGPs) combined with and without TTg that are
most predictive of celiac disease using high-density in situ synthesis in combina-
torial analysis. We also explored the epitope recognition in patients with likely
undiagnosed celiac disease in the community. Methods: 2 sets of serum were used
(biopsy proven untreated CD (n48) with controls (n50) as a training cohort
and undiagnosed celiac disease (n306) with age-and gender- matched controls
for a validation cohort). Undiagnosed CD patients were confirmed by the serol-
ogy CD test. A 2-stage process was utilized for the biomarker discovery. In the
1st stage high-density microarrays with systemically native deamidated gliadin
and tissue transglutaminase, 12-mer overlapping sequences and 3-mer subse-
quences were paired. Then synthetic DGPs were synthesized with combining
other different 3-mer subsequences, random 3-mer, and 6-mer. ROC curves
were constructed for each peptide. A matrix of subsequences and the highest
percentage of sequences showing IgG and IgA antibody response among all
positive samples were then filtered out using a novel algorithm; then we com-
bined the sequences from both TTg and DGPs to generate the peptides with the
highest accuracy.
RESULTS: Two distinct consensus native DGPs sets (IgG or IgA) were identi-
fied for discriminating CD in the training cohort, exhibiting 80% sensitivity and
85% specificity in peptide set 1, 86% sensitivity and 89% specificity in peptide set
2. Two synthetic DGPs sets, which were synthesized by combining other different
3-mer subsequences of the native DGPs, random 3-mers, and 6-mers subse-
quences, showed much higher sensitivities (IgG97% or Ig A99%) and speci-
ficities (IgG98% or IgA100%) in the training cohort. Two synthetic peptides
sets was further tested in a validation cohort and showed a high accuracy for
undiagnosed CD with roughly two distinct groups by the antibody binding
A41
intensity. The cross-validated area under the curve of a Receiver Operating
Characteristic (ROC) curve using deamidated sequences for predicting undiag-
nosed CD was 0.99. While TTg peptides sequences were not sensitive nor specific
to identify the undiagnosed CD, the combining peptides sequences of DGPs and
transglutaminase were both highly sensitive (98.9 %) and highly specific (100 %).
CONCLUSION: Combining subsequences in a specific order shows a high
degree of specificity and sensitivity for celiac disease. Specially, the combination
of transglutaminase and deamidated gliadin seems likely to be a high-fidelity test
with a high degree of accuracy. This method also may provide insight into the
shift in epitope recognition as patients progress from undiagnosed to sympto-
matic disease
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
MANAGEMENT OF COMPLICATED CROHNS DISEASE HALL F2_____________________
OP122 EFFICACY OF ADALIMUMAB IN PATIENTS WITH CROHNS
DISEASE AND SYMPTOMATIC SMALL BOWEL STRICTURE: A
MULTICENTRE, PROSPECTIVE, OBSERVATIONAL COHORT
STUDY
Y. Bouhnik1,*, D. Laharie2, C. Stefanescu1, X. Hebuterne3, V. Abitbol4,
M. Nachury5, H. Brixi-Benmansour6, A. Bourreille7, L. Picon8, A. Bourrier9,
M. Allez10, L. Peyrin-Biroullet11, J. Moreau12, G. Savoye13, M. Fumery14,
S. Nancey15, X. Roblin16, R. Altwegg17, G. Bouguen18, G. Bommelaer19,
E. Louis20, J. Mary21, F. Carbonnel22
1
Gastroenterologie, MICI et Assistance Nutritive, Hopital Beaujon, Clichy,
2
Service d hepato-gastroenterologie et d oncologie digestive, Hopital Haut-
Leveque, Pessac, 3Service de Gastro-Enterologie & Nutrition Clinique, Hopital de
lArchet 2, Nice, 4Service de Gastro Enterologie, Hopital Cochin, Paris, 5Service
des Maladies de lappareil digestif et nutrition, Hopital Claude Huriez, Lille,
6
Service de Gastro Enterologie, Hopital Robert Debre, Reims, 7Service dHepato-
gastro-enterologie et cancerologie digestive, Hopital Hotel Dieu, Nantes, 8Service
dHepato-Gastro-Onco-Enterologie, Hopital Trousseau, Tours, 9Service de
Gastroenterologie & Nutrition, Hopital Saint-Antoine, 10Service Hepato-gastro-
enterologie, Hopital Saint-Louis, Paris, 11Service Hepato Gastro-Enterologie,
Hopital de Brabois, Nancy, 12Service Gastro-enterologie et Nutrition, Hopital
Rangueil, Toulouse, 13Service dhepato-gastro-enterologie et de nutrition, Hopital
Charles Nicolle, Rouen, 14Service dHepato-Gastroenterologie, Hopital Nord,
Amiens, 15Service dHepato-gastro-enterologie, Centre Hospitalier Lyon-Sud,
Lyon, 16Service Gastro-enterologie et Hepatologie, CHU Saint-Etienne, Saint-
Etienne, 17Service dHepato-gastro-enterologie, Hopital Saint Eloi, Montpellier,
18
Service des maladies de lappareil digestif, Hopital Pontchaillou, Rennes,
19
Service dHepatologie Gastro-Enterologie, CHU Estain, Clermont Ferrand,
France, 20Service de Gastro-enterologie, hepatologie et oncologie digestive, CHU
Sart Tilman, Liege, Belgium, 21DBIM, Hopital Saint-Louis, Parsi, 22Service
dHepato-gastro-enterologie, Hopital Bicetre, Le Kremelin Bicetre, France
Contact E-mail Address: yoram.bouhnik@gmail.com
INTRODUCTION: Efficacy and safety of anti-TNF therapy in patients with
Crohns disease (CD) and intestinal strictures is poorly known. The aim of this
study was to identify predictive factors of adalimumab (ADA) failure in patients
with CD and symptomatic small bowel stricture (SSBS). (ClinicalTrials.gov
No.NCT01183403).
AIMS & METHODS: We performed a multicentre, prospective, observational
cohort study in patients with CD and a SSBS (defined by a CD obstructive score
(CDOS)  3 on a scale from 0 to 6, evaluated over the 8 previous weeks). Patients
with a contraindication to ADA or who were exposed to an anti-TNF therapy
within the last 12 months were excluded. ADA was administered subcutaneously
as following: 160 mg at W0, 80 mg at W2, and then 40 mg every 2 weeks. MR
enterography was performed at baseline and at W24. The primary endpoint was
ADA failure at W24, as defined by at least one of the following criteria during
the study period: a) use of an prohibited treatment (corticosteroids after the 8th
week following inclusion, artificial nutrition, other anti-TNF); b) endoscopic
dilatation; c) bowel surgery including stricturoplasty; d) severe adverse effect
leading to ADA discontinuation; d) loss to follow-up. Secondary endpoints
included CDOS and MR items evolution from W0 to W24. Predictive factors
were searched using univariate and multivariate logistic regression analyses. We
computed that a minimum of 80 patients would provide a 80% power to detect a
relative risk of failure of 2.0 to 4.0, according to a prevalence of patients at high
risk of failure of 25 to 75%.
RESULTS: From January 2010 to December 2012, 118 patients from 20
GETAID centers were included. After exclusion of 21 non evaluable patients,
97 (53W; median age: 36 yrs [inter-quartile range (IQR): 29-49]; median duration
of obstructive symptoms: 3.6 months [IQR: 1.2-11.2]) were analysed. At W24, 35/
97 (36%) patients experienced failure of ADA including 10 who needed surgical
bowel resection. CDOS values at baseline and at W24 (n86) were 5.0 and 3.0
(IQR 1-5), respectively. Prognostic factors including demographic data, charac-
teristics of CD and MR items are currently analysed. At the end of follow-up
period (median duration: 71 weeks [IQR 50-123]), failure was observed in 51 (53
%) patients.
CONCLUSION: In a large prospective cohort of CD patients suffering from
SSBS, ADA failure was observed in 36% of patients at W24 and in approxi-
mately 50% at 18 months. Analysis of prognostic factors, including MR enter-
ography items, will help to select CD patients with symptomatic stricture who
could benefit from anti TNF.
Disclosure of Interest: Y. Bouhnik Lecture fee(s) from: Abbvie, Falk, Ferring,
Given Imaging, Mayoli-Spindler, Norgine Pharma, Vifor Pharma, Consultancy
for: Sanofi, Abbvie, Norgine Pharma, MSD, Takeda Millenium, Roche,
Shareholder of: Inception IBD, D. Laharie: None declared, C. Stefanescu:
None declared, X. Hebuterne: None declared, V. Abitbol: None declared, M.
A42
Nachury: None declared, H. Brixi-Benmansour: None declared, A. Bourreille:
None declared, L. Picon: None declared, A. Bourrier: None declared, M. Allez:
None declared, L. Peyrin-Biroullet: None declared, J. Moreau: None declared,
G. Savoye: None declared, M. Fumery: None declared, S. Nancey: None
declared, X. Roblin: None declared, R. Altwegg: None declared, G. Bouguen:
None declared, G. Bommelaer: None declared, E. Louis: None declared, J. Mary:
None declared, F. Carbonnel: None declared
OP123 GROWTH PATTERN IN PEDIATRIC CROHN DISEASE IS
RELATED TO INFLAMMATORY STATUS BUT NOT TO
DURATION OF STEROID THERAPY
D. Ley1,*, H. Behal2, C. Gower-Rousseau3, A. Duhamel2, F. Vasseur3,
M. Fumery4, L. Michaud1, I. Rousseau3, G. Savoye5, D. Turck1 on behalf of The
EPIMAD group
1
Pediatric GI Unit, 2Biostatistics Unit, EA 2694, 3Epidemiology Unit, EA 2694,
CHU Lille; Lille-2 University, Lille, 4Gastroenterology Unit, CHU Amiens;
Amiens University, Amiens, 5Gastroenterology Unit, CHU Rouen; Rouen
University, Rouen, France
Contact E-mail Address: delphine.ley@etu.univ-lille2.fr
INTRODUCTION: Growth failure is the main complication of pediatric-onset
Crohn disease (CD). The respective role of disease activity and steroid therapy in
growth faltering is still a matter of debate.
AIMS & METHODS: The aim of the present study was to investigate whether
the growth pattern of children with CD was correlated with the evolution of
inflammatory status during the disease course, whatever the cumulative duration
of steroid therapy. 107 patients (63 boys and 44 girls) from the inflammatory
bowel diseases cohort in Nothern France (EPIMAD registry), with a diagnosis of
CD made 517 years of age, followed in the University Childrens Hospital of
Lille during 2 years and for whom 2 height measures were available during
follow-up, were identified between 1998 and 2010. Height, C-reactive protein
(CRP), orosomucoid and duration of steroid therapy were collected at each
visit. Growth velocity was compared to the evolution of inflammatory status
during follow-up in a longitudinal multivariate analysis using a mixed model.
RESULTS: Median age at CD diagnosis was 11.7 years (Q1-Q3: 9.8-13.5).
According to the Paris classification, location of CD at diagnosis and at maximal
follow-up was respectively as follows: L3 (70%; 86%); L2 (16%; 5%); L1 (14%;
9%); L4a (39%; 52%); L4b (11%; 22%). Behaviour at diagnosis and at maximal
follow-up was respectively as follows: B1 (90%; 62%); B2 (7%; 28%); B3 (3%;
10%). Mean Height (H)/Age (A) Z-score at diagnosis was 0.11.3. Growth
failure (H/A Z-score 52) was present in seven (8%) patients at diagnosis and
in five (5%) at maximal follow-up (median: 4.9 years; Q1-Q3: 3.8-6.4). Among
the 75 patients who had reached their final height at maximal follow-up, mean H/
A Z-score was 0.1  1.2. Twenty (29%) patients had a final height that was at
least 4 cm below their targeted height. Growth velocity was not influenced by the
cumulative duration of steroid therapy (median: 7.1 months; Q1-Q3: 4.9-12.5),
but was negatively correlated with the evolution of CRP (coefficient of the equa-
tion of regression (e) 0.16; p50.0001) and orosomucoid (e 0.60; bowel preparation according to the Boston Bowel Preparation Scale (BBPS). The
p50.0001) during follow-up.
CONCLUSION: CD children with uncontrolled inflammatory status have a
lower growth velocity, regardless of cumulative duration of steroid therapy.
The inflammatory status should be kept as close to normal as possible in pedia-
tric-onset CD patients in order to optimize their growth pattern.
Disclosure of Interest: None declared
OP124 DUAL ENERGY COMPUTERIZED TOMOGRAPHY (DE-CT) A
NOVEL DECISION MAKING TOOL IN PREDICTING THE NEED
FOR SURGERY IN PATIENTS WITH CROHNS DISEASE AND
OBSTRUCTING INTESTINAL LESIONS
T. Adar1,*, R. Biron1, A. B.-G. Shitrit1, D. Wenrower1, R. Cytter2, I. H. Halpern
2
, E. Goldin1, N.R. Bogot2
1
Digestive Diseases Institute, 2Department of radiology, Shaare Zedek Medical
Center, Jerusalem, Israel
Contact E-mail Address: adartom@szmc.org.il
INTRODUCTION: Intestinal strictures are common in patients with Crohns
(CD) disease and may result in intestinal obstruction. Current available imaging
studies can usually identify and locate the stricture, but can not reliably differ-
entiate the patients who will require surgery from those who will respond to
medical therapy. Dual Energy computerized tomography (DE-CT) uses two
energy sources using high and low tube voltage, thus creating two data sets.
Dedicated software creates overlay of the low and high energy images, in
which enhancement of tissues with iodine can be better appreciated and quanti-
fied compared to standard CT. We hypothesize that dual energy can better
visualize the iodine uptake in bowl wall as a marker of inflammation within
intestinal lesions, and may help in identifying the patients who will or will not
require surgery.
AIMS & METHODS: To evaluate the efficacy of DE-CT studies in predicting
need for surgery within 3 months.
Patients with known CD undergoing abdominal CT for possible obstructive
presentation prospectively underwent a DE-CT using intravenous iodinated con-
trast material, and were followed for 3 months for an outcome of surgery.
The DE-CT was interpreted by a radiologist blinded to the clinical outcome,
and the attending physicians of the patients were blinded to the interpretation
of the DE-CT. DE-CT parameters assessed at the intestinal lesions included the
degree of enhancement in overlay images (Hounsfield Units-HU) and Iodine
content (mg/ml)
RESULTS: The study group included 25 patients, (mean age 38.3 years; F/M
ratio of 12/13); 3 patients were treated with steroids (1 over 20mg), 5 with
United European Gastroenterology Journal 2(5S)
thiopurines and 4 with anti-TNF agents. Of the 25 studies 19 were performed
from the emergency department. A total of 39 intestinal lesions were demon-
strated (1-3 per patient) and 26 had pre-stenotic dilatation. Location of the
lesions was classified as small intestinal, terminal ileum or colonic (30, 9 and
10 respectively). Mean degree of enhancement in overlay images was 33.9712.09
HU and the mean iodine content was 1.850.99 mg/ml.
A total of 6 patients (9 lesions) underwent surgery, within a mean of 5.4 weeks
from the CT study.
Using cut-off values of less than 2 mg/ml iodine content and less than 30 HU
measured on the overlay as predictors for requiring surgery in 3 months achieved
negative predictive value (NPV) 0.84 and 0.88 respectively.
CONCLUSION: DE-CT can be performed in patients with CD and suspected
obstructive symptoms, and is valuable in evaluating the severity of intestinal
inflammation, with a negative predictive value of 88% for identifying patients
which will not require surgery. This study marks DE-CT as valuable decision
making tool in managing patients with Crohns disease, useful also in acute
settings.
DISCLOSURE: This abstract has been accepted for presentation at DDW 2014.
Disclosure of Interest: T. Adar Financial support for research from: Synageva,
Lecture fee(s) from: Shire, Consultancy for: Janssen, Other: Boston scientific,
Immune Pharma, R. Biron: None declared, A. Shitrit: None declared, D.
Wenrower: None declared, R. Cytter: None declared, I. Halpern: None declared,
E. Goldin Consultancy for: Immune Pharma, Bioline Rx Ltd, N. Bogot: None
declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
OPTIMISING LESION DETECTION IN COLONOSCOPY HALL G/H_____________________
OP125 COMPARISON OF IMPACT OF REINFORCED EDUCATION
BETWEEN TELEPHONE AND SHORT MESSAGE SERVICE ON
THE QUALITY OF BOWEL PREPARATION: A PROSPECTIVE,
COLONOSCOPIST-BLINDED, RANDOMIZED, CONTROLLED
STUDY
E.S. Kim1,*, K.B. Cho1, K.S. Park1, E.S. Choi1, S.M. Lee1
1
Internal Medicine, KEIMYUNG UNIVERSITY SCHOOL OF MEDICINE,
Daegu, Korea, Republic Of
Contact E-mail Address: dandy813@hanmail.net
INTRODUCTION: High-quality bowel preparation is essential for a successful
colonoscopy.
AIMS & METHODS: This study aimed to compare the impact of reinforced
education between telephone and short message service on the quality of bowel
preparation. A prospective, endoscopist-blinded, randomized, controlled study
was conducted at a tertiary hospital. All subjects received regular instructions on
the day of their colonoscopy appointment. Reinforced group was provided with
additional education for reminding by telephone (TRE) or short message service
(SMS) a day before colonoscopy. The primary outcome was the quality of the
secondary outcomes included polyp detection rate (PDR), patients compliance
and subjective feelings.
RESULTS: 390 subjects were included in the study (TRE 126, SMS 127, control
137). Mean scores of BBPS were 7.091.15, 6.761.29, and 6.31  1.43 in TRE,
SMS and control group, respectively (p50.001). Rates of poor preparation
(BBPS 55) were 0.8%, 5.5%, and 13.1% in TRE, SMS and control groups,
respectively (p50.001). PDRs of TRE (48.4%) and SMS (44.9%) were higher
than that of control group (32.8%) (p0.026). Fewer subjects in reinforced edu-
cation groups showed a high anxiety before colonoscopy (p0.013). Reinforced
education group had a high level of compliance with preparation instructions
compared with control (p0.019). Willingness to repeat bowel preparation was
observed by 92.1%, 89.0%, and 81.8% of TRE, SMS, and control group, respec-
tively (p0.034). Multivariate analysis revealed that TRE (OR, 15.63, p0.009),
480% amount of purgative ingestion (OR, 5.75, p0.003) and interval of pre-
paration to colonoscopy time 5 6 hrs (OR, 3.981, p0.003) were independent
factors associated with adequate bowel preparation.
CONCLUSION: Reinforced education with telephone and SMS few days before
colonoscopy improves quality of bowel preparation, PDR, patients compliance
and subjective feelings. TRE is more effective for preparation of colonoscopy
than SMS in healthy screening subjects.
Disclosure of Interest: None declared
OP126 PRACTICE, INDICATION AND PREDICTIVE FACTORS OF
SECOND LOOK COLONOSCOPY IN A SCREENING POPULATION
E.J. Grobbee1,*, A. Kapidzic1, A. J. van Vuuren1, M. E. van Leerdam1,
I. Lansdorp-Vogelaar2, C.W. Looman2, M.J. Bruno1, E.J. Kuipers1, M. C.
W. Spaander1
1
Gastroenterology and Hepatology, 2Public Health, Erasmus MC University
Medical Center, Rotterdam, Netherlands
Contact E-mail Address: e.grobbee@erasmusmc.nl
INTRODUCTION: Screening programs for colorectal cancer (CRC) are imple-
mented worldwide. European guidelines recommend fecal immunochemical test-
ing for primary screening followed by colonoscopy in case of a positive fecal
immunochemical test (FIT, e.g. iFOBT). Although there are many studies focus-
ing on the quality aspects of colonoscopy, no information is currently available
on the practice of second look colonoscopies in a screening setting. These colo-
noscopies are a substantial burden for patients and the health care system. This is
the first study to evaluate the number, indications and predictive indicators of
second look colonoscopies following a screening colonoscopy.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We prospectively registered all colonoscopies performed
in average risk subjects, aged 50-74 years, who were approached for a maximum
of three rounds of FIT screening. A second look colonoscopy was defined as any
colonoscopy performed following a screening colonoscopy within one year.
RESULTS: A total of 1216 patients with a positive FIT underwent colonoscopy
(57.4% male, median age 63 years (IQR 57-68 years), median fecal Hb level 142
ng/ml (IQR 77-426 ng/ml)). Unadjusted cecal intubation rate was 96% and the
overall adenoma detection rate was 55%. A total of 97 (8.0%) patients under-
went a second look colonoscopy within one year, with a median time between the
index colonoscopy of 61 days (IQR 35-99 days). Twenty-four patients (2.0%)
underwent more than one second look colonoscopy (range 2-9). The most fre-
quently reported reasons for a second look colonoscopy were assessment of
completeness of removal of a neoplastic lesion (41.2%), need for further poly-
pectomy (30.9%), and poor bowel preparation (15.5%). In multivariate analysis,
the level of fecal hemoglobin was the only significant predictor for the need of a
second look colonoscopy.
CONCLUSION: In this population-based screening program using FIT, a
second look colonoscopy was performed in 8% of the patients within one
year. In two thirds of the patients a second look colonoscopy was performed
for control of completeness of removal of a neoplastic lesion or for polypectomy.
A higher fecal hemoglobin level was the only independent predictor in identifying
patients at risk for a second look colonoscopy and complex polypectomy.
Disclosure of Interest: None declared
OP127 DYNAMIC POSITION CHANGE INCREASE ADENOMA
DETECTION DURING COLONOSCOPE WITHDRAWAL: A
RANDOMIZED CONTROLLED MULTICENTER TRIAL
J.-S. Ji1,*, S.-W. Lee2, J.H. Chang3, D.Y. Cheung4, J.S. Kim1, Y.-S. Cho5, S.-
W. Kim6, H. Choi7
1
Incheon St. Marys Hospital, The Catholic University of Korea, Incheon,
2
Daejeon St. Marys Hospital, The Catholic University of Korea, Daejeon,
3
Bucheon St. Marys Hospital, The Catholic University of Korea, Bucheon,
4
Yeouido St.Marys Hospital, The Catholic University of Korea, Seoul, 5Uijeongbu
St. Marys Hospital, The Catholic University of Korea, Uijeongbu, 6Seoul St.
Marys Hospital, The Catholic University of Korea, Seoul, 7Incheon St. Marys
Hospital, The Catholic University of Korea, Incheong, Korea, Republic Of
Contact E-mail Address: jjsdr@catholic.ac.kr
INTRODUCTION: Adequate luminal distention is essential to maximize ade-
noma detection during colonoscope withdrawal. There was an only single opera-
tor study reporting dynamic position change improves luminal distension and
has the potential to improve adenoma detection rate.
AIMS & METHODS: We designed a randomized, controlled multicenter trial to
verify the effect of dynamic position change in colonic adenoma detection.
Patients aged 45 to 80 years who underwent colonoscopy for the first time
were included. In position change group, position changes during colonoscope
withdrawal were as follows: cecum, ascending colon, and hepatic flexure: left
lateral position; transverse colon: supine position; splenic flexure, descending
colon, sigmoid colon and rectum: right lateral position. In control group, exam-
ination was performed entirely in left lateral position during colonoscope with-
drawl. The primary outcome measure was the proportion of patients with 1
adenoma detected from transverse colon to rectum, namely, in the segments in
which the patient position was different from left lateral.
RESULTS: A total 1000 patients were randomized to position change group (500
patients) and control group (500 patients). At least 1 adenoma was detected in
33% of patients in colon areas in which the patient position differed from left
lateral (from transverse colon to rectum) compared with 24% examined with the
patient in the left lateral position alone (P0.005). Most of the apparent
improvement in adenoma detection appeared to occur through supine position-
ing for examination of the transverse colon (21% and 14% in the position change
group and contol group, respectively, P0.003). The mean number of adenoma
was 0.8  1.4 (standard deviation) in position change group and 0.4  0.8 in
control group from transverse colon to rectum (p 0.019).
CONCLUSION: Dynamic position change during colonoscope withdrawal
increased adenoma detection rate.
Disclosure of Interest: None declared
OP128 G-EYE COLONOSCOPY SIGNIFICANTLY IMPROVES
ADENOMA DETECTION RATES INITIAL RESULTS OF A
MULTICENTER PROSPECTIVE COHORT STUDY
Z. Halpern1, S. Ishaq2, H. Neumann3, M. Dobosz4, E. Viale5, A. Hoffman6,
J. Hendel7, H. Senturk8, H. Jacob9, R. Kiesslich6,*
1
Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 2Russells Hall Medical
Center, Dudley, United Kingdom, 3University Clinic Erlangen, Erlangen, Germany,
4
COPERNICUS Podmiot Leczniczy Sp. z o.o, Gdansk, Poland, 5San Raffaele
Hospital, Milano, Italy, 6St. Marienkrankenhaus, Frankfurt, Germany,
7
Copenhagen University Hospital Herlev, Copenhagen, Denmark, 8Bezmialem
Vakif University hospital, Istanbul, Turkey, 9Hadassah Medical Center, Jerusalem,
Israel
Contact E-mail Address: info@ralf-kiesslich.de
INTRODUCTION: The adenoma detection rate (ADR) is an important quality
marker of colonoscopy. Higher ADR lead to reduced interval cancers and missed
adenomas.
The G-EYETM endoscope (Smart Medical Systems, Raanana, Israel), is a newly
developed system which combines a forward viewing HD endoscope with an
integral, reusable and reprocessable balloon at its bending section. Following
cecal intubation, the endoscope is withdrawn with the balloon inflated thereby
straightening colonic folds, reducing bowel slippage and centering the optic of the
A43
endoscope in the middle of the lumen. Aim of the study was to compare the ADR
of standard colonoscopy with G-EYE colonoscopy (with balloon partially
inflated) at nine European centers.
AIMS & METHODS: From May 2013 to February 2014, patients (age 450)
with indication for regular screening or surveillance were included and assigned
to either conventional colonoscopy or G-EYETM colonoscopy. The G-EYETM
endoscope was based on the same instrument as the conventional HD-colono-
scope (3890i Series, Pentax Medical, Japan).
RESULTS: 222 patients are included, 117 patients underwent conventional colo-
noscopy and 105 patients underwent G-EYETM colonoscopy. Conventional colo-
noscopy detected in average 0.36 adenomas per patient. G-EYETM colonoscopy
detected an average of 0.63 adenomas per patient, 75% higher than the conven-
tional colonoscopy (Table 1). Reported ADR was 23.5% in the conventional
colonoscopy group and 35.4% in the G-EYE group. Compared with conven-
tional colonoscopy, G-EYETM colonoscopy increased ADR by 50%. Mean with-
drawal times were 7:071:29 minutes and 7:051:44 minutes for standard
colonoscopy and G-EYETM colonoscopy, respectively. Cecal intubation was
accomplished in all patients and no adverse events were reported in either group.
Table 1 Results summary
SC G-EYE
Number of Patients 117 105
Adenoma per patient 0.36 0.63
Adenoma detection rate 23.5% 35.4%
Withdrawal time 7:071:29 minutes 7:051:44 minutes
Adverse Events None None
CONCLUSION: The distal balloon of the G-EYE colonoscope which is mod-
erately inflated during withdrawal is highly effective for straightening colonic
folds and identifying polyps and adenomas in a regular screening population.
The use of the balloon was safe (no adverse events). This multicenter work
reports a significant increase in adenoma detection rates by using the G-
EYETM colonoscope compared to standard HD-colonoscopy. The results of
this ongoing prospective cohort study will be reported at UEGW 2014.
Disclosure of Interest: Z. Halpern Consultancy for: Consultant to Smart Medical
Systems Ltd., S. Ishaq: None declared, H. Neumann: None declared, M. Dobosz:
None declared, E. Viale: None declared, A. Hoffman: None declared, J. Hendel:
None declared, H. Senturk: None declared, H. Jacob: None declared, R.
Kiesslich: None declared
OP129 G-EYE ADVANCED COLONOSCOPY FOR INCREASED POLYP
DETECTION RATE - RANDOMIZED TANDEM STUDY WITH
DIFFERENT ENDOSCOPIST
J.W. Rey1, J. Haschemi1, A. Tresch2, S. Duemcke2, D. Borger1, D. Teubner1,
R. Kiesslich1, A. Hoffman1,*
1
St Mary hospital, Frankfurt, 2Max Planck Institute, Cologne, Germany
Contact E-mail Address: ahoff66286@aol.com
INTRODUCTION: An apparently leading cause of missed polyps during colo-
noscopy is attributed to polyps that are located behind haustral folds in the
colon, and are therefore hidden from the conventional, forward-viewing endo-
scope optics. The new G-Eye system is a balloon-colonoscope (NaviAidTM G-
EYE, Smart Medical Systems, Israel), comprising a standard colonoscope having
a re-processable, permanently integrated balloon at its distal tip.
AIMS & METHODS: Patients referred to colonoscopy, were randomized into
two groups. Group A underwent Standard Colonoscopy (SC) followed by
Balloon Colonoscopy (BC); group B underwent BC followed by SC. During
the BC, the endoscope is inserted with the balloon deflated till the cecum.
Then, the balloon is inflated to intermediate pressure and the balloon-colono-
scope is withdrawn, thus straightening intestinal folds, smoothening colon topo-
graphy and improving colon visibility. All polyps detected were removed. For the
first time in this randomized, tandem study the endoscopists changed after each
withdrawal and were blinded to the results of the first withdrawal. Also the
degree of expertise was changing after each withdrawal (expert vs. trainee).
RESULTS: 45 patients were enrolled, randomized into two groups having simi-
lar baseline properties.23 patients underwent SC followed by BC and 22 under-
went BC followed by SC. In Group A, SC detected a total of 25 polyps, and the
following second pass BC detected 23 additional polyps, yielding 92.0% addi-
tional detection, the polyp miss-rate of the standard colonoscopy was 48%. In
group B, BC detected 35 polyps, and the following SC detected 8 additional
polyps, implying a BC miss- rate of 18.6%. The polyp miss-rate of the BC was
significantly lower than the SC polyp miss-rate, fisher exact test p50.05. BC
additional detection over SC was 100% for adenomas and BC ratio of adenoma
additional detection to miss rate, relative to SC was 5.988. BC detected more flat
and small polyps (55mm) than SC. For comparison, average procedure time of
Standard Colonoscopy and Ballon Colonoscopy was similar. No adverse event
occurred.
CONCLUSION: Balloon-colonoscopy is safe, easy to use and exhibits substan-
tial increase in polyp detection rate, and presents significant reduction in miss
rate during colonoscopy. For the first time a tandem study was conducted with
changing endoscopists after each withrawal to decrease the bias to a minimum.
Disclosure of Interest: None declared
A44
OP130 ENDOCUFF-ASSISTED COLONOSCOPY SIGNIFICANTLY
INCREASES THE ADENOMA DETECTION RATE: A RANDOMIZED
CONTROLLED MULTICENTER TRIAL WITH 652 PATIENTS
M. Floer1, E. Biecker2, D. Ameis3, A. Heinecke4, P. Strobel5, D. Domagk6,
M. Schepke2, T. Meister1,*
1
Department of Medicine II, HELIOS Albert-Schweitzer Hospital, Gottingen
University Teaching Hospital, Northeim, 2Department of Gastroenterology,
HELIOS Medical Center Siegburg, Siegburg, 3Department of Gastroenterology,
HELIOS Medical Center Helmstedt, Helmstedt, 4Department of Biostatistics and
Clinical Research, University of Munster, Munster, 5Department of Pathology,
University Medical Center Gottingen, Gottingen, 6Department of Medicine B,
University Medical Center Munster, Munster, Germany
Contact E-mail Address: tobiasmeister@gmx.de
INTRODUCTION: Screening colonoscopy for colorectal cancer has proven to
reduce mortality rates. Recently the Endocuff (EC), an attachment to the distal
tip of the colonoscope, was introduced. The aim of our study was to further
compare Endocuff (EC)-assisted colonoscopies with standard colonoscopies (SC)
for the detection of colonic polyps.
AIMS & METHODS: This study is a randomized prospective multicenter trial.
The study was conducted at three tertiary care centers. Participants: 652 patients
(320 males, mean age 6415 years) for colon adenoma screening purposes were
included. All patients underwent SC with or without the use of Endocuff. Overall
polyp detection rate, the number of colonic polyps and the polyp distribution in
the colon were measured. Difference in recognition of polyps with or without the
use of Endocuff was assessed. Statistical analysis was applied. This study has
been supported by the HELIOS Research Center (No HRC003053).
RESULTS: Total colonoscopy was performed in almost all patients (98.5 with
EC, 99.1% without EC). The mean cleanliness score of each group did not differ
significantly (EC: 1.36 vs. SC: 1.41, p0.282). A total of 765 polyps in the patient
cohort could be detected (EC:464 vs. SC: 301 polyps). Overall, we found signifi-
cant differences in the polyp detection rate and overall number of polyps detected
per patient. In the EC group, the number of polyps detected per patient was 59%
higher (1.452.42 vs. 0.912.21, p50.0001). The polyp detection rate in patients
increased by 15.5% with the use of EC (55.4% vs. 39.9%, p50.0001). For polyp
detection, superiority by use of EC could be observed in the sigmoid region
(p50.0001) and caecum (p0.008) for polyps51cm in diameter. In the EC
group, the adenoma detection rate significantly increased by 66% (EC:
0.902.19 vs. SC: 0.541.34, p0.014). No major complications occurred attri-
butable to EC. The withdrawal time did not differ significantly between the two
groups (p0.603).
CONCLUSION: The use of the EC is feasible and safe with a significantly higher
adenoma detection rate in the coecum and sigmoid. The Endocuff system has the
potential to improve the accuracy of screening colonoscopies.
Disclosure of Interest: None declared
OP131 INTERVAL COLORECTAL CANCER AFTER COLONOSCOPY;
TIME FOR NATIONAL REPORTING SYSTEMS?
D. Tate1,*, F. Rana2, B. Colleypriest1
1
Department of Gastroenterology, Royal United Hospital, Bath, 2Department of
Gastroenterology, Great Western Hospital, Swindon, United Kingdom
INTRODUCTION: Colonoscopy is known to prevent colorectal cancer by resec-
tion of adenomatous polyps. An interval colorectal cancer has been defined as
one diagnosed 6-36 months after an index colonoscopy[1]. It follows that interval
cancer is surrogate measure of quality in colonoscopy. Poor bowel preparation,
incomplete colonoscopy, poor management of particularly sessile and right sided
polyps and short withdrawal time have been identified as contributory factors[2].
We sought to indentify a regional rate of interval colorectal cancer as an audi-
table quality outcome in centres performing a total of 7150 colonoscopies during
2013.
AIMS & METHODS: All colorectal cancer cases presenting to the Royal United
Hospital (RUH) Bath and the Great Western Hospital Swindon (GWH) United
Kingdom, were indentified for the year 2013. The local endoscopy databases
were interrogated for flexible sigmoidosopy or colonoscopy performed in the
preceding 3 years.
RESULTS: 331 cases of colorectal cancer were indentified and managed at RUH
and 152 at GWH. Of these 7 patients (2%) had undergone colonoscopy within
the preceding 3 years at RUH and 10 (7%) at GWH. The average period from
index procedure until cancer diagnosis was 15 months at RUH and 16 months at
GWH. At RUH 6 of the 7 interval cancers could potentially be related to poor
quality of the index endoscopic procedure; at GWH this was 7 out of the 10
interval cancers. The table below details the potential attributable reasons for
interval cancer at the index procedure.
Factor at index procedure likely to explain interval cancer GWH RUH
Poor bowel preparation 1 2
Inadequate management of right sided colonic polyps 5 2
Inadequate surveillance interval 0 1
Incomplete procedure 1 1
No feature identified 3 1
Total interval cancers diagnosed in 2013 10 7 lesions in CD. We analyzed the relationships between levels of fCal and the
Total cancers diagnosed in 2013 152 331
CONCLUSION: From these data it is evident that the quality of colonoscopy,
both regionally and nationally, is vital in terms of preventing colorectal cancer
and should be audited routinely. While the rate regionally is comparable to
United European Gastroenterology Journal 2(5S)
published series of interval cancer[3], we have undertaken review of these proce-
dures to improve practice; focus has been on careful review of right sided and
sessile lesions at both centres, ensuring that completion procedures are adequate
and a review of the local bowel preparation guidelines at RUH. It is vital that this
small but significant miss-rate is considered in managing patients presenting with
persistent symptoms despite normal endoscopy. It could be argued that patients
should be consented appropriately. We suggest that a nationally defined interval
cancer rate should be recorded routinely as part of local audit within the UK
GRS system.
REFERENCES
[1] Samadder NJ, Curtin K, Tuohy TM, et al. Gastroenterology 2014: pii: S0016-
5085(14)00026-2
[2] Faiss SS. Dig Dis 2011; 29(Suppl. 1): 60-63. Epub 2011 Nov 15. DOI: 10.1159/
000331119
[3] le Clercq CM, Bouwens MW, Rondagh EJ, et al. Gut gutjnl-2013-304880 ePub
Disclosure of Interest: None declared
OP132 LEADERSHIP IN TRAINING TO IMPROVE ADENOMA
DETECTION RATE IN SCREENING COLONOSCOPY: A
NATIONWIDE RANDOMIZED TRIAL
M.F. Kaminski1,*, J. Anderson2, R. Valori3, E. Kraszewska1, M. Rupinski1,
J. Pachlewski1, E. Wronska4, M. Bretthauer5, S. Thomas-Gibson6, E.J. Kuipers7,
J. Regula1
1
Medical Centre for Postgraduate Education and the Maria Sklodowska-Curie
Memorial Cancer Centre and Institute of Oncology, Warsaw, Poland,
2
Gloucestershire Hospitals NHS Foundation Trust, 3Gloucestershire Royal
Hospital, Gloucester, United Kingdom, 4the Maria Sklodowska-Curie Memorial
Cancer Centre and Institute of Oncology, Warsaw, Poland, 5University of Oslo,
and Department of Gastroenterology, Oslo University Hospital Rikshospitalet,
Oslo, Norway, 6Wolfson Unit for Endoscopy, St. Marks Hospital, London, United
Kingdom, 7Erasmus Medical Centre, Rotterdam, Netherlands
Contact E-mail Address: mfkaminski@coi.waw.pl
INTRODUCTION: Suboptimal adenoma detection at colonoscopy is associated
with increased risk of interval colorectal cancer. It is uncertain how to improve
adenoma detection skills.
AIMS & METHODS: We compared the effect of teaching leadership in training
versus feedback-only on colonoscopy quality in a nationwide randomized trial.
Forty colonoscopy screening centres with suboptimal performance in the Polish
colorectal cancer screening program (centre leader adenoma detection rate 25%
during pre-intervention period January to December 2011) were randomized to
either a train-the-colonoscopy leaders (TCL) program (pre-training assessment,
hands-on-training courses, post-training feedback) or feedback only (individual
performance quality indicators). Colonoscopies performed June to December
2012 (after intervention) were used to calculate changes in quality measures at
leaders and screening centers level. Primary outcome was change in leaders
adenoma detection rate. Mixed effect models using odds ratios (OR) and 95%
confidence intervals (95%CI) were computed.
RESULTS: The study included 17,341 colonoscopies performed by 40 colono-
scopy leaders, of which 38 completed the study (19 in each group). Mean ade-
noma detection rate of screening centre leaders improved by 8.2% (17.4% -
25.6%) in the TCL group, compared to 1.1% (18.5% - 19.6%) in the feedback
group. In mixed effect models, the TCL group had larger improvements in
adenoma detection rate (OR1.61; 95%CI1.29 to 2.01; p50.001), proximal ade-
noma detection rate (OR1.58; 95% CI1.19 to 2.11; p50.001), and non-polypoid
lesion detection rate (OR2.78; 95%CI 1.53 to 5.05; p0.001). Moreover, in the
TCL group non-polypoid lesion detection rate improved significantly at the
screening centre level (OR 1.85; 95% CI 1.19 to 2.86; p0.006).
CONCLUSION: Teaching colonoscopy leaders in training improved important
quality outcome measures in screening colonoscopy. This may translate into a
reduced interval cancer risk after screening colonoscopy. ClinicalTrials.gov,
NCT01667198.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
OLD AND NEW BIOMARKERS IN IBD HALL I/K_____________________
OP134 LEVELS OF FECAL CALPROTECTIN ARE ASSOCIATED WITH
THE SEVERITY OF POSTOPERATIVE ENDOSCOPIC
RECURRENCE IN PATIENTS WITH CROHNS DISEASE
G. Boschetti1,*, M. Laidet1, D. Moussata1, C. Stefanescu2, X. Roblin3,
G. Phelip1, E. Cotte4, Y. Francois4, J. Drai5, Y. Bouhnik2, B. Flourie1,
S. Nancey1
1
Gastroenterology, Lyon-Sud Hospital, Lyon, 2Gastroenterology, Beaujon
Hospital, Clichy, 3Gastroenterology, North Hospital, Saint-Etienne, 4Surgery,
5
Biochemistry, Lyon-Sud Hospital, Lyon, France
Contact E-mail Address: gilles.boschetti@inserm.fr
INTRODUCTION: Despite surgery in Crohns disease (CD) being almost una-
voidable, disease endoscopic recurrence is common and its presence during the
first year after surgery is predictive of subsequent clinical recurrence. Fecal cal-
protectin (fCal) represents the most studied and widely used marker of gut
inflammation associated with a strong correlation with the severity of endoscopic
presence and severity of postoperative endoscopic recurrence in a cohort of
CD patients after ileo-colonic resection.
AIMS & METHODS: Blood and Fecal samples were collected in 114 CD
patients with a past history of ileocolonic resection followed by an ileo-colonic
anastomosis. A routine ileocolonoscopy was performed in all of them to detect
United European Gastroenterology Journal 2(5S)
endoscopic disease recurrence, according to the Rutgeerts score (graded as  i2).
CRP and fCal were measured and the respective performance and usefulness of
both surrogate markers with respect to the presence and severity of postoperative
endoscopic disease recurrence were assessed by computing correlations, sensitiv-
ity, specificity and predictive values at adjusted cutoffs and also tests operating
characteristics.
RESULTS: A moderate (i2) and a severe ( i3) endoscopic recurrence was
observed in 18 and 36 patients, respectively. FCal concentrations differed sig-
nificantly in patients experiencing evidences for endoscopic recurrence when
compared with those in endoscopic remission (mean  SEM 484.3  71 g/g
vs 118  17 g/g; p50.0001). The area under the ROC curve (AUROC) to
discriminate between patients in endoscopic remission and recurrence was 0.85
for fCal and lower 0.70 for CRP. The best cutoff point for fCal to distinguish
between endoscopic remission and recurrence after surgery was 100 mg/g, as
determined by the ROC curve and its sensitivity, specificity, positive and negative
predictive values as well as overall accuracy were 93 %, 57 %, 66 %, 89 % and 74
%, respectively. In our cohort, fCal concentrations lower than 100 mg/g would
allow with a high accuracy to avoid colonoscopy in almost 31 % of patients.
CONCLUSION: Measurement of fCal concentrations may be a promising and
useful tool for monitoring CD patients after ileocolonic resection. Patients with a
concentration of fCal below 100 mg/g are highly likely to be exempt of endoscopic
recurrence and therefore fCal measurement in CD patients who had undergone
surgery would get some help in making decision for colonoscopy.
Disclosure of Interest: None declared
OP135 PROGNOSTIC VALUE OF COMPLETE REMISSION
PATIENTS WITH MUCOSAL HEALING IN ULCERATIVE COLITIS
T. Lobaton1,2,*, T. Bessissow1, G. De Hertogh3, A. Ruiz-Cerulla2, S. Vermeire1,
G. Van Assche1, B. Lemmens3, R. Bisschops1, J. Guardiola2, M. Ferrante1
1
GASTROENTEROLOGY, LEUVEN UNIVERSITY HOSPITAL, Leuven,
Belgium, 2GASTROENTEROLOGY, HOSPITAL UNIVERSITARI DE
BELLVITGE, Barcelona, Spain, 3PATHOLOGY, LEUVEN UNIVERSITY
HOSPITAL, Leuven, Belgium
Contact E-mail Address: tlobaton@bellvitgehospital.cat
INTRODUCTION: The presence of endoscopic remission (ER) in patients with
ulcerative colitis (UC) predicts better outcome with fewer relapses and colectomy
rates. However, there is scarce data on the additive prognostic value of histolo-
gical and biological activity among patients with both clinical and endoscopic
remission (complete remission).
AIMS & METHODS: To assess the prognostic value of histological and biolo-
gical activity in UC patients with clinical and endoscopic remission.
METHODS: Prospective observational study including 77 UC patients in clinical
and endoscopic remission from 2 referral centres. Clinical remission was defined
as clinical Mayo score53 and no blood in the stools. Biological activity was
assessed with C-reactive protein haemoglobin and albumin levels, and by leuko-
cyte, and platelet counts. ER was defined as a Mayo endoscopic subscore (MES)
of 0-1. Histological activity was assessed according to Geboes score (GS).
Histological activity was defined as GS3.1 (neutrophils in the epithelium).
Patients were followed up after the endoscopy for 12 months. Clinical relapse
(CR) was defined as a clinical Mayo score 3. Univariate and multivariate
analyses were performed to assess predictors of CR.
RESULTS: Baseline characteristics are summarized in Table 1. During follow
up, 21 patients relapsed (9/27 patients with MES grade 1 and 12/50 with MES
grade 0; P0.38), but no colectomies occurred. A GS3.1 was present more
often in patients with MES 1 than in patients with MES 0 (48 vs. 14%;
P0.002). CR was more frequent among patients with GS3.1 (43 vs. 20%;
P0.034). After adjusting for endoscopic activity, a GS3.1 remained as an
independent risk factor for CR (OR 3.1 (95% CI 1.03-9.09), P0.043).
Patients with basal plasmacytosis presented numerically more CR, but differ-
ences were not statistically significant (19 vs. 11%; P0.45). None of the demo-
graphic and biological variables included were predictive for CR (Table 1).
All patients No relapsers Relapsers
Baseline characteristics (n77) (n56) (n21) P Nijhuis A et al. In Crohns disease fibrosis reduced expression of the miR-29
Female (%) 27 (35) 21 (38) 6 (28)
Median (IQR) age (years) 51 (41-60) 51 (42-58) 50 (37-66)
Median (IQR) disease 11 (6-18) 12 (9-20) 8 (2-15)
duration (years)
Montreal classification(%): 13/39/25(17/51/32) 7/29/20(13/52/35) 4/13/4(19/62/19) 0.75
E1/E2/E3
C reactive protein (mg/L): 1.2 (0.9-2.7) 1.2 (0.7-2.5) 1.5 (1-3.6)
median(IQR)
Hemoglobin (g/dL):median(IQR) 14.2 (13.2-15.4) 14.5 (13.2-14.5) 14.1 (13.3-15.6) 0.89
WBC (10**9/L): (IQR) 5.9 (5-7.9) 6.0 (4.9-8) 5.7 (5.1-6.9)
Platelets (10**9/L):median(IQR) 241 (211-295) 249 (212-300) 232 (209-263)
Albumin (g/L):median(IQR) 46 (43-47) 46 (42-47) 46 (44-47)
CONCLUSION: In a prospective cohort, histological activity defined as GS
3.1 predicts CR at 1 year among patients with both clinical and endoscopic
remission.
Disclosure of Interest: T. Lobaton: None declared, T. Bessissow Lecture fee(s)
from: Janssen, AbbVie, Takeda, Shire, Aptalis, Consultancy for: Janssen,
AbbVie, Takeda, Shire, Aptalis, G. De Hertogh Consultancy for: Genentech,
A45
Centocor, Novartis, Shire, Galapagos, A. Ruiz-Cerulla: None declared, S.
Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie,
Lecture fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor,
Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring,
Shire, Pfizer, G. Van Assche: None declared, B. Lemmens: None declared, R.
Bisschops Lecture fee(s) from: Pentax, Fujifilm and Olympus, J. Guardiola:
None declared, M. Ferrante Financial support for research from: Janssen
Biologics, Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy
for: Abbvie, Merck, Janssen Biologics
OP136 PROFILING OF SERUM MICRORNA IDENTIFIES NOVEL
BIOMARKERS OF FIBROSTENOSING CROHNS DISEASE
A. Lewis1,*, L.N. Hanna1, L.A. Rogalski1, A. Nijhuis1, S.J. Mehta1,
T. Kumagai1, P. Biancheri2, J.G. Bundy3, C.L. Bishop4, A. Di Sabatino5,
J.O. Lindsay1, A. Silver1
1
Centre for Digestive Diseases and National Centre for Bowel Research and
Surgical Innovation, Queen Marys University London, 2Centre for Immunology
and Infectious Disease, Barts and The London School of Medicine and Dentistry,
3
Department of Surgery and Cancer, Imperial College London, 4Centre for
Cutaneous Research, Blizard Institute, Barts and The London School of Medicine
and Dentistry, London, United Kingdom, 5Department of Internal Medicine, S.
Matteo Hospital, University of Pavia, Pavia, Italy
Contact E-mail Address: a.lewis@qmul.ac.uk
INTRODUCTION: Fibrostenosing Crohns disease (CD) leads to stricture for-
IN mation and bowel obstruction and is the main indication for surgery. A strictur-
ing phenotype is associated with increased healthcare costs, increased morbidity
and a worse quality of life. It is often difficult to differentiate inflammation from
fibrosis using currently available imaging modalities, and no investigation can
predict the future risk of stricture formation. The development of non-invasive
biomarkers of fibrostenosing CD would represent a significant clinical advance.
MicroRNAs (miRNAs) inhibit protein translation and thereby co-ordinate gene
expression networks. MiRNAs are also present in the circulation, where they are
resistant to degradation and can act as accurate biomarkers of disease. Our lab
has recently demonstrated through targeted assays that the expression of the
miR-29 family is reduced in the mucosa overlying stricture and in the serum of
patients with a stricturing phenotype (SCD). These data suggest that miRNAs
may act as biomarkers of SCD (Nijhuis et al 2014).
AIMS & METHODS: In this study we aimed to explore the potential of serum
miRNAs as biomarkers of fibrostenosing CD. Profiling of RNA isolated from
serum was performed by qPCR array and used to identify miRNAs associated
with SCD (n6) relative to inflammatory CD (n11) and healthy controls (n5).
Differentially expressed miRNAs were subsequently validated by single qPCR
assay in an independent cohort of CD patients (SCD n35; inflammatory n26;
and penetrating n19) and healthy controls (n10).
RESULTS: A supervised modeling approach indicated that the SCD patients
had a unique serum miRNA signature. In this model miR-19a-3p and 19b-3p
contributed most strongly to the separation of SCD patients and inflammatory
CD patients; changes in miR-29a-3p and 29c-3p also contributed, albeit to a
lesser extent. Subsequent qPCR validation in an independent cohort demon-
strated a significant reduction in miR-19a-3p and 19b-3p in SCD patients relative
to inflammatory and penetrating CD groups (i.e. non-stricturing CD). In this
cohort, stepwise linear regression confirmed that the association of the miRNAs
with SCD was not affected by confounding factors, e.g. age, smoking status,
disease duration etc. Levels of miR-19a-3p and 19b-3p also remained low in
SCD patients following surgical resection.
CONCLUSION: We have demonstrated that miR-19a-3p and 19b-3p in serum
are novel predictors of fibrostenosing CD. SCD was associated with low levels of
miR-19a-3p and 19b-3p. The levels remained low in SCD patients after surgical
resection indicating that miR-19a-3p and 19b-3p are markers of an SCD pheno-
type, and not merely the presence of stricture at the time of sampling. A long-
itudinal study is required to determine whether a reduction in serum miR-19
levels predates the development of stricture.
REFERENCES
family enhances collagen expression in intestinal fibroblasts. Clin Sci Immediate
0.47 Publication, 2014. DOI:10.1042/CS20140048
0.86 Disclosure of Interest: None declared
0.06
OP137 CD62L (L-SELECTIN) SHEDDING FOR ASSESSMENT OF
FUNCTIONAL BLOCKADE OF TNF-ALPHA IN ANTI-TNF
TREATED INFLAMMATORY BOWEL DISEASE PATIENTS:
CLINICAL FEASIBILITY AND PERSPECTIVES
0.09
P. Juillerat1,2,*, P. Andrew2, J. Macpherson2, E. Slack2, J. Cahenzli2,
F. Seibold1,3, K.D. McCoy2, A.J. Macpherson1,2
1
University Clinic for Visceral Surgery and Medicine, Gastroenterology, 2Maurice
E Muller Laboratories, Bern University Hospital, 3Gastroenterology,
0.62
Tiefenauspital, Bern, Switzerland
0.37 Contact E-mail Address: pascal.juillerat@insel.ch
0.66
INTRODUCTION: Tumor necrosis factor (TNF) inhibition is central to the
therapy of inflammatory bowel diseases (IBD). However, the durability and
efficacy of this blockade hasnt been well studied and a better understanding is
crucial for the prognosis of long-term treatment and decision making in case of
loss of response (LOR) to these costly anti-TNF agents. Besides the presence of
antibodies against the drug and serum trough levels additional tests to predict
LOR are needed.
AIMS & METHODS: Consecutive IBD Patients receiving anti-TNF therapy
(infliximab (IFX) or adalimumab) from Bern University Hospital were identified
A46
and followed prospectively. Patient whole blood was stimulated with a dose-
titration of either human TNF or the TLR agonist lipopolysaccharide (LPS)
followed by flow cytometry. Median fluorescence intensity of CD62L on the
surface of granulocytes was quantified by surface staining with fluorochrome
conjugated antibodies against CD33 and CD62L. Logistic curves of these data
permit the calculation of EC50 or the concentration of TNF required to induce a
50% shedding of surface CD62L [Patuto et al, DDW 2011]. The change in EC50
following the anti-TNF agent infusion, was used to predict the in vivo response
to the anti-TNF agent. This predicted response was correlated to the clinical
evolution of the patients in order to analyze the ability of this test to identify
LOR.
RESULTS: We collected prospective clinical data and 2 blood samples, before
and after anti-TNF agent administration, on 33 IBD patients, 25 Crohns disease
and 8 ulcerative colitis patients (45% females) between June 2012 and November
2013. The assay showed a functional blockade (PFR) for 22 patients (17 CD and
5 UC) whereas 11 (8 CD and 3 UC) had no functional response (NR). Selected
R) may affect the efficacy
clinical characteristics between predicted PFR and NR are compared below
(Table). Among the 22 Patients with PRF, only 1 patient was a clinical non
responders (LOR to IFX), based on clinical prospective evaluation by IBD gas-
troenterologists (PJ, FS and AJM), and among the 11 predicted NR, 3 had no
RIIa,
clinical LOR. Sensitivity of this test was 95% and specificity 73% and AUC
RIIIa and Fc
RIIIb genes are predictive of sustained clinical remission (SCR)
adjusted for age and gender was 0.81. During follow up (median 10 months,
range 3-15) 8 hard outcomes occurred (3 medic. flares, 4 resections and 1
new fistula) 2 in the PFR and 6 in the NR group (25% vs. 75%; p50.01).
Predicted Predicted
responders non responders
(N22) (N11) p value
RIIa (n84), 158V/F in Fc
RIIIa (n91) and NA1/NA2 in
RIIIb (n87) were analyzed by PCR-RFLP / TaqMan.
Age (years /-SD) 34.8 (/-11) 31 (/- 11) 0.35
Clinical LOR: No/partial/complete 68%/27%/1% 27%/27%/46% 0.01
Perianal 41% 12% 0.15
Dis. Dur. start IFX (years /-SD) 6.9 (/- 6) 3.6 (/- 4) 0.07
RIIIb was
interval reduction needed 23% 73% 5 0.01
Smokers 33% 36% 0.684
CONCLUSION: CD62L (L-Selectin) shedding is the first validated test of func-
tional blockade of TNF alpha in anti-TNF treated IBD patients and will be a
RIIIb NA2/NA2 homozygosity is an
useful tool to guide medical decision on the use of anti-TNF agents. Prospective
comparative studies with antibodies against the drug and trough levels are
ongoing.
Disclosure of Interest: P. Juillerat Lecture fee(s) from: AbbVie, Merck Sharp &
Dohme and Vifor, Consultancy for: AbbVie, Merck Sharp & Dohme and UCB,
P. Andrew: None declared, J. Macpherson: None declared, E. Slack: None
declared, J. Cahenzli: None declared, F. Seibold Consultancy for: AbbVie,
Merck Sharp & Dohme, UCB, K. McCoy: None declared, A. Macpherson:
None declared
OP138 THE NEW FECAL MARKER MATRIX METALLOPROTEASE-9 IS
MORE SENSITIVE FOR DIAGNOSING ULCERATIVE COLITIS AND
POUCHITIS AND FOR DIFFERENTIATING THEM FROM CROHNS
DISEASE THAN FECAL CALPROTECTIN
K. Farkas1,*, Z. Sarodi1, A. Balint1, I. Foldesi1, G. Lazar2, Z. Simonka2,
L. Tiszlavicz3, M. Szu cs4, T. Nyari4, F. Nagy1, Z. Szepes1, R. Bor1,
00
A. Annahazi1, R. Roka1, T. Wittmann1, T. Molnar1
1
First Department of Medicine, 2Department of Surgery, 3Department of
Pathology, 4Department of Medical Physics and Informatics, University of Szeged,
Szeged, Hungary
Contact E-mail Address: farkas.klaudia@gmail.com
INTRODUCTION: Inflammatory biomarkers that correlate with enteric inflam-
mation would be beneficial for monitoring the course of disease and targeting
treatment in patients with inflammatory bowel disease (IBD). Only limited data
are available about the diagnostic accuracy of fecal matrix metalloprotease
(MMP)-9 in IBD.
AIMS & METHODS: The aims of our prospective study was to assess the
diagnostic accuracy of fecal MMP-9 in patients with active Crohns disease
(CD), ulcerative colitis (UC) and pouchitis assessed by clinical, endoscopic and
histological scores and to compare the diagnostic accuracy of fecal MMP-9 and
fecal calprotectin (CP) in IBD. Stool and blood samples were collected in 50 CD,
54 UC and 34 ileal pouch-anal anastomosis patients before control endoscopy.
Biopsies were taken for histology. The activities of CD, UC and pouchitis were
defined with the use of clinical, endoscopic and histological activity scores
(CDAI, partial Mayo score, PDAI, SES-CD, Mayo endoscopic subscore,
DHaens and Riley score). Fecal CP and MMP-9 levels were quantified by use
of enzyme-linked immunosorbent assay.
RESULTS: Active CD, UC and pouchitis was detected in 38%, 54% and 29% of the
patients. Significant correlation was revealed between fecal CP and the clinical activ-
ities of CD and UC, and between fecal CP and the endoscopic activity of UC and
pouchitis. No correlation was found between fecal CP and the other examined
activity scores in CD, UC and pouchitis. Fecal MMP-9 did not correlate with any
of the activity indices of CD, however strong association was shown between fecal
MMP-9 and clinical, endoscopic and histological activities of both UC and pouchitis.
CONCLUSION: This is the first study assessing the diagnostic accuracy of
MMP-9 in different types of IBD. Our results showed that fecal MMP-9 has
an exclusively high specificity in the detection of active UC and pouchitis. These
non-invasive methods help assessing intestinal inflammation and also differen-
tiating between CD and UC.
United European Gastroenterology Journal 2(5S)
Disclosure of Interest: None declared
OP139 FC GAMMA RECEPTOR MUTATIONS FOR PREDICTION OF
SUSTAINED CLINICAL REMISSION AFTER INFLIXIMAB
DISCONTINUATION IN CROHNS DISEASE PATIENTS
K. Papamichail1,*, M. Arias1, M. Ferrante1, V. Ballet1, K. Claes1,
W.J. Wollants1, G. Van Assche 1, P.J. Rutgeerts1, S. Vermeire1
1
KU Leuven, Department of Clinical and Experimental Medicine and University
Hospitals Leuven, Department of Gastroenterology, Leuven, Belgium
Contact E-mail Address: konstantinos.papamichail@med.kuleuven.be
INTRODUCTION: Genetic markers, as compared to serologic markers, could
theoretically be superior for predicting inflammatory bowel disease (IBD) out-
comes as genes are not affected by disease activity and are stable over time.
Genetic polymorphisms of Fc gamma receptors (Fc
of immunoglobulin (Ig)-based therapies by influencing the affinity of Ig to the
receptors. We therefore hypothesized that these could facilitate prediction of
sustained remission after anti-TNF discontinuation in IBD.
AIMS & METHODS: We aimed to investigate if polymorphisms in the Fc
Fc
after infliximab (IFX) cessation for clinical remission in Crohns disease (CD)
patients. In this single-center retrospective study, 100 CD patients who discon-
tinued IFX for clinical remission (luminal CD, n57) were identified from an
electronic database. The majority of patients (n84) continued on immunomo-
dulators. SCR was defined as maintained disease remission without the need to
re-introduce medical therapy (biologicals, corticosteroids, thiopurines or metho-
trexate) or surgery until the end of follow up. The functional polymorphisms
131H/R in Fc
Fc
RESULTS: With a median follow up of 9.7 (IQR 8-11.5) years, 52/100 patients
had SCR. Univariate (Log-Rank) analysis revealed no significant association of
the investigated polymorphisms with either SCR or relapse after IFX disconti-
nuation for clinical remission. Nevertheless, individual analysis of patients with
luminal CD interestingly showed that NA2/NA2 homozygosity in Fc
associated with increased risk for relapse (HR:2.4, 95%CI:1.1-5.3, p0.021).
Multiple COX regression analysis identified NA2/NA2 homozygosity as an inde-
pendent variable predicting relapse after IFX cessation (HR:2.3, 95%CI:1.03-5.1,
p0.043).
CONCLUSION: We identified that Fc
independent factor predicting relapse in patients with luminal CD who discon-
tinue IFX for clinical remission. The lack of NA1 variant, which shows a higher
affinity for IgG1 and probably leads to a more efficient downstream effects
(antibody-dependent cellular cytotoxicity), may therefore predispose to relapse
after IFX cessation in patients with luminal CD. Of note, NA1/NA1 homozyg-
osity was previously found to be associated with higher biological response to
IFX in IBD patients.1
REFERENCES
Arias MT, et al. Gastroenterology 2011; 140 (Suppl. 1): S1.
Disclosure of Interest: K. Papamichail Consultancy for: MSD Hellas, M. Arias:
None declared, M. Ferrante Financial support for research from: Janssen
Biologics, Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy
for: Abbvie, Merck, Janssen Biologics, V. Ballet: None declared, K. Claes:
None declared, W. J. Wollants: None declared, G. Van Assche Financial support
for research from: Abbvie, Ferring, Lecture fee(s) from: Janssen-Cilag, Merck,
Abbvie, Consultancy for: PDL BioPharma, UCB Pharma, Sanofi-Aventis,
Abbvie, Ferring; Novartis, Biogen Idec, Janssen Biologics, NovoNordisk,
Zealand Pharma A/S, Millenium/Takeda, Shire, Novartis, BMS, P. Rutgeerts
Financial support for research from: UCB Pharma, Abbvie, Janssen Biologics,
Merck, Prometheus, Lecture fee(s) from: Abbvie, Merck, Consultancy for:
Amgen, Merck, UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics,
Millenium, Neovacs, Actogenics, Prometheus, S. Vermeire Financial support
for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from: Abbvie,
Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB Pharma,
AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer
OP140 PHARMACOLOGICAL INTERVENTION BASED ON FECAL
CALPROTECTIN LEVELS IN PATIENTS WITH ULCERATIVE
COLITIS AT HIGH RISK OF A RELAPSE: A PROSPECTIVE,
RANDOMIZED, CONTROLLED STUDY
A. Lasson1,*, L. Ohman2,3, S. Per-Ove3, S. Isaksson2,3, O. Uberbacher4, K.-
A. Ung5, H. Strid3
1
Department of Internal Medicine, Sodra Alvsborgs Hospital, Boras, 2Department
of Biomedicine, Sahlgrenska Academy, 3Department of Internal Medicine,
Sahlgrenska University Hospital, Gothenburg, 4Department of Internal Medicine,
Hallands Hospital, Varberg, 5Department of Internal Medicine, Skaraborgs
Hospital, Skovde, Sweden
Contact E-mail Address: anders.lasson@vgregion.se
INTRODUCTION: Pharmacological treatment of ulcerative colitis (UC) is tra-
ditionally divided into treatment of active disease and treatment to maintain
remission. Recently, targeted therapy for patients at increased risk of a flare,
using biomarkers to detect subclinical disease activity, has been proposed.
The objective of this study was to assess if fecal calprotectin (FC), as a marker for
inflammatory activity, can be used to guide medical intervention, to maintain
remission in patients with UC.
AIMS & METHODS: In this open-label, prospective, controlled study, 91 adult
patients with UC in clinical remission, and under treatment with an oral 5-ASA
agent, were randomized to either an intervention group (n51) or a control
group (n40). All patients had at least one flare within one year prior to the
United European Gastroenterology Journal 2(5S)
inclusion. Patients on corticosteroids or anti-TNF therapy at inclusion were
excluded. A stool sample for analysis of FC was delivered monthly during 18
months. A FC value of 4 300 mg/g was set as cut-off for intervention. Provided
that a second stool sample, delivered within a week, confirmed a FC value above
the cut-off level, a dose escalation of the 5-ASA agent was performed in the
intervention group. Accordingly, the dosages of Asacol (mesalazine),
Pentasa (mesalazine), or Colazid (balsalazide) were increased to 4.8 g, 4.0 g
and 6.75 g, respectively. This dose was maintained until the FC value was 5 200
mg/g, but for at least 3 months. No action was taken in the control group until
clinical signs of a relapse were recorded. The primary end-point was the number
of patients to have relapsed at month 18. Secondary end-points were time to
relapse and the need for corticosteroids.
RESULTS: Eighteen (35.3 %) patients in the intervention group suffered at least
one relapse over the 18-month period, compared with 20 (50.0 %) of those in the
control group (p0.231). The time to first relapse was 14.2  5.9 vs 12.1  6.9
(mean  SD) months in the two groups, respectively (p0.125). Dose escalation
due to a FC value above the cut-off level was accomplished in 28 (54.9 %)
patients in the intervention group. In the control group, 28 patients (70.0 %)
had at least one FC value 4 300 mg/g. In all, 8 (28.6 %) and 16 (57.1%) of these
patients with a FC 4 300 mg/g experienced a relapse, in the intervention and
control groups, respectively (p 5 0.05). In all, 9 and 6 patients in the intervention
group and 6 and 5 patients in the control group were treated with oral and topical
corticosteroids during a flare, respectively (NS).
CONCLUSION: In this trial with UC patients at high risk of disease relapse, we
found no significant difference in relapse rates between the patients with targeted
therapy based on FC levels and the patients in the control group. However,
among the patients with active intervention due to a FC above the cut-off
level, the relapse rate was significantly lower as compared to the patients in
the control group with a FC value 4 300 mg/g. Thus, our results indicate, that
FC-levels might be used to identify patients with UC at risk for an imminent
disease flare before symptoms develop, and that dose escalation of a 5-ASA agent
is a therapeutic option for these patients.
Disclosure of Interest: None declared
OP141 STOOL TESTS CAN POTENTIALLY RULE OUT SIGNIFICANT
BOWEL DISEASE IN SYMPTOMATIC PATIENTS IN PRIMARY
CARE
J. Digby1,*, R. J. C. Steele2, J.A. Strachan3, C. Mowat4
1
University of Dundee, Dundee, United Kingdom, 2Medical Research Institute,
University of Dundee, 3Scottish Bowel Screening Centre, 4Department of
Gastroenterology, Ninewells Hospital and Medical School, Dundee, United
Kingdom
Contact E-mail Address: jaynedigby@nhs.net
INTRODUCTION: Assessment of colorectal symptoms in primary care is diffi-
cult as they are poor predictors of underlying pathology. Patients presenting with
new symptoms are frequently referred for colonoscopy, which is the gold stan-
dard for detection of significant bowel disease (SBD; colorectal cancer (CRC),
high risk adenoma (HRA, defined as  3 or any  1 cm) and inflammatory bowel
disease (IBD)). When symptomatic patients are brought to colonoscopy, yield of
SBD is low, with local audit revealing CRC yield of only 2%. Faecal immuno-
chemical tests for haemoglobin (FIT) are established in colorectal cancer screen-
ing, as faecal calprotectin (CPT) tests are in IBD clinics. We aimed to test their
performance in primary care as a means to reduce unnecessary colonoscopy.
AIMS & METHODS: Over a six-month period, general practitioners (GPs) in one
health board in Scotland were prompted when referring patients with colorectal
symptoms to the Colorectal Service to obtain single samples of faeces for each
stool test (OC-Sensor FIT and BUHLMANN Calprotectin ELISA). Patients
referred to endoscopy were appointed within six weeks of referral. Clinical out-
comes were collected for all patients completing the tests and undergoing endo-
scopy. Analysis of test performance for identification of SBD was performed.
RESULTS: To date, 1000 patients have participated and analysis is ongoing. At
present, a total of 569 patients (52.7% female, median age 64 years (range: 16-90,
IQR: 52-73) have completed both stool tests and had clinical outcomes available.
CRC was detected in 24 patients, 36 had HRA and 32 cases of IBD were diag-
nosed. FIT at the manufacturers recommended cut-off concentration of 50ng/ml
or above was present in 25.2% of referrals and at this cut-off, positive predictive
value (PPV) for SBD would be 43.0%, negative predictive value (NPV) 92.9%,
sensitivity 67.0% and specificity 82.8%; no CRC cases were below 50ng/ml but
48.6% patients with HRA and 40.6% of IBD cases were below this cut-off. The
CPT test at the manufacturers recommended cut-off concentration of 50mg/ml
or above was present in 60.0% of referrals and would give a PPV 19.9%, NPV
90.5%, sensitivity 75.9% and specificity 42.9%, however two cases of CRC had a
reading of below 50mg/ml along with 39.2% of HRA and 17.2% of IBD cases.
Further results will be available once analysis is complete.
CONCLUSION: If we use FIT at a 50ng/ml cut-off concentration in primary
care it would potentially reduce referrals by around 75% whilst affording GPs
confidence that CRC in negative patients is highly unlikely, with no CRC cases
were present below this concentration in our cohort. The CPT test did not per-
form as well, but combining the tests is an option to reduce missed cases of HRA
and IBD; however, this would produce many more referrals and false positives. If
we are setting an arbitrary cut-off concentration for FIT of 50 ng/ml, we would
have to accept that a number of HRA would be missed and we would have to
balance the risk of not referring patients with these lesions against the risks
associated with unnecessary colonoscopy. Using FIT in primary care may help
target colonoscopy more appropriately when patients present with colorectal
symptoms.
Disclosure of Interest: None declared
A47
OP142 FECAL CALPROTECTIN AFTER ILEOCAECAL RESECTION
FOR CROHNS DISEASE: CORRELATION WITH RUTGEERTS
SCORE
D.G. Ferreira1,*, P. Lago 1, C. Caetano1, M. Salgado1, I. Pedroto1
1
Gastroenterology, Centro hospitalar do porto, Oporto, Portugal
INTRODUCTION: Crohns Disease (CD) has a high frequency of recurrence
after ileocaecal resection. Ileocolonoscopy remains the gold standard method to
assess postoperative recurrence. The severity of endoscopic findings in the ana-
stomotic area according to Rutgeerts score is considered to reflect the subsequent
clinical course. However ileocolonoscopy is an invasive method and suboptimal
when a dynamic evaluation of the inflammatory process is desired. Fecal calpro-
tectin (FC) has been shown to correlate with findings at ileocolonoscopy in CD.
However few studies and with few patients have evaluated the accuracy of FC in
predicting postoperative recurrence in CD. Currently the role of this biomarker
in this specific scenario of postoperative recurrence is largely unknown.
n
AIMS & METHODS: The aim of this study was to assess the correlation
w
between the concentration of fecal calprotectin and endoscopic findings one
d ra
year after ileocaecal resection for Crohns Disease.
Prospective cohort study. Adult patients with CD that performed ileocaecal
i t h
resection between September 1, 2011 and December 31, 2013 were considered
W
for inclusion. Variables analyzed: age, sex, Montreal classification, smoking
habits, concentration of FC one year after surgery, ileocolonoscopy findings
one year after ileocaecal ressection according with Rutgeerts score. The sensitiv-
ity and specifity of FC was assessed using endoscopic findings as gold standard.
Endoscopic recurrence was considered if the Rutgeerts score was  i2. A ROC
curve was performed to assess the best cut-off value for FC.
RESULTS: 22 patients were included. 48% males; 36% smokers. Endoscopic
findings one year after ileocaecal resection according to Rutgeerts score was: i0
(n9), i1 (n4); i2 (n2); i3 (n2) and i4 (n5). Average fecal calprotectin
concentration one year after surgery was 149.12 ug/g [minimum 10, maximum
562] in i0 group; 751.7 ug/g [minimum 81, maximum 1888] in the i1 group; 181
ug/g [minimum 157, maximum 205] in the i2 group; 424 ug/g [minimum 55,
maximum 793] in the i3 group and 529.8 ug/g [minimum 33, maximum 1117]
in the i4 group. In this study the concentration of fecal calprotectin was not
statistically different between the group with endoscopic remission and the
group with endoscopic recurrence (p0.31). However, all patients with fecal
calprotectin concentration 4 570ug/g had endoscopic recurrence. Some patients
(n4) with endoscopic recurrence had FC 5 200ug/g. The sensibility and speci-
ficity of FC was calculated using 5 cut-offs. The best cut- off for a 67% sensitivity
and 81% specificity was 4 200ug/g. Thus, a value greater than 200ug/g of FC 1
year after surgery shows a strong correlation with the presence of endoscopic
recurrence of CD, although we have observed a high number of patients with
endoscopic recurrence with values below this cut -off.
CONCLUSION: Fecal calprotectin is a biomarker that, according to this study,
has a high specificity but moderate sensitivity for predicting postoperative recur-
rence in CD. All patients with FC 4 570ug/g had endoscopic recurrence. Studies
with a larger number of patients are needed to better define the role of calpro-
tectin in this scenario.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
IMPLICATIONS OF MOLECULAR PATHOGENESIS ON ENDOSCOPIC THERAPY FOR
BARRETTS OESOPHAGUS HALL L/M_____________________
OP143 A FISH BIOMARKER PANEL FOR THE PREDICTION OF HIGH-
GRADE DYSPLASIA AND ADENOCARCINOMA IN NON-
DYSPLASTIC BARRETTS ESOPHAGUS; RESULTS FROM A LONG-
TERM PROSPECTIVE COHORT STUDY
M.R. Timmer1,*, C.T. Lau1, W. Rosmolen1, S.L. Meijer2, M.G. Dijkgraaf3,
P. Fockens1, J.J. Bergman1, K.K. Krishnadath1 on behalf of On behalf of the
North Holland, GUT club
1
Department of Gastroenterology and Hepatology, 2Department of Pathology,
3
Clinical Research Unit, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: m.r.timmer@amc.uva.nl
INTRODUCTION: Barretts esophagus (BE) with no dysplasia is associated
with a risk as low as 0.1% per year of developing esophageal adenocarcinoma
(EAC). Predictive biomarkers would be of great clinical value in facilitating more
cost-effective surveillance. Due to the low progression rate of non-dysplastic BE,
biomarker studies require long-term follow-up as well as a robust sample size and
are therefore scarce.
AIMS & METHODS: We conducted a prospective multicenter cohort study in a
community-based setting of Barrett patients with no dysplasia to determine
genetic predictors of progression. All patients were enrolled in an endoscopic
surveillance program. Genetic abnormalities were detected on endoscopic cytol-
ogy brushes by fluorescence in situ hybridization (FISH) using a probe-set
including probes for P16, P53, Her-2/neu, 20q, and MYC, and the chromosomal
centromeric probes 7 and 17 to detect aneuploidy. All markers were dichoto-
mized into normal/abnormal based on cut-off values determined using ROC
curves. Endpoints were progression to high-grade dysplasia (HGD) or EAC.
RESULTS: A total of 428 patients were included in the study (345 males; age 59
 12 y.o.; BE length 3 cm, IQR 2-6) Median follow-up was 45 months (IQR 35
72). There were 22 patients (5%) with histologic progression after review by 2
expert pathologists; 13 cases of HGD and 9 cases of EAC. Univariable analysis
revealed that P16, and aneuploidy were significantly associated with progression,
as well as the clinical variables age and maximum Barrett segment length (M).
The remaining markers showed a non-significant tendency towards increased
odds of progression. Patients who tested positive for P16 and/or aneuploidy
were designated as marker-positive. Kaplan-Meier analysis revealed that there
A48
was a significant difference in time to progression between the two groups (Log-
rank P0.009; Figure 1). The overall rate of progression to HGD/EAC was
1.09% per patient-year. Marker-positive patients had a higher annual risk to
progress to HGD/EAC (1.85%) than marker-negative patients (0.58%)
(P0.015). In a multivariate proportional hazards model, controlling for M
and age, a positive FISH result was a significant predictor of histological pro-
gression to HGD/EAC (HR 3.23; 95% CI 1.32-7.95).
CONCLUSION: A FISH panel assessing aneuploidy and P16, can be used as a
decision making tool to stratify nondysplastic Barrett patients into low- and
high-risk disease categories to improve the efficacy of surveillance programs.
Disclosure of Interest: M. Timmer Other: The FISH probes used in this study
were donated by Abbott Molecular., C. T. Lau: None declared, W. Rosmolen:
None declared, S. Meijer: None declared, M. Dijkgraaf: None declared, P.
Fockens: None declared, J. Bergman: None declared, K. Krishnadath: None
declared
OP144 PERSISTENT HUMAN PAPILLOMAVIRUS INFECTION AND
P53 OVEREXPRESSION ARE ASSOCIATED WITH TREATMENT
FAILURE AFTER ENDOSCOPIC ABLATION OF BARRETTS
OESOPHAGUS
S. Rajendra1, B. Wang2, D. Pavey3, P. Sharma4, T. Yang5, C.S. Lee5,
N. Gupta6,*, R.S. Gill3, X.J. Wu5
1
Gastroenterology/Hepatology, Bankstown-Lidcombe Hospital, 2South Western
Sydney Clinical School, University of New South Wales, 3Department of
Gastroenterology/Hepatology, Bankstown-Lidcombe Hospital, Sydney, Australia,
4
Gastroenterology & Hepatology, Veterans Affairs Medical Center & University of
Kansas City, Kansas, United States, 5Anatomical Pathology, South Western Area
Pathology Service, Sydney, Australia, 6Gastroenterology & Nutrition, Loyola
University Medical Center, Maywood, United States
Contact E-mail Address: Shan.Rajendra@sswahs.nsw.gov.au
INTRODUCTION: Recently, we reported that transcriptionally active high-risk
HPV was strongly associated with Barretts dysplasia (BD) and oesophageal
adenocarcinoma (OAC) suggesting a potential role in oesophageal carcinogen-
esis.1 Moreover, increasing viral load and integration status was significantly
associated with disease severity along the Barretts metaplasia-BD-OAC
pathway.2
AIMS & METHODS: Thus, HPV and p53 (a good predictor of dysplasia pro-
gression in Barretts oesophagus) clearance was examined in relation to treatment
outcome after endoscopic ablation of BD/OAC. Forty patients with BD/neopla-
sia undergoing RFA/-EMR were included in the study. Pre/post-treatment
biopsies obtained from the lesion/neo-squamous epithelium were analysed for
HPV DNA (nested PCR), viral transcriptional markers (E6/E7mRNA and
p16INK4A) and p53.
RESULTS: Post-ablation, 34/40 subjects achieved complete eradication of dys-
plasia and 24 reverted to squamous epithelium and 10 to intestinal metaplasia.
Pre-ablation, 15 patients were positive for transcriptionally active hr-HPV. 13/15
patients cleared HPV and transcriptional markers after a median of 6.7 months
(range 4 to 23.1). All but one who cleared the virus eliminated dysplasia/OAC
whereas 2 who continued to have detectable HPV oncogene activity had persis-
tent dysplasia (p50.05). A single patient with biologically active HPV and high-
grade dysplasia at pre-ablation, cleared the virus post-treatment and subse-
quently developed persistent p53 positivity with progression to cancer. Of thir-
teen p53 positive patients pre-ablation, 2 had non-biologically active HPV. 10/13
patients cleared p53 overexpression after a median of 6.7 months (range 3 to
36.4) becoming disease free, whilst 3/13 with persistent p53 mutation continued
to have detectable dysplasia at the end of the investigation (p0.004). 12/40
patients negative for both HPV & p53 at pre-ablation eradicated dysplasia/neo-
plasia. All patients with persistent/progressive dysplasia/neoplasia at the end of
the study (6/40) had either detectable biologically active hr-HPV (n2) or over-
expression of p53 (n4). Only 1/10 patients with intestinal metaplasia (post-
treatment) had persistent laboratory abnormality (p53 over-expression) at the
end of the investigation. 0/24 individuals who reverted to squamous epithelium
had any detectable transcriptionally active hr-HPV or p53 mutation. There were
no cases of recurrence.
CONCLUSION: Most HPV infected BD/OAC patients cleared the infection
with endotherapy. Persistence/progression of dysplasia/neoplasia after endo-
scopic ablation of BO was associated with the presence of either HPV oncogenic
activity (viral persistence) or p53 overexpression.
REFERENCES
1. Rajendra S, Wang B, Snow ET, et al. Transcriptionally active human papillo-
mavirus is strongly associated with Barretts dysplasia and esophageal adenocar-
cinoma. Am J Gastroenterol 2013; 108: 1082-1093.
2. Wang B, Rajendra S, Pavey D, et al. Viral load and integration status of high-
risk human papillomaviruses in the Barretts metaplasia-dysplasia-adenocarci-
noma sequence. Am J Gastroenterol 2013; 108: 1814-1816.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
TUESDAY, OCTOBER 21, 2014 8:3010:30
RISK FACTORS AND MANAGEMENT OF UPPER GI BLEEDING HALL
N_____________________
OP145 DERIVATION AND VALIDATION OF A PROGNOSTIC SCORE
IN OVER 12,000 PATIENTS WITH ACUTE UPPER
GASTROINTESTINAL BLEEDING
B. Kahan1, A. Barkun2, M. Martel2, R. Bryant3, Q. Nyguen3, V. Jairath4,*
1
Queen Mary University, London, United Kingdom, 2McGill University Health
Centre, Montreal, Canada, 3Royal Adelaide Hospital, Adelaide, Australia,
4
Nuffield Department of Medicine, University of Oxford, Oxford, United Kingdom
INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common med-
ical emergency worldwide. Early risk assessment is an essential part of manage-
ment to help identify appropriate support and timely endoscopy for high risk
patients as well as early discharge for low risk patients. The Rockall and
Glasgow-Blatchford (GBS) scores are the most commonly utilised indices, with
the former a better prediction tool for mortality and the latter for identification
of low risk patients.
AIMS & METHODS: We aimed to derive and validate a new risk score which
combines features of both the Rockall and GBS scores to create a single scale
which could better identify low risk patients, as well as higher risk patients
requiring intervention (therapeutic endoscopy, surgery/embolisation) and at
risk of adverse outcome (mortality, rebleeding). Variables were selected for inclu-
sion in the model based upon widespread association with outcomes plus clinical
judgement. The new score was derived using three large observational data-sets
(UK audit, Canadian RUGBE and REASON studies) and ranged on a scale
from 0-20. The score was then validated in two independent data-sets (a UK
randomised trial and an Australian database). Receiver operating characteristics
were used to compare the performance of the new score with the Rockall and
GBS scores, as well as quantifying the number of patients with events (thera-
peutic endoscopy, mortality, rebleeding, and surgery) at a score of 3 in com-
parison to the GBS.
RESULTS: Variables in the new score were age, blood pressure, pulse, haema-
temsesis, melaena, syncope, haemoglobin, urea, liver disease and malignancy.
The score was derived in 10639 cases of UGIB and validated in 1606 cases.
The new score was superior to the GBS in predicting mortality (AUROC 0.77
vs. 0.74; P0.05), had a higher AUROC for surgery/radiological embolisation
(0.72 vs. 0.70; P0.51), and was identical for rebleeding (AUROC 0.68 vs. 0.68);
it performed less well than the GBS for predicting therapeutic endoscopy
(AUROC 0.77 vs. 0.78; P0.05). The new score was superior to the Rockall
score in predicting need for therapeutic endoscopy (AUROC 0.77 vs. 0.66;
50.01), transfusion (AUROC 0.90 vs. 0.75; P50.01), rebleeding (AUROC
0.68 vs. 0.64; P0.09), surgery/embolisation (AUROC 0.72 vs. 0.72; P0.01);
it had a lower AUROC than the Rockall score for mortality (0.77 vs. 0.79,
P0.43). Using a threshold of 3 for the new score, fewer patients experienced
all of the clinical endpoints of need for therapeutic endoscopy [2.3% (10/437) vs.
3.3% (20/600)], rebleeding [2.3% (10/436)] vs. 2.7% (16/597)], mortality [0.5%
(2/437) vs. 1.3% (8/600)] or surgery [0.5% (2/437) vs. 0.7% (4/600)] in compar-
ison to patients with a GBS score of 3.
CONCLUSION: We have successfully derived and externally validated a novel
risk score for UGIB which can be used to triage both low and high risk patients
with UGIB. It performs better than the Rockall score for all outcomes apart
from mortality and better than GBS in predicting mortality and need for surgery/
embolisation. It also performs more favourably than the GBS in identifying low
risk patients with a score of 3. The study was performed in a large sample size
across three continents, enhancing the generalisability of the results. Further
validation of the score is now warranted.
Disclosure of Interest: None declared
OP146 A MODEL TO ASSESS THE RISK FOR ASA/NSAID-RELATED
ULCER BLEEDING FOR THE INDIVIDUAL PATIENT BASED ON
THE NUMBER OF RISK FACTORS
J.M. Petersen1,*, J. Hallas2, M. Dall1, O.B. Scaffalitzky de Muckadell1, J. Mller
Hansen1
1
Department of Medical Gastroenterology, Odense University Hospital, 2Research
Unit of Clinical Pharmacology, University of Southern Denmark, Odense,
Denmark
Contact E-mail Address: jmpetersen@health.sdu.dk
INTRODUCTION: Aspirin/NSAID related peptic ulcer bleeding occurs in 1-3%
of patients and with a mortality rate of 10-15%. A number of risk factors are well
established, but the incidence rate for the individual patient with a given set of
risk factors is unknown. The aim of this study was to develop a model that could
predict the incidence rate of UGB in users of ASA/NSAID based on the presence
of well-defined risk factors for the individual patient.
AIMS & METHODS: The model was developed on data from a case-control study.
Cases were all diagnosed with upper gastrointestinal bleeding (UGB) from 1995-2006.
Controls were sampled from the source population by use of a risk-set technique. All
cases and controls were characterized in terms of factors known to affect the risk of
UGB. By use of census data, we inflated the control group, so that their composition
accurately reflected the age and gender distribution of the source population.
The incidence rate of UGB was calculated among 80-89 year old women, who
were users of NSAID, but not corticosteroids, ASA or SSRI and had no ulcer
history. This constituted the largest subgroup and could thus be used as refer-
ence. We used multivariate logistic regression and included first-order interac-
tions which could be meaningfully interpreted.
RESULTS: Number of cases was 1388. The adjusted incidence rate ratios (IRR)
for each risk factor was found with the reference: woman aged 80-89 and in
NSAID-treatment:incidence UGB: 12.1/1000 patient-year.
United European Gastroenterology Journal 2(5S)
OP146
Adjusted incidence 95% Confidence
rate ratio intervals
Male 1.23 1.11-1.38 Warfarin-treatment
Age 60 ar 0.10 0.08-0.12 ADP-inhibitor (clopidogrel)
60-69 ar 0.27 0.23-0.32 Dipyridemol
71-79 0.47 0.42-0.54 Corticosteroids
80-89 1.0 Reference group SSRI
90 ar 1.35 1.10-1.65 Prior ulcer
Low dose ASA-alone 0.55 0.48-0.62 Interactions: age 5 60 years* Aspirin and NSAID
ASA and NSAID 2.13 1.80-2.50 Interaction: age 5 60 years * Aspirin alone
An example: Male (1.23) aged 85 (1.0) in warfarin-treatment (2.56). corticoster-
oids (1.84) and SSRI (1.80). 1.23*1.0*2.56*1.84*1.80*12.1 125.74 risk/1000
pers /year.
CONCLUSION: This model allows an estimate of the incidence rate for UGB
for each patient group based on the individual pattern of risk factors. Further
studies are needed to confirm the validity of the model.
Disclosure of Interest: None declared
OP147 RISK FACTORS FOR EARLY AND DELAYED POST-OPERATIVE
BLEEDING AFTER ENDOSCOPIC SUBMUCOSAL DISSECTION OF
GASTRIC NEOPLASMS
T. Matsumura1,*, M. Arai1, K. Okimoto1, S. Minemura1, D. Maruoka1,
T. Nakagawa1, O. Yokosuka1
1
Department of Gastroenterology and Nephrology, Chiba University, Chiba, Japan
Contact E-mail Address: matsumura919@yahoo.co.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely
recongnized as the optimal treatment for gastric neoplasms. Safety of gastric
ESD has been almost established, post-operative bleeding is sill the main concern
affecting the safety, effectiveness, and outcome of the procedure.
AIMS & METHODS: Our aim of this study was to identify risk factors for post-
operative bleeding after gastric ESD, and to evaluate the relevance between such
risk factors and the time of post-operative bleeding.
There were 413 patients with 425 gastric neoplasms consecutively treated by ESD
from June 2005 to March 2014. Demographic and clinical parameters associated
with post-operative bleeding were investigated. 83 patients (20.0%) were receiv-
ing antithrombotic agents, and they were assessed separately by the methods of
how to use such agents during ESD procedure. Post-operative bleeding that
occurred during the first 5 postoperative days was defined as early post-operative
bleeding, whereas subsequent bleeding was defined as delayed post-operative
bleeding.
RESULTS: Overall post-operative bleeding rate was 4.8%. In multivariate ana-
lysis, intravenous heparin replacement (HR), chronic kidney disease (CKD)
undergoing hemodialysis, and a specimen size of  40 mm were predictive factors
for post-operative bleeding (odds ratio 5.77, 95 % CI: 1.67-19.96, odds ratio
33.86, 95 % CI: 4.72-242.74, and odds ratio 3.70, 95 % CI: 1.09-12.52, respec-
tively). A specimen size of  40 mm was a predictive factor for early post-
operative bleeding (odds ratio 6.08, 95 % CI: 1.74-21.27), and HR and CKD
undergoing hemodialysis are risk factors for delayed one (odds ratio 12.23, 95 %
CI: 2.63-56.77 and odds ratio 28.35, 95 % CI: 4.67-172.11, respectively).
CONCLUSION: Large size of specimen is a risk factor for early post-operative
bleeding, and intravenous HR and CKD undergoing hemodialysis are risk fac-
tors for delayed one. Patients with one or more risk factors should be watched
carefully allowing for the timing of post-operative bleeding after ESD.
Disclosure of Interest: None declared
OP148 VALIDATION OF A NEW BEDSIDE PROGNOSTIC SCORE
(AIMS65) IN UPPER GASTROINTESTINAL BLEED
R.B. Thandassery1,*, M. Sharma1, S.A. Mohiuddin1, S.R. Al Kaabi1
1
Gastroenterology, Hamad General hospital, Doha, Qatar
Contact E-mail Address: doc.ragesh@gmail.com
INTRODUCTION: There are various risk stratification scores available for pre-
dicting outcome in upper gastrointestinal (GI) bleed. However they are cumber-
some and sometimes require endoscopic evaluation and therefore are rarely
applied for early risk stratification.
AIMS & METHODS: To prospectively evaluate the newly proposed early bed-
side score, AIMS65 (A-albumin, I-INR, M-Mental status, S Systolic Blood
pressure), in patients with acute upper GI bleed admitted to our tertiary care
hospital
251 consecutive patients presenting with acute upper GI bleed, from January
2012 to December 2012, were included in the study. The AIMS65 scores were
calculated by allotting 1 points each for albumin (A) 530g/l, INR (I) 41.5,
alteration in mental status (M), systolic blood pressure (S) 90mmHg and age
 65 years. The risk stratification was completed within 24 hours of hospital
admission. Patients were managed as per standard protocol and outcomes were
evaluated.
RESULTS: The mean age of study group was 52.4 years with 193 males. The
etiology for upper GI bleed was duodenal ulcer in 74 (29.6%), gastric ulcer in 38
(15.2%) and esophageal varices in 32 (12.8%) patients. 51 patients (20.3%)
required intensive care unit (ICU) admission. The mean hospital and ICU stay
A49
Adjusted incidence 95% Confidence
rate ratio intervals
2.56 1.98-3.28
5.47 3.88-7.72
1.29 1.02-1.61
1.84 1.56-2.17
1.80 1.53-2.10
2.67 2.18-3.27
4.83 2.41-9.67
2.82 1.82-4.36
were 10.616.9 and 4.65.4 days respectively. The overall mortality was 10.3%
(n26).
The mortality in those with AIMS65 scores of 0,1,2,3 and 4 were 3%, 7.8%,
20%, 36% and 40% respectively. The mortality was significantly higher in those
with score 3 (37.1%) as compared to those with score 53 (6%), p50.001. The
predictive accuracy for mortality with a score 3 was high (area under the
receiver operator characteristics curve 0.70, 95% CI 0.57-0.82). The mean
hospital stay (21.531.1 versus 9.012.8 days, p0.040) and ICU stay (5.1 6.1
versus 3.53.6 days, p0.042) were significantly higher in patients with scores 3
as compared to those with 53.
CONCLUSION: AIMS65 is a simple, accurate, non endoscopic risk score that
can be applied early (within 24 hours of hospital admission) in patients with acute
upper GI bleeding. AIMS65 score 3 predicts high in-hospital mortality and
increased duration of hospital and ICU stay.
REFERENCES
1. Saltzman JR, Tabak YP, Hyett BH, et al. A simple risk score accurately
predicts in-hospital mortality, length of stay, and cost in acute upper GI bleeding.
Gastrointest Endosc 2011; 74: 1215-24.
Disclosure of Interest: R. Thandassery Financial support for research from: Nil,
Lecture fee(s) from: Nil, Consultancy for: Nil, Shareholder of: Nil,
Directorship(s) for: Nil, Other: Nil,: Nil, M. Sharma Financial support for
research from: Nil, Lecture fee(s) from: Nil, Consultancy for: Nil, Shareholder
of: Nil, Directorship(s) for: Nil, Other: Nil,: Nil, S. Mohiuddin Financial support
for research from: Nil, Lecture fee(s) from: Nil, Consultancy for: Nil,
Shareholder of: Nil, Directorship(s) for: Nil, Other: Nil,: Nil, S. Al Kaabi
Financial support for research from: Nil, Lecture fee(s) from: Nil, Consultancy
for: Nil, Shareholder of: Nil, Directorship(s) for: Nil, Other: Nil,: Nil
OP150 USE OF GASTROPROTECTIVE AGENTS AND RISK OF
DABIGATRAN ASSOCIATED GASTROINTESTINAL BLEEDING: A
POPULATION-BASED RETROSPECTIVE COHORT STUDY
W. Lau1, E.W. Chan1, I. C. Wong1, Y. He1, T.S. Tong2, W.-K. Leung2,*
1
Department of Pharmacology and Pharmacy, 2Department of Medicine,
University of Hong Kong, Hong Kong, Hong Kong
Contact E-mail Address: waikleung@hku.hk
INTRODUCTION: Dabigatran, a direct thrombin inhibitor, is the first new oral
anticoagulant available as an alternative to warfarin. Despite its convenience and
superiority over warfarin in the prevention of stroke and thromboembolism,
recent studies suggested an increase risk of gastrointestinal bleeding (GIB) in
patients treated with dabigatran when compared to warfarin. These data were
however largely derived from clinical trials in selected patient population.
AIMS & METHODS: This study determined the risk of dabigatran associated
GIB and the role of gastroprotective agents, including proton pump inhibitors
(PPIs) and H2-receptor antagonists (H2RAs), in preventing dabigatran related
GIB in a population-based retrospective cohort study. Data were extracted from
the central database of the Hong Kong Hospital Authority, which is the provider
of all public medical services to a 7 million population. We identified all patients
who were newly prescribed with dabigatran between Jan 2010 and Dec 2013. The
primary endpoint is the onset of clinical GIB. Multivariate analysis was used to
characterize the risk of GIB after adjusting for baseline patients characteristics,
medical illnesses and concurrent medications.
RESULTS: 5,041 patients, who were newly prescribed dabigatran, were included
in the analysis. Among them, 222 (4.4%) patients developed GIB with a median
time to bleeding of 97 (IQR 262) days. Patients who were aged 75 years (OR
1.83; 95% CI, 1.36 to 2.47), had prior ischemic stroke, transient ischemic attack
or systemic embolic events (OR 1.62; 1.19 to 2.2), and a prior history of peptic
ulcer or GIB (OR 2.48; 1.81 to 3.39) were found to have higher risks of GIB.
Concurrent use of gastroprotective agents (OR 0.61; 0.44-0.84; log rank test P
0.018) or statin (OR: 0.58; 0.43-0.78) reduced the likelihood of GIB. Subcategory
analysis showed that the use of either PPIs (OR 0.70; 0.51-0.98) or H2RAs (OR
0.67; 0.50-0.90) significantly lowered the bleeding risk. The risk reduction by
gastroprotective agents was significant only in patients with prior history of
ulcers or GIB (OR 0.24; 0.14 to 0.43) but not in patients with no prior history
(OR 0.83; 0.56 to 1.21).
CONCLUSION: The risk of GIB associated with dabigatran use in real life
clinical settings is 4.4%. The use of gastroprotective agents significantly reduced
the risk of dabigatran related GIB, particularly in high-risk patients with prior
history of peptic ulcer or GIB.
Disclosure of Interest: W. Lau: None declared, E. Chan: None declared, I. Wong:
None declared, Y. He: None declared, T. Tong: None declared, W.-K. Leung
Lecture fee(s) from: Takeda, Ferring, Consultancy for: Janssen.
A50
OP151 ENDOSCOPIC TREATMENT OF UPPER GASTROINTESTINAL
BLEEDING WITH A NOVEL HEMOSTATIC POWDER: RESULTS
FROM A MULTICENTER PROSPECTIVE REGISTRY PERFORMED
IN ROUTINE PRACTICE (THE GRAPHE REGISTRY)
S. Haddara1, S. Lecleire2, S. Leblanc3, J. Branche4, J. Jeremie5, J. Privat6,
L. Heyries7, J.-F. Bourgaux8, Y.L. Baleur9, P. Bichard10, J. Levy11, B. Godart12,
A. Charachon13, U. Chaput14, P. Grandval15, V. Quentin16, L. Vuitton17,
E. Coron1,* on behalf of The GRAPHE
1
CHU Hotel Dieu, Nantes, 2Hopital Charles Nicolle, Rouen, 3Hopital Cochin,
Paris, 4Centre Hospitalier Universitaire, Lille, 5Centre Hospitalier Universitaire,
Limoges, 6Centre Hospitalier, Vichy, 7Hopital Sainte Marguerite, Marseille,
8
Centre Hospitalier, Nimes, 9Hopital Henri Mondor, Creteil, France, 10Centre
Hospitalier Universitaire, Gene`ve, Switzerland, 11Clinique des Ce`dres, Toulouse,
12
Centre Hospitalier Universitaire, Tours, 13Centre Hospitalier Princesse Grace,
Monaco, 14Hopital La Riboisie`re, Paris, 15Hopital de La Timone, Marseille,
16
Centre Hospitalier, Saint-Brieuc, 17Centre Hospitalier Universitaire, Besancon,
France
Contact E-mail Address: emmanuel.coron@chu-nantes.fr
INTRODUCTION: In recent pilot studies, the use of a hemostatic powder
showed promising results to treat gastrointestinal bleeding. However, few data
exist in routine practice with this new method.
AIMS & METHODS: The aims of registry were to determine 1) the feasibility of
the application of the hemostatic powder in routine clinical practice, and 2) its
effectiveness in the short and medium term in different clinical situations. We
performed a prospective multicenter study in 17 centers, with 46 endoscopists. All
patients receiving the hemostatic powder (HemosprayTM, Cook Medical, USA)
were included. The hemostatic powder was sprayed endoscopically onto the
bleeding site using a catheter passed through the operative channel of the endo-
scope. The quantity of powder was administered at the discretion of the endos-
copist based on clinical efficacy. The following parameters were analyzed:
demographic characteristics, type of exteriorization (hematemesis, melena, hema-
tochezia), type of bleeding lesion, use of hemostatic powder as a first-line treat-
ment or a rescue therapy (i.e. after failure of conventional treatment) and ease of
use of the hemostatic powder as well as the main outcomes parameters, which
were: firstly, the immediate efficacy defined by hemostasis achieved at the end of
the endoscopic procedure, and secondly the absence of clinical recurrence eight
days after the procedure.
RESULTS: Ninety-six patients (69M/27F) aged 70  14 years were included in
the study between June 2013 and April 2014. Patients were hospitalized for
hematemesis (n 34), melena (n 54) or hematochezia (n 11). Initial hypo- AIMS & METHODS: We conducted a multicenter, randomized, double-blind,
tension was noted in 28 patients. At endoscopy, an active bleeding was noted in
88/96 (91%) cases, either pulsatile (14.6%) or oozing (85.4%). The location of
bleeding was esophageal (n 14), gastric (n 31) or duodenal (n 50). The glandin synthesis, for the healing of LDA-induced moderate to severe small
bleeding lesion was identified in 89/96 (92.7%) cases. These lesions were 31
tumors (32%), 43 ulcers (45%), 8 bleeding margins following endoscopic muco-
sal resection (8%) and 14 (15%) others bleeding lesions. The duration of the
endoscopic procedure (including both the diagnostic and therapeutic steps) was
32  23 minutes. Application of the hemostatic powder was found to be very
easy, easy, moderately easy or difficult in respectively 39%, 50%, 5% and 6% of
cases. This treatment was used as a first-line treatment in 51.6% of cases and as a
rescue therapy in 48.4% of cases. The immediate efficacy rate was 93.6%. No
recurrence of bleeding was noted in 74% of cases.
CONCLUSION: Our multicenter data obtained in routine practice conditions
suggest the good feasibility and effectiveness of the hemostatic powder applied
endoscopically for gastrointestinal bleeding, even after failure of conventional
methods.
Disclosure of Interest: None declared
OP152 RESTRICTIVE VERSUS LIBERAL BLOOD TRANSFUSION FOR
ACUTE UPPER GASTROINTESTINAL BLEEDING (TRIGGER):
PRAGMATIC, CLUSTER RANDOMISED, FEASIBILITY TRIAL
V. Jairath1,*, B. Kahan2, A. Gray3, C. Dore2, K. Palmer4, S. Travis5, R. Logan6,
T. Walsh7, M. Murphy8 on behalf of on behalf of the TRIGGER Trial
Investigators
1
Translational Gastroenterology Unit, Nuffield Department of Medicine,
University of Oxford, Oxford, 2MRC Clinical Trials Unit, London, 3Emergency
Medicine, University of Edinburgh, 4Western General Infirmary, Edinburgh,
5
Translational Gastroenterology Unit, Oxford, 6University of Nottingham,
Nottingham, 7Critical Care, University of Edinburgh, Edinburgh, 8NHS Blood and
Transplant, Oxford, United Kingdom
Contact E-mail Address: vipul.jairath@nhsbt.nhs.uk
INTRODUCTION: Transfusion thresholds for upper gastrointestinal bleeding
(UGIB) are controversial. Observational studies suggest associations between
liberal red blood cell (RBC) transfusion and adverse outcome, and a recent
trial reported increased mortality following liberal transfusion.
AIMS & METHODS: Pragmatic cluster randomised trial to evaluate the feasi-
bility and safety of implementing a restrictive (transfusion when haemoglobin
(Hb) 58gdL) versus liberal (transfusion when Hb 510g/dL) RBC transfusion
policy for UGIB. Hospitals were randomised to a policy which was implemented
through a multi-faceted educational intervention targeting all staff caring for
patients with UGIB. All adult patients were eligible to participate, regardless
of co-morbidity; the only exclusion criterion was exsanguinating haemorrhage.
Feasibility and exploratory clinical outcomes were recorded up to day 28.
RESULTS: 936 patients were enrolled in six hospitals (three restrictive, three
liberal). Although there were some baseline imbalances, Rockall and Blatchford
risk scores were identical between policies. Protocol adherence was 96% in the
restrictive policy vs 83% in the liberal policy (difference 14%, 95% CI 7 to 21%).
In patients with Hb5120 g/L, Hb at discharge was lower for the restrictive policy
United European Gastroenterology Journal 2(5S)
(difference -0.7; 95% CI -1.4 to 0.0; p0.05). For the restrictive policy fewer
patients received RBCs (difference -13%, 95% CI -35 to 11%) with on average
08 (-19 to 03) fewer RBC units transfused. Clinical outcomes were better in the
restrictive policy: 28-day further bleeding, 5% restrictive vs 9% liberal (difference
-37%, 95% CI -122 to 48%); 28-day mortality, 5% restrictive vs 7% liberal
(difference -1.3%, 95% CI -8.0 to 5.5%).; serious adverse events, 18% restrictive
vs 22% liberal (difference -4.9%, 95% CI -22.6 to 12.8%). In the subgroup with
IHD, there was a large observed difference for mortality (12% restrictive arm
(n6) vs. 3% liberal arm (n2); interaction P0.11).
CONCLUSION: Adherence to both policies was high, resulting in a reduction in
RBC transfusion and separation in the degree of anaemia and RBC exposure.
There was a trend towards improved safety in the restrictive policy, apart from
the increased mortality observed in patients with IHD. We have demonstrated
that a large-scale cluster randomised trial is feasible and is now warranted to
determine the effectiveness of implementing restrictive RBC transfusion for all
patients with AUGIB.
Disclosure of Interest: None declared
OP153 A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED TRIAL OF HIGH-DOSE REBAMIPIDE FOR LOW-
DOSE ASPIRIN-INDUCED MODERATE TO SEVERE SMALL
INTESTINAL DAMAGE IN CHRONIC ASPIRIN USERS
O. Handa1,*, T. Watanabe2, T. Tanigawa2, M. Shiba2, T. Takeuchi3, Y. Sakata4,
Y. Naito1, K. Higuchi3, K. Fujimoto4, T. Yoshikawa1, T. Arakawa2
1
Molecular Gastroenterology and Hepatology, KYOTO PREFECTURAL
UNIVERSITY OF MEDICINE, Kyoto, 2Gastroenterology, OSAKA CITY
UNIVERSITY GRADUATE SCHOOL of MEDICINE, 32nd Department of
Internal Medicine, OSAKA MEDICAL COLLEGE, Osaka, 4Internal Medicine,
SAGA MEDICAL SCHOOL, Saga, Japan
Contact E-mail Address: handao@koto.kpu-m.ac.jp
INTRODUCTION: Recent studies using capsule endoscopy have shown that
prevalence of small intestinal damage in patients taking low-dose aspirin
(LDA) is high. Although some drugs have been shown to be effective in treating
LDA-induced small intestinal damage, patients with mild damage which was
thought to be clinically insignificant have not been excluded and not a few
patients with such damage have been enrolled in most studies. Furthermore,
few randomized, double-blind, placebo-controlled trials to evaluate the efficacy
of drugs in the treatment of the LDA-induced damage have been reported.
placebo-controlled trial to assess the efficacy of high-dose of rebamipide, which is
a gastro-protective drug with various actions including enhancement of prosta-
intestinal damage. Methods: Patients received 100 mg enteric-coated aspirin
daily for more than 3 months for primary or secondary prevention of cardiovas-
cular and cerebrovascular disease, and were found to have more than 3 mucosal
breaks (i.e., erosions or ulcers) in the small intestine by capsule endoscopy were
enrolled, whereas patients who had less than 3 mucosal breaks (mild damage)
were excluded. Since we used inactive placebo, patients with overt gastrointest-
inal bleeding were also excluded. Eligible patients were assigned to receive either
rebamipide 300 mg three times daily or placebo for 8 weeks with an allocation
ratio of 2:1. Then capsule endoscopy was performed again to investigate the
treatment effects on the damage. The primary endpoint was change in the num-
bers of mucosal breaks in 8 weeks. Secondary endpoints included complete heal-
ing of small intestinal mucosal breaks and improvement of the severity of the
damage (from the damage of more than 3 mucosal breaks to the damage of less
than 3 mucosal damages or complete healing).
RESULTS: A total of 43 patients were enrolled between February 2011 and
January 2014 and were randomly assigned to rebamipide group (n29) or pla-
cebo group (n14). Five patients were excluded because of cessation of LDA
therapy (n2), incomplete visualization at the second capsule endoscopy (n1),
patients intention to withdraw from the trial (n1), and development of overt
gastrointestinal bleeding (n1). Remaining 38 patients (rebamipide group; n25,
placebo group; n13) completed the study. After 8 weeks treatment, rebamipide
significantly decreased the number of mucosal breaks (p0.046), whereas pla-
cebo did not. Although the difference was not significant (p0.13), the rate of
complete healing of mucosal breaks in rebamipide group (32%, 8 of 25) had a
tendency to be high, compared with placebo group (7.7%, 1 of 13). The rate of
improvement of severity of the damage in rebamipide group (63%, 17 of 25) was
significantly higher than that in placebo group (23.1%, 3 of 13, p0.016). Triple
dose of rebamipide was well-tolerated.
CONCLUSION: High-dose rebamipide is effective in the treatment for LDA-
induced moderate to severe enteropathy.
Disclosure of Interest: O. Handa: None declared, T. Watanabe: None declared, T.
Tanigawa: None declared, M. Shiba: None declared, T. Takeuchi: None
declared, Y. Sakata: None declared, Y. Naito Financial support for research
from: Takeda Pharmaceutical Co. Ltd, Otsuka Pharmaceutical Co. Ltd, Eisai
Co. Ltd, K. Higuchi Financial support for research from: Otuka Pharmaceutical,
Lecture fee(s) from: Otuka Pharmaceutical, K. Fujimoto: None declared, T.
Yoshikawa: None declared, T. Arakawa: None declared
United European Gastroenterology Journal 2(5S)
TUESDAY, OCTOBER 21, 2014 8:3010:30
GASTRIC CANCER: NEW INSIGHTS INTO PATHOGENESIS AND MANAGEMENT
LOUNGE 5_____________________
OP154 H. PYLORI INFECTION ALTERS HUMAN GASTRIC
MICROBIOTA AND BACTERIAL DIVERSITY
T.H. Li1,*, Y. Qin2, P.C. Sham2, W.K. Leung1
1
Department of Medicine, 2Department of Psychiatry, The University of Hong
Kong, Hong Kong, Hong Kong
Contact E-mail Address: silviath@hku.hk
INTRODUCTION: H. pylori (HP) is classified by the World Health
Organization as a type I carcinogen. However, the distribution and significance
of other bacteria in the human stomach remain poorly characterized.
AIMS & METHODS: This study aims to characterize the gastric microbiota in
individuals with and without HP infections; and determine the changes in micro-
biota after HP eradication. Endoscopic gastric biopsies were obtained from the
antrum and corpus of informed consent patients. Patients should have no ulcer
or tumor found on gastroscopy. HP infection status was determined by rapid
urease test and histology exam. Bacterial DNA was extracted and sequenced on
next generation sequencing platform (454 pyrosequencing), targeting the V3 and
V4 regions of bacterial 16S rRNA genes. Operational taxonomic unit (OTU)
clustering, diversity indexes calculation, taxonomic classification, PCoA and sta-
tistical analyses were performed after quality control and raw sequence proces-
sing. Hierarchical clustering based on weighted UniFrac distance of samples
using Wards algorithm was implemented.
RESULTS: A cohort of 27 patients was studied including 13 HP infected
patients, among which 3 had repeated endoscopic biopsy after receiving antibio-
tics for HP eradication. In total, 494 non-singleton OTUs were identified from
165,651 high-quality sequencing reads. 27 OTUs accounted for over 90% of all
sequencing reads, which belong to three phyla of Proteobacteria (5 OTUs),
Firmicutes (16 OTUs) and Actinobacteria (6 OTUs). Hierarchical clustering pre-
sents two cluster groups: first group contains mostly HP negative samples (n37)
while the second group exclusively comprises HP positive samples only (n16).
The phylum Fusobacteria was only found in the first group of predominantly HP
negative samples. The first group has markedly greater microbial species diversity
A51
A multicenter follow-up study was carried-out including 649 patients, diagnosed
with PL between 1995 and 2004, in 9 participating hospitals from Spain, which
repeated the endoscopy and biopsy (following the Sidney protocol) during 2011-
2013. Fresh gastric mucosa, a sample of saliva, and a questionnaire on medical
information and habits of life were collected. DNA from paraffin blocks of
recruitment biopsy was used for analysis of H. pylori by PCR, and for the
analysis of methylation patterns by the Infinium 450 K methylation arrays.
Based on morphology, IM was sub-classified as complete (small intestinal type,
CIM) and incomplete (colonic type, IIM). Analysis was done using Cox propor-
tional hazards risk (HR) models.
RESULTS: At baseline, 24% of patients had atrophic gastritis, 38% CIM, 34%
IIM, and 4% dysplasia. The mean of follow-up was 12 ys. 24 patients (3.7%)
developed a gastric adenocarcinoma during follow-up. The incidence rate of GC
was 2.76 and 5.76 per 1,000 person-years, for those with CIM and IIM respec-
tively. The HR of progression to CG was 6.4 (95%CI 0.8-49.6) and 2.4 (0.3-19.8)
for those with IIM and CIM at baseline, compared with those with chronic
atrophic gastritis, after adjusting for sex, age, family history of GC and use of
NSAIDs.
CONCLUSION: Patients with IIM have the highest risk of progression to GC.
Disclosure of Interest: None declared
OP156 ZIPPER-INTERACTING PROTEIN KINASE INDUCES
EPITHELIAL-MESENCHYMAL TRANSITION IN GASTRIC
CANCER CELL THROUGH AKT-BETA CATENIN SIGNALING
J. Bi1,*, J. Li2, Q. Su1, L. Zhang1
1
Lab of General surgery, The first affliated hospital of Sun Yet-sen university,
2
State Key Laboratory of Oncology in South China, Sun Yat-Sen University
Cancer Center, guangzhou, China
Contact E-mail Address: jiongbi@gmail.com
INTRODUCTION: Zipper-interacting Protein Kinase (ZIPK) belongs to the
death-associated protein kinase family [1]. In accordance with its cell death pro-
moting activity, some evidences suggest that ZIPK functions as a tumor suppres-
sor[2]. However, the DAPK family exhibits anti-apoptotic activity under certain
conditions. ZIPK is described as a novel co-activator of the AR and provide a
with an average Shannon diversity index of 4.08 (SD 0.50) comparing to 1.95 (SD
0.46) of the second group (p 5 0.01); the species richness estimator Chao 1 index
is also distinctly greater in the first group (SChao 1 61.71, SD 19.21) than that of
the HP positive group (SChao 1 35.66, SD 14.19) (p 5 0.01). Consistent with the
Chao 1 index, 227 and 58 OTUs specifically appeared in the first and second
group, respectively. The average Shannon diversity index increases from 2.42 (SD
0.97) to 4.37 (SD 0.35) (p 5 0.01) after antibiotics treatment for HP. Besides the
increase in diversity and species richness, two genera Corynebacterium (p 0.03)
and Haemophilus (p 0.03) were significantly enriched in the post treatment
samples. Clustering analysis however shows minimal correlation between micro-
biota composition and the anatomical site of the biopsy or patients age.
growth advantage to prostate cancer cells [3]. ZIPK induces Wnt/-catenin -
mediated gene expression and cell growth in human colon carcinoma cells [4].
In the current study, both in vitro and in vivo assays have been used to char-
acterize the function of ZIPK. The possible molecular mechanism of ZIPK in
cancer cell growth and metastasis has been emphasized.
AIMS & METHODS: ZIPK was stably expressed in BGC-823 cells using lenti-
viral vector. Foci formation and soft agar assays were performed to detect cell
growth, and cell proliferation was tested by XTT as well. Cell migration and
invasion were investigated by wound healing and transwell invasion experiments.
For in vivo tumorigenicity and metastatic assays, subcutaneous and intravenous
injections were done in the 4- to 5-week old nude mice. EMT markers and AKT-
CONCLUSION: H. pylori colonization of the stomach results in alteration in
gastric microbiota and reduction in bacterial diversity. The changes in gastric
microenvironment by HP may contribute to gastric carcinogenesis that deserves
further investigations.
Disclosure of Interest: None declared
OP155 INCOMPLETE TYPE OF INTESTINAL METAPLASIA HAS THE
GSK3 signaling were detected by western blot. ZIPK and AKTp308 were tested
by immunohistochemistry in primary gastric cancers and matched metastatic
lymph nodes, the patient survival time was also analyzed.
RESULTS: ZIPK could markedly increase BGC-832 cell proliferation, colony
formation, migration and invasion in vitro. The nude mouse tumor growth
curves showed that tumors induced by ZIPK-transfected cells grew much more
rapidly. A significantly larger number of metastatic nodules were found at the
surface of the lungs of mice injected with the ZIPK- BGC823 cells. Through
HIGHEST RISK TO PROGRESS TO GASTRIC CANCER: RESULTS western blot, we found that ZIPK increased expression of -catenin and vimen-
OF THE SPANISH FOLLOW-UP MULTICENTER STUDY tin, and decreased the levels of E-cadherin. In addition, the expression levels of
C.A. Gonzalez1,*, J.M. Sanz-Anquela2, O. Companioni1, C. Bonet1, Snail and Slug, were dramatically elevated by ZIPK expression. The expression
M. Berdasco3, C. Lopez4, J. Mendoza5, M. Martin-Arranz6, J.J. Pozo7, E. Rey8, of pAkt was increased when ZIPK was overexpressed. However, the phosphor-
F. Sanchez-Ceballos8, E. Poves9, L. Espinosa9, J. Barrio10, M.A. Torres11, ylation of GSK-3 was not changed. These results suggested that ZIPK plays a
M. Cuatrecasas12, I. Elizalde13, L. Bujanda14, M. Garmendia15, A. Ferrandez16, key role in regulation of EMT through AKT/-catenin. Consistent with our
G. Munoz17, M. Barenys18, M.J. Paules19, S. Lario20, M.J. Ramirez20, J. Gisbert5 finding in gastric cancer cells, co-expression of ZIPK and phosphorylated
1
Unit of Nutrition, Environment and Cancer, Catalan Institute of Oncology, AKT in metastatic lymph nodes predicted unfavorable outcome in gastric
Hospitalet del Llobregat, Barcelona, 2Dept of Pathology, Hospital Principe de cancer patients.
Asturias, Alcala de Henares, 3Cancer Epigenetics and Biology Program, CONCLUSION: ZIPK promoted cell growth, migration and tumor formation in
IDIBELL, Hospitalet del Llobregat, Barcelona, 4Dept of Pathology, 5Dept of nude mice. ZIPK enhanced AKT activity, inducing EMT and promoting tumor
Gastroenterology, Hospital Universitario de la Princesa, 6Dept of invasion and metastasis.
Gastroenterology, 7Dept of Pathology, Hospital Universitario La Paz, 8Dept of REFERENCES
Gastroenterology, Hospital Clnico San Carlos, Madrid, 9Dept of 1. Kawai T, Matsumoto M, Takeda K, et al. ZIP kinase, a novel serine/threonine
Gastroenterology, Hospital Universitario Prncipe de Asturias, Alcala de Henares, kinase which mediates apoptosis. Mol Cell Biol 1998; 18: 1642-1651.
10
Dept of Gastroenterology, 11Dept of Pathology, Hospital Universitario Ro 2. Bi J, Lau SH, Hu L, et al. Downregulation of ZIP kinase is associated with
Hortega, Valladolid, 12Dept of Pathology, 13Dept of Gastroenterology, Hospital tumor invasion, metastasis and poor prognosis in gastric cancer. Int J Cancer
Universitari Clnic de Barcelona, Barcelona, 14Dept of Gastroenterology, 15Dept of 2009; 124: 1587-1593.
Pathology, Hospital Universitario Donostia, Donostia, 16Dept of Gastroenterology, 3. Leister P, Felten A, Chasan AI, et al. ZIP kinase plays a crucial role in
17
Dept of Pathology, Hospital Clnico Universitario Lozano Blesa, Zaragoza, androgen receptor-mediated transcription. Oncogene 2008; 27: 3292-3300.
18
Dept of Gastroenterology, Hospital de Viladecans, Viladecans, Barcelona, 19Dept 4. Togi S1, Ikeda O, Kamitani S, et al. Zipper-interacting protein kinase (ZIPK)
of Pathology, Hospital Universitari de Bellvitge, Barcelona, 20Dept of modulates canonical Wnt/beta-catenin signaling through interaction with Nemo-
Gastroenterology, Corporacio Sanita`ria Universita`ria Parc Taul, Sabadell, Spain like kinase and T-cell factor 4 (NLK/TCF4). J Biol Chem 2011; 286: 19170-
Contact E-mail Address: aexposito@iconcologia.net 19177.
Disclosure of Interest: None declared
INTRODUCTION: In high or moderate risk population, periodic surveillance of
patients at risk of progression from gastric precursor lesions (PL) to gastric
cancer (GC) is recommended, as it represents the most effective strategy for
reducing the burden of GC. The incomplete type of intestinal metaplasia (IM)
may be considered as the best candidate, but more research is needed to confirm
it, and to identify other markers of progression.
AIMS & METHODS: 1)To evaluate the risk of progression to GC in patients
with PL and 2)To assess the effect of virulence factors of H. pylori infection, the
effect of polimorphisms of candidate genes, and the effect of epigenetic variants.
Results regarding the first aim are described in this presentation.
A52
OP157 HELICOBACTER PYLORI-RELATED LONG NONCODING RNA
(LNCRNA) DOWN-REGULATED EXPRESSION (DREG) INHIBITS
GASTRIC CANCER PROLIFERATION AND METASTASIS BY
TARGETING MUC2
X. Zhou1,*, G. Zhang1
1
Gastroenterology, the First Affiliated Hospital of Nanjing Medical University,
Nanjing, China
Contact E-mail Address: zhouxiaoying0926@sina.cn
INTRODUCTION: Gastric cancer is one of the most frequent malignancies in
East Asian countries [1]. Despite efforts in multiple fields, there has been little
success in improving the disease-free survival rate of patients [2]. H. pylori has
infected more than 50% of the total population and has been recognized as type I
carcinogen of gastric cancer [3]. A significantly association has been identified in
the relationship between H. pylori infection and gastric cancer but the underlying
mechanism was still unclear
AIMS & METHODS: Long non-coding RNAs (lncRNAs) have been shown to
have critical regulatory roles in cancer biology. In this study, we investigated
whether H. pylori infection could promote gastric cancer by regulating the
expression of lncRNAs. Differentially expressed lncRNAs between H. pylori
positive and negative tissues were identified by microarray and validated using
quantitative real-time polymerase chain reaction.
RESULTS: Our results indicated that H. pylori positive tissues have a specific
profile of lncRNAs. Cell biological assays in combination with small interfering
RNA-mediated knockdown or lentivirus vector-mediated over-expression were
performed in order to probe the functional relevance of these lncRNAs. We
identified an lncRNA, AF147447 (termed as Dreg), down-regulated expression
by H. pylori infection, which can inhibit gastric cancer growth and invasion
in vitro, act as a tumor suppressor in the development of H. pylori induced gastric
cancer. LncRNA-Dreg could combine with the oncogene MUC2 and repress its
expression. We also found that Dreg was regulated by transcription factor E2F1
by RNA immunoprecipatation and RNA pull down assays. These findings sup-
port a role of lncRNA- Dreg in tumor suppression.
CONCLUSION: This discovery contributes to a better understanding of the impor-
tance of the deregulated lncRNAs by H. pylori in gastric cancer and provides a
rationale for the potential development of lncRNA-based targeted approaches for
the treatment of H. pylori-related gastric cancer.
REFERENCES
1. Song JH and Meltzer SJ. MicroRNAs in pathogenesis, diagnosis, and treat-
ment of gastroesophagel cancers. Gastroenterology 2012; 143: 35-47.
2. Ohnita K, Isomoto H, Shikuwa S, et al. Early and long-term outcomes of
endoscopic submucosal dissection for early gastric cancer in a large patient series.
Exp Ther Med 2014; 7: 594-598.
3. Kupcinskas J, Wex T, Link A, et al. Gene polymorphisms of micrornas in
Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer. PLoS
One 2014; 9: e87467.
4. Akhavan-Niaki H and Samadani AA. Molecular insight in gastric cancer
induction: an overview of cancer stemness genes. Cell Biochem Biophys 2013.
Disclosure of Interest: None declared
OP158 MICRORNA-18A PROMOTES CELL PROLIFERATION BY
TARGETING IRF2 IN HUMAN GASTRIC CANCER AND PREDICTS
POOR SURVIVAL IN GASTRIC CANCER PATIENTS
Y.-J. Chen1,*, H. Wu1, X.-Z. Shen1 on behalf of The staff of Prof. Xi-Zhong
Shens laboratory
1
Department of Gastroenterology, Zhongshan Hospital of Fudan University,
Shanghai, China
Contact E-mail Address: shen.xizhong@zs-hospital.sh.cn
INTRODUCTION: MicroRNAs (miRNAs) are regulatory factors which are
believed to play a crucial role in oncogenesis. Gastric carcinoma is one of the
most common malignancies and the second most lethal cancer worldwide. In this
study, we assessed the value of miR-18a in predicting outcome after curative
resection in gastric cancer (GC) patients and defined the oncogenic significance
and function of miR-18a.
AIMS & METHODS: We analyzed miR-18a expression in 90 clinicopathologically
characterized GC tissues by in situ hybridization, and 53 gastric juice samples (24
GC patients, 14 healthy controls, and 16 gastric ulcer patients) by quantitative RT-
PCR. The prognostic significance was assessed using Kaplan-Meier survival esti-
mates and log-rank tests. Biological roles of miR-18a were also explored in vivo. The
interferon regulatory factor 2 (IRF2) were validated as targets of miR-18a by luci-
ferase assay, quantitative RT-PCR, and western blot. The expression of IRF2 in the
same 90 GC cases was also analyzed by immunohistochemistry.
RESULTS: In this study, we found that overexpressed intratumoral miR-18a
was associated with poor survival rate (P 5 0.001), and was an independent
prognostic factor for overall survival rate (P 5 0.001) in the GC patients.
High expression of miR-18a was also found in the gastric juice of GC patients.
Forced expression of miR-18a remarkably enhanced cell proliferation, migration,
and invasion in GC cells, while inhibition of miR-18a by inhibitor caused the
opposite effects. Bioinformatics analysis identified the IRF2 as a potential miR-
18a target. Further studies confirmed the miR-18a suppressed the expression of
IRF2 by directly binding to is 3-untranslated region. Moreover, miR-18a expres-
sion levels correlated inversely with IRF2 in human GC tissues. Western blot
showed that forced expression of miR-18a in GC cells could not only down-
regulate the expression of IRF2, but also inhibit the expression of P53, suggesting
that IRF2 might play as a tumor suppressor by regulating P53 signaling in GC.
CONCLUSION: Taken together, these results demonstrated that miRNA-18a
promoted cell proliferation by targeting IRF-2 in human GC and predicted poor
survival in GC patients.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP159 EFFECTS OF ALDH2-GENOTYPE, PPI-TREATMENT AND L-
CYSTEINE ON THE LEVELS OF CARCINOGENIC
ACETALDEHYDE IN GASTRIC JUICE AND SALIVA AFTER
INTRAGASTRIC ALCOHOL ADMINISTRATION
R. Maejima1,*, K. Iijima1, P. Kaihovaara2, T. Koike1, T. Shimosegawa1,
M. Salaspuro2
1
Tohoku University Hospital, Sendai, Japan, 2Research Unit on Acetaldehyde and
Cancer, University of Helsinki, Helsinki, Finland
Contact E-mail Address: kiijima@med.tohoku.ac.jp
INTRODUCTION: Acetaldehyde (ACH) associated with alcoholic beverages is
Group 1 carcinogen to humans (IARC/WHO). Aldehyde dehydrogenase
(ALDH2), a major ACH eliminating enzyme, is genetically deficient in 30-50%
of Eastern Asians. In alcohol drinkers ALDH2-deficiency is well known risk
factor for upper digestive tract cancers. Presence of alcohol in systemic blood
circulation of ALDH2-deficient subjects results in significantly elevated salivary
ACH levels. This provides strong evidence for the causal relationship between
local ethanol-derived ACH and oral, pharyngeal and esophageal cancers.
Alcohol and ALDH2-deficiency are established risk factors also for stomach
cancer. Normal human gastric mucosa expresses three alcohol dehydrogenase
(ADH) isozymes and low Km ALDH2-enzyme activity. High-Km and high-
Vmax ADH4 plays a key role in the gastric first pass metabolism of ethanol to
ACH at high intragastric ethanol concentrations during the first 1 2 hours after
alcohol intake. ADH-containing oral microbes, colonizing hypochlorhydric sto-
mach, contribute significantly to local intragastric production of ACH. However,
the combined role of ALDH2-genotype, PPI-induced achlorhydria and ACH
eliminating L-cysteine in the regulation of ACH levels in gastric juice and
saliva is not yet known.
AIMS & METHODS: To assess the effect of ALDH2-genotype, achlorhydria
produced by PPI-treatment and slowly L-cysteine releasing capsule on the levels
of ACH in gastric juice and saliva following an intra-gastric infusion of ethanol.
15. ALDH2-active and 10 ALDH2-deficient H. pylori negative healthy volun-
teers were included in the study. Through a nasogastric tube 15% ethanol (0.5g/
kg) was infused into the stomach. 5ml of gastric aspirate and 1-2 ml of saliva were
collected at 30-min intervals up to 120 min. The first two samplings were done
before and after 7-day administration of proton pump inhibitor (PPI, rabepra-
zole 10mg b.i.d.) (experiment 1 and 2). After 3 more days on PPI, sampling of
gastric juice and saliva was repeated with 200mg of slowly L-cysteine releasing
capsule administered before ethanol infusion (experiment 3).
RESULTS: After intragastric infusion of alcohol ALDH2-deficiency resulted in
mean 5.6-fold increase in gastric juice ACH and mean 2.1-fold increase in sali-
vary ACH compared to the subjects with normal ALDH2-enzyme (p50.0001 for
both). In ALDH2-active subjects PPI-treatment increased gastric juice ACH to
3.3.-fold (p50.0001), but had no effect on salivary ACH. L-cysteine eliminated
effectively gastric juice ACH both in PPI-treated ALDH2-active and ALDH2-
deficient subjects (mean 75% and 60%, p5 0.0001 and 50.0031, respectively).
CONCLUSION: Alcohol-induced marked increase in gastric juice ACH in
ALDH2-deficient subjects provides strong evidence for the local carcinogenic
action of ACH in gastric carcinogenesis. Nondependent changes in gastric
juice and salivary ACH levels caused by PPI-treatment and intragastric L-
cysteine indicate that gastric juice ACH level is locally regulated by gastric
mucosal ADH- and ALDH2-enzymes and by oral microbes colonizing acid
free or achlorhydric stomach.
Disclosure of Interest: R. Maejima: None declared, K. Iijima Financial support
for research from: Biohit Oyj and TEKES the Finnish Funding Agency for
Innovation, P. Kaihovaara: None declared, T. Koike: None declared, T.
Shimosegawa: None declared, M. Salaspuro Consultancy for: Board member,
medical advisor and stock owner of Biohit Oyj
OP160 MIR-21, MIR-223 AND MIR-155 ARE NOVEL MUCOSAL
BIOMARKERS FOR HIGH-RISK GASTRITIS
A. Link1,*, W. Schirrmeister1, C. Langner1, M. Varbanova1, J. Bornschein1,
T. Wex1, P. Malfertheiner1
1
Gastroenterology, Hepatology and Infectious Diseases, OTTO-VON-
GUERICKE UNIVERSITY HOSPITAL MAGDEBURG, Magdeburg, Germany
Contact E-mail Address: alinkmail@gmail.com
INTRODUCTION: Gastric carcinogenesis is a multifactorial H.pylori-triggered
dynamic process that goes through a cascade of preneoplastic conditions.
Identification of biomarkers predictive for gastric cancer development may
help to improve current screening and surveillance programs.
AIMS & METHODS: In this study, we systematically characterized expression
of miR-21, miR-155 and miR-223, microRNAs that are frequently deregulated in
gastric cancers (GC), with regard to preneoplastic precursor conditions in gastric
mucosa, H. pylori infection and gastric region. In a prospective study, 80 patients
(normal (N), chronic gastritis (CG), atrophic gastritis  intestinal metaplasia
(AG) and GC) underwent upper GI endoscopy and H.pylori status, mucosal
inflammation, atrophic or malignant changes were systematically evaluated
according to the updated Sydney classification. Biopsies were assessed from
corpus, antrum and in case of gastric tumor also from the tumor (T-GC) and
near the tumor (NT-GC). Expression of miR-21, miR-223 and miR-155 was
analyzed by qRT-PCR from total RNA. Normalization was performed using
RNU6b. Potential diagnostic utility was tested using a simple miRNA expression
score.
RESULTS: All three studied miRNAs are differentially expressed in normal
gastric mucosa compared to tumor, especially for miR-21 and miR-223.
Remarkably, miRNA expression pattern was different between normal gastric
corpus and antrum mucosa (p50.001) and therefore, further analyses were per-
formed for different localizations independently. In correlation with Correas
cascade of mucosal alterations, we observed gradual increase in miR-155, miR-
United European Gastroenterology Journal 2(5S)
223 expression in corpus mucosa and increase of all 3 miRNAs in antrum from N
to CG to AG (p50.001). In GC patients, adjusted non-tumorous corpus and
antrum mucosa showed increased miRNA expression compared to subjects with
normal mucosa, although, we also observed heterogeneous and miRNA-specific
expression pattern between different regions including non-tumorous and tumor-
ous tissues. H.pylori infection was associated with increased miR-155 and miR-
223 expression both in corpus and antrum, and slight increase of miR-21 expres-
sion in antrum. Lastly, using calculated summary score of three miRNAs, we
were able to distinguish atrophic gastritis from normal mucosa with area under
the curve (AUC) 0.90 (95% CI 0.81.0) for corpus and AUC 0.98 (95% CI
0.961.01) for antrum.
CONCLUSION: Gastric cancer-associated miRNAs are differentially expressed
in preneoplastic gastric mucosa and surrounding mucosa of GC patients.
Gradual increase in miRNA expression correlates with Correas cascade of pre-
neoplastic alterations and H.pylori, suggesting miRNAs as diagnostic and poten-
tial predictive biomarkers. However, regional differences in miRNA expression
pattern within the stomach need to be considered in future studies.
Disclosure of Interest: None declared
) and FISH at central laboratory in a blinded manner.
OP161 HIGH LEVELS OF RELM-ALPHA CORRELATE WITH POOR
PROGNOSIS AND PROMOTE METASTASIS IN GASTRIC CANCER
C. Ping1,*, Y. yaozong1
1
Department of Gastroenterology, Ruijin Hospital, Shanghai Jiaotong University
School of Medicine, Shanghai, China
Contact E-mail Address: chenping714@medmail.com.cn
INTRODUCTION: Accumulating evidence indicates that Resistin-like mole-
cule (RELM-) is involved in the angiogenesis of endothelial cells and indu-
cing of vascular of remodeling, while the clinical significance of RELM- in
gastric cancer is poorly understood and the exact role of RELM- in gastric
cancer remains obscure.
AIMS & METHODS: The aim of this study is to evaluate the expression of
RELM- and its clinical significance in gastric cancer, to investigated its effective
mechanism in order to the new therapeutic target. In the present study, expres-
a w n
sion levels of RELM- in 96 gastric carcinoma tissues, adjacent normal tissue,
and 2 types of gastric cancer cell lines were quantified by immunohistochemical
ithdr
staining or Western blot, and the relationship between RELM- expression and
cliniopathological characteristics of cancer was explored. To investigate the
potential role of RELM- in gastric cancer cell biological behavior, the study
W
performed cell proliferation, migration and invasion assays in two gastric cancer
cell lines (SGC7901 and MKN45), and the study tested whether knockdown of
RELM- modulates vascular endothelial growth factor (VEGF) expression by
small interference RNA in cancer lines, and dissected the possible signaling path-
ways that link RELM- to VCAM-1 up-regulation by western blot, and further
explored its effect on NF-B activation by EMSA method.
RESULTS: 65 (67.7%) tested positive for RELM- expression, mainly in the
cytoplasm of gastric cancer mucosa. Contrasting sharply with the strongly
RELM--positive tumors, adjacent normal tissue and cell lines was negative or
weakly positive expression (P 5 0.01). Higher expression levels of RELM- were
associated with more advanced stage (P 5 0.01). Additionally, the expression of
RELM- was significantly correlated with lymph node metastasis and tumor size
but had no correlation with the patients prognosis. The knockdown expression
of RELM- by SiRNA treatment could significantly inhibited cell migration and
invasion ability in SGC7901 and MKN45 gastric cancer cells compared with
control cell lines (P 5 0.01). However, the knockdown expression of RELM- and Childrens Health, Karolinska University Hospital Solna, Karolinska
also significantly blocked NF-B activation and attenuated VEGF production in
two cancer lines.
CONCLUSION: The data demonstrated that RELM- is a novel biomarker for
metastasis in patients with gastric cancer. The study identified that up-regulation
of RELM- may regulate the proliferation, invasion and migration of gastric
cancer cells, its mechanism was involved into VEGF up-regulation induced by
RELM- promotes tissue angiogenesis by NF-B signaling pathway activation.
REFERENCES
1. Liu X, Yu H, Cai H, et al. The expression and clinical significance of miR-132
in gastric cancer patients. Diagn Pathol 2014; 12: 9-57.
2. Li X, Yang Y, Fang J, et al. FIZZ1 could enhance the angiogenic ability of rat
aortic endothelial cells. Int J Clin Exp Pathol 2013; 15: 1847-1853.
3. Yamaji-Kegan K, Su Q, et al. Hypoxia-induced mitogenic factor has proan-
giogenic and proinflammatory effects in the lung via VEGF and VEGF receptor-
2. Am J Physiol Lung Cell Mol Physiol 2006; 291: 1159-1168.
Disclosure of Interest: None declared
OP162 THE CLINICAL UTILITY OF SERUM HER2 IN GASTRIC
CANCER
M. Saito1,2,*, K. Yamashita1, H. Kaneto3, H. Okuda4, T. Hagiwara5,
M. Yoshimoto2, K. Suzuki6, T. Adachi7, K. Nakachi8, A. Yawata9,
T. Tanuma10, Y. Adachi11, M. Nojima12, Y. Arimura1, Y. Shinomura1
1
Department of Gastroenterology, Rheumatology and Clinical Immunology,
Sapporo Medical University, 2Department of Hematology and Gastroenterology,
Tenshi Hospital, Sapporo, 3Division of Gastroenterology, Muroran City General
Hospital, Muroran, 4Department of Medical Oncology, Keiyukai Sapporo
Hospital, 5Department of Gastroenterology, Sapporo-Kosei General Hospital,
Sapporo, 6Department of Gastroenterology, Kushiro City General Hospital,
Kushiro, 7Department of Gastroenterology, Otaru Municipal Hospital, Otaru,
8
Department of Gastroenterology, Obihiro Kyokai Hospital, Obihiro, 9Department
of Gastroenterology, Hakodate Goryoukaku Hospital, Hakodate, 10Center for
Gastroenterology, Teine Keijinkai Hospital, 11Division of Gastroenterology,
Sapporo Shirakaba-dai Hospital, Sapporo, 12Division of Advanced Medicine
A53
Promotion, The Advanced Clinical Research Center, The Institute of Medical
Science, The University of Tokyo, Tokyo, Japan
INTRODUCTION: Immunohistochemistry (IHC) and fluorescence in situ
hybridization (FISH) are the current mainstays of diagnosis of tissue HER2
status in gastric cancer. In contrast to breast cancer, however, HER2 expression
in gastric cancer occasionally demonstrates intratumoral heterogeneity, raising
concern about false-negative cases. Serum HER2, concentrations of the HER2
extracellular domain (ECD) shed into the bloodstream, evaluates a different
aspect of HER2 status but has not been well studied in gastric cancer.
AIMS & METHODS: To elucidate the clinical utility of serum HER2 in gastric
cancer, we performed a prospective multicenter study (SHERLOCK trial, UMIN
000009773). Patients with gastric or gastro-oesophageal junction cancer of all
stages were recruited. Pretreatment serum HER2 level was measured using che-
miluminescense immunoassay (CLIA), and tissue HER2 status was assessed by
IHC and FISH for IHC 2 cases at central laboratory. For stage IV cases, tissue
HER2 status was firstly assessed by various anti-HER2 antibodies at local
laboratories of each hospital, then reevaluated using two antibodies (Dako
HercepTest II and SV2-61
RESULTS: From June 2011 to July 2013, a total of 224 patients were enrolled
from 14 centers. Both tissue HER2 status and serum HER2 level were success-
fully determined in 194 patients (stage I: 103, stage II: 11, stage III: 16, stage IV:
64). Tissue HER2 was positive in 42 patients (21.6%) and HER2 positive rate
was higher in an advanced stage. Serum HER2 level ranged from 4.5 to 148.0 ng/
ml (median 10.3 ng/ml), and significantly correlated with tissue HER2 status
(p0.0058). With a cut-off level of 16.5 ng/ml determined by receiver operating
characteristics (ROC) analysis, sensitivity, specificity, positive predictive value
and negative predictive value of serum HER2 were 26.2%, 95.4%, 61.1% and
82.4%, respectively.
Among 64 stage IV patients, tissue HER2 results from both local and central
laboratories were available in 56 patients. Local laboratories initially diagnosed
18 cases as tissue HER2-positive and 38 as negative. Serum HER2 levels were
elevated (416.5ng/ml) not only in 9 of 18 tissue HER2-positive cases but also in
7 of 38 tissue HER2-negative cases. Reevaluation of tissue by central laboratory
had identified 4 false-negative cases among 38 initially judged as HER2-negative.
Of these 4 cases, 2 demonstrated extremely high serum HER2 level (61.2 and 53.3
ng/ml). Consequently, serum HER2 thus rescued 2 false-negative cases out of 4.
CONCLUSION: Serum HER2 level was correlated with tissue HER2 status in
gastric cancer. Although the low sensitivity is a drawback, serum HER2 might be
useful to salvage tissue HER2 false-negative patients who will benefit from anti-
HER2 treatment.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 8:3010:30
HOT TOPICS IN CHOLESTATIC AND PANCREATIC DISEASES LOUNGE
6_____________________
OP163 INTRAHEPATIC CHOLESTASIS OF PREGNANCY AND RISK OF
AUTOIMMUNE, CARDIOVASCULAR AND MALIGNANT DISEASES:
A POPULATION-BASED COHORT STUDY OF 125,281 SWEDISH
WOMEN
E. Wikstrom Shemer1, O. Stephansson2, M. Thorsell1, J.F. Ludvigsson3, H.-
U. Marschall4,*
1
Department of Clinical Sciences, Danderyd Hospital, 2Department of Womens
Institutet, Stockholm, 3Department of Pediatrics, Orebro University Hospital,
Orebro, 4Department of Molecular and Clinical Medicine, Sahlgrenska Academy,
Institute of Medicine, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: hanns-ulrich.marschall@gu.se
INTRODUCTION: Intrahepatic cholestasis of pregnancy (ICP) is the most
common liver disease in pregnancy and closely associated with prevalent and
future hepatobiliary diseases. In addition, ICP bears an almost 3-times higher
risk of gestational diabetes and preeclampsia.
AIMS & METHODS: We now aimed to find possible associations between ICP
and autoimmune, cardiovascular and major malignant diseases. We analyzed
data of women with births between 1973 and 2009 and registered in the
Swedish Medical Birth Register. By linkage with the Swedish Patient Register,
we identified 11,388 women with ICP who were matched to 113,893 women
without this diagnosis. Diagnoses of autoimmune, cardiovascular and major
malignant diseases (breast, uterus, lung, colorectal, hepatobiliary) were obtained
from the Patient Register. Main outcome measures were hazard ratios (HRs) for
later disease in women with ICP at 51 year, 1-5 years, 45 years after delivery.
Risk estimates were calculated through Cox regression and logistic regression
analysis.
RESULTS: Women with ICP were more often diagnosed with later autoimmune
disease (HR 1.25; 95% CI 1.16 - 1.35; p50.0001). The risk was specifically
increased for diabetes mellitus (HR 1.46; CI 1.25 - 1.71), thyroid disease (HR
1.26; CI 1.11-1.23), Crohns disease (HR 1.55; CI 1.14-2.11), psoriasis (HR 1.23;
CI 1.04-1.46) and inflammatory polyarthropathias (HR 1.32; CI 1.10-1.56), as
compared to women without ICP. Women with ICP were also at increased risk
for liver (HR 3.51; CI 1.64-7.58) and biliary (HR 2.49; CI 1.19-5.21) malignan-
cies. The risk of cardiovascular disease was not increased.
CONCLUSION: Women with ICP have increased risk to be later diagnosed with
autoimmune diseases, in particular diabetes mellitus. This however, was not
reflected by increased risk of cardiovascular diseases. The close association of
ICP with hepatobiliary diseases also comprises increased risk of liver and biliary
tree cancers.
Disclosure of Interest: None declared
A54
OP164 PAEDIATRIC ONSET PRIMARY SCLEROSING CHOLANGITIS
IN FINLAND: CLINICAL COURSE AND PROGNOSIS
A. Tenca1,*, M. Farkkila1, T. Jaakkola2, J. Arola3, K.-L. Kolho2
1
Department of Medicine, Clinic of Gastroenterology, Helsinki University Central
Hospital, 2Childrens Hospital, University of Helsinki, 3Department of Pathology,
Haartman Institute, University of Helsinki and HUSLAB, Helsinki, Finland
INTRODUCTION: Natural history of paediatric onset primary sclerosing cho-
langitis (PSC) and PSC/autoimmune hepatitis (PSC/AIH) overlap syndrome is
poorly known1.
AIMS & METHODS: Aim of this retrospective observational cohort study was
to evaluate the clinical course and prognosis of patients with a paediatric onset
PSC-PSC/AIH over a long follow-up. Between 1993-2011, 41 paediatric (5 18
years) PSC and PSC/AIH patients (pts) referred to Helsinki University Central
Hospital, comprised the study group. The diagnosis was confirmed in all pts
reviewing clinical, pathological and radiological data at the disease onset and
in the end of the follow-up (31st December 2013). All ERC images (endoscopic
retrograde cholangiography) were re-reviewed by 2 experienced endoscopists. All
liver biopsies were also re-reviewed by one experienced pathologist. PSC was
defined when typical biliary duct changes were present (i.e., strictures and dila-
tions); PSC/AIH when pts met both the diagnostic criteria for PSC and AIH
(e.g., interface hepatitis and ANA/SMA antibodies). Timing of ERC follow-up
was decided according to (i) severity of cholangiography changes and (ii) pre-
sence of dysplasia (Dys) or aneuploidy (Ane) on brush cytological samples.
RESULTS: In the final analysis 37 pts (Median age: 16 years; range: 5-18. Male:
24; 65%) were included. Median follow-up was 9 years; range: 2-20. PSC/AIH
overlap syndrome was present in 12/37 (32%). Concomitant inflammatory bowel
disease was associated in 28/37 (75%), mostly ulcerative colitis (25/28; 89%).
Autoimmune diseases were present in 6/37 (16%). The insidious onset (none or
slight symptoms) was the most common presentation (20/37; 54%). Number of
patients with liver lab tests elevation at disease onset and in the end of follow-up
is shown in Table 1. All the pts underwent ERC at diagnosis; 29/37 (78%) at the
end of follow-up (Table 1). Liver biopsy was performed in 34/37 (92%) at diag-
nosis. All patients were managed with UDCA and immunosuppression. Four pts
(11%) underwent LTx (2 for severe Dys and Ane, 1 for Budd-Chiari syndrome, 1
for acute liver failure and 1 for suspicion of malignancy due to persistent eleva-
tion of Ca19-9 and CEA); no pts had disease recurrence on the graft during a
mean follow up of 3 years (SD 2.9). None of the pts developed cholangio-
carcinoma and all are still alive.
TABLE 1
AT DIAGNOSIS AT THE END OF
(%) FOLLOW-UP (%)
ALT 30/37 (81%)* 11/37 (30%)*
AST 27/37 (73%)* 8/37 (22%)*
GGT 30/37 (81%)* 14/37 (38%)*
ALP 21/37 (57%)* 16/37 (43%)*
BILIARY CHANGES
- INTRA-HEPATIC 26/37 (70%) 18/29 (62%)
-INTRA AND EXTRA HEPATIC 11/37 (30%) 11/29 (38%)
CONCLUSION: This retrospective observational cohort study showed a better
prognosis of PSC and PSC/AIH with a paediatric onset compared to previous
published. The careful endoscopic follow-up conducted in these patients could
prevent complications.
REFERENCES
1. Deneau M et al. Hepatology 2013; 58: 1392-400.
Disclosure of Interest: None declared
OP165 EVIDENCE OF A NORTH SOUTH GRADIENT IN THE
OCCURRENCE OF PRIMARY BILIARY CIRRHOSIS IN THE UK
USING TWO DECADES OF NATIONAL DATA
C.J. Crooks1,*, T.R. Card1, J. West1
1
Epidemiology and Public Health, UNIVERSITY OF NOTTINGHAM,
Nottingham, United Kingdom
Contact E-mail Address: colin.crooks@nottingham.ac.uk
INTRODUCTION: Previous studies of the occurrence of Primary Biliary
Cirrhosis (PBC) have been small and regional, but in combination they suggest
a north south gradient in incidence in the UK, and elsewhere geospatial cluster-
ing.1-4 This raises the possibility of specific environmental factors related to
geographical location leading to PBC occurrence. However few studies have
been truly national or population based. We have therefore assessed the patterns
in occurrence of PBC across the whole of the UK over 2 decades.
AIMS & METHODS: Patients with Primary Biliary Cirrhosis (PBC) were iden-
tified in the Clinical Practice Research Datalink between 1990 and 2010 using
specific Read codes for PBC. Incidence rates and prevalence were calculated by
age group, sex, year, socio-economic status and region of residence. Incidence
rate ratios (IRR) adjusted for these variables were then calculated with Poisson
regression.
RESULTS: 1390 incident cases of PBC were identified from the CPRD. 88% of
cases were women with the highest incidence in those aged over 70 years of age.
Between 1990 and 2010 the overall incidence rate of PBC increased from 1.2/
100,000 (95% CI, 0.62.1) in 1990 to 2.9/100,000 ((95% CI, 2.4-3.7) in 2010, with
an adjusted 2-fold increase (IRR 1.9 (95% CI, 1.1-3.5)). There was a clear north
south gradient in PBC incidence that persisting after adjusting for socioeconomic
differences (table, p 0.001 for a trend). When time trends were stratified by
United European Gastroenterology Journal 2(5S)
region there was a significant increase in incidence in the north of England (p 5
0.02) that was not reflected elsewhere in the country. We did not find an associa-
tion between PBC incidence with socioeconomic status (likelihood ratio test, p
0.3). Prevalence of PBC followed a similar pattern to incidence across the country
and over time.
Table .Average incidence rates for Primary Biliary Cirrhosis (1990-2010, per
100,000 person years) and the corresponding incidence rate ratios adjusted for
age group, sex, year, and socio-economic status.
Regions (Aggregated) Incidence 95% CI IRR 95% CI
Scotland and Northern Ireland 4.8 (4.25.3) 2.8 (2.6-2.9)
Northern England and Yorkshire 2.8 (2.5-3.2) 1.8 (1.7-1.9)
Mid England and Wales 2.0 (1.8-2.4) 1.1 (1.1-1.2)
Southern England and London 1.8 (1.6-2.0) 1.0 -
CONCLUSION: We found that across a 20 year period there was a 2-fold
increase in the incidence of PBC in the UK with large regional variations. The
greatest increases were seen in the north of England with small rises elsewhere.
Although geographical differences raise the possibility that specific environmen-
tal exposures are responsible, the lack of association with socioeconomic status
makes some of the suggested culprits, smoking and living conditions, less prob-
able.3 The most likely reasons for these variations were therefore differences in
ascertainment of disease.
REFERENCES
1. Ala A, et al. Hepatology 2006; 43, 525531.
2. Myers RP, et al. Hepatology 2009; 50, 18841892.
3. McNally et al. American Journal of Epidemiology 2014; 179: 492498.
4. Williams JG, et al. Gut 2007; 56(Suppl 1): 1113.
Disclosure of Interest: None declared
OP166 THE CLINICAL SIGNIFICANCE OF SPHINCTER OF ODDI
INSUFFICIENCY AFTER CHOLECYSTECTOMY
M., V. Repin1,*, A., V. Popov2, V. Y. Mikryukov1, T.E. Vagner3
1
Department of advanced training, 2Hospital surgery, Perm State Medical
Academy named after E.A. Vagner, 3Perm Regional Clinical Hospital, Perm,
Russian Federation
Contact E-mail Address: max_repin@inbox.ru
INTRODUCTION: Its usual to expect organic obstacles of bile flow in patients
with postcholecystectomical abdominal pain and dyspeptic disorders but more
often it must be distinguished from sphincter of Oddi functional disorders.
AIMS & METHODS: To evaluate the clinical significance of the loss of sphinc-
ter of Oddis closing contraction function in patients after cholecystectomy.
The study included 100 patients after cholecystectomy (17 men, 83 women, aged
17-72 yrs), excluding those who had signs of cholestasis. Two groups were iden-
tified: 1st - 86 patients after cholecystectomy; 2nd - 14 patients after cholecystect-
omy combined with papillotomy, in whom we assumed that the sphincter of
Oddis closing contraction function was lost.
Clinical manifestations, biochemical blood tests, the results of X-ray and endo-
scopic studies were evaluated. Patients underwent hepatobiliary scintigraphy
(HBSG) using radionuclide tracer 99 m Tc-HIDA within 90 minutes, with
fatty meal ingestion on the 45th minute. The function of the common bile duct
(CBD) and the duodenum was measured. Specific time-activity histogram were
made, time-to-peak CBD activity (TP CBD), half time of excretion (R CBD),
latent period of CBD (T lat CBD), duodenal appearance time (DAT), half time
of excretion of the duodenum (R duodenum), degree of duodeno-gastric reflux
(DGR) were calculated.
RESULTS: According to HBSG in 20 (23.2%) patients of the 1st group the
appearance of radionuclide tracer small portions in the duodenum (DAT) was
recorded at 27.710.2 minute (min), and the intensive removal from time-to-
peak CBD activity started immediately after fatty meal ingestion at 45.91.8
min, with T CBD 27.713.9 min, which corresponds to normal. In 66
(76.8%) patients of the 1st group DAT was registered already in 18.66.0 min
and the choledoch started to empty before the fatty meal ingestion, TP CBD was
determined on 32.96.8 min and T CBD on 26.410.8 min. These indicators
were regarded as the sphincter of Oddi insufficiency. In all cases of the 2nd group
a premature start (TP CBD 30.40.8 min) and rapid emptying of the CBD (CBD
T 27.511.2 min) were observed, with the appearance of the radionuclide
tracer in duodenum at 17.60.8 min. These figures were identical to those in
patients with sphincter of Oddi failure in the 1st group, but differed from those
with normal sphincter of Oddi function (p 50.05). TP CBD correlated with R
duodenum (r0.57, p50.001) and degree of DGR (r0.74, p50.01). DGR
degree was associated with belching bitter complaints (r0.36, p50.01), heart-
burn (r0.24, p0.025). X-ray duodenum antistalsis was accompanied by reflux
into the stomach (r0.73, p50.01) and endoscopic data of antral gastritis and
esophagitis (r0.39, p50.048). Diarrhea was observed in 73% patients of the 1st
group with the sphincter of Oddi insufficiency and 86% - after papillotomy
versus 10% of normal bile flow (p 50.01). Diarrhea rate correlated with TP
CBD(r -0.43, p50.01).
CONCLUSION: Sphincter of Oddi insufficiency develops in 77% cases after
cholecystectomy and becomes most clinical significant in patients with duode-
num dyskinesia. The relationship of functional disorders of biliary tract and the
duodenum should be taken into account while choosing therapeutic manage-
ment, complementing therapy with regulating intestinal motility.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP167 INTERSTITIAL CAJAL-LIKE CELLS/TELOCYTES AND
GALLBLADDER AUTONOMIC NERVOUS SYSTEM INTERPLAY IN
THE PATHOGENESIS OF CHOLELITHIASIS
A. Pasternak1,2,*, M. Szura1, A. Matyja1, M. Kurnik3, J.A. Walocha2, K. Gil3
1
1st Chair of General Surgery, 2Department of Anatomy, 3Department of
Pathophysiology, Jagiellonian University Medical College, Krakow, Poland
Contact E-mail Address: artur.pasternak@uj.edu.pl
INTRODUCTION: The major mechanisms of gallstone formation include bili-
ary cholesterol hypersecretion, supersaturation and crystallization, mucus hyper-
secretion, gel formation and bile stasis. Gallbladder hypomotility seems to be a
key event that triggers the precipitation of cholesterol microcrystals from super-
saturated lithogenic bile. Recently, we reported a significant decrease in inter-
stitial Cajal-like cell (ICLC) density in gallbladders of patients with cholelithiasis.
Such cells in the gallbladder were strongly influenced by lithogenic bile. ICLCs,
ra w n
as well as the autonomic neurons located within gallbladder muscularis propria
are considered as predominant regulatory cells of gallbladder motility.
d
AIMS & METHODS: The purpose of the current study was to determine the
W i t h
influence of lithogenic bile on the gallbladder autonomic neurons, in relationship
to ICLCs. Gallbladder specimens were collected from 20 patients (8 males and 12
females) who underwent elective laparoscopic cholecystectomy for symptomatic
gallstone disease. The control gallstone-free group consisted of 20 consecutive
patients (9 males and 11 females) who received elective treatment for pancreatic
head tumors. ICLCs were visualized in paraffin sections of gallbladders with
double immunofluorescence using primary antibodies against c-Kit (anti-
CD117) and anti-mast cell tryptase. The telocytes were stained with anti-CD34
antibody and assessed simultaneously. Autonomic neurons within the gallblad-
der wall were visualized by immunohistochemistry using anti-PGP9.5, anti-
ChAT and anti-NOS antibodies and assessed semi-quantitatively. Cholesterol,
phospholipid and bile acid concentrations were measured in bile samples
obtained by needle aspiration from the gallbladder during surgery.
RESULTS: The number of ICLCs in the gallbladder wall was significantly lower
in the study group than in the control group (3.2  1.5 vs. 6.6  1.8 cell/area of
view in the muscularis propria, P 5 0.001) and correlated with a significant
increase in the cholesterol saturation index, so did the telocytes count. The glyco-
cholic and taurocholic acid levels were significantly elevated in the control sub-
jects compared with the study group. Numerous PGP9.5 positive neural fibers
were present, including some neuron bodies. Only sparse cholinergic (ChAT-
positive) as well as nitrergic (NOS-positive) neurons were found. The cumulative
neurons count was slightly decreased in patients with gallstones.
CONCLUSION: These results suggest that bile composition plays an important
role in the reduction of ICLC and autonomic neurons density in the gallbladder,
and this might lead to the gallbladder dysmotility in patients with cholelithiasis.
Disclosure of Interest: None declared
OP168 SMALL FIBERS PERIPHERAL NEUROPATHY IN WILSON
DISEASE: AN IN VIVO DOCUMENTATION BY CORNEAL
CONFOCAL MICROSCOPY
1, 2 2 2
O. Bartolo *, D. Lazzarini , M. Berton , A. Leonardi , I. A. Fregona , 2 CONCLUSION: In our study we demonstrate that the majority of patients
E. Midena2, G.C. Sturniolo1
1
Department of Gastroenterology, University of Padova, Padova, Italy,
2
Department of Ophthalmology, University of Padova, Padova, Italy, University of
Padova, Padova, Italy, Padova, Italy
Contact E-mail Address: ottjbartolo@gmail.com
INTRODUCTION: Wilson disease (WD) is a rare inherited autosomal recessive
disorder of copper metabolism whose hallmarks are: liver damage, neuropsychia-
tric symptoms and Kayser-Fleischer (KF) corneal ring. The presence of KF ring
correlates with central nervous system (CNS) involvement, being detectable in
nearly 100% of subjects with CNS involvement, and in about 50% of those with
hepatic and pre-symptomatic WD. Corneal confocal microscopy (CCM) is a fast
reliable and repeatable technique to analyze the human cornea in vivo, allowing a
high magnification imaging of different corneal structures, including corneal
nerves.
AIMS & METHODS: We aimed to investigate central corneal changes and to
assess the parameters of corneal subbasal nerve plexus (CSNP) in patients
affected by Wilson disease (WD), using corneal confocal microscopy (CCM).
Twenty-four patients affected by WD and 24 healthy control subjects were
enrolled in this cross-sectional comparative study. One eye of each subject was
examined to quantify different corneal parameters, by means of non invasive
corneal confocal microscopy. Mean cell diameter and mean cell density of the
epithelium; number of fibers (NF), nerve fiber length density (NFLD), number of
branchings (NBr), number of beadings (NBe) and fiber tortuosity (FT) of the
subbasal nerve plexus; mean cell density of keratocytes of the anterior, medium
and posterior stroma and mean cell density, polimegatism and pleomorphism of
the endothelium were analyzed.
RESULTS: WD induced significant alterations in both corneal subbasal nerve
plexus, and corneal epithelium. All the parameters of the subbasal nerve plexus
were altered in WD: NFLD (P50.0001), NF (P0.001), NBe (P0.025) and NBr
(P50.0001) were significantly lower, whereas FT (P50.0001) was significantly
higher in WD subjects compared to controls, documenting, for the first time, a
(corneal) peripheral nerve damage in WD. The decrease of major CSNP para-
meters confirms the damage (and death) of a significant number of small nerve
fibers, whereas the increase of FT is a sign of tentative nerve regeneration. Mean
epithelial cell diameter (P50.0001) and mean epithelial cell density (P50.0001)
resulted significantly higher and lower compared to controls, respectively. No
significant difference in corneal stroma and endothelium were observed.
CONCLUSION: CCM showed significant corneal changes in subbasal nerve
plexus, with secondary corneal epithelium changes in WD, demonstrating the
presence of small fibers peripheral neuropathy in these patients. CCM may
A55
contribute to diagnose and monitor the peripheral nervous system involvement
in WD. Further larger studies needed to confirm these findings.
Disclosure of Interest: None declared
OP169 PANCREATIC ENZYME REPLACEMENT THERAPY IN
PANCREATIC CANCER ARE WE GETTING IT RIGHT?
S. Subramaniam1,1,*, N. Nobar1, K. Besherdas1
1
Department of Gastroenterology, Barnet & Chase Farm Hospitals NHS Trust,
London, United Kingdom
Contact E-mail Address: sharmila.subramaniam@nhs.net
INTRODUCTION: Pancreatic cancer (PC) is the 10th most common cancer in
the UK, accounting for 8500 all new cases per year. PC is unique compared to
other cancers, as weight loss and malabsorption are present in 80%90% of
patients at the time of diagnosis. Pancreatic enzyme replacement therapy
(PERT) in the form of enteric coated pancreatin microspheres is recommended
in pancreatic cancer patients with these symptoms to prevent weight loss and
malnutrition and improve quality of life. Given that the probability of pancreatic
exocrine insufficiency is high in PC, PERT is recommended without the use of
formal diagnostic tests. The optimal dose of pancreatic enzyme replacement
therapy is 40-50000 lipase units per main meal with half that dose for each snack.
AIMS & METHODS: The aim of this study was to evaluate the use of PERT in
pancreatic cancer and to ascertain if patients were being prescribed the recom-
mended dose. A single centre retrospective analysis of patients diagnosed with PC
in a large North London district general hospital was performed. The database of
all patients diagnosed with PC since 2010 was obtained from the local upper
gastrointestinal cancer multidisciplinary team records. 149 patients were identi-
fied but 32 excluded from the study due to poor documentation in the records
leading to insufficient information surrounding enzyme supplementation and
dosages. Information was collected from electronic patient records on the
patients symptoms, evidence of PERT and the dose prescribed.
RESULTS: Symptoms of pancreatic enzyme insufficiency (weight loss and/or
steatorrhoea) were recorded in 72/117 (61.5%) of patients included in this
study. Only 14 out of the 117 (8%) patients included in this study were prescribed
PERT. The table below shows the enzyme formulation and dosages used.
Pancreatic enzyme formulationDose (units) Number of patients
Creon 50 000 three times/day (TDS)1
40 000 TDS 1
30 000 TDS 1
25 000 TDS 4
10 000 TDS 4
Not documented 2
Creon Micro Not documented 1
(92%) with PC are not prescribed PERT despite the presence of symptoms
indicating pancreatic enzyme insufficiency. Of the 14 patients prescribed
PERT, only 2 patients were treated with the recommended dose. This study
highlights the missed opportunity to reduce symptoms and improve quality of
life in PC patients with simple PERT. Increased awareness of the availability of
this simple treatment amongst those treating patients with PC is required.
Disclosure of Interest: None declared
OP170 FAST TRACK RECOVERY REDUCES COMPLICATIONS AND
COSTS AFTER PANCREATICODUODENECTOMY
C. Williamsson1,*, R. Andersson1, G. Lindell1, B. Tingstedt1
1
Department of Surgery, Lund University, Lund, Sweden
Contact E-mail Address: bobby.tingstedt@med.lu.se
INTRODUCTION: Enhanced recovery after surgery is multimodal, evidence
based approach to optimize the patient outcome. Enhanced recovery after sur-
gery (ERAS) or fast track programmes were developed and described by Kehlet
et al. more than 10 years ago for colorectal surgical patients.
Pancreaticoduodenectomy (PD) is a very complex operation with a high morbid-
ity rate and long post-operative hospital stay.
AIMS & METHODS: The aim of this study was to evaluate the safety and
clinical outcome of a fast track programme after PD. 100 pancreaticoduodenec-
tomies were prospectively followed at Skane University Hospital Lund, Sweden.
50 patients were evaluated before adopting the perioperative routine changes
(preFastTrack) and 50 patients after (FastTrack). The postoperative care was
challenged and changes were made according to the basic ERAS concept. A
programme was adopted that standardized the care and automated certain func-
tions. Changes made include; preoperative nutrition, secondary antibiotic pro-
phylaxis, standardized withdrawal of nasogastric tubes and abdominal drains.
Patients were also put on a standardized pain relief scheme. Patients were thor-
oughly informed preoperatively regarding the proposed care and discharge cri-
teria. Data regarding demographics, symptoms, blood, operations and
postoperative course was prospectively and continuously registered.
RESULTS: There was no difference between the groups regarding background
data on age, sex, symptoms, histopathological diagnosis and TNM stage. 30
days-mortality was zero in both groups.
Complications were decreased in the Fast Track group with delayed gastric
emptying (DGE) significantly decreased (Table 1). Patients with complications
(55% vs 34%) and severity of complications according to Clavien-Dindo was
significantly reduced (p0.013 and p0.0.001 respectively).
A56
Table 1.
Table to abstract OP170
Pre Fast Track Fast Track P-value
Wound infection 12 (24%) 7 (14%) 0.067
Seroma 3 (6%) 1 (2%) 0.096
Postoperative bleeding 2 (4%) 2 (4%) 1.0
Pancreatic fistula 14 (28%) 11 (22%) 0.288
Serious complications * 5 (10%) 6 (12%) 1.0
Delayed Gastric Emptying * 25 (48%) 11 (22%) 0.029
CONCLUSION: The result of this study shows it is feasible to perform an
enhanced recovery even after a major operation such as the pancreatodudode-
nectomy without increasing mortality or morbidity. The shorter hospital stay and
less frequent use of radiology decrease the in-hospital cost significantly with
almost 25%.
Disclosure of Interest: None declared
OP171 ELEVATED ALKALINE PHOSPHATASE IS AN INDEPENDENT
PREDICTOR OF GOOD RESPONSE DURING SOMATOSTATIN
ANALOGUE THERAPY: A MULTI-CENTER POOLED ANALYSIS ON
INDIVIDUAL PATIENT DATA
T. J. G. Gevers1,*, F. Nevens2, V. E. Torres3, M.C. Hogan3, J.P. Drenth1
1
Gastroenterology and Hepatology, Radboudumc, Nijmegen, Netherlands,
2
Hepatology, KU leuven, Leuven, Belgium, 3Division of Nephrology and hyper-
tension, Mayo clinic, Rochester, United States
Contact E-mail Address: tom.gevers@radboudumc.nl
INTRODUCTION: Somatostatin analogues (SA) reduce liver volumes in
patients with polycystic liver disease. However, polycystic liver disease patients
show a great variety in treatment responses, which makes it difficult to predict
which patients will respond to SA therapy.
AIMS & METHODS: Our aim was to identify specific patient, disease or treat-
ment characteristics that predict good response to SA in polycystic liver disease.
We pooled the individual patient data of 4 trials (NCT00771888, NCT00426153,
NCT01157858, NCT01354405) that evaluated the effect of long-acting SAs (120
mg lanreotide or 40 mg octreotide) for 6-12 months in polycystic liver disease
patients and had liver volume as a primary outcome. We performed univariate
and multivariate logistic regression analysis with preselected patient, disease and
drug characteristics to identify predictors of good-response. Good-response was
defined as a reduction of 120 ml in liver volume, as this was associated with a
clinical response1. All analyses were adjusted for center and baseline liver volume.
RESULTS: We included 153 polycystic liver disease patients (86% female, mean
age 50 years, median liver volume 4974 ml) from 3 international centers that were
treated with octreotide (n70) or lanreotide (n83). Median reduction in liver
volume was 4% (range -32 to 10%), and 57% patients achieved a good
response during therapy. Multivariate logistic regression revealed that elevated
alkaline phosphatase (ALP) (odds ratio 2.61, 95% confidence interval 1.17
5.83, p 0.019) as a predictor of good response during SA therapy, independent
of baseline liver volume. Renal function, elevated bilirubin, duration of therapy
(6 versus 12 months) and SA type (octreotide or lanreotide) did not affect the
probability for a response. Elevated ALP remained an independent predictor for
response when it was defined as percent change in liver volume instead of abso-
lute change. Our model, including ALP, performed well in differentiating
patients with and without good response during SA therapy (AUC 0.72, p 5
0.001).
CONCLUSION: Elevated ALP is an independent predictor for good response
during SA therapy in polycystic liver disease, and could possibly serve as a
marker to select patients for initiating therapy.
REFERENCES
1. Temmerman F, Gevers T, Ho TA, et al. Safety and efficacy of different
lanreotide doses in the treatment of polycystic liver disease: pooled analysis of
individual patient data. Aliment Pharmacol Ther 2013; 38: 397-406.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 11:0012:30
INFLAMMATION AND CELL DEATH IN GI DISORDERS HALL R_____________________
OP172 ADIPOSE TISSUE REGULATORY LYMPHOCYTES MISMATCH
WITH ANTHROPOMETRIC PARAMETERS IS ASSOCIATED WITH
INSULIN RESISTANCE IN OBESE PATIENTS
T. Adar1,*, R.S. Spira2, S. Shteingart1, A. Ben-Yaacov1, S. Shmorak1,
A. Jarjoui1, G. Kalak1, S. Abu-Khalaf1, M. Yisraeli 1, A. B.-G. Shitrit1,
M. Mahamid1, E. Broide3, E. Goldin1
1
Digestive Diseases Institute, 2Department of General Surgery, 3Flow cytometry
unit, Department of immunology, Shaare Zedek Medical Center, Jerusalem, Israel
Contact E-mail Address: adartom@szmc.org.il
INTRODUCTION: Insulin resistance is associated with obesity. The mechanism
for why some obese patients develop insulin resistance (IR) while others retain
normal IR is unknown, and may be multifactorial. Adipose tissue is recognized
as an inflammatory active organ, harboring several types of regulatory lympho-
cytes, which may be involved in the development of IR.
AIMS & METHODS: To identify different adipose tissue regulatory lympho-
cytes population patterns in obese patients with and without insulin resistance.
Peripheral blood samples and intra-operative visceral adipose tissue biopsies
were taken from consenting patients undergoing elective abdominal surgery.
United European Gastroenterology Journal 2(5S)
Patients were divided into normal, moderate and high IR according to their
homeostatic model assessment (HOMA score).
Flow cytometry (FACS) was used to identify CD4CD25FOXP3 regulatory
lymphocytes (Tregs) and CD4IL17 (TH17) cells from both the peripheral
blood and visceral adipose tissue, which were then compared with anthropo-
metric parameters.
RESULTS: Intra-operative biopsies and blood samples were collected from 28
patients. 16 patients had normal IR (HOMA score 53) and 9 patients had
moderate IR (HOMA score 3-5). 3 patients had high HOMA score and were
excluded from final analysis because of a small group size.
Mean age and body mass index (BMI) of the normal and moderate IR groups
were 44.5 and 38.5 years (NS) and 39.5 and 41.6 kg/m2 (NS).
In patients with normal IR, Tregs positively correlated both BMI and waist
circumference [r 0.6 (p0.01) and 0.66 (p50.01), respectively). However in
patients with moderate IR, the correlation between Tregs and BMI was lost, and
the correlation to waist circumference was actually reversed and became negative
[r -0.86 (p50.01)]. No significant difference was demonstrated in waist cir-
cumference (122 and 127.6 cm in normal and moderate IR groups).
Similarly, a positive correlation between the adipose tissue Treg/TH17 ratio and
the BMI and waist circumference which was demonstrated in normal IR patients
[r 0.59 (p50.05) and 0.74 (pp50.01) respectively] was lost in the moderate IR
group.
CONCLUSION: In this study we identify two opposite distribution patterns for
adipose tissue Tregs, differentiating obese patients according to their insulin
resistance status.
Combined analysis of anthropometric parameters with adipose tissue Tregs may
offer a new insight into the pathogenesis of insulin resistance in obese patients,
and may mark adipose tissue Tregs as potential therapeutic targets.
Disclosure of Interest: T. Adar Financial support for research from: Synageva,
Lecture fee(s) from: Shire, Consultancy for: Janssen, Other: Boston Scientific,
Immune Pharma, R. Spira: None declared, S. Shteingart: None declared, A. Ben-
Yaacov: None declared, S. Shmorak: None declared, A. Jarjoui: None declared,
G. Kalak: None declared, S. Abu-Khalaf: None declared, M. Yisraeli: None
declared, A. Shitrit: None declared, M. Mahamid: None declared, E. Broide:
None declared, E. Goldin Consultancy for: Immune Pharma, Bioline Rx Ltd
OP173 HELICOBACTER PYLORI INFECTION CAUSES INSULIN
RESISTANCE THROUGH C-JUN/MIR-203/SOCS3 PATHWAY
X. Zhou1,1,*, G. Zhang1
1
Gastroenterology, the First Affiliated Hospital of Nanjing Medical University,
Nanjing, China
INTRODUCTION: Epidemiological studies indicate that patients with
chronic Helicobacter pylori (H. pylori) infection have an increased risk of devel-
oping type 2 diabetes mellitus (1, 2), but the underlying mechanism remain
largely unknown.
AIMS & METHODS: This study aims to investigate whether H. pylori infection
contributes to the development of insulin resistance, as well as the underlying
mechanism both in vivo and in vitro.
RESULTS: We found that average fasting glucose levels were increased in
patients and mice with H. pylori infection. Diabetic mice with H. pylori infection
showed impaired glucose and insulin tolerance and hyperinsulinemia.
Furthermore, H. pylori infection impairs insulin signaling in primary hepato-
cytes. H. pylori infection can upregulate suppressors of cytokine signaling
(SOCS)-3, a well-known insulin signaling inhibitor by down-regulating miR-
203. SOCS-3 over-expression interfered with insulin signaling proteins and
knockdown of SOCS-3 alleviates H. pylori-induced impairment of insulin signal-
ing. We also identified c-Jun, a transcription factor which affect gene expression,
could induced by H. pylori infection and suppress miR-203 expression.
CONCLUSION: Our results demonstrated that H. pylori infection could induce
hepatic insulin resistance by c-Jun/miR-203/SOCS3 signaling pathway and pro-
vide possible implications toward resolving insulin resistance.
REFERENCES
1. Jeon CY, Haan MN, Cheng C, et al. Helicobacter pylori infection is associated
with an increased rate of diabetes. Diabetes Care 2012; 35: 520-525.
2. Zhou X, Zhang C, Wu J, et al. Association between Helicobacter pylori
infection and diabetes mellitus: a meta-analysis of observational studies.
Diabetes Res Clin Pract 2013; 99: 200-208.
Disclosure of Interest: None declared
OP174 A UBIQUITIN-MODIFYING ENZYME A20 CONTROLS THE
DYNAMICS OF AUTOPHAGY
Y. Matsuzawa1,*, S. Oshima1, M. Takahara1, K. Nozaki1, M. Kobayashi1,
Y. Nibe1, C. Maeyashiki1, Y. Nemoto1, A. Ma2, M. Watanabe1
1
Gastroenterology and Hepatology, Tokyo Medical and Dental University, Tokyo,
Japan, 2Medicine, University of California, San Francisco, San Francisco, United
States
INTRODUCTION: Crohns disease is a chronic inflammatory disease, mainly
affecting the gastrointestinal tract. Genome wide association studies identified
autophagy related genes as conferring susceptibility to Crohns disease. We have
also reported that A20 (Tnfaip3), a ubiquitin-modifying enzyme, is a Crohns
disease susceptibility gene. A20 is critical for preventing inflammation in vivo.
A20 may play important roles in human autoimmune diseases and Crohns dis-
ease. However, the physiological role of A20 in T cells is not fully understood.
AIMS & METHODS: In this research, we analyze A20s potential function in T
cells, and demonstrate how important A20 is for autophagy regulation and
inflammation.
United European Gastroenterology Journal 2(5S)
To analysis the function of A20 and autophagy in vivo, we generated mice
lacking A20 and ATG5 specifically in T cells by breeding A20FL and
ATG5FL mice with CD4-Cre transgenic mice. Single-cell suspensions were pre-
pared from thymus, spleen, and peripheral lymph nodes of mice, and were ana-
lyzed by flow cytometry and immunoblotting. To determine whether A20
regulates autophagy in T cells, A20 deficient na ve CD4 T cells were puriEed
from spleens and lymph nodes. Cells were stimulated with anti-CD3 plus anti-
CD28 in vitro. Live cells were analyzed by immunohistochemistry using LC3
antibody (LC3 is generally considered as a marker of autophagosome). Images
were acquired on a confocal laser microscope.
RESULTS: A20 and ATG5 double deficient (DKO) mice were obtained in
Mendelian numbers and developed normally. Enlarged spleen and lymph node
were observed in DKO mice. Surprisingly, the absolute number of peripheral T
cells was significantly reduced in DKO mice as compared to control mice.
Moreover, both B cells and myeloid cells were expanded in DKO mice. These
data indicate that T cell lineage deletion of A20 and ATG5 perturbs lymphoid
homeostasis. The immunohistochemistry analysis of na ve CD4 T cells revealed
that the LC3 punctae formation was reduced in A20 deficient cells after stimula-
tion. To understand the biochemical mechanisms by which A20 may regulate
autophagy, we studied CD4 T cells in vitro and found the target of A20 in
autophagy signaling. Thus, A20 regulates induction of autophagy in na ve
CD4 T cells.
CONCLUSION: Our studies demonstrate that A20 regulates autophagy, and
provide new insights into how Crohns disease susceptibility genes in T cells
regulate inflammation.
REFERENCES
1. Mizushima N and Levine B. Autophagyin mammalian development and dif-
ferentiation. Nat Cell Biol 2010; 12: 823-830.
2. Levine B, Mizushima N and Virgin HW. Autophagy in immunity and inflam-
mation. Nature 2011; 469: 323-335.
3. Ma A and Malynn BA. A20: linking a complex regulator of ubiquitylation to
immunity and human disease. Nat Rev Immunol 2012; 12: 774-785.
Disclosure of Interest: None declared
OP175 PREVENTION OF GENOTOXICITY AND PROTUMORAL
EFFECT MEDIATED BY COLIBACTIN-PRODUCING BACTERIA
A. Cougnoux1, J. Delmas1,2, L. Gibold1,2, T. Fa s1,2, C. Romagnoli3, F. Robin1,2,
G. Cuevas-Ramos4,5, E. Oswald4,5, A. Darfeuille-Michaud6, F. Prati7,
G. Dalmasso6,*, R. Bonnet2,6
1
Medicine, Inserm U1071, 2Centre Hospitalier Universitaire, Clermont-Ferrand,
France, 3Department of Life Sciences, University of Modena and Reggio Emilia,
Modena, Italy, 4Inserm U1043, 5CNRS UMR5282, Toulouse, 6Inserm U1071,
Clermont-Ferrand, France, 7University of Modena and Reggio Emilia, Modena,
Italy
Contact E-mail Address: guillaume.dalmasso@udamail.fr
INTRODUCTION: Colorectal cancers are frequently colonized by Escherichia
coli producing the toxin called colibactin. Those bacteria induce DNA damage in
host cells, exhibit protumoral activities and increase the number of tumors in
colorectal cancer mouse model.
AIMS & METHODS: Our objectives were to identify drug-like molecules that
prevent the toxic effects mediated by colibactin-producing bacteria. Using a
structural approach, we selected putative ligand of the ClbP enzyme, which is
involved in the synthesis of colibactin. The activity of compounds was evaluated
in vitro and in vivo using intestinal epithelial cells and a colorectal cancer mouse
model.
RESULTS: Crystallography revealed that two drug-like molecules were able to
bind the active site of ClbP. These compounds suppressed both in vitro and
in vivo the genotoxic activity of colibactin-producing E. coli. In addition, they
prevented cellular proliferation, as well as tumourigenesis mediated by those
bacteria in mouse.
CONCLUSION: These demonstrate that targeting colibactin production con-
trols genotoxicity and protumoral effects mediated by this toxin.
Disclosure of Interest: None declared
OP176 DEOXYCHOLIC ACID INDUCES MIR-21/PDCD4-DEPENDENT
CYTOTOXICITY BY HAMPERING NF-JB SURVIVAL SIGNALLING
IN PRIMARY RAT HEPATOCYTES
P.M. Rodrigues1,*, M.B. Afonso1, A.L. Simao1, P.M. Borralho1,2, C. M.
P. Rodrigues1,2, R.E. Castro1,2
1
Instituto de Investigacao do Medicamento (iMed.ULisboa), 2Department of
Biochemistry and Human Biology, Faculdade de Farmacia, Universidade de
Lisboa, Lisbon, Portugal
Contact E-mail Address: pmvrsrodrigues@ff.ul.pt
INTRODUCTION: Toxic bile acids have been implicated in the development of
several liver diseases, including non-alcoholic fatty liver disease (NAFLD). In
particular, deoxycholic acid (DCA) is increased in the liver of NAFLD patients,
correlating with disease progression.We have recently shown that microRNA-21
(miR-21) is decreased in response to DCA in primary rat hepatocytes.
AIMS & METHODS: Our aim was to describe the mechanisms by which DCA
modulates miR-21-dependent pathways and whether these contribute to DCA-
induced cytotoxicity. Primary rat hepatocytes were treated with 25-200 mM DCA
for 24 h. Cell death, viability and caspase-3 activity were measured by the
ApoTox-GloTM Triplex Assay and the presence of apoptotic nuclei confirmed
by Hoechst staining. miR-21 expression was measured by qRT-PCR.
Programmed cell death 4 (PDCD4), a miR-21 pro-apoptotic target, was evalu-
ated by both immunoblotting and after transfecting cells with a specific luciferase
plasmid, containing the miR-21 3-UTR-binding fragment of the PDCD4 mRNA.
A57
NF-B, IB and active caspase-2 levels were also measured by immunoblotting.
NF-B activation was evaluated using a specific luciferase assay and by analysing
NF-B subcellular localization. In functional studies, miR-21, PDCD4, caspase-2
and NF-B were modulated using both genetic and pharmacologic modulators.
Finally, reactive oxygen species (ROS) levels were determined by using the fluor-
escent probe 2,7-dichlorodihydrofluorescein diacetate.
RESULTS: Our results show that the miR-21/PDCD4 pathway is modulated by
DCA in a dose-dependent manner, with a concomitant decrease in cell viability
and an increase in cell death, apoptotic nuclei, caspase-2/-3 activation and ROS
production. Importantly, miR-21 overexpression and either PDCD4 or caspase-2
silencing counteracted DCA-induced apoptosis. Furthermore, NF-B activity
was decreased in a similar pattern to miR-21 expression after incubation of
hepatocytes with DCA. In fact, NF-B inhibition, using a selective chemical
inhibitor (BAY 11-7085), potentiated the effects of DCA impacting on the
miR-21/PDCD4 pathway, further decreasing miR-21, while increasing PDCD4
expression levels and apoptosis. In agreement, NF-B overexpression had oppo-
site effects.
CONCLUSION: In conclusion, the miR-21/PDCD4/apoptosis axis is modulated
by DCA in a dose-dependent manner. Mechanistically, DCA targets miR-21 via
inhibition of NF-B activity, likely as a downstream result of caspase-2 engage-
ment in response to DCA-induced ROS production. A better understanding of
the network of signalling mechanisms activated by toxic bile acid species may
allow the development of new therapeutic tools to treat bile acid-associated liver
pathologies. (Supported by PTDC/SAU-ORG/111930/2009, PTDC/BIM-MEC/
0873/2012, SFRH/BD/88212/2012 and SFRH/BD/91119/2012 from FCT,
Portugal)
Disclosure of Interest: None declared
OP177 ROLE OF NECROPTOSIS IN MURINE MODELS OF BILE ACID
TOXICITY
M.B. Afonso1,*, M. Caridade1, P.M. Rodrigues1, R.E. Castro1,2, C. M.
P. Rodrigues1,2
1
Instituto de Investigacao do Medicamento (iMed.ULisboa), Faculdade de
Farmacia, Universidade de Lisboa, 2Department of Biochemistry and Human
Biology, Faculdade de Farmacia, Universidade de Lisboa, Lisbon, Portugal
Contact E-mail Address: mbafonso@ff.ul.pt
INTRODUCTION: Cholestasis is a common pathological condition caused by
disruption of bile flow, resulting in retention of bile acids in serum and in liver,
with a concomitant toxic response in hepatocytes. Accumulating evidence sug-
gests that regulated necrosis or necroptosis may be involved in hepatocyte injury
during cholestasis, through unclear signalling pathways.
AIMS & METHODS: Thus, we aimed to evaluate the role of necroptosis in
hepatocytes exposed to toxic bile acids and in animal models of bile acid toxicity.
Bile duct ligation (BDL) was performed in male C57BL/6 mice to induce cho-
lestasis and secondary fibrosis. Serum and livers were collected 3, 7 and 14 days
after BDL. To further explore the role of toxic bile acids in necroptosis activa-
tion, deoxycholic acid (DCA; 250 mg/Kg/day, oral gavage, 5 days) was adminis-
tered to male Wistar rats. Necroptotic markers were evaluated in liver tissue and
serum. HepG2 cells and primary rat hepatocytes were incubated with glycoche-
nodeoxycholic acid (GCDCA; 200 mM) or DCA (400 mM), in the presence or
absence of pan-caspase inhibitor, zVAD-fmk (50 mM), and/or necroptosis inhi-
bitor, necrostatin-1 (100 mM), or ursodeoxycholic acid (UDCA; 100 mM).
RESULTS: Our results showed that BDL-operated mice displayed a strong
increase of serum transaminases, alkaline phosphatase and bilirubin.
Histological analysis revealed that BDL resulted in bile duct hyperplasia, multi-
focal necrosis and fibrosis. Moreover, BDL increased liver proinflammatory
cytokines. Similarly, DCA induced hepatocellular necrosis and inflammatory
cell infiltration in rat liver, with a concomitant increase of liver proinflammatory
cytokines and serum transaminases. Serum markers of necroptosis, namely high
mobility group box 1 (HMGB1) and cyclophilin A, were increased in both
animal models. Further biochemical pathway analysis in the liver of BDL and
DCA animals, namely receptor interacting protein 3 (RIP3) expression, con-
firmed the role of necroptosis in pathogenesis. Finally, DCA and GCDCA
were strong inducers of apoptosis in both HepG2 cells and rat hepatocytes. In
HepG2 cells, bile acid-induced cell death was completely abolished by zVAD-
fmk. On the contrary, DCA and GCDCA induced caspase-3-independent cell
death, inhibited by necrostatin-1, representing necroptosis of primary rat hepa-
tocytes. UDCA was also effective at modulating necroptosis.
CONCLUSION: In conclusion, necroptosis is involved in liver injury induced by
toxic bile acids both in vitro and in vivo. As such, necroptosis may play a role in
the pathogenesis of cholestatic liver disease and should be regarded as a potential
therapeutic target. (Supported by FCT, Portugal; PTDC/SAU-ORG/119842/
2010, HMSP-ICT/0018/2011, SFRH/BD/91119/2012 and SFRH/BD/88212/
2012).
Disclosure of Interest: None declared
A58
OP178 STUDY THE ROLE OF MIR-223 IN COLITIS ASSOCIATED
CARCINOGENESIS
N. Bouznad1,*, L. Servais1, S. Jacques1, C. Josse1, C. Delierneux1, V. Bours1,
C. Oury1
1
Unit of Human Genetics, GIGA Research - Laboratory of Thrombosis and
Hemostasis, Lie`ge, Belgium
Contact E-mail Address: n.bouznad@doct.ulg.ac.be
INTRODUCTION: MicroRNAs are short non-coding single-stranded RNAs
that modulate gene expression by destabilizing mRNA and/or inhibiting transla-
tion. They are also implicated in many pathophysiological processes, including
inflammation and cancer. Patients diagnosed with inflammatory bowel disease
(IBD) have an increased risk of developing a colorectal cancer. Inflammatory
conditions are increasingly being acknowledged to contribute to tumor forma-
tion; however, there is a limited understanding of the mechanisms that are
involved in the transition from intestinal inflammation to cancer. Myeloid
derived suppressor cells (MDSC) represent immature heterogenous cells that
are recruited from bone marrow under inflammatory conditions and in cancer.
These cells have immunosuppressive properties contributing to the inhibition of
anti-tumor immunity. However, the molecular mechanisms responsible for
MDSC expansion remain elusive. Recent studies revealed that miRNA could
be involved in the expansion of MDSC.
miR-223 is the main miRNA linked to myeloid development, and its role in
myeloid cell proliferation and diGerentiation has been extensively studied both
in vitro and in vivo. In a recent work in our laboratory, we identified miR-223 as
one of the main miRNA showing strong upregulation in mouse colons during
tumor formation. Cell sorting enabled us to confirm high expression of miR-223
in infiltrating myeloid cells (CD45 CD11b Gr-1) as compared to colono-
cytes, but also in the blood and spleen as compared to other immune cells
(CD45 CD11b Gr-1 ).
AIMS & METHODS: We used the well-established Azoxymethane (AOM)/
Dextran Sulfate Sodium (DSS) mouse model of colitis-associated cancer in
order to characterize miR-223 expression in the different myeloid cell subpopula-
tions, during tumor development and to determine whether inhibition of miR-
223 activity or its overexpression by means of a lentiviral vector strategy can
affect the recruitment of myeloid cells and carcinogenesis.
RESULTS: Flow cytometry and cell sorting revealed 4 myeloid subpopulations
in spleen and blood of AOM/DSS-treated mice. Using real-time QPCR, we
found that one monocytic subpopulation and the granulocytic cells are the
main sources of miR-223 in mouse spleen and blood during periods preceding
tumor development. We generated lentiviral vectors to specifically overexpress
miR-223 or inhibit its activity by expressing miR-223 Target sequences (miR-
223T). We verified that intravenous injection of the miR-223 expressing lentivirus
in mice resulted in an increase of circulating miR-223 that persisted for at least 3
weeks. We are currently assessing whether this lentivirus based strategy affects
MDSC recruitment and subsequent tumor development.
CONCLUSION: miR-223 may contribute to myeloid cell recruitment, differen-
tiation and function during colon tumor development. Our lentiviral vectors
represent valuable tools to investigate its role in mouse models of colorectal
cancer.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
colonic epithelial wound healing in Sdc4-/- mice was significantly impaired
(wound closure at day 6: 62%2.3 vs. 98.1%3.1, P50.05).
After induction of DSS-colitis, sdc4-/- mice lost significantly more body weight
compared to WT animals (day 8: 24.8%1.9 vs. 9.2%3.1; P0.008).
Furthermore, colonic inflammatory damage in Sdc4-/- mice was dramatically
increased as reflected by increased colonic shortening (63.3 mm2.4 vs. 74.8
mm2.3; P0.01), increased histological damage (Dieleman Score: 16AU3.7
vs. 3.4AU0.2; P0.016) as well as enhanced mucosal infiltrate of macrophages
and neutrophils. Additionally, aggravated damage of intestinal barrier function
in Sdc4-/- animals was indicated by significantly reduced Cl-1, Cl-3 and ZO-1
expression and increased Evans blue uptake compared to WT mice (extinction:
4.30.03 vs. 2.70.07; P50.01). Notably, Evans Blue uptake and tight junction
protein expression was not altered in healthy Sdc4-/- compared to WT mice.
CONCLUSION: Loss of Syndecan-4 significantly impaired intestinal epithelial
wound healing in vivo and in vitro and resulted in a markedly aggravated course
of experimental colitis. Future studies are needed to elucidate the potential ther-
apeutic effects of Syndecan-4 in inflammatory bowel disease.
Disclosure of Interest: None declared
OP180 RECEPTOR FOR ADVANCED GLYCATION END PRODUCTS
(RAGE): A NEW FRONTIER IN INTESTINAL FIBROSIS
S. Speca1,*, M. Body-Malapel1, M. Djouina2, E. Boulanger2, A.-M. Schmidt3,
P. Desreumaux1, C. Vignal2
1
Inserm U995 Lille, 2Universite Lille-Nord, Lille, France, 3NYU Langone Medical
Center, New York, United States
INTRODUCTION: Intestinal fibrosis is a common and severe complication of
inflammatory bowel disease (IBD) characterized by excessive deposition of extra-
cellular matrix components (ECM) and for which efficient and well-tolerated
therapies are currently lacking. Inflamed colonic mucosa of patients with
active IBD show a significant increase in expression of the receptor for advanced
glycation end products (RAGE), a member of the immunoglobulin superfamily
of cell surface receptors, able to regulate chronic inflammation by activating the
NF-kB pathway and inducing inflammatory and oxidative stress. In addition, a
growing body of evidences in kidney, liver and lung fibrosis shows how the
increased myofibroblast activation and numbers and the consequent ECM accu-
mulation are regulated by RAGE. All these data may place this receptor among
the most innovative and promising targets for new antifibrotic therapies in IBD
AIMS & METHODS: We propose to investigate the involvement of RAGE in
the development of the DSS-induced intestinal fibrosis in mice. Chronic colitis
and fibrosis were induced in C57BL/6 wild type (WT) and RAGE null mice by
administration of 2.5% (w/v) dextran sulfate sodium (DSS) in drinking water for
5 days followed by 7 days of water, for three cycles. Three days after the last cycle
of treatment, the entire colon was rapidly excised and scored for the assessment
of macroscopic lesion, including dilation, thickness and adhesion, on a 0-3 scale
by an investigator na ve to the experimental conditions. The sum of the scores of
colonic lesions was expressed as total macroscopic score. Tissue specimens, col-
lected from distal colon, were subject to Hematoxylin/Eosin staining, to assess
the degree of inflammation, and Picrosirius red staining was performed to assess
collagen deposition. Thus, a total microscopic score was calculated evaluating
presence of ulceration, inflammatory degree, depth of lesions and fibrotic degree.
mRNA expression of the main profibrotic mediator, Tgf-1, and the expression
TUESDAY, OCTOBER 21, 2014 11:0012:30 of ECM components, mainly collagen types I-III (Col1A1 gene) and fibronectin
TOWARDS BETTER UNDERSTANDING OF IBD PATHOGENESIS HALL (Fn-1 gene), were evaluated by quantitative RT-PCR
N_____________________ RESULTS: Compared to WT mice, DSS-treated C57/Bl6 RAGE null mice
showed a significant 29% decrease of the colon weight/length ratio
OP179 SYNDECAN-4 IS A KEY REGULATOR OF INTESTINAL (p50.0001), an indicator of wall thickening. A total macroscopic score of 6 
EPITHELIAL REGENERATION AND INFLAMMATION 0.92 was assessed in colons recovered from DSS-treated WT mice, but in mice
D. Bettenworth1,*, M. Frohling2, M. Bruckner1, R. Mennigen3, T. Nowacki1, devoid of RAGE, the appearance of the macroscopic lesions was significantly
A. Lugering4, T. Pap2, A. Stratis2 reduced, 1.43  0.54 (p50.0001, n15). DSS-treated RAGE null mice showed
1
Medicine B, University Hospital Munster, 2Institute of Experimental also a significant 49% decrease of total microscopic score compared to WT mice.
Musculoskeletal Medicine, University of Munster, 3Department of General and
Visceral Surgery, University Hospital Munster, 4MVZ Portal 10, Munster,
Germany
Contact E-mail Address: dominik.bettenworth@ukmuenster.de
INTRODUCTION: Syndecan(Sdc)4 is a transmembrane protein with receptor
function and was found to modulate wound healing and inflammation, e.g. in the
skin. However, the role of Sdc4 in intestinal epithelial wound healing/regenera-
tion and inflammation has not been investigated yet. The aim of this study was to
evaluate the impact of Sdc4 deficiency on intestinal epithelial wound healing
in vitro and in vivo as well as to evaluate its potential impact on experimental
colitis.
AIMS & METHODS: In vitro, impact of Sdc4 on intestinal epithelial wound
healing was evaluated by scratch assays in WT human T84 and murine colon-26
cells as well as after blockade of Sdc4 by siRNA or anti-Sdc4 antibody admin-
istration (n6). In vivo, epithelial wounds were mechanically generated using a
biopsy forceps during colonoscopy of Sdc4-/- and WT mice (n5/group).
Monitoring of wound closure was performed by daily endoscopic examination.
To evaluate the susceptibility of Sdc4-/- mice to intestinal inflammation, experi-
mental colitis was induced by DSS (n6/group). The course of colitis was
assessed by weight loss, colon length, histological damage as well as immunohis-
tochemical staining for F4/80, Gr1 and CD20. Finally, intestinal barrier function
as reflected by mucosal permeability was determined by mucosal uptake of Evans
Blue and immunohistochemical analysis of tight junction proteins composition
including Cl-1, Cl-3, Cl-5 and ZO-1.
RESULTS: In vitro, administration of anti-Sdc4 antibody or siRNA targeting
Sdc4 resulted in significantly delayed wound closure compared to WT cells
(wound closure at day 7: 61%4,3 vs. 88%3.7; P50.05). Similarly, in vivo,
mRNA Tgf-1 expression was significantly increased 3.4 fold by the DSS admin-
istration in WT mice colon, whereas it was unchanged in RAGE null mice
compared to mice receiving only tap water. Col1A1 and Fn-1 genes were upre-
gulated in DSS-treated WT mice (5.52 folds, p 0.137 and 53 folds, p 0.0016,
respectively). Lack of RAGE decreased 3.17 folds (p 0.0341) Col1A1 expression
and totally prevents the Fn-1 upregulation induced by DSS treatment
CONCLUSION: The potential profibrotic role of RAGE in IBD could both
shed light into the complex and dynamic fibrogenic processes in IBD and pave
the way for new anti-fibrotic agents and approaches in this disease.
Disclosure of Interest: None declared
OP181 ENHANCED NOD2-DRIVEN IMMUNITY TO ENTERIC
BACTERIAL INFECTION IN NLRP12-DEFICIENT MICE
S. Normand1,2, N. Waldschmitt1,2,*, C. Chauvin1,2, L. Huot1, M. Delacre1,2,
A. Couturier-Maillard3, D. Hot1,2, L. Poulin1,2, M. Chamaillard1,2
1
Pasteur Institut, 2Inserm Lille, Lille, 3CNRS, Orleans, France
Contact E-mail Address: mathias.chamaillard@pasteur-lille.fr
INTRODUCTION: The Nucleotide-binding oligomerization domain protein 12
(Nlrp12) is thought to negatively regulate inflammatory response to intracellular
bacteria, but its role on the growth and colonization by extracellular bacteria
remains largely undefined. In this study, we aim to investigate the role of Nlrp12
in bacterial-driven colitis using Citrobacter rodentium as an infection model for
attaching and effacing infections.
AIMS & METHODS: Age and sex-matched wild-type, Nlrp12 -/-, Nod2 -/-, and
Nlrp12-/-Nod2-/- mice were orally inoculated with 1  109 CFU of either C.
rodentium strain DBS100 or kanamycin (Kn)-resistant C. rodentium strain
DBS120 for non-invasive monitoring of bacterial growth in vivo. Lamina propria
United European Gastroenterology Journal 2(5S)
mononuclear cell influx to the site of the infection was examined by FACS
analysis before and one week after infection. Gene expression profiling was
determined in the caecum of non-infected and infected wild-type and Nlrp12-/-
mice. Vali dation of gene expression changes was performed by qRT-PCR ana-
lysis on RNAs isolated from either the caecum, the colon, the intestinal epithelial
cells and the lamina propria mononuclear cells.
RESULTS: An enhanced inflammatory response was found to correlate with
improved clearance of C. rodentium in the early phase of the infection of
Nlrp12-deficient mice. Mechanistically, the colonic mucosa of Nlrp12-deficient
mice showed spontaneous signs of colitis which was improved in the absence of
the major Crohns disease predisposing Nod2 gene. The protective immune
response in Nlrp12-deficient mice was primarily restricted to the intestinal epithe-
lium and corroborated with enhanced recruitment of monocyte-derived dendritic
cells.
CONCLUSION: Overall, our results suggest that Nlrp12 repress Nod2-mediated
host defense against enteric bacterial infection, which may have contributed to a
selective advantage of Nlrp12 variants. Exploitation of the Nlrp12-coupled
inflammasome represents a novel gene-for-gene model of pathogen evolution
alongside host immunity.
Disclosure of Interest: None declared
OP182 STAT6 DEFICIENCY IMPAIRS M2 MACROPHAGE
POLARIZATION AND DELAYS WOUND HEALING IN A MURINE
MODEL OF COLITIS
J. Cosin-Roger1, D. Ortiz-Masia1,*, S. Calatayud1, C. Hernandez2,
D. Barrachina1
1
Pharmacology, CIBERehd-Universidad de Valencia, 2Pharmacology, FISABIO,
Valencia, Spain
Contact E-mail Address: mdorma@uv.es
INTRODUCTION: Inflammatory Bowel Disease (IBD) is a chronic disorder of
the intestinal tract caused by a deregulated mucosal immune response and epithe-
lial barrier disruption. These changes are mainly produced by an alteration of the
cytokine production. STAT6 has diverse biological functions within immune
system and is a critical mediator of cytokine signalling. It has been shown that
STAT6 promotes in vitro polarization towards M2 macrophages. We aim to
evaluate the role of STAT6 in M2 polarization in vivo and to determine its
relevance on wound healing in a murine model of colitis.
AIMS & METHODS: Peritoneal macrophages were isolated from wild type
(WT) and STAT6-/- balb/c mice by an injection of 10ml DMEM in the peritoneal
cavity, RNA was extracted and gene expression of M1 markers (iNOS, IL-6 and
Cd11c) and M2 markers (Arg1, Ym1, and Fizz1) was analyzed by qPCR. Colitis
was induced in WT and STAT6-/- balb/c mice by an intrarectal injection of 17.5
mg TNBS/100g mice dissolved in EtOH 40% (day 0). Mice were weighted diary
(results are expressed as percentage vs the weigth at day 0) and were sacrificed on
day 2, 4 and 6 after TNBS administration. The colon length was measured and
the histology was evaluated according to Wallace Score (1-10). Vehicle mice
received an intrarectal injection of 40% ethanol.
RESULTS: Analysis of the expression of M1- and M2-markers in peritoneal
macrophages reveal that macrophages isolated from knock-out mice exhibited
higher expression levels (fold induction) of iNOS (4.11.1), IL-6 (5.81.0) and
Cd11c (5.70.6) than macrophages from WT mice. In contrast, in macrophages
from knock-out mice the expression of Arg1 (0.420.12), Ym1 (0.320.04) and
Fizz-1 (0.540.19) was reduced compared with WT mice. In STAT6 knockout
mice either the body weight or the histological score were similar to that observed
in WT mice, and these parameters were not significantly altered at any time
analyzed. TNBS administration induced, 2 days later, a peak reduction in
body weight in both WT mice (91.31.9%) and STAT6 knockout
(87.71.8%). Three days after TNBS administration, the body weight started
to recover in WT mice (97.61.6%) and it was completely recovered at day 4
(99.11.0%) and day 6 (101.71.8%). In contrast, in knockout mice the body
weight recover was slower (87.22.7% at day 3, 90.82.2% at day 4 and
96.21.7% at day 6) and differ significantly (P50.05) than that observed in
WT mice. In a similar manner, TNBS administration induced intestinal
damage that peaked 2 days later and was similar between WT mice (6.50.6)
and knockout mice (6.40.5). However, significant differences in damage were
observed at day 4 and day 6 between WT mice (4.60.5 and 3.10.4, respec-
tively) and knockout animals (6.90.5 and 4.40.7, respectively). Finally, TNBS
induced a significant reduction at day 2 in the colon length in both WT and
knockout mice, compared with the respective vehicle. However, at day 4 only
knockout animals still maintained a reduced colon length.
CONCLUSION: STAT6 deficiency delays wound healing in a murine model of
colitis which may be related to an impaired M2 macrophage polarization.
Disclosure of Interest: None declared
OP183 GPR84, A NOVEL TARGET FOR THE DEVELOPMENT OF
THERAPIES FOR IBD
S. Dupont1,*, F. Labegue`re1, R. Blanque1, S. de Vos2, P. Clement-Lacroix1,
L. Nelles2, A. Hagers2, C. Cottereaux1, D. Merciris1, M.-C. Ceccotti1,
C. Belleville Da Costa1, S. Fletcher1, R. Brys2
1
GALAPAGOS, ROMAINVILLE, France, 2GALAPAGOS, MECHELEN,
Belgium
Contact E-mail Address: sonia.dupont@glpg.com
INTRODUCTION: Among the GPCRs demonstrated to be activated by FFAs,
GPR84 is less characterized and suggested not to play a role in energy home-
ostasis. It is liganded by medium chain fatty acids, has a restricted expression
profile (mainly immune cells as macrophages and polymorphonuclear leukocytes
(PMN)) and is upregulated under inflammatory conditions. In addition, a
A59
GPR84 agonist is described to mediate PMN and macrophage activation and
migration. In view of these data, we set out at developing GPR84 inhibitors to
confirm the pro-inflammatory role of GPR84 in vitro and in vivo. Several series of
GPR84 inhibitors were developed and shown to inhibit immune cell migration.
As the infiltration of immune cells to the inflamed intestinal tissue is a hallmark
of inflammatory bowel diseases (IBD), we further tested the capacity of these
compounds at reducing disease severity in an IBD model.
AIMS & METHODS: Activity of GPR84 antagonists was measured in a GTPgS
assay using membranes of HEK293 cells expressing GPR84 and the di-indolyl
methane agonist of GPR84. The capacity of GPR84 antagonists to inhibit the
GPR84 agonist (Embelin)-induced neutrophil chemotaxis was assessed in pri-
mary cells using the Transwell system. This assay was also used to test the activity
on ortholog receptors using primary neutrophil from different species. In vivo
efficacy was evaluated in the well-validated mouse chronic dextran sodium sul-
phate (DSS)-induced colitis model for IBD using disease activity index score,
histology lesion score and neutrophil infiltration score as readouts.
RESULTS: Several series of GPR84 inhibitors were developed with potencies at
the target in GTPgS assay down to low nM levels and clear SAR. The series
displayed strong developability properties and PK, with GLPG1205 as lead
compound. GPR84 inhibitors were shown to inhibit GPR84 agonist-driven neu-
trophil and macrophage migration in vitro, with an IC50 matching their potency
at GPR84. GPR84 antagonism also modulated rat macrophage biology, as
GPR84 antagonists specifically inhibit Embelin-induced macrophage migration.
The impact of GPR84 inhibitors on the migration of neutrophils from different
species was assessed to confirm activity at orthologs and support the proposed
development path towards the clinic. GPR84 gene expression level was found
increased in DSS colon versus intact colon. In the DSS model, GLPG1205 dose-
dependently hampered the development of the disease, by reducing the disease
activity index, to a similar level as sulphasalazine and cyclosporine. The histolo-
gical score for colon lesion, neutrophil influx as well as MPO content was sub-
stantially reduced by GLPG1205 oral administration, providing hints forthe
mode of action of GPR84 inhibition in IBD.
CONCLUSION: GLPG1205 is characterized as a potent and selective antagonist
of GPR84 with strong developability properties. It demonstrates good in vitro
activity in primary neutrophil assays, as well as pronounced in vivo activity in the
mouse chronic DSS model. These studies support GPR84 antagonism as novel
mode-of-action for the treatment of IBD and the progression of GLPG1205
towards the clinic.
Disclosure of Interest: S. Dupont Other: employee, F. Labegue`re Other:
employee, R. Blanque Other: employee, S. de Vos Other: employee, P.
Clement-Lacroix Other: employee, L. Nelles Other: employee, A. Hagers
Other: employee, C. Cottereaux Other: employee, D. Merciris Other: employee,
M.-C. Ceccotti Other: employee, C. Belleville Da Costa Other: employee, S.
Fletcher Other: employee, R. Brys Other: employee
OP184 SILENCING OF PROLYL HYDROXYLASE 1 IN INTESTINAL
MICROVASCULAR ENDOTHELIAL CELLS PREVENTS
INFLAMMATION-INDUCED ENDOTHELIAL DYSFUNCTION AND
DAMPENS MURINE COLITIS
S. Van Welden1,*, D. Laukens1, L. Devisscher1, C. Correale2, S. DAlessio2,
S. Danese2, M. De Vos1, P. Hindryckx1
1
Ghent University, Ghent, Belgium, 2Clinico Humanitas, Milan, Italy
Contact E-mail Address: sophie.vanwelden@ugent.be
INTRODUCTION: Active inflammatory bowel disease (IBD) is characterized by
extensive mucosal angiogenesis. However, these newly formed blood vessels are
likely dysfunctional, as they are unable to resolve the inflammation-induced
mucosal hypoxia. Prolyl hydroxylases (PHD1-3) are oxygen sensing enzymes
that are actively involved in tumoral vascular dysfunction. We previously
showed that the expression of PHD1, but not PHD2 and 3, is increased in
inflamed biopsies of IBD patients.
AIMS & METHODS: The aim was to characterize endothelial dysfunction in
IBD patients and to investigate the role of PHD1, 2 and 3 in the vascular
endothelium during experimental colitis. The expression of endothelial dysfunc-
tion markers was analyzed by qRT-PCR in inflamed and non-inflamed colonic
biopsies from IBD patients and compared to samples from healthy controls and
infectious colitis patients. Human colonic microvascular endothelial cells (freshly
isolated from resection specimens) and mouse endothelial cells were subjected to
TNF to mimic inflammatory angiogenesis. The expression of endothelial dys-
function markers and PHD isoforms was analyzed. We then generated endothe-
lial specific PHD1, PHD2 and PHD3 knock-out mice and subjected these mice to
dextran sulfate sodium (DSS)-induced colitis, after which they were assessed for
histological inflammation. Colonic vascular leakage was quantified using
dynamic contrast-enhanced T1-weighted micro-MRI.
RESULTS: Inflamed colonic biopsies from both UC and CD patients showed a
significant up-regulation of the endothelial dysfunction markers ICAM-1,
VCAM-1, vWF and VEGFR-2 (all p50.0001). Moreover, these markers all
displayed a strong positive correlation with PHD1 (r0.667, r0.792, r0.731
and r0.747 respectively) and TNF (r0.908, r0.881, r0.806 and r0.860).
Endothelial cells showed a significant up-regulation of PHD1 (p50.01) in
response to TNF. In accordance, PHD1-/- cko mice had significantly less
weight loss (p50.0001), reduced colon shortening (p50.01) and a lower histo-
logical inflammation score (p50.001) during DSS-induced colitis, when com-
pared to the littermate controls. Furthermore, the PHD1-/- cko mice showed
significantly less vascular leakage (p50.05) and a significant down-regulation
of the endothelial dysfunction markers ICAM-1, VCAM-1, vWF and VEGFR-
2 (all p50.05) in their colonic lysates. Pharmacological hydroxylase inhibition in
mouse endothelial cells significantly reduced the expression of ICAM-1, VCAM-
1 and the inflammatory marker CXCL2 (all p50.05) in response to TNF.
A60
Genetic inhibition of endothelial specific PHD2 and PHD3 had no effect on the
course of DSS-colitis.
CONCLUSION: Our findings characterize a dysfunctional endothelial pheno-
type in IBD and show that selective silencing of PHD1 in microvascular colonic
endothelial cells is sufficient to restore endothelial function and to dampen
experimental colitis.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 11:0012:30
NOVEL ENDOSCOPIC INTERVENTIONS IN THE OESOPHAGUS HALL
O_____________________
OP185 EFFICACY AND SAFETY OF HYBRID-APC FOR THE ABLATION
OF BARRETTS ESOPHAGUS: RESULTS OF THE PILOT SERIES
H. Manner1,*, I. Kouti1, A. May2, O. Pech3, M. Vieth4, C. Ell2
1
HSK Wiesbaden, Wiesbaden, 2Sana Klinikum, Offenbach, 3St. John of God
Hospital, Regensburg, 4Institute of Pathology, Klinikum Bayreuth, Bayreuth,
Germany
Contact E-mail Address: HSManner@gmx.de
INTRODUCTION: The widely used methods for the ablation of Barretts eso-
phagus (BE) are radiofrequency ablation and argon-plasma coagulation (APC).
However, these methods lead to stricture formation in 5-15% of patients. The
question arises whether submucosal fluid injection prior to thermal ablation may
lower the risk of stricture formation.
AIMS & METHODS: The aim of the present study was to evaluate the efficacy
and safety of the new technique of Hybrid-APC for BE ablation. Patients who
had a residual Barretts segment of at least 1 cm after endoscopic resection of
early Barretts neoplasia underwent thermal ablation of BE by Hybrid-APC.
During Hybrid-APC, submucosal injection of sodium chloride 0.9% was carried
out using an ErbeJet probe (Erbe Elektromedizin, Tuebingen, Germany). Check-
up upper GI endoscopy was carried out 3 months after macroscopically complete
ablation including biopsies from the Neo-Z-line and the former BE segment.
Potential stricture formation was recorded.
RESULTS: A total of 60 patients were included into the study during a 2-yr
interval. 55 patients were male (92%), 5 female (8%). The mean age was 629
Jahre (42-79). The LSBE:SSBE ratio was 41:19. 10/60 patients were excluded
from the study. In 5 of these 10 patients, poor mucosal healing after ablation
had been observed, and the patients could not be treated according to the study
protocol. In 48 of the remaining 50 patients (96%), macroscopically complete
Barretts ablation was achieved after a mean of 42 APC sessions (range 1-10).
In ITT analysis, macroscopic ablation success was 80% (48/60). The 2 other
patients had ablation rates of 495%. In 48/50 patients, the biopsy protocol
was complete. Freedom from BE was histopathologically observed in 39/48
patients (78%). In 6% of patients, buried glands without intraepithelial neoplasia
were detected in the area of the neosquamous epithelium. There was no treat-
ment-related stricture.
CONCLUSION: According to this pilot series, Hybrid-APC was effective and
safe during BE ablation. There was no treatment-related stricture. Further stu-
dies are required to confirm the present results.
Disclosure of Interest: None declared
OP186 IS A COMPLETE REMISSION OF INTESTINAL METAPLASIA A
SUITABLE ENDPOINT IN PATIENTS UNDERGOING
RADIOFREQUENCY ABLATION (RFA)? LONG-TERM RESULTS OF
RFA TREATMENT IN 67 CONSECUTIVE PATIENTS
J. Krajciova1,*, M. Stefanova2, J. Maluskova3, M. Kollar3, J. Spicak1,
J. Martinek1
1
Hepatogastroenterology, Institute for Clinical and Experimental Medicine
Prague, 2Internal Medicine, Hospital Na Frantisku, 3Pathology, Institute for
Clinical and Experimental Medicine Prague, Prague, Czech Republic
Contact E-mail Address: kraj@ikem.cz
INTRODUCTION: Radiofrequency ablation (RFA) in combination with endo-
scopic resection (ER) is a method of choice for treatment of early esophageal
neoplasia. Complete remission of intestinal metaplasia (CR-IM) and complete
remission of dysplasia (CR-D) are commonly used as the endpoints of successful
treatment. The relevance of CR-IM (in patients with macroscopically normal
neo-Z-line) has recently been challenged.
AIMS & METHODS: The aim of this prospective, single center study was to
assess the long-term efficacy of RFA. Main outcome measurements were com-
plete remission of intestinal metaplasia (CR-IM) or dysplasia (CR-D) in patients
with/without a complete macroscopic eradication of Barretts esophagus and
recurrence rate of IM and dysplasia. Conover one-way analysis was used to
calculate the risk factors for recurrence of IM.
RESULTS: The study involved 67 consecutive patients (mean age 62, range 20-
86; 60 males and 7 females) undergoing endoscopic treatment for esophageal
neoplasia in our center during 1/2009-4/2014. Sixty-five patients were diagnosed
with Barretts esophagus related neoplasia, the remaining 2 patients had squa-
mous neoplasia. The median follow-up was 30 months (range 4-64). In 20
patients (30%), RFA was a single treatment modality while in 47 patients
(70%), RFA was combined with endoscopic resection or dissection of a visible
lesion. The indications for endoscopic treatment were as follows: early adeno-
carcinoma (EAC): 25 (37,3%), early squamous carcinoma (ESC): 2 (3%), high-
grade dysplasia (HGD): 22 (32,8%), low-grade dysplasia (LGD): 18 (26,9%).
A total of 125 RFA treatment sessions were performed (38x with HALO 360, 86x
with HALO 90 and once with HALO 60).
CR-IM and CR-D were achieved in 66% (95% CI 36-70%) and 94,5% (95% CI
93-99%), respectively. In a majority of patients without CR-IM (83%), the neo-
United European Gastroenterology Journal 2(5S)
Z-line was normal without macroscopically visible islands or tongues of meta-
plastic mucosa.
During the follow-up, there were 10 recurrences of IM at the level of neo-Z-line
(out of 35 patients with BE with the follow-up of at least 18 months after
finishing the treatment; 28,6%). In 9 of these patients, the neo-Z-line was macro-
scopically normal. LGD (within the Z-line) recurred in 2 patients (3,8%). HGD
and/or carcinoma have not recurred. The risk factors for recurrence of IM were
male sex, younger age and diagnosis of cancer. We did not detect burried glands
beneath the new neosquamous epithelium in any patient.
CONCLUSION: Treatment of BE with RFA results in CR-D and CR-IM in a
high proportion of patients with a low recurrence rate. A majority of patients
without CR-IM or with a recurrence of IM have macroscopically normal neo-Z-
line. CR-IM and a recurrence of IM might not be clinically relevant endpoints in
patients with macroscopically normal neo-Z-line after RFA.
Disclosure of Interest: None declared
OP187 PREVENTION OF POST-ESD ESOPHAGEAL STRICTURE
USING ENDOSCOPIC TRANSPLANTATION OF TISSUE-
ENGINEERED AUTOLOGOUS ORAL MUCOSAL EPITHELIAL CELL
SHEETS AT THE END OF ROUND TRIP TRANSPORTATION
BETWEEN TOKYO AND NAGASAKI
H. Isomoto1,*, N. Yamaguchi1, H. Fukuda1, K. Nakao1, S. Kobayashi1,
K. Kanetaka1, Y. Sakai1, S. Eguchi1, N. Kanai2, T. Ohki2, M. Yamato2,
T. Okano2
1
NAGASAKI UNIVERSITY HOSPITAL, Nagasaki, 2Institute of Advanced
Biomedical Engineering and Science, Tokyo Womens Medical University, Tokyo,
Japan
Contact E-mail Address: hajimei2002@yahoo.co.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) is a treatment of
choice for superficial esophageal neoplasms. However, largely extended esopha-
geal ESD requires multiple balloon dilations due to postoperative luminal stric-
ture. Endoscopic transplantation of tissue-engineered autologous oral mucosal
epithelial cell sheets offers a treatment of choice for management of post-ESD
stricture.
AIMS & METHODS: We investigated the safety and efficacy of endoscopic
transplantation of tissue-engineered autologous oral mucosal epithelial cell
sheets following the transportation of 1200 km between Tokyo and Nagasaki
in the clinical settings of large esophageal ESD. For this aim, we collected speci-
mens of oral mucosal tissue and sufficient serum from 7 patients themselves with
superficial esophageal squamous cell carcinoma in Nagasaki University Hospital,
and the samples were transferred into Institute of Advanced Biomedical
Engineering and Science, Tokyo via air. Then, epithelial cell sheets were fabri-
cated ex vivo by culturing isolated cells for 16 days on temperature-responsive
cell culture surfaces nourished using auto-sera. Again, the cell sheets were trans-
ferred into Nagasaki which is distant from Tokyo with 1200 km by airplane.
After a reduction in temperature, these sheets were endoscopically transplanted
directly onto the ulcer surfaces of patients who had just undergone esophageal
ESD on the day. All patients were monitored by endoscopy once a week until
epithelialization was complete. Untra-magnification endoscopy employing
Endocyte (Olympus) was performed after 4 weeks.
RESULTS: Autologous cell sheets were successfully grown despite the transpor-
tation of 1200 km-distance in each case and were transplanted to ulcer surfaces.
Complete re-epithelialization occurred within a median time of 4 weeks.
Endocytoscopic observation under approximate 400-fold magnification revealed
that almost normal squamous epithelial cells were grown over each transplanted
area more than 4 weeks after transplantation. The nuclei of cells showed nominal
abnormality in size and configuration. Notably, this transplantation substantially
reduced sessions of endoscopic balloon dilation or even nullified in 4 cases. There
were no adverse events in association with cell sheet transplantation.
CONCLUSION: Endoscopic transplantation of autologous oral mucosal epithe-
lial cell sheets promotes re-epithelialization of the esophagus after ESD, prevent-
ing post-operative luminal stricture. This study paves the way for clinical
application and dissemination of cell sheet engineering for the intractable stenosis
diseases and provides new possibilities in the field of regenerative medicine.
Disclosure of Interest: H. Isomoto: None declared, N. Yamaguchi: None
declared, H. Fukuda: None declared, K. Nakao: None declared, S. Kobayashi:
None declared, K. Kanetaka: None declared, Y. Sakai: None declared, S.
Eguchi: None declared, N. Kanai: None declared, T. Ohki: None declared, M.
Yamato: None declared, T. Okano Financial support for research from: Teruo
Okano is a founder and director of the board of CellSeed Inc., a cell sheet
regenerative medicine company in Japan, licensing technologies and patents
from Tokyo Womens Medical University related to this presentation. The pre-
sentator is also a stake holder of the company listed at JASDAQ (Code: JQG
7776).
OP188 EFFICACY OF PROPHYLACTIC STEROID ADMINISTRATION
FOR STRICTURES AFTER ENDOSCOPIC RESECTION FOR LARGE
SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL CARCINOMA
T. Kadota1,*, T. Yano1, T. Kato1, M. Imajoh1, H. Morimoto1, S. Osera1,
Y. Yoda1, T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1
1
Department of Gastroenterology, Endoscopy Division, National Cancer Center
Hospital East, Kashiwa, Japan
INTRODUCTION: Esophageal stricture is a major problem after endoscopic
resection (ER) for large superficial esophageal squamous cell carcinomas
(SESCC). Steroid administration is reported as a prophylactic treatment for
strictures, however, it is uncertain regarding steroid administration technique
and esophageal circumference of mucosal defect after ER. We evaluated the
United European Gastroenterology Journal 2(5S)
efficacy of prophylactic administration of steroids in patients with large SESCC
receiving endoscopic resection.
AIMS & METHODS: Between 2009 and 2013, 951 consecutive SESCC patients
underwent ER in our institution. Eligibility criteria showed as follows: 1) a
mucosal defect after ER for a solitary lesion was 3/4ths or more circumference
of the esophageal lumen, and 2) follow-up periods of 3 months or longer. In
December 2009, steroid (triamcinolone acetonide 50 mg) injections into ulcer bed
after ER were introduced for the patients with 3/4ths and larger mucosal defects.
Furthermore, from November 2012, we commenced oral steroid administration
(30 mg daily, tapered gradually for 8 weeks) in addition to the local injections in
case of the mucosal defect of 7/8ths and larger the circumference after resection.
The mucosal defect circumference in all cases was retrospectively estimated by
independent endoscopists in endoscopic pictures taken immediately after ER. We
defined as an esophageal stricture in case the endoscope could not pass through
the stricture, and then endoscopic balloon dilation (EBD) was required. All
patients were classified into 3 groups according to the width of the mucosal
defect (group A: 3/45, 57/8; group B: 7/85, subentire circumference;
group C: completely entire circumference), and the frequency of esophageal
strictures and the efficacy of individual prophylactic therapies were compared
among 3 groups. This study was approved by an institutional review board in our
institution.
RESULTS: Of 951 patients, 121 patients (104 men, 17 women; median age 69
years, range 4685) were eligible. Endoscopic submucosal dissection and endo-
scopic mucosal resection were performed in 112 and 9 patients, respectively.
There were 49 patients in group A (no treatment: 37%, local injection of steroid:
55%, oral steroid: 8%); 45 in group B (13%, 64%, 22%), and 27 in group C
(11%, 26%, 63%), respectively. The frequencies of stricture after ER of group A,
B, and C were 22%, 53% (vs group A, p 0.0027), and 85% (vs group B, p
0.0098), respectively. A significant efficacy of the prophylactic steroid adminis-
tration was not found in group A. However, oral steroids were effective in group
B, since there was a significantly lower stricture rate (no treatment: 100%, local:
59%, oral: 10% (vs local; p 0.011)). Conversely, a higher stricture rate was
found in group C regardless of prophylactic treatment (no treatment: 100%,
local: 100%, oral: 77%).
CONCLUSION: The stricture rate after ER for SESCC increased in the larger
mucosal defect circumference. Oral steroid administration was most effective to
prevent strictures when the mucosal defect was from 7/8ths to subentire circum-
ference. However, the efficacy of steroid treatments was limited in cases of com-
pletely entire circumference and stricture formation remains a major problem to
be resolved.
Disclosure of Interest: None declared
OP189 MANAGEMENT OF ACUTE VARICEAL BLEEDING USING
HEMOSTATIC POWDER
M. Ibrahim1,2,*, A. El-Mikkawy 2, H. Abdalla2, I. Mostafa2, J. Deviere1
1
Gastroenterology & Hepato-Pancreatology, ERASME HOSPITAL,
UNIVERSITE LIBRE DE BRUXELLES, Brussels, Belgium, 2Gastroenterology
and Hepatology, Theodor Bilharz Research Institute, Cairo, Egypt
Contact E-mail Address: mostafa.ibrahim@me.com
INTRODUCTION: The treatment of acute variceal bleeding (AVB) includes
restrictive transfusion, vaso-active drugs, antibiotics and endoscopic therapy.
Early endoscopic treatment is recommended, however it is not always possible
in daily practice mainly due to the lack of treatment capabilities available in every
center in an emergency setting. A hemostatic powder (Hemospray ) has recently
been introduced for management of non variceal upper GI bleeding and was
shown effective in preliminary studies for managing peptic ulcer bleeding,
cancer related bleeding or temporizing uncontrollable bleeding in severe
situations.
AIMS & METHODS: A bi-centric prospective trial to evaluate the effectiveness
of hemospray application for emergency control of AVB. (Clinical-Trials.gov
under number NCT01783899). In addition to routine medical treatment, emer-
gency endoscopy was performed confirming acute variceal bleeding, identifica-
tion of a bleeding site was assessed; esophageal, gastric or duodenal varices, then
hemostatic powder was administered diffusely covering the mucosa over the
bleeding varices in order to obtain immediate endoscopic hemostasis. Clinical
surveillance was performed to every patient with second endoscopy and definitive
therapy the next day.
RESULTS: Thirty eight patients with suspected acute variceal bleeding were
included. 8 were excluded because bleeding was not variceal. Endoscopy was
performed under sedation without endotracheal intubation, bleeding site was
from esophageal varices in 83.4%, from gastric varices in 10% and from duode-
nal varices in 6.6 % and the bleeding was active at the time of endoscopy in 43.4
%. Primary endoscopic hemostasis was observed in all patients after Hemospray
application. Clinical hemostasis was achieved in 29/30 (96.7%) patients. One
patient experienced hematemesis 6 hours after Hemospray application and was
OP191
Motility Disorders None Achalasia EGJ obstruction
Immediate diagnosis (N 245)
CM, n (%) 64 (52) 15 (12) 6 (5)
HRM, n (%) 35 (28)* 32 (26)* 9 (7)
6 months (N 218)
CM, n (%) 57 (52) 18 (17) 8 (7)
HRM, n (%) 31 (28)* 29 (27) 9 (8)
A61
treated by emergency band ligation. No mortality was reported for all those
patients over 30 days follow-up.
CONCLUSION: Hemospray application appears to be safe and easy technique
to control, at least temporally, AVB in this series. Further studies, preferably
randomized controlled trials are required to determine its role and effectiveness
in acute variceal bleeding and its potential impact on patients outcome.
Disclosure of Interest: None declared
OP190 EVOLVING ENDOSCOPIC MANAGEMENT OPTIONS FOR
SYMPTOMATIC STENOSIS POST-LAPAROSCOPIC SLEEVE
GASTRECTOMY FOR MORBID OBESITY: EXPERIENCE AT A
LARGE BARIATRIC SURGERY UNIT IN NEW ZEALAND
R. Ogra1,*, P.K. geogry1
1
Gastroenterology & hepatology, Middlemore Hospital, Auckland, New Zealand
Contact E-mail Address: rogra@xtra.co.nz
INTRODUCTION: Symptomatic stenosis is an increasingly recognized compli-
cation following laparoscopic sleeve gastrectomy (LSG) to treat obesity with a
reported prevalence between 0.1 to 3.9%. Common findings are stricture and
twisting at the incisura of the stomach remnant resulting in functional
obstruction.This study aimed to determine the prevalence and management
options for symptomatic stenosis (SS) after LSG.
AIMS & METHODS: All cases referred for management of symptomatic steno-
sis after LSG were recorded between May 2008 and June 2013. Patients were
followed up until resolution of the symptoms and up to 1 year following resolu-
tion. A total of 857 morbidly obese patients underwent LSG at Counties Health
in the study timeframe. Methods of management included Balloon dilatation
with CRE Balloons 12-20 mm size, Rigiflex Achalasia Balloon dilators 30-35
mm size and use of removable fully covered self expanding metal stents. The
area of deformity at and near the stricture was noted as short (53cm) and long
(43 cm). Peustow metal guidewire was used to facilitate the passage of the
rigiflex balloons to the area of the sleeve requiring dilatation.
RESULTS: Symptomatic stenosis developed in 26 (3.03%) of these patients.
Eleven (42%) were males and 15 (58%) females with a mean age of 45.3  9
years and a mean body mass index of 46.5  8.1 kg/m2. Four (15.4%) patients
had SS following stent placement for sleeve leaks. The remaining 22 (84.6%)
patients showed fixed stenosis at the incisura angularis on barium swallow.
Endoscopic treatment was initiated with standard CRE balloon dilators ranging
between 12-20 mm in diameter in the majority of patients (n19, 73%). The
mean number of dilatations was 1.6. Nine (34.6%) patients required only one
dilatation with CRE Balloon. Out of patients who required more than one dila-
tation (n11, 42.3%) only 1 (3.84%) was successfully treated with 520mm
dilators. All of these had long (43 cm) segment of stricture and deformity.
Seven (78%) of the Non-responders (All long segment strictures) (n9, 35%)
were trialled with 30mm achalasia dilators and 2 (22%) with metal stents with
100% success. Achalasia balloon dilatation (30 mm) was attempted as primary
treatment in 7(27%) patients with long segment strictures at the incisura success-
fully in 5(71%) success and 2(29%) of these required metal stents. In total
5(19.2%) patients were sucessfully treated with metal stents. No adverse events
were recorded amongst any patients treated endoscopically and none needed
surgical intervention.
CONCLUSION: Endoscopic techniques of dilatation are safe and effective for
management of SS post LSG. The use of 30 mm achalasia balloon dilators was
also found to be safe and effective in patients who failed standard dilators.
Encouraged by our results, we now inititate dilatation therapy with 30mm acha-
lasia balloon for those with SS post LSG
Disclosure of Interest: R. Ogra Other: Member Australia New Zealand Medical
Advisory board for Boston Scientific corporation, P. geogry: None declared
TUESDAY, OCTOBER 21, 2014 11:0012:30
UPPER GI MOTILITY DISEASES: MECHANISMS, DIAGNOSTICS AND NEW
TREATMENT OPTIONS LOUNGE 5_____________________
OP191 HIGH RESOLUTION MANOMETRY IMPROVES THE
DIAGNOSIS OF ESOPHAGEAL MOTILITY DISORDERS IN
PATIENTS WITH DYSPHAGIA: RESULTS OF A RANDOMIZED
MULTICENTER TRIAL
S. Roman1,2,*, L. Huot3, F. Zerbib4, S. Bruley des Varannes5, G. Gourcerol6,
A. Roux7, B. Coffin8, A. Roppert9, F. Mion1
1
Digestive Physiology, Hospices Civils de Lyon, 2Digestive Physiology, Lyon I
university, 3Departement dInformation Medicale, Hospices Civlls de Lyon, Lyon,
4
Gastroenterology, CHU Bordeaux, Bordeaux, 5Gastroenterology, CHU Nantes,
Nantes, 6Physiology, CHU Rouen, Rouen, 7Departement dInformation Medicale,
Hospices Civils de Lyon, Lyon, 8Gastroenterology, Assistance Publique Hopitaux
Hypertensive disorders Hypotensive disorders UES disorders Non classified
9 (7) 9 (7) 0 (0) 19 (16)
6 (5) 33 (27)* 4 (3) 4 (3)*
9 (8) 7 (6) 2 (2) 8 (7)
6 (6) 28 (26)* 3 (3) 3 (3)
A62
de Paris, Collombes, 9Digestive Physiology, CHU Rennes, Rennes, France
Contact E-mail Address: sabine.roman@chu-lyon.fr
INTRODUCTION: High resolution manometry (HRM) may facilitate the diag-
nosis of esophageal motility disorders compared to conventional manometry
(CM).
AIMS & METHODS: Our aim was to compare HRM to CM in patients with
dysphagia in a randomized multicenter trial. Patients with dysphagia and normal
upper endoscopy were randomized to be investigated with either HRM or CM in
6 centers. Dysphagia severity was assessed using the Sydney swallow score.
Duration of both procedure and interpretation were recorded. Esophageal moti-
lity disorders were diagnosed using the Castell and Spechler classification for CM
and the Chicago classification for HRM. Patients were followed up 6 months
after manometry. Results of immediate diagnosis and after 6-months follow up
were compared between the 2 groups (CM and HRM), using Student t-test or
Mann-Whitney test for quantitative parameters and using chi-square or Fisher
exact test for qualitative parameters.
RESULTS: 245 patients (99 males, mean age 58 years, range 19-94) were ana-
lyzed: 122 were randomized in the CM group and 123 in the HRM group.
Patients in the CM group were significantly older than in the HRM group (61
vs 56 years, p0.02); gender and dysphagia severity were not significantly differ-
ent. Procedure duration and data analysis were significantly shorter with HRM
compared to CM (126 minutes vs 1911 and 64 minutes vs 99 respectively,
p50.01). Immediately after manometry, a motility disorder was more frequently
identified with HRM than with CM (97% vs 84%, p5 0.01) (Table). This
difference remained significant after adjustment for age. Dysphagia tended to
be more severe in patients with normal CM compared to those with normal
HRM (Sydney score /1700 490278 vs 403308, p0.07). Six months follow
up data were available in 109 patients in each group. The initial diagnosis was
confirmed in 83% of patients in the CM group versus 90% in the HRM group
(p0.12). Nine out of 15 patients initially with non-classified disorder in CM
presented finally achalasia (n2), EGJ outflow obstruction (n2), hypotensive
disorders (n 1), hypertensive disorders (n2) and UES disorders (n2) while AIMS & METHODS: A cross-sectional study was carried out from April 2010 to
the 2 patients initially non classified with HRM had achalasia and EGJ outflow
obstruction.
CONCLUSION: This is the first randomized trial demonstrating that HRM
might be superior to CM regarding diagnostic yield for achalasia and esophageal
motility disorders. Six months outcome data tended to show that HRM might
diagnose esophageal motility disorders sooner than CM.
Disclosure of Interest: S. Roman Lecture fee(s) from: Given Imaging,
Consultancy for: Given Imaging, L. Huot: None declared, F. Zerbib: None
declared, S. Bruley des Varannes: None declared, G. Gourcerol: None declared,
A. Roux: None declared, B. Coffin: None declared, A. Roppert: None declared,
F. Mion: None declared
OP192 MOTILITY PATTERNS IN RESPONSE TO A RAPID DRINK
CHALLENGE TEST DISCRIMINATE BETWEEN DIFFERENT
MOTILITY DISORDERS
I. Marin1,*, C. Julia1, J. Serra1
1
University Hospital Germans Trias i Pujol, Badalona, Spain
Contact E-mail Address: gridin_8@hotmail.com
INTRODUCTION: We have previously shown that a rapid drink challenge test
during high resolution manometry can detect motor disturbances not detected by
standard manometry. However, the specific motility patterns in response to this
test are not characterized.
AIMS & METHODS: To characterize specific motor patterns in response to a
rapid drink challenge test in patients with esophageal motility disorders.
A rapid drink challenge test (rapid drink of 200 ml water in sitting position) was
performed in 29 healthy controls (17 F, 12 M, age range 18-68 yrs) and 275
patients with esophageal motility disorders (170 F, 105 M, age range 12-88
yrs): 65 weak peristalsis, 20 aperistalsis, 28 hypercontractile esophagus, 27 eso-
phageal spasm, 33 non-treated achalasia and 100 normal manometry. During the
test we evaluated the pressure responses of the esophageal body at isobaric con-
tour 20 mmHg and pressure gradient across the EGJ.
RESULTS: Healthy controls had an almost complete lack of pressure activity
during the drink test (0.20.8 pressurizations of 21 sec duration) resulting in a
14% of swallowing time with pressure 4 20 mmHg and a pressure gradient
across EGJ of -2.23.2 mmHg. Pressure responses in patients showed 3 distinct
patterns: Patients with weak peristalsis and aperistalsis alike showed similar
responses as healthy controls: 0.61.0 pressurizations of 0.70.6 sec duration
resulting in 13 % of time with pressure 4 20 mmHg, and a pressure gradient
across UEG -0.63.0 mmHg (pooled data, NS vs health for all; hypopressive or
normal pattern). Patients with hypercontractil esophagus and esophageal spasm
had an increment in the number and time of pressurisations above 20 mmHg
(2.53.0 pressurizations resulting in 810 % of time with pressure 4 20 mmHg,
and a pressure gradient across UEG 4.49.0 mmHg (p50.05 vs health for all;
non-obstructive hyperpressive pattern). Finally, patients with non-treated achala-
sia developed the greatest pressurizations of the esophageal body (7.85.5 pres-
surisations with 4130% of time pressure 4 20 mmHg, and a pressure gradient
across UEG 1613 mmHg (p50.05 vs all; prolonged hyperpressive or obstructive
pattern). Using ROC-curve analysis the cut-off values that could discriminate
between the hypopressive or normal pattern from the hyperpressive patterns
are: less than 1 pressurization (sens 80%, sp 75%), 51% of time over 20
mmHg (sens 60%, sp 90%) and pressure gradient across EGJ 51 mmHg (sens
72%, sp 80%). The prolonged hyperpressive or obstructive pattern is character-
ized by more than 3 pressurizations (sens 70%, sp 75%), 4 6% of time over 20
mmHg (sens 90%, sp 50%) and a pressure gradient 4 9 mmHg (sens 80%, sp
75%). Using these patterns, we found that 64 % of patients with esophageal
symptoms and normal manometry had a normal pattern in response to the drink
United European Gastroenterology Journal 2(5S)
challenge test, 27 % had a non-obstructive hyperpressive pattern, and 9 % had a
prolonged obstructive hyperpressive pattern.
CONCLUSION: Different patterns of responses to a rapid drink challenge test
could be used to identify specific motility disorders in patients with esophageal
symptoms and unclear or normal esophageal manometry.
Disclosure of Interest: None declared
OP193 CHAGAS DISEASE IN EUROPE: ESOPHAGEAL MOTILITY
DISORDERS IN INFECTED IMMIGRANTS IN A NON-ENDEMIC
EUROPEAN AREA
S. Roure1,2, L. Valerio1, X. Valle`s1, C. Julia`3, M. Pedro-Botet2, M. Garcia-Diaz4,
J. Serra3,*
1
North Metropolitan Internacional Health Unit, Institut Catala` de la Salut, Santa
Coloma de Gramenet, 2Infectious Diseases Unit, Internal Medicine Department,
3
Motility and Functional Gut Disorders Unit, University Hospital Germans Trias i
Pujol, Badalona, 4Radiology Unit, Institut Catala` de la Salut, Santa Coloma de
Gramenet, Spain
Contact E-mail Address: sroura.mn.ics@gencat.cat
INTRODUCTION: Immigration-related new diseases suppose a new and grow-
ing challenge for health care services in Europe. Following Latin American
migration, Chagas disease has inevitably appeared in Europe and other countries
where the parasite involved, Trypanosoma cruzi, is not vectorially-transmitted.
Up to 30% of infected patients develop severe cardiologic or digestive disease.
The typical esophageal involvement consists in an achalasia-like magaesophagus
which is commonly diagnosed by barium x-ray examination. However, in the last
years more sensitive tools to study esophageal motility disorders, like high reso-
lution manometry, have been available. The main objective of this study was to
determine the prevalence and characteristics of esophageal motility disorders in
immigrants infected with Trypanosoma cruzi, studied with high resolution eso-
phageal manometry (HRM).
December 2013. All newly-diagnosed cases of chronic Chagas infection referring
any upper digestive symptom underwent a protocolized clinical evaluation and
complementary tests including barium x-ray examination and HRM. The proto-
col and interpretation of the HRM results was conducted according to the
Chicago classification (J Clin Gastroenterol 2008).
RESULTS: We included 62 patients (47 women, 15 men; age range 26-63 yrs)
most of whom were Bolivian natives (97%). The referred symptoms were dys-
phagia (43%), chest pain (40 %), heartburn (85 %), and regurgitation (56 %).
Only 7 patients (11 %) had an alteration on barium examination, 6 patients had a
slow transit with minor retention of contrast, and 1 had a small-moderate
increase in calibre of the esophageal body. By contrast, 47 (76 %) of patients
showed an alteration in esophageal manometry, mainly peristaltic dysfunction
(30 %), hypotensive lower esophageal sphincter (32 %) or both (32%). Only one
patient had esophageal aperistalsis, and none patient had the typical achalasia-
like motility pattern. Dysphagia was the only symptom statistically related to
presence the esophageal motility abnormalities (p0.021) and regurgitation
showed a trend (p0.082). Likewise, esophageal motor abnormalities correlated
with the presence of an alteration in electrocardiomyography (p0.05).
Furthermore, HRM abnormalities were observed as a unique pathological find-
ing among 26% of individuals.
CONCLUSION: Esophageal motor disorders in infected immigrants with
Chagas disease in Europe are common, and are mainly characterized by a peri-
staltic dysfunction with hypocontractility. The typical achalasia-like megaeso-
phagus is unusual in this specific group of infected patients.
These results suggest that HRM should be the gold-standard for the study of
esophageal involvement in this group of patients.
Disclosure of Interest: None declared
OP194 THE BITTER TASTE RECEPTOR AGONIST QUININE
HYDROCHLORIDE ALTERS INTRAGASTRIC PRESSURE
PROFILES DURING NUTRIENT DRINK TEST IN HEALTHY
VOLUNTEERS
A. Rotondo1,*, E. Deloose1, M. Corsetti1, I. Depoortere1, J. Tack1
1
targid, KULeuven, Leuven, Belgium
Contact E-mail Address: alessandra.rotondo@med.kuleuven.be
INTRODUCTION: Bitter taste receptors are expressed in the stomach and the
duodenum but their function is unclear.
AIMS & METHODS: We assessed the effects of a potent bitter tastant, quinine
hydrochloride (QHCl) on intragastric pressure (IGP, a measure of gastric accom-
modation) and satiation in response to a liquid meal.
We conducted a single-blind crossover trial in 12 healthy volunteers (6 female;
mean age 35.13.5 yrs; mean BMI 23.80.5) given intragastrically 10 mol/kg
(0.1mL/kg) of a 100 mM QHCl solution or placebo in random order on separate
occasions at least 1 week apart. First, both a standard high-resolution manome-
try (HRM) catheter and a 4mm feeding catheter were positioned intra-gastrically
via the nose with location confirmed by detection of the lower esophageal sphinc-
ter (LES) and/or fluoroscopy. After an adjustment period, QHCl or placebo was
administered through the feeding catheter. After 30 min, nutrient drink (ND;
30% fat, 42% carbohydrate, 28% protein) was infused into the stomach at
60mL/min until maximum satiation, at which point it was stopped. Satiation
(scored on 0-5 scale) was assessed every minute. IGP was measured as average
pressure over 5 channels in the proximal stomach at least 1cm below the LES,
with 5-minute baseline measured 5 minutes before ND start. Outcomes were
compared with paired t-test. All data are expressed as meanSEM.
RESULTS: Baseline IGP prior to ND infusion was similar between QHCl and
placebo (-0.20.7 mmHg placebo vs 0.51.2 mmHg QHCl). During the
United European Gastroenterology Journal 2(5S)
intragastric nutrient drink infusions, the IGP decreased initially and gradually
increased thereafter both in placebo and QHCl. The nadir intragastric pressure
during nutrient drink infusion was significantly lower after QHCl administration
compared to placebo (-7.21.0 mmHg vs -3.41.2 mmHg after placebo and
QHCl, respectively; p0.03). The average IGP drop during the nutrient drink
infusion was significantly reduced after QHCl treatment (4.70.7 mmHg vs.
1.41.1 mmHg after placebo and QHCl, respectively; p0.01). Moreover, the
total area under the IGP curve during nutrient infusion was significantly smaller
after QHCl (66.811.6 mmHg*min for placebo vs 13.912.2 mmHg*min for
QHCl, p0.006), consistent with attenuation of the gastric accommodation
response. At maximum satiation, the volume of ND ingested (805.181.7 ml
vs 692.669.9 ml, placebo and QHCl respectively, p0.08) and the duration of
the nutrient infusion (13.41.4 min vs 11.51.2 min, for placebo and QHCl
respectively, p0.08) tended to be lower after QHCl. No adverse effects were
noted after either agent.
CONCLUSION: The potent bitter tastant QHCl inhibits gastric accommodation
to a meal independently of taste receptor stimulation on the tongue. This is
associated with a tendency for decreased nutrient volume tolerance in healthy
volunteers. The mechanism involved in this action, and its application in the
treatment of obesity, warrant further study.
Disclosure of Interest: None declared
OP195 THE EFFECT OF PRUCALOPRIDE ON GASTRIC
ACCOMMODATION IN HEALTHY VOLUNTEERS
F. Carbone1,*, J. Tack1
1
Gastroeneterology, KULeuven, Leuven, Belgium
Contact E-mail Address: florencia.carbone@med.kuleuven.be
INTRODUCTION: Functional dyspepsia Postprandial Distress Syndrome (FD-
PDS), one of the most common functional disorders, is characterised by meal-
related symptoms such as early satiation and postprandial fullness. Disturbances
of gastric motor function have been implicated the pathogenesis of PDS symp-
toms, and hence, motility modifying agents are considered for the treatment of
PDS. Prucalopride (Resolor), a highly selective 5-TH4 receptor agonist which
stimulates gastrointestinal motility throughout the GI tract, is currently
approved for the treatment of chronic constipation.
AIMS & METHODS: The objective of this study was to evaluate the effect of
prucalopride on gastric sensorimotor function in healthy volunteers (HV). A
total of 10 HV (50% females) underwent 2 barostat studies with administration
of placebo or prucalopride 2 mg in a blinded cross-over fashion. Isobaric disten-
tions with stepwise increments of 2 mm Hg starting from minimal distending
pressure and scoring of intensities of gastric sensations (0-6: pain) were used to
determine gastric compliance and sensitivity. Gastric accommodation was quan-
tified as the difference (delta) in intra-balloon volume 30 min before and 60 min
after ingestion of 200 ml of a nutrient drink (ND) (1.5 kcal mL(-1)). On 2 separate
days, the intragastric pressure (IGP) response to intragastric infusion of ND
(60 ml min(-1)) was studied by high resolution manometry (HRM) of the sto-
mach. Before and during intragastric infusion, HV scored satiation on a
graded scale (0-5: maximal satiation). Throughout the studies, HVs scored
their epigastric symptoms on visual analogue scales (0-100: bothersome sensa-
tion) every 5 minutes.
RESULTS: Prucalopride did not affect proximal stomach compliance. However,
fasting sensitivity to isobaric balloon distention was significantly enhanced by
prucalopride. The mean sensitivity curve slope after placebo treatment was
0.60.1 mmHg(-1) and the mean slope after resolor treatment was 0.90.1
mmHg(-1) (P0.001). Moreover, the gastric accommodation was significantly
increased after treatment with resolor (Delta placebo: 55.436.3 mL and delta
resolor: 166.932.2 mL; P0.002). During the barostat study, HVs reported
significantly higher ratings for symptoms of nausea and belching after prucalo-
pride (P50.05), and vomiting was induced after the meal in 50% of the HVs (all
females). The drop in IGP during nutrient-drink infusion was not affected by
prucalopride treatment (placebo:-4.60.9 vs. prucalopride:-4.00.9 mmHg;
p40.05). The nutrient tolerance (placebo: 61868 ml; prucalopride: 65480
ml; P40.05) and the epigastric symptom scores were not affected by
prucalopride.
CONCLUSION: This study shows that prucalopride increases sensitivity to gas-
tric distention. Barostat and IGP show seemingly differential effects on gastric
accommodation. However, it seems that prucalopride enhances responses to
gastric distention and sensitizes to gastric distention-induced nausea, which
may be accompanied by enhanced gastric relaxatory responses. This interpreta-
tion is supported by the lack of an effect on nutrient volume tolerance.
Disclosure of Interest: None declared
OP196 IMPAIRED VASOACTIVE INTESTINAL PEPTIDE PATHWAY IN
HUMAN GASTRIC ANTRUM IN OBESITY
A. Scirocco1, M. Carabotti1,*, G. Silecchia2, A. Ignazzi3, G. Tellan4, A. Liguori2,
L. Pallotta1, P. Trisolini3, M.A. Maselli3, E. Corazziari1, C. Severi1
1
Department of internal medicine and medical specialties, 2Department of Medical
Surgical Sciences and Biotechnology, Universita` Sapienza, Roma, 3Experimental
Pharmacology Laboratory, Scientific Institute of Gastroenterology "S. de Bellis",
Castellana Grotte (BA), 4Department of Surgery, F. Durante, Universita` PUD during the 10-year study period. We found that PM2.5 concentration,
Sapienza, Roma, Italy
INTRODUCTION: Biological pathway-based genome-wide association analysis
identified a relevant role of Vasoactive Intestinal Peptide (VIP) pathway for
obesity. VIP is a neuropeptide that elicits a broad spectrum of biological func-
tions, including anti-inflammatory and relaxant actions. According to the tissue,
VIP interacts with VPAC1 and VPAC2 receptors coupled to the cAMP signaling
pathways and with Natriuretic Peptide Clearance Receptor (NPR-C) coupled,
A63
via endothelial nitric oxide synthase (eNOS), to the cGMP-pathway. In inflam-
matory conditions a switch from VPAC2 to VPAC1 expression has reported as
well as a decrease in eNOS expression.
AIMS & METHODS: Aim of the study was to investigate VIP actions in obesity
in terms of biological effects, receptor subtypes expression and related signalling
pathways in human gastric antrum, whose relaxation is predominantly VIP-
related. Smooth muscle cells (SMC) and strips were isolated separately from
human gastric antrum obtained from 13 normoglycemic-normocholesterolemic
morbid obese patients (40.95BMI552.0 Kg/m2; 375age545 years) submitted
to sleeve gastrectomy and 7 patients submitted to gastrectomy for gastric cancer
(control: 19.05BMI525.0 Kg/m2; 565age575 years). qPCR analysis was per-
formed for mRNA encoding for VPAC1, VPAC2, NPR-C, e-NOS and inflam-
matory cytokines. On muscle strips and cells relaxant effects were tested on
maximal cholecystokinin (1nM)-induced contraction for VIP (1M), the adeny-
late cyclase activator forskolin (FSK,10 mM), the guanylate cyclase activator
sodium nitroprusside (SNP,1M) and the 2nd messengers cAMP and cGMP
(0.1 mM). Data are expressed as meanSE, p50.05 considered significant.
RESULTS: In obese SMC the mRNA encoding for VPAC2 was significantly
decreased in comparison to control: (VPAC2: 3.60.6 vs 6.30.8) while the
expression of VPAC1 lacking in control SMC, was detected (6.371.81). The
expression of NPR-C receptor, was slightly reduced in obese SMC (8.70.4) in
comparison to control (10.82.2) whereas mRNA expression encoding for eNOS
was not detected, while was present in control (6.60.4). Finally, the mRNA
encoding for inflammatory cytokines was increased in obese in comparison to
control SMC (TNF: 4.931.2 and 4.000.4; COX2 4.630.63 and 1.100.1
respectively). In obese antrum, VIP-induced relaxation resulted almost abolished
both on muscle strips (13.85.2%) and SMC (14.57.3%) in comparison to
control (strips:78.17.4; SMC:75.60.9%). No differences between obese and
control SMC were observed in relaxation induced by FSK (52.95.0 and
53.54.2% respectively) as well as that induced by SNP (38.14.44 and
37.05.5% respectively). The 2 cyclase activators induced also similar relaxation
in obese muscle strips. Likewise, no differences were observed in obese and
control SMC in response to cAMP (59.17.1 and 50.38.2% respectively) as
well as in response to cGMP.
CONCLUSION: The present study confirms a VIP pathway alteration in obesity
reflected by an impaired relaxant transmembrane signaling caused by a reduction
in expression of VPAC2 receptors and coupled molecules.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 11:0012:30
PEPTIC ULCER DISEASE: RISK FACTORS AND TREATMENT LOUNGE
6_____________________
OP198 LONG-TERM EXPOSURE TO PARTICULATE MATTER AIR
POLLUTION AND HOSPITAL ADMISSIONS FOR PEPTIC ULCER
DISEASE
H.-K. Lai1, C.-M. Wong1, H. Tsang1, T.-Q. Thach1, G.N. Thomas2, K.P. Chan1,
R.S. Lee3, J.G. Ayres4, T.-H. Lam1, W.-K. Leung5,*
1
School of Public Health, University of Hong Kong, Hong Kong, Hong Kong,
2
Public Health Epidemiology and Biostatistics, University of Birmingham,
Birmingham, United Kingdom, 3Elderly Health Service, Department of Health,
Hong Kong, Hong Kong, 4Institute of Occupational and Environmental Medicine,
University of Birmingham, Birmingham, United Kingdom, 5Department of
Medicine, University of Hong Kong, Hong Kong, Hong Kong
Contact E-mail Address: hrmrwcm@hku.hk
INTRODUCTION: Air pollution is a major health hazard and leading cause of
death, particularly in developing countries. Among various pollutants, particu-
late matter (PM) is of much clinical relevance. Specifically, PM2.5 is an airborne
particle with aerodynamic diameter less than 2.5 mm that is linked to cardiovas-
cular and respiratory illnesses. Little, however, is known about the effect of
PM2.5 on the gastrointestinal system.
AIMS & METHODS: We investigated the association between long-term expo-
sures to PM2.5 and hospital admissions for peptic ulcer diseases (PUD) in a large
cohort of older persons in Hong Kong. Subjects aged 65 or older, have enrolled
voluntarily in the Government Elderly Health Centres between 1998 and 2001.
All subjects had medical, socio-demographic, lifestyle and anthropometric data
recorded during an interview at baseline. The annual mean exposures to PM2.5 at
individuals residence were estimated by regressing of PM2.5 concentrations from
monitoring site measurements against heights of individuals residence and satel-
lite data through linkage with their address details. All hospital admission
records of the subjects up to year 2010 were retrieved from the central electronic
database of the Hospital Authority. We used Cox regression to model the hazard
ratios (HR) of hospitalization due to PUD (including subcategories of gastric
and duodenal ulcers) per 10g/m3 increase of PM2.5 after adjustment for indivi-
dual, ecological and environmental covariates. Sensitivity analyses were per-
formed by adjusting for or excluding baseline hospitalizations for ischemic
heart disease, stroke, chronic obstructive pulmonary disease and diabetes
mellitus.
RESULTS: A total of 60,273 subjects with complete baseline information were
included in the Cox model. Among them, 1,991 (3.3%) were hospitalized for
age, male gender, high BMI, smoking habits, low education level and underlying
medical diseases were all associated with PUD hospitalizations and they were all
mutually adjusted for in the analyses. The adjusted HR for PUD hospitalization
per 10g/m3 of PM2.5 was 1.18 (95% CI, 1.02 - 1.36). Sensitivity analyses yielded
similar HRs for the association between PM2.5 and PUD (1.18; 1.02 - 1.35 and
1.18; 1.00 - 1.36, respectively). Subcategory analysis showed that the associations
with PM2.5 were significant with gastric ulcers (HR 1.28; 1.08 1.52) but not with
duodenal ulcers (HR 0.98; 0.79 1.21). There was no association between PM2.5
A64
concentration and hospitalization for other GI diseases including reflux esopha-
gitis and gastroenteritis.
CONCLUSION: Long-term exposures to PM2.5 are associated with PUD hos-
pitalization in this older Hong Kong population. Long term exposure to fine
particulate air pollutants may be a new risk factor of gastric ulcer development.
Disclosure of Interest: H.-K. Lai: None declared, C.-M. Wong: None declared, H.
Tsang: None declared, T.-Q. Thach: None declared, G. Thomas: None declared,
K. P. Chan: None declared, R. Lee: None declared, J. Ayres: None declared, T.-
H. Lam: None declared, W.-K. Leung Lecture fee(s) from: Ferring, Takeda,
Consultancy for: Janssen
OP199 LONG-TERM PREVENTION OF RECURRENCE OF PEPTIC
ULCERS BY RABEPRAZOLE IN PATIENTS TAKING LOW-DOSE
ASPIRIN A PHASE 2/3, RANDOMIZED, PARALLEL-GROUP,
MULTICENTER, EXTENSION STUDY
N. Tsuruoka1,*, R. Iwakiri2, K. Higuchi3, M. Kato4, M. Fujishiro5,
Y. Kinoshita6, T. Watanabe7, T. Takeuchi3, N. Sugisaki8, S. Ichikawa8,
Y. Okada9, H. Ogawa10,11, T. Arakawa7, K. Fujimoto1
1
Department of Internal Medicine, 2Department of Internal Medicine &
Gastrointestinal Endoscopy, Saga Medical School, Saga, 3Second Department of
Internal Medicine, Osaka Medical College, Osaka, 4Division of Endoscopy,
Hokkaido University Hospital, Sapporo, 5Department of Endoscopy and
Endoscopic Surgery, Graduate School of Medicine, The University of Tokyo,
Tokyo, 6Department of Internal Medicine II, Faculty of Medicine, Shimane
University, Izumo, 7Department of Gastroenterology, Osaka City University
Graduate School of Medicine, Osaka, 8Clinical Development Japan/Asia Clinical
Research Product Creation Unit, Eisai Co., Ltd., Tokyo, 9Clinical Research
Institute and Cerebrovascular Medicine, National Hospital Organization, Kyushu
Medical Center, Fukuoka, 10Department of Cardiovascular Medicine, National
Cerebral and Cardiovascular Center, Osaka, 11Department of Cardiovascular
Medicine, Graduate School of Medical Sciences, Kumamoto University,
Kumamoto, Japan
INTRODUCTION: In a recent randomized, double-blind, 24-week study with
patients receiving low dose aspirin (LDA) for cardiovascular and cerebrovascular
protection, we demonstrated that both rabeprazole 10 mg and 5 mg once daily
were significantly more efficacious in preventing ulcer recurrence than teprenone
(geranylgeranylacetone: active control, mucosal protective agent, 50 mg three
times a day). However, once LDA treatment is begun as a routine clinical
care, treatment will continue on a semi-permanent basis. So we planned a
United European Gastroenterology Journal 2(5S)
Otsuka Pharmaceutical Co. Ltd., Shionogi & Co., Ltd. and Takeda
Pharmaceutical Co. Ltd., Lecture fee(s) from: Pfizer Japan Inc. and Sanofi
K.K., Consultancy for: Eli Lilly Japan K.K, Novartis Pharma K.K., Pfizer
Japan Inc. and Takeda Pharmaceutical Co. Ltd., T. Arakawa Consultancy for:
Eisai Co., Ltd, and Otsuka Pharmaceutical Co. Ltd., K. Fujimoto Consultancy
for: Eisai Co., Ltd.
OP200 EFFECTS OF PRO-GLY-PRO AND N-ACETYL-PRO-GLY-PRO
ON ACETIC ACID-INDUCED ULCER FORMATION IN RATS AND
CYTOKINES RELEASE FROM RAT GASTRIC EPITHELIAL CELLS
A.D. Sangadzhieva1,*, Z. Bakaeva2, T. Tanaka3, S. Tani3, N.F. Myasoedov4
1
Human and Animal Phisiology, Lomonosov Moscow State University, 2Pirogov
Russian National Research Medical University, Moscow, Russian Federation,
3
Department of Pharmaceutical and Health Sciences, Josai University, Sakado,
Japan, 4Human Molecular Genetics Department, Institute of Molecular Genetics,
Moscow, Russian Federation
Contact E-mail Address: annasangadzhieva@gmail.com
INTRODUCTION: The Glyprolines peptide family includes the simplest pro-
line-containing peptides: Pro-Gly, Gly-Pro, Pro-Gly-Pro, Hyp-Gly, Gly-Hyp,
cycloPro-Gly and etc. Glyprolines are generated during synthesis and catabolism
of collagen. Glyprolines have a broad spectrum of biological activity including
protective and therapeutic anti-ulcer effects.
AIMS & METHODS: In our research we studied the influence of PGP and N-
acetyl-PGP on acetic acid-induced ulcer formation/healing and the release of
cytokines in vivo and in vitro.
Chronic gastric ulcers in male Wistar rats were induced experimentally according
to method Okabe [1]. In vivo: single intranasal administration of PGP and N-
acetyl-PGP was administrated in a dose of 3.7 mmol/kg during 1-3 days and 4-6
days after ulceration. Estimation of ulcer area and histomorphological study
were carried out on the 4th and 7th after ulcerogenesis. All stomachs were homo-
genized for cytokines evaluation. In vitro: rat gastric surface epithelial cells were
isolated and inoculated in a 1.5106 cells/dish [2]. Peptides were added in volume
20 ml/dish in concentration 10-3- 10-5 M. RT-PCR, Real time PCR and ELISA
were used for quantative and qualitive analyzes of cytokines.
RESULTS: A maximal ulcer area had developed on the 4th day after application
of acetic acid to gastric serous mucosa. PGP and N-acetyl-PGP significantly
reduce ulcers by 76.4 % and 86.4 %; respectively, compared to the control
group. Antiulcer effects of peptides on the 7th day were equal to 76.41 % and
65.9%, respectively, vs the control group. In vivo experiments we have detected
long-term administration study, extending the treatment period by additional cytokines GRO/CINC-1, IL-12a, IL-17a, TGF and TGF. Expression of
28 - 52 weeks (the maximum total duration of treatment of 76 weeks) GRO/CINC-1, TGF and TGF was increased in the control group in compar-
(ClinicalTrials.gov Identifier: NCT01398410). ison with the intact rats. Glyprolines suppressed GRO/CINC-1 (p50,05) on the
AIMS & METHODS: Eligible patients for the extension trial had an endosco- 4th and 7th days, TGF expression was only on the 4th day. In vitro experiments
pically confirmed history of peptic ulcers, were receiving long-term LDA (81 mg/ the rat gastric surface epithelial cells can secrete GRO/CINC-1, TGF and
day or 100 mg/day) therapy for cardio- and cerebro-vascular protection, and
were confirmed to have no recurrence of peptic ulcers by endoscopy at the end
of 24-week double-blind phase. The patients allocated to the rabeprazole 10 mg
group and the rabeprazole 5 mg group in the double-blind phase were maintained
on the same doses of rabeprazole in the 28 - 52-week extension phase: that is,
TGF. We have found no effect of the peptides at the different concentrations
on expression and production of GRO/CINC-1 in intact rats and rats after
ulceration.
CONCLUSION: 1) Intranasal administration of PGP and N-acetyl-PGP signif-
icantly inhibits the development of acetic ulcers and enhances their healing.
patients were treated with rabeprazole for the maximum period of 76 weeks (76- 2) Cytokines gene expression GRO/CINC-1, TGF, TGF, IL-12a, IL-17a was
week rabeprazole 10- and 5-mg groups). The patients allocated to the teprenone identified in stomach tissue.
group in the double-blind phase were randomized to take rabeprazole 10 mg or 3) The rat gastric surface epithelial cells secrete GRO/CINC-1, TGF and TGF.
rabeprazole 5 mg at the ratio of 1:1 in the 28 - 52-week extension phase (52-week 4) Acetic acid-induced ulceration increases expression of GRO/CINC-1, TGF
rabeprazole 10- and 5-mg groups). The presence or absence of ulcer recurrence and TGF, but epithelial cells do not have changes of expression of these
was determined by the endoscopy central review panel. cytokines.
RESULTS: 301 subjects (rabeprazole 10 mg, n151; rabeprazole 5 mg, n150) 5) One of the mechanisms of anti-ulcer action PGP and N-acetyl-PGP in vivo can
in the 76-week rabeprazole groups and 91 subjects (rabeprazole 10 mg, n47; be caused by the suppression of proinflammatory cytokines expression GRO/
rabeprazole 5 mg, n44) in the 52-week rabeprazole groups constituted the full
analysis set. The cumulative recurrence rates of peptic ulcers in the 76-week
rabeprazole 10- and 5-mg groups were 2.2% and 3.7%, respectively (Kaplan-
Meier estimates). Furthermore, very low cumulative recurrence rates were also
observed in the subgroup over 70 years of age (1.4% and 2.8%, respectively), in
the subgroup with H. pylori negative (1.5% and 5.6%, respectively), and in the
subgroup with a history of bleeding ulcers (0% and 0%). Recurrent peptic ulcers
were not observed in the 52-week rabeprazole 10- or 5-mg groups. No bleeding
ulcers were reported in all subjects during the extension phase. Incidence of
gastroduodenal damage, reflux esophagitis, and dyspeptic symptoms were also
inhibited by both rabeprazole 10- and 5-mg treatments. Rabeprazole was well-
tolerated at both doses, and no clinically significant safety findings, including
cardiovascular events, emerged.
CONCLUSION: Rabeprazole 10 mg and 5 mg once daily prevent the recurrence
of peptic ulcers in patients with long-term LDA therapy, and are well-tolerated.
Disclosure of Interest: N. Tsuruoka: None declared, R. Iwakiri: None declared,
K. Higuchi Financial support for research from: Eisai Co., Ltd., Daiichi Sankyo
Company, Ltd., Lecture fee(s) from: Eisai Co., Ltd., Daiichi Sankyo Company,
Ltd., M. Kato Financial support for research from: Eisai Co., Ltd., Takeda
Pharmaceutical Co. Ltd., Daiichi Sankyo Company, Ltd., AstraZeneca and
Astellas Pharma Inc., Lecture fee(s) from: Eisai Co., Ltd., Daiichi Sankyo
Company, Ltd., Takeda Pharmaceutical Co. Ltd., Otsuka Pharmaceutical Co.,
Ltd. and AstraZeneca, M. Fujishiro Financial support for research from:
Dainippon Sumitomo Pharma Co., Ltd., Lecture fee(s) from: Eisai Co., Ltd.,
Y. Kinoshita Financial support for research from: Eisai Co., Ltd., Lecture fee(s)
from: Eisai Co., Ltd., T. Watanabe Financial support for research from: Eisai
Co., Ltd., T. Takeuchi: None declared, N. Sugisaki Other: Employee of Eisai
Co., Ltd., S. Ichikawa Other: Employee of Eisai Co., Ltd., Y. Okada: None
declared, H. Ogawa Financial support for research from: AstraZeneca, Astellas
Pharma Inc., Bayer Holding Ltd., Boehringer Ingelheim, Chugai Pharmaceutical
Co. Ltd., Daiichi Sankyo Company, Ltd., Eisai Co., Ltd, Kowa Company, Ltd.,
Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novartis Pharma K.K.,
CINC-1, TGF  and TGF.
REFERENCES
1. Okabe S, Roth JL and Pfeiffer CJ. A method for experimental, penetrating
gastric and duodenal ulcers in rats. Observations on normal healing. Am J Dig
Dis 1971; 16: 277-284.
2. Tani S, Okuda M, Morishige R, et al. Gastric mucin secretion from cultured
rat epithelial cells. Biol Pharm Bull 1997; 20: 482-485.
Disclosure of Interest: None declared
OP201 SEQUENTIAL AND CONCOMITANT TREATMENTS IN H.
PYLORI ERADICATION: A NETWORK META-ANALYSIS
A.G. Mcnicholl1,*, O.P. Nyssen2, J.P. Gisbert1
1
H. La Princesa and IP, CIBERehd, 2H. La Princesa and IP, Madrid, Spain
Contact E-mail Address: adrian.mcn@gmail.com
INTRODUCTION: Conventional meta-analyses comparing non-bismuth quad-
ruple sequential (SEQ) and concomitant (CON) regimens in H. pylori eradication
have been unable to demonstrate differences on treatment efficacy. Network
meta-analyses combining pooled data from direct comparisons and comparisons
with a common control treatment (standard triple therapy, STT) may provide
more complete and consistent information for the selection of the most effective
treatment.
AIMS & METHODS: To perform a network meta-analysis of randomized trials
comparing SEQ vs. CON treatment, or with STT as common comparator.
Selection of studies: randomized clinical trials comparing CON vs. SEQ, or com-
paring them with STT. Studies with different treatment arm lengths were
excluded. Search strategy: bibliographical searches in electronic databases, and
manual search of abstracts from Congresses, were conducted up to May 2013.
Data synthesis: intention-to-treat eradication rate. Outcome: Odds Ratio (OR)
pooled using random effects model.
United European Gastroenterology Journal 2(5S)
RESULTS: 26 trials were included: 13 SEQ vs. STT (3,648 patients), 8 CON vs.
STT (1,230 patients) and 5 CON vs. SEQ (966 patients). Only the SEQ vs. STT
comparison was heterogeneous (I262%). Direct comparisons showed signifi-
cantly lower eradication efficacy of STT than SEQ (OR1.74; 95%CI1.27-
2.38) and CON (OR2.57; 95%CI1.85-3.58) treatments. Direct CON vs.
SEQ meta-analysis showed significantly better results for CON than for SEQ
treatment (OR1.47; 95%CI1.02-2.12). Indirect comparison obtained similar
results: OR1.48 (95%CI0.98-2.36). Network meta-analysis (combining the
results from direct and indirect comparisons) demonstrated that CON regimen
was significantly more effective than SEQ (OR1.47; 95%CI1.06-2.05) and
that results were consistent. Number needed to treat was 11.
CONCLUSION: The results from this network meta-analysis demonstrate that
non-bismuth quadruple concomitant treatment offers consistent and significantly
better cure rates than sequential treatment in the eradication of H. pylori.
Disclosure of Interest: None declared
OP202 SEQUENTIAL THERAPY ACHIEVES HIGH ERADICATION
RATES IN TREATMENT NAIVE PATIENTS HARBOURING MULTI-
DRUG RESISTANT STRAINS OF H PYLORI
G. Fiorini1,*, N. Vakil2, V. Castelli1, I. M. Saracino1, C. Zaccaro1, C. Ricci3,
A. Zullo4, L. Gatta5, D. Vaira1
1
Department of Medical and Surgical Sciences, University of Bologna, Bologna,
Italy, 2School of Medicine & Public Health, University of Wisconsin, Madison,
United States, 3Gastroenterology Unit, University of Brescia, Brescia, 4Department
A65
TUESDAY, OCTOBER 21, 2014 14:0015:30
NEW DRUGS IN IBD HALL C_____________________
OP203 MONGERSEN, AN ORAL SMAD7 ANTISENSE
OLIGONUCLEOTIDE, IN ACTIVE CROHNS DISEASE
G. Monteleone1,*, M.F. Neurath2, S. Ardizzone3, A.D. Sabatino4, M.C. Fantini1,
F. Castiglione5, M.L. Scribano6, A. Armuzzi7, F. Caprioli8, G.C. Sturniolo9,
F. Rogai10, M. Vecchi11, R. Atreya2, F. Bossa12, S. Onali1, M. Fichera3,
G.R. Corazza4, L. Biancone1, V. Savarino13, R. Pica14, A. Orlando15, F. Pallone1
1
Department of Systems Medicine, University of Tor Vergata, Rome, Italy,
2
Department of Medicine, University of Erlangen-Nurnberg, Erlangen, Germany,
3
Department of Surgery, "L. Sacco" University Hospital, Milan, 4Internal
Medicine, University of Pavia, Pavia, 5Gastroenterology, University "Federico II"
of Naples, Naples, 6Gastroenterology Unit, Hospital San Camillo-Forlanini, 7IBD
Unit, Catholic University, Rome, 8Department of Pathophysiology and
Transplantation, University of Milan, Milan, 9Surgical and Gastroenterological
Oncology, University of Padova, Padova, 10Gastroenterology SOD2, AOU Careggi
University Hospital, Florence, 11Department of Biomedical Sciences, University of
Milan, Milan, 12Division of Gastroenterology, Casa Sollievo Sofferenza
Hospital, IRCCS, San Giovanni Rotondo, 13Gastroenterology and Hepatology
Unit, University of Genoa, Genoa, 14IBD Unit, Sandro Pertini Hospital, Rome,
15
Villa Sofia-Cervello Hospital, University of Palermo, Palermo, Italy
INTRODUCTION: Crohns disease (CD)-related inflammation is characterized
by defective activity of the immunosuppressive cytokine transforming growth
of Gastroenterology and Digestive Endoscopy, Nuovo Regina Margherita factor (TGF)-1, due to high Smad7 (an inhibitor of TGF-1) signalling. The
Hospital, Rome, 5Gastroenterology and Digestive Endoscopy Unit, Versilia effects of an oral, topically active Smad7 antisense oligonucleotide, Mongersen,
Hospital, Lido di Camaiore, Italy were evaluated in a phase II study in patients with active CD.
Contact E-mail Address: berardino.vaira@unibo.it AIMS & METHODS: In a double-blind, placebo-controlled trial, the efficacy of
Mongersen as induction therapy was evaluated in steroid-dependent or steroid-
INTRODUCTION: Sequential therapy has been shown to achieve acceptably resistant patients (utilizing ECCO consensus definition) with active CD (CD
high eradication rates also in those patients harbouring H. pylori resistant strains. activity index [CDAI] score 220-400). Patients were randomized to Mongersen
AIMS & METHODS: To prospectively assess the efficacy of Sequential therapy 10, 40 or 160 mg/day or placebo for 2 weeks. The primary outcomes were clinical
in eradicating H pylori in treatment naive patients with multi-drug resistant remission (CDAI score 5150 at Day 15 and maintained for 2 weeks) and
strains. Between 2010 and 2014, consecutive patients undergoing upper endo- safety. Secondary endpoints included clinical response (CDAI score reduction
scopy were evaluated. Each patient had a 13C-UBT, and during endoscopy 2 of 100 points) at Day 28.
biopsies each from the antrum, angulus, and corpus were obtained to perform RESULTS: Clinical remission was achieved by significantly greater proportions of
histology. Further biopsies from antrum were also taken to perform ultrafast patients receiving Mongersen 40 (55.0%) and 160 mg/day (65.1%) compared with
urease test and to carry out culture and antimicrobial sensitivity by Epsilometer placebo (9.5%; p50.0001 for both). No significant difference in clinical remission
test (Etest). According to new EUCAST 2012 the following MIC breakpoints was seen for 10 mg/day (12.2%) vs. placebo. The rate of clinical response was
were used to evaluate resistance:4 0.5, 48 and 1 microgram/ml for clarithro- significantly greater among patients receiving 10 (36.6%), 40 (57.5%) or 160 mg/
mycin (Cla), metronidazole (Met) and levofloxacin (Lev), respectively. Patients day (72.1%) of Mongersen vs. placebo (16.7%; p0.039, p0.0001 and p50.0001,
were considered infected if culture alone or histology and ultrafast urease test respectively). The rates of adverse events (AEs) and serious AEs (SAEs) were similar
were positive. All received standard Sequential therapy. Four to six weeks after across groups. Nine SAEs occurred in 6 patients (placebo, n1; Mongersen 10 mg,
the end of the treatment, eradication was assessed by 13C-UBT. n3; 40 mg, n1; 160 mg, n1). Most SAEs consisted of hospital admissions for
RESULTS: So far, 908 H. pylori infected patients have been enrolled. Follow up CD-associated complications or symptoms, and included: pyrexia and cough (pla-
is now available in 887 and eradication was achieved in 844 patients (95.1%; 95% cebo); abdominal pain (n2), CD worsening and pyrexia (Mongersen 10 mg); seton
CI: 93.8-97); 90.4% in clarithromycin, 92.9 in metronidazole, and 94.4% in placement for perianal fistula and surgery for hemorrhoid thrombosis (Mongersen
levofloxacin resistant strains (single or combined). Eradication rates according 40 mg); and thermal burn (Mongersen 160 mg).
to antibiotic resistance patterns are provided in the Table. CONCLUSION: Induction therapy with orally administered, topically active
Mongersen for CD was well tolerated; toxicities previously reported with sys-
temically active antisense agents were not observed. Mongersen treatment
Resistance Total cases Cases followed-up Eradication rate (%) resulted in significant improvements in clinical remission and response rates
within 4 weeks of initiation of treatment (EUDRACT NUMBER 2011-
Cla (single) 77 75 94.6 002640-27).
Metro (single) 87 83 97.5 Disclosure of Interest: G. Monteleone Other: Giovanni Monteleone reports being
holder of a patent for the use of Smad7 antisense, M. Neurath: None declared, S.
Levo (single) 49 49 95.9 Ardizzone: None declared, A. Sabatino: None declared, M. Fantini: None declared,
Cla & Metro 155 137 88.3 F. Castiglione: None declared, M. Scribano: None declared, A. Armuzzi: None
Cla & Levo 106 97 91.5 declared, F. Caprioli: None declared, G. Sturniolo: None declared, F. Rogai:
Metro & Levo 128 121 94.5 None declared, M. Vecchi: None declared, R. Atreya: None declared, F. Bossa:
None declared, S. Onali: None declared, M. Fichera: None declared, G. Corazza:
Cla & Metro & Levo 84 77 91.4 None declared, L. Biancone: None declared, V. Savarino: None declared, R. Pica:
CONCLUSION: Sequential therapy is able to overcome the problem of multi- None declared, A. Orlando: None declared, F. Pallone: None declared
resistant strains in a large proportion of patients. Sequential therapy may be the
optimal treatment for patients suspected of having multi-drug resistant strains
especially if clarithromycin is involved. OP204 AVX-470, AN ORALLY DELIVERED ANTI-TNF ANTIBODY FOR
Disclosure of Interest: G. Fiorini: None declared, N. Vakil Consultancy for: Astra TREATMENT OF ACUTE ULCERATIVE COLITIS: RESULTS OF A
Zeneca, Takeda, Shareholder of: Meridian Diagnostic, Orexo, V. Castelli: None FIRST-IN-HUMAN TRIAL
declared, I. M. Saracino: None declared, C. Zaccaro: None declared, C. Ricci: M.S. Harris1,*, D. Hartman1, S. Spence1, S. Kennedy1, T. Ptak2, R. Pruitt3,
None declared, A. Zullo: None declared, L. Gatta: None declared, D. Vaira: S. Vermeire4, B. Fox1
None declared 1
Avaxia Biologics, Lexington, United States, 2Toronto Digestive Disease
Associates, Toronto, Canada, 3Nashville Medical Research Institute, Nashville,
United States, 4Medicine, University Hospital Gasthuisberg, Leuven, Belgium
Contact E-mail Address: sharris@avaxiabiologics.com
INTRODUCTION: AVX-470 is an oral, enteric-coated, polyclonal bovine-
derived anti-TNF antibody in development for treatment of IBD. AVX-470 is
delivered orally to neutralize TNF locally in the gastrointestinal tract, minimizing
potential for systemic exposure. This was a double-blind, placebo-controlled,
first-in-human trial designed to assess the safety, pharmacokinetics, immunogeni-
city, and early efficacy of 4 weeks of AVX-470 administration in patients with
acute ulcerative colitis (UC).
AIMS & METHODS: 36 patients were randomized 3:1 to receive active drug or
placebo in 3 ascending dose cohorts (AVX-470 0.2g/d, 1.6g/d, or 3.5g/d) over 4
weeks. Symptomatic patients with Mayo Score between 5 and 12 and Mayo
endoscopic subscore of 2 or greater 15 cm from the anal verge were eligible for
participation. Concomitant use of 5-ASA, corticosteroid ( 20mg prednisone),
and immunosuppressive agents, and prior use of a systemically administered anti-
TNF antibody with secondary failure, were permitted. Pancolonoscopies were
scored centrally by Mayo and UCEIS (Ulcerative Colitis Index of Severity)
A66
scales. The primary endpoint was safety (adverse events (AEs)). Secondary end-
points included pharmacokinetics (bovine Ig in serum, tissue, and stool); immu-
nogenicity (human anti-bovine antibodies (HABA) in serum); and efficacy
(clinical and endoscopic response and remission by Mayo Score).
RESULTS: 36 patients received treatment with AVX-470 0.2g/d (n8), 1.6g/d
(n12), 3.5g/d (n7) or placebo (n9). 50% of patients had pancolitis on entry;
66.7% of patients had prior or concomitant use of corticosteroids, and 41.7% and
33.3% had failed use of immunosuppressive or anti-TNF agents, respectively. 33
patients completed treatment; there were no AE-related dropouts. The incidence of
AEs was similar across treatment groups, and no allergic reactions or opportunistic
infections were reported. Bovine Ig with TNF binding capacity was detected in
stool, while levels of TNF-specific antibody in serum remained 1000-fold lower
than concentrations associated with the activity of systemic TNF therapies.
Mucosal bovine Ig penetration was demonstrated in all colonic segments.
Reduction in tissue TNF levels was noted at 3.5 g/d. AVX-470 therapy did not
induce serum HABA. 28% patients across all AVX-470 doses achieved clinical
response compared to 14.3% on placebo, with clinical and endoscopic remissions
at higher doses. Dose-related improvement in total Mayo Score (-2.1 vs. -1.4) and
CRP (-7.2 vs. -0.7) were observed at higher dose (3.5g/d vs. placebo). A linear
gradient was observed in the magnitude of endoscopic improvement, with a 1.5-
point improvement in UCEIS score (8-pt scale) at 3.5g/d compared to placebo in the
proximal colon and lesser improvement distally.
CONCLUSION: AVX-470 appeared to be safe and well tolerated in this first-in-
human trial of UC patients, with efficacy trends at the highest dose group and a linear
gradient of response on endoscopy from proximal to distal colon after only 4 weeks of
treatment. This is the first study to suggest the benefit of an orally delivered locally
active agent in a moderate-severe UC population. Future studies are planned to assess
the effects of higher dose and longer duration of treatment on disease activity.
Disclosure of Interest: M. S. Harris Consultancy for: Avaxia Biologics, Rhythm
Pharmaceuticals, Theravance, Symbiomix, Biomedical Systems, ZS Pharma,
Drais Pharmaceuticals, Shareholder of: Ocera Therapeutics, D. Hartman
Shareholder of: Avaxia Biologics, Other: Avaxia Biologics, S. Spence
Consultancy for: Avaxia Biologics, S. Kennedy: None declared, T. Ptak: None
declared, R. Pruitt: None declared, S. Vermeire Financial support for research
from: Abbott Laboratories, Merck Sharp and Dohme, UCB, Consultancy for:
Merck Sharpe and Dohme, Abbott Laboratories, UCB, Ferring, Chiesi, Pfizer,
Shire, B. Fox Shareholder of: Avaxia Biologics, Directorship(s) for: Avaxia
United European Gastroenterology Journal 2(5S)
CONCLUSION: The efficacy of VDZ observed in GEMINI 2 was maintained
over the course of an additional 52 weeks in GEMINI LTS, regardless of TNF
antagonist exposure prior to GEMINI 2.
REFERENCES
1. Sandborn WJ, et al. N Engl J Med 2013; 369: 711-721.
2. Colombel JF, et al. Poster presented at: American College of Gastroenterology
Annual Scientific Meeting, San Diego, CA, 11-16 October 2013.
Disclosure of Interest: S. Hanauer Financial support for research from: AbbVie
Inc., Janssen Pharmaceuticals, Inc, Takeda Pharmaceuticals International Co.,
and UCB S.A., Lecture fee(s) from: AbbVie Inc., Janssen Pharmaceuticals, Inc,
Takeda Pharmaceuticals International Co., and UCB S.A., Consultancy for:
AbbVie Inc., Janssen Pharmaceuticals, Inc, Takeda Pharmaceuticals
International Co., and UCB S.A., P. Rutgeerts Consultancy for: Centocor
(Johnson & Johnson), Merck, UCB, Abbott Laboratories, Millennium
Pharmaceuticals, Genentech, Neovacs, Merck Serono, Bristol-Myers Squibb,
Robarts Clinical Trials, Tillotts Pharma, Pfizer, J. Xu Other: Employee of
Takeda Pharmaceuticals International Co., D. Rubin Consultancy for: Abbvie,
Bristol Meyers Squibb, Centocor/Janssen, Cornerstones Health, Inc., Elan
Pharmaceuticals, Emmi, Given Imaging, Ironwood, Lifecore Biomedical, LLC,
Prometheus Pharmaceuticals, Santarus, Shire, Takeda-Millennium, Telsar
Pharmaceuticals, UCB Pharma, Vertex Pharmaceuticals, Warner Chilcott, M.
Smyth Other: Employee of Takeda Global Research & Development Centre
(Europe) Ltd., B. Abhyankar Other: Employee of Takeda Global Research &
Development Centre (Europe) Ltd.
OP206 LONG-TERM EFFICACY OF VEDOLIZUMAB THERAPY FOR
ULCERATIVE COLITIS
B. Feagan1,*, A. Kaser2, M. Smyth3, R. Panaccione4, S. Sankoh5, B. Abhyankar3
1
Robarts Research Institute, University of Western Ontario, London, Canada,
2
Department of Medicine, University of Cambridge, Addenbrookes Hospital,
Cambridge, 3Takeda Global Research & Development Centre (Europe) Ltd,
London, United Kingdom, 4Department of Medicine, University of Calgary,
Calgery, Canada, 5Takeda Pharmaceuticals International Co., Cambridge, United
States
Contact E-mail Address: brian.feagan@robartsinc.com
Biologics, Other: Avaxia Biologics
OP205 LONG-TERM EFFICACY OF VEDOLIZUMAB THERAPY FOR
CROHNS DISEASE
S. Hanauer1, P. Rutgeerts2,*, J. Xu3, D.T. Rubin4, M. Smyth5, B. Abhyankar5
1
Digestive Health Center, Northwestern University Feinberg School of Medicine,
Chicago, United States, 2Department of Gastroenterology, University Hospital
Gasthuisberg, Leuven, Belgium, 3Takeda Pharmaceuticals International Co.,
Cambridge, 4Inflammatory Bowel Disease Center, University of Chicago Medicine,
Chicago, United States, 5Takeda Global Research & Development Centre
(Europe) Ltd., London, United Kingdom
Contact E-mail Address: shanauer@northwestern.edu
INTRODUCTION: Vedolizumab (VDZ) is an anti47 integrin monoclonal
antibody with demonstrated efficacy and safety in the 52-week GEMINI 1
study of patients with moderately to severely active ulcerative colitis.1 Eligible
patients from GEMINI 1 could enroll in an ongoing, long-term, open-label
extension study (GEMINI LTS; ClinicalTrials.gov No. NCT00790933;
EudraCT No. 2008-002784-14). Here, we describe the long-term efficacy of
VDZ in patients who completed GEMINI 1 and enrolled in GEMINI LTS.
AIMS & METHODS: The double-blind, randomized, placebo (PBO)-controlled
GEMINI 1 study consisted of induction (weeks 0-6) and maintenance (weeks 6-
52) phases. Patients who completed GEMINI 1 (n344) and those who withdrew
early (n313) could enroll in GEMINI LTS, wherein open-label VDZ was admi-
nistered every 4 weeks. The following efficacy end points were assessed and are
reported here for GEMINI 1 completers: clinical remission (partial Mayo Clinic
[pMC] score 2 with no individual subscore 41) and clinical response (decrease
INTRODUCTION: The efficacy and safety of the anti47 integrin monoclonal in pMC score of 2 and 25% from baseline and decrease in rectal bleeding
antibody vedolizumab (VDZ) were evaluated in the 52-week GEMINI 2 study of subscore of 1 from baseline or absolute rectal bleeding subscore 1). Two
patients with Crohns disease (CD).1 The long-term efficacy of VDZ 300 mg analyses are presented, 1 prespecified analysis involving the efficacy population
administered every 4 weeks to patients who completed GEMINI 2 and enrolled (EP; GEMINI 1 completers who received any amount of study drug in GEMINI
in an open-label extension study (GEMINI LTS; ClinicalTrials.gov No. LTS) and a post hoc analysis involving observed cases (OC; EP patients who had
NCT00790933; EudraCT No. 2008-002784-14) is described here. baseline and 1 postbaseline measurement) at each time point.
AIMS & METHODS: The double-blind, randomized, placebo (PBO)-controlled RESULTS: Efficacy outcomes at weeks 52, 80, and 104 for the EP and OC are
GEMINI 2 study of patients with CD involved an induction trial (weeks 0-6) and shown in the Table. Proportions of GEMINI 1 completers who had clinical
a maintenance trial (weeks 6-52). Patients who completed the study and those remission and those who had clinical response were maintained from weeks 52
who withdrew early were eligible for enrollment in GEMINI LTS, with VDZ to 104. The efficacy of VDZ from GEMINI 1 was maintained during GEMINI
administered every 4 weeks. For the subgroup of patients who completed LTS. Of patients with previous tumor necrosis factor (TNF) antagonist failure,
GEMINI 2, clinical remission (Harvey-Bradshaw Index [HBI] score 4 points) 65.3% (EP) and 79.5% (OC) had clinical remission and 79.6% (EP) and 89.7%
and response (decrease in HBI score of 3 points from baseline) were assessed (OC) had a clinical response at week 104; 76.7% (EP) and 85.7% (OC) of TNF
and are reported here for weeks 52, 80, and 104. Prespecified analyses were antagonistnaive patients had clinical remission and 82.8% (EP) and 92.5%
performed at each time point for the efficacy population (all GEMINI 2 patients (OC) had a clinical response at week 104. Long-term safety data for VDZ
who received any amount of study drug in GEMINI LTS). have been previously described.2
RESULTS: Of 814 patients treated with VDZ in GEMINI 2, 295 completed week
52 assessments and entered into GEMINI LTS. Clinical remission outcomes at
weeks 52, 80, and 104 are shown in the Table. Proportions of GEMINI 2 completers
who had clinical remission (week 52, 57%; week 104, 61%) and of those who had a
clinical response (week 52, 81%; week 104, 74%) were maintained from weeks 52 to
104. Among completers with previous tumor necrosis factor (TNF) antagonist fail-
ure, clinical remission was seen in 51% of patients and clinical response in 70% of
patients at week 104. Of VDZ-treated TNF antagonistnaive completers, 69% were
in clinical remission and 77% had a clinical response at week 104. Long-term VDZ
safety data have been previously described.2
Table to abstract OP205

GEMINI 2 Completers (VDZ Combined) Efficacy Population

All Patients (n295) TNF Antagonist Na ve (n159) Previous TNF Antagonist Failure (n136)

Clinical Remission (HBI score 4 points)

Wk 52 167 (57) 97 (61) 70 (52)
Wk 80 190 (64) 114 (72) 76 (56)
Wk 104 179 (61) 110 (69) 69 (51)
Data are No. of patients (%). Study wk refers to time since start of GEMINI 2.
United European Gastroenterology Journal 2(5S) A67

GEMINI 1 Completers (VDZ Combined) Mean (SD) Score Change From Baselinea
Study Time Point n Baselinea On Study Mean (SD) 95% CI
Observed Cases
pMC score for UC 32 5.9 (1.7) 2.6 (1.6) 3.3 (1.7) 3.9, 2.7
Efficacy Population
GEMINI 1 9 6.2 (1.6) 4.3 (3.2) 1.9 (3.6) 4.6, 0.9
No. (%) of Patients n275a No. (%) of Patients n Wk 6 31 5.9 (1.7) 5.8 (1.8) 0.1 (1.6) 0.7, 0.5
Wk 26 19 5.9 (1.6) 2.4 (1.7) 3.5 (2.1) 4.5, 2.5
Clinical Remission GEMINI LTS 16 5.8 (1.6) 1.8 (1.7) 4.0 (2.4) 5.3, 2.7
Wk 52 181 (65.8) 181 (72.4) 250 Wk 0
Wk 28
Wk 80 212 (77.1) 212 (83.8) 253
Wk 52
Wk 104 200 (72.7) 200 (83.7) 239 HBI score for CD 56 11.4 (3.0) 6.4 (3.1) 5.0 (3.3) 5.9, 4.1
Clinical Response GEMINI 2 19 11.4 (2.2) 8.5 (4.1) 2.9 (4.7) 5.2, 0.6
Wk 52 216 (78.5) 216 (86.4) 250 Wk 6 57 11.5 (3.0) 10.1 (4.1) 1.4 (4.3) 2.5, 0.2
Wk 26 40 11.3 (2.7) 6.0 (3.4) 5.3 (3.7) 6.5, 4.1
Wk 80 234 (85.1) 234 (92.5) 253 GEMINI LTS 30 11.1 (2.4) 4.1 (3.0) 7.0 (3.4) 8.2, 5.7
Wk 104 219 (79.6) 219 (91.6) 239 Wk 0
Wk 28
CONCLUSION: The efficacy of VDZ observed in GEMINI 1 was maintained Wk 52
for an additional 52 weeks in GEMINI LTS, regardless of previous TNF antago-
nist exposure.
REFERENCES Consistent with the findings above, median predicted average wk 52 VDZ con-
1. Feagan BG, et al. N Engl J Med 2013; 369: 699-710. centrations in patients on VDZ Q8W were higher for those who completed the
2. Colombel JF, et al. Poster presented at: American College of Gastroenterology studies (GEM 1: 36.9 mcg/mL, n75; GEM 2: 39.5 mcg/mL, n74) than for
Annual Scientific Meeting, San Diego, CA, 11-16 October 2013. those who discontinued (GEM 1: 30.5 mcg/mL, n32; GEM 2: 32.7 mcg/mL,
Disclosure of Interest: B. Feagan Consultancy for: Abbott Laboratories, n57).
Actogenix, Albireo Pharma, AstraZeneca, Athersys, Axcan, Berlex, Bristol- CONCLUSION: Patients who lost response to VDZ Q8W had improvements in
Myers Squibb, Celgene, Centocor, Cerimon Pharma, CombinatoRx, Elan/ mean disease activity scores with an increase in VDZ dosing frequency to Q4W
Biogen, Genentech, GICare Pharma, Gilead, Given Imaging Inc, without an apparent accompanying increased risk for AEs. Although uncon-
GlaxoSmithKline, Johnson and Johnson, Napo Pharma, Nektar, Novo trolled, these data provide insight regarding possible utility of VDZ Q4W dosing.
Nordisk, Ore Pharmaceuticals, Pfizer, Procter and Gamble, Prometheus Disclosure of Interest: B. Sands Consultancy for: Abbott Immunology, Amgen,
Therapeutics and Diagnostics, Salix Pharma, Serono, Shire, Sigmoid Pharma, Astellas Pharma Global Development, Avaxia Biologics, Baxter Healthcare,
Takeda Pharmaceuticals International, Inc., Tillotts, UCB Pharma, Unity Bracco Diagnostics Inc., Bristol-Myers Squibb, Creative Educational Concepts,
Pharmaceuticals, Wyeth, Zealand Pharma, Zyngenia, A. Kaser: Nothing to dis- Curatio CME Institute/Axis Healthcare Communications, LLC, Dainippon
close., M. Smyth Other: Employee of Takeda Global Research & Development Sumitomo Pharma, Dyax Corp, Elan Pharmaceuticals, Emmi Solutions LLC,
Centre (Europe) Ltd, R. Panaccione Consultancy for: Abbott, Abbvie Amgen, GlaxoSmithKline, Glaxo Wellcome, IMEDEX, Immune Pharmaceuticals,
Aptalis, AstraZeneca, Baxter, Eisai, Ferring, Janssen, Merck, Schering-Plough, Kyowa Hakko Kirin Pharma, Inc., Mechanisms in Medicine, Millennium/
Shire, Centocor, Elan, Glaxo-Smith Kline, UCB, Pfizer, Bristol-Myers Squibb, Takeda, Pfizer, Prometheus Laboratories, PureTech Ventures, LLC, Sigmoid
Warmer Chilcott, Takeda, S. Sankoh Other: Employee of Takeda Pharma, Teva Pharmaceutical Industries, M. Dubinsky Consultancy for:
Pharmaceuticals International Co., B. Abhyankar Other: Employee of Takeda Abbvie, Janssen, Pfizer, Prometheus, UCB Pharma, S. Vermeire Financial sup-
Global Research & Development Centre (Europe) Ltd port for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from:
Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB
Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, S.
OP207 EFFECTS OF INCREASED VEDOLIZUMAB DOSING Sankoh Other: Employee of Takeda Pharmaceuticals International Co., M.
FREQUENCY ON DISEASE ACTIVITY IN ULCERATIVE COLITIS Rosario Other: Employee of Takeda Pharmaceuticals International Co., C.
AND CROHNS DISEASE Milch Other: Employee of Takeda Pharmaceuticals International Co.
B.E. Sands1, M.C. Dubinsky2, S. Vermeire3,*, S. Sankoh4, M. Rosario4,
C. Milch4
1
Icahn School of Medicine at Mount Sinai, New York, 2Cedars-Sinai Medical OP208 HOW LONG SHOULD GOLIMUMAB TREATMENT BE
Center, Los Angeles, United States, 3University Hospital Gasthuisberg, Leuven, CONTINUED IN PATIENTS WITH ULCERATIVE COLITIS WHO
Belgium, 4Takeda Pharmaceuticals International Co., Cambridge, United States DO NOT RESPOND TO INITIAL INDUCTION THERAPY?
Contact E-mail Address: bruce.sands@mssm.edu P. Rutgeerts1,*, W. Reinisch2, B. Feagan3, W. Sandborn4, D. Tarabar5,
Z. Hebzda6, H. Weng7, R. Yao7, H. Zhang8, C. Marano8, R. Strauss8
INTRODUCTION: Efficacy and safety of vedolizumab (VDZ) in patients with 1
University Hospital Gasthuisberg, Leuven, Belgium, 2McMaster University,
ulcerative colitis (UC) and Crohns disease (CD) were established in the Hamilton, 3U Western Ontario, London, Canada, 4University of California San
GEMINI (GEM) 1 (Feagan BG, et al. N Engl J Med.2013;369 (8):699-710) Diego, La Jolla, United States, 5Military Medical Academy, Belgrade, Serbia,
and 2 (Sandborn WJ, et al. N Engl J Med.2013;369(8):711-21) trials, respectively. 6
Wojskowy Szpital Kliniczny z Poliklinika, Krakow, Poland, 7Merck & Co., Inc.,
To investigate whether increased VDZ dosing frequency benefits patients who Whitehouse Station, 8Janssen R&D, LLC., Spring House, United States
lost response to VDZ every 8 wks (Q8W) during GEM 1 or 2, disease activity was Contact E-mail Address: paul.rutgeerts@uz.kuleuven.ac.be
assessed when these patients received VDZ every 4 wks (Q4W) in an open-label,
long-term extension study (GEM LTS; EudraCT No. 2008-002784-14). INTRODUCTION: To determine an appropriate time to discontinue golimumab
AIMS & METHODS: The randomized placebo-controlled GEM 1 and 2 studies (GLM) maintenance therapy for ulcerative colitis (UC) in patients (pts) who do
included a 6-wk induction phase and a 46-wk maintenance phase. Data from not respond to initial induction treatment.
patients who responded to VDZ 300 mg induction therapy but later discontinued AIMS & METHODS: The PURSUIT study enrolled pts with moderate to
for lack of efficacy on VDZ 300 mg Q8W maintenance therapy and who enrolled severe, active UC (Mayo scores 612 inclusive; endoscopic subscore 42) with
in GEM LTS (to receive VDZ 300 mg Q4W) were analyzed. Mean partial Mayo inadequate response or intolerance to conventional UC therapy. Pts were rando-
Clinic (pMC) scores (UC) and mean Harvey-Bradshaw Index (HBI) scores (CD) mized to receive at wk 0/2 either placebo (PBO)/PBO, GLM 200mg/100mg, or
were calculated. For patients who discontinued from GEM 1 and 2, average wk GLM 400mg/200mg. Pts who were not in clinical response (30% and 3 points
52 VDZ concentrations were predicted to standardize pharmacokinetic data at Mayo score decrease from wk 0 with a rectal bleeding subscore of 0/1 or decrease
the same time point relative to study entry (Rosario M, et al. Presented at: 9th 1) after 6-wk induction received GLM 100mg every 4 wk. Partial Mayo
Congress of the ECCO; Feb 20-22, 2014; Copenhagen). These values were com- response (improvement 3 from wk 0) and remission (score 2) without endo-
pared with predicted VDZ concentrations in those who completed GEM 1 or 2. scopy were evaluated through wk 22. There was no control group; all nonre-
RESULTS: Among those who received VDZ Q8W in GEM 1 (n122) or GEM 2 sponders received GLM. Pts who had a prohibited medication change, ostomy or
(n154), 32 patients (26%) from GEM 1 and 57 (37%) from GEM 2 discon- colectomy, dose adjustment, missing partial Mayo scores, or discontinued for
tinued for lack of efficacy. Mean disease activity scores for these patients lack of efficacy were considered nonresponders.
improved after transition to VDZ Q4W dosing in GEM LTS (Table). AE profiles RESULTS: Among GLM induction nonresponders (N398, 7 pts excluded due
were generally similar for the VDZ Q8W and Q4W regimens in GEM 1 and 2. to site misconduct), further GLM therapy resulted in additional pts achieving
response/remission (table; data from induction responders are shown for com-
parison). At wk 10 of GLM exposure, 11.8% of induction nonresponders had
achieved partial Mayo remission, and 23.1% had achieved partial Mayo
response. At wk 14, 15.6% achieved remission; 28.1% achieved response.
Although the proportion of pts who achieved remission/response increased
beyond wk 14, the incremental benefit was minimal. While adverse events
(AEs) were reported with a slightly greater frequency during the first months
of maintenance treatment, the majority of pts did not report an AE during
continued treatment.
A68
Table. Partial Mayo Response/Remission With Continued GLM Treatment
Table to abstract OP208
Induction Responders
Induction (50 and 100mg dose groups)
Nonresponders (N398) (N302)
Wk of GLM Partial Mayo Partial Mayo Partial Mayo Partial Mayo
exposure remission, n (%) response, n (%) remission, n (%) response, n (%)
Wk 6a 7 (1.8) 14 (3.5) 205 (67.9) 234 (77.5)
Wk 10 47 (11.8) 92 (23.1) 190 (62.9) 232 (76.8)
Wk 14 62 (15.6) 112 (28.1) 186 (61.6) 206 (68.2)
Wk 18 77 (19.4) 129 (32.4) 181 (59.9) 201 (66.6)
Wk 22 84 (21.1) 129 (32.4) 172 (57.0) 186 (61.6)
CONCLUSION: Among patients who were nonresponders after initial GLM
induction, 15.6% achieved partial Mayo score remission, and 28.1% achieved
response by wk 14. Continued therapy may not be useful in patients who show no
evidence of therapeutic benefit after 1214 wks of GLM treatment. (Financial
support for this study was provided by Janssen Research & Development, LLC.,
Spring House, PA, USA.)
Disclosure of Interest: P. Rutgeerts Financial support for research from: Merck
Sharp & Dohme Corp, Consultancy for: Merck Sharp & Dohme Corp, W.
Reinisch Lecture fee(s) from: Abbott Laboratories, AbbVie, Aesca, Amgen,
AM Pharma, Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen
IDEC, Bristol-Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor,
Danone Austria, Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech,
Grunenthal, Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC,
Consultancy for: Abbott Laboratories, AbbVie, Aesca, Amgen, AM Pharma,
Aptalis, Astellas, Astra Zeneca, Avaxia, Bioclinica, Biogen IDEC, Bristol-
Myers Squibb, Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria,
Elan, Falk Pharma GmbH, Ferring, Galapagos, Genentech, Grunenthal,
Janssen, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Lipid
Therapeutics, Millennium, Mitsubishi Tanabe Pharma Corporation, MSD,
Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & Gamble,
Prometheus, Robarts Clinical Trial, Schering-Plough, Setpointmedical, Shire,
Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Zyngenia, and 4SC, B.
Feagan Financial support for research from: Abbott/AbbVie, Amgen, Astra
Zeneca, Bristol-Myers Squibb (BMS), Janssen Biotech (Centocor), JnJ/Janssen,
Roche/Genentech, Millennium, Pfizer, Receptos, Santarus, Sanofi, Tillotts, UCB
Pharma, Lecture fee(s) from: Abbott/AbbVie, JnJ/Janssen, Takeda, Warner-
Chilcott, UCB Pharma, Consultancy for: Abbott/AbbVie, Actogenix, Albireo
Pharma, Amgen, Astra Zeneca, Avaxia Biologics Inc., Axcan, Baxter
Healthcare Corp., Boehringer-Ingelheim, Bristol-Myers Squibb, Calypso
Biotech, Celgene, Elan/Biogen, EnGene, Ferring Pharma, Roche/Genentech,
GiCare Pharma, Gilead, Given Imaging Inc., GSK, Ironwood Pharma,
Janssen Biotech (Centocor), JnJ/Janssen, Kyowa Kakko Kirin Co Ltd.,
Lexicon, Lilly, Merck, Millennium, Nektar, Novonordisk, Prometheus
Therapeutics and Diagnostics, Pfizer, Receptos, Salix Pharma, Serono, Shire,
Sigmoid Pharma, Synergy Pharma Inc., Takeda, Teva Pharma, Tillotts, UCB
Pharma, Vertex Pharma, Warner-Chilcott, Wyeth, Zealand, Zyngenia, W.
Sandborn Financial support for research from: Janssen, Consultancy for:
Janssen, D. Tarabar: None declared, Z. Hebzda: None declared, H. Weng
Other: Merck Employee, R. Yao Other: Merck Employee, H. Zhang Other:
Janssen Employee, C. Marano Other: Janssen Employee, R. Strauss Other:
Janssen Employee
TUESDAY, OCTOBER 21, 2014 14:0015:30
IBD: DYSPLASIA AND CANCER HALL I/K_____________________
OP209 RARITY OF ADENOMATOUS POLYPS IN ULCERATIVE
COLITIS: IMPLICATIONS FOR COLONIC CARCINOGENESIS
S. Ben-Horin1,*, Z. Izhaki1, O. Haj-Natur1, S. Segev1, R. Eliakim1, B. Avidan1
1
SHEBA MEDICAL CENTER, Tel-Hashomer, Israel
Contact E-mail Address: shomron.benhorin@gmail.com
INTRODUCTION: Despite ample research on dysplasia-carcinoma risk in
ulcerative colitis (UC) there are scant data on sporadic adenomas risk in this
population.
AIMS & METHODS: The aim of this study was to investigate the prevalence of
sporadic colon adenoma in UC patients in order to gain insight of possible role of
chronic immune-driven inflammation on adenoma development. For this pur-
pose, the number and histology of all polyps detected at colonoscopies of UC
patients during 2006-2012 were compared to controls undergoing screening colo-
noscopy. The analysis was deliberately restricted to patients who were over 50
years-old at the time of the index colonoscopy to reinforce the validity of the
comparison to screening colonoscopy controls. However, to exclude a potential
bais, an additional analysis was performed including all prior colonoscopies
undergone by the UC group. A third group comprising of Crohns disease
patients was also evaluated to dissect the role of colonic IBD versus ileal IBD
on sporadic adenoma rate.
RESULTS: 206 UC patients and 624 controls (mean age 61.78.7 versus
60.86.1, respectively, P0.15) were included. Adenomatous polyps were
detected in only 13/206 UC colonoscopies compared to 162/624 colonoscopies
United European Gastroenterology Journal 2(5S)
of controls (6.3% vs. 25.9% respectively, OR 0.19, 95%CI 0.1-0.34, p50.0001).
When also considering all prior colonoscopies performed over 7.74.6 years of
follow-up (mean 4.12.9 colonoscopies/patient, range 1-15, total 832 colonosco-
pies), the risk of ever finding an adenoma in UC patients was still significantly
lower compared to controls (14.1% vs.25.9% respectively, OR 0.47, 95%CI 0.3-
0.72, p0.0005). On multi-variate analysis, the incidence of adenomas was posi-
tively associated with advanced age (OR 1.07/year, 95%CI 1.04-1.09, P50.0001)
and with male gender (OR1.54, 95%CI 1.02-2.3, p0.04) and negatively asso-
ciated with having UC (OR 0.16, 95%CI 0.09-0.30, P50.0001). Among 115
Crohns patients 450 years old, the rate of ever-adenomas in Crohns ileitis
patients and controls was similar (p0.8), whereas patients with Crohns disease
involving the colon had significantly lower rate of adenomas compared to con-
trols (3.9% vs. 25.9%, p0.002).
CONCLUSION: Patients with UC or colonic Crohns disease seldom develop
sporadic adenomatous polyps. These data provide novel insight into possible
mechanisms restricting the adenoma-carcinoma sequence and suggest organ-spe-
cific immune activation may confer protection against development of colonic
adenomas.
Disclosure of Interest: S. Ben-Horin Consultancy for: Abbott, Janssen, Takeda &
Schering-Plough, Z. Izhaki: None declared, O. Haj-Natur: None declared, S.
Segev: None declared, R. Eliakim Consultancy for: Abbott, Janssen &
Schering-Plough, B. Avidan: None declared
OP210 CHARACTERIZATION OF INCIDENT CASES OF CANCER IN
INFLAMMATORY BOWEL DISEASE PATIENTS: RELATION WITH
IMMUNOMODULATORY TREATMENTS AND DISEASE
PHENOTYPE IN A PROSPECTIVE MULTICENTER MATCHED-PAIR
IG-IBD STUDY
L. Biancone1,*, G. Condino1, A. Armuzzi2, M.L. Scribano3, R. DInca`4, C. Papi5,
L. Spina6, L. Guidi2, A. Kohn3, E. Calabrese1, C. Petruzziello1, S. Onali1,
F. Mocciaro7, R. Monterubbianesi3, P. Alvisi8, W. Fries9, G. Riegler10,
F. Castiglione11, I. Frankovic4, G. Margagnoni5, G. Meucci12, F. Rogai13,
A. Orlando14, S. Ardizzone15, F. Pallone1
1
Systems Medicine, Universita` Tor Vergata, Rome, 2GI, CIC, Universita`
Cattolica, Roma, 33AO S. Camillo Forlanini, Roma, Rome, Rome, 4Universita`
Padova, Padova, Padova, 5UOC GE/Hep, AO S.Filippo Neri, Roma, Rome, Rome,
6
Universita` S. Donato, Milano, Milano, Milano, 7ARNAS Civico-DI Cristina
Benfratelli, Palermo, Palermo, Palermo, 88Osp. Maggiore Bologna, Bologna,
Bologna, 9Universita` Messina, Messina, Messina, 10SUN, Seconda Universita`,
Napoli, 11Universita` Federico II, Napoli, Napoli, Napoli, 12Ospedale S. Giuseppe,
Milano, Milano, Milano, 13AOU Careggi, Firenze, Firenze, Firenze, 14Ospedale
Cervello, Palermo, Palermo, Palermo, 15Universita` "Sacco", Milano, Milano, Italy
Contact E-mail Address: biancone@med.uniroma2.it
INTRODUCTION: Concern exists about cancer risk using thiopurines (IMM)
and/or anti-TNFs in Inflammatory Bowel Disease (IBD).
AIMS & METHODS: In a prospective, multicenter, case-control study, we
aimed to characterize incident cases of cancer in IBD. The role played by clinical
characteristics of IBD vs IMM and/or anti-TNFs use in determining the fre-
quency of cancer was also investigated. From Jan 2012 to April 2014, character-
istics of all incident cases of cancer in IBD patients (pts) referring to 15 centers
were recorded. In each center, each IBD pt developing cancer (IBD-K) was
matched with 2 IBD pts with no cancer (IBD-C) for: IBD type (CD/UC),
gender, age (5yrs). Data reported as median (range):chi-squared, Fisher
exact, Student t test, univariate analysis as appropriate.
RESULTS: The study included 106 IBD-K and 212 IBD-C. Cancer occurred in
106 IBD-K (54M, age 59 [16-85];2 cancers in 8 pts).The frequency of cancer was
higher in CD (CD-K)(n61;57%) vs UC (UC-K)(n45;43%; p0.03). IBD-C
included 212 pts (110M, age 57[15-83]). IBD duration was comparable between
IBD-K and IBD-C (yrs:12[1-54] vs 12.5[10-50]. Cancers included: GI tract
(n42;40%;colorectal, CCR 24%), genitourinary (n26;25%), skin (n9;8%),
lung (n9;8%), breast (n9;8%), hematologic cancers (n7;7%:5NHL/
1HL,5%;1 leukemia (0.9%), others (4%). Cancers involved: GI tract (n42; 18
CD/28UC; CCR n26: 7CD/19UC; ileal carcinoma 6CD/0UC), genitourinary
tract (n26:15CD/11UC; cervix 5CD/0UC), skin (n9; 6CD/3UC;CD:3 mela-
noma [2 noIMM/anti-TNFs;1 IMM], 3 NMSC [2IMManti-TNFs,1IMM]; UC:
1 melanoma,1 Kaposi [no IMM/anti-TNFs both];lung (n9;5CD/4UC), breast
(n9;6CD/3UC), lymphoma (n6; 5NHL/1HL, 6CD, 6M, [2 IMManti-TNFs,
1 IMM, 2 no IMM/anti-TNFs], others (n5). Cancer-related death: 10/106
(9.4%) pts. GI cancers were more frequent in UC (53%) vs CD (29%;
p0.02), lymphoma and ileal carcinoma in CD vs UC (9.8% vs 0%;
p0.03both). The frequency of any cancer was higher in pancolitis (59%) vs
distal (30%; p0.01), subtotal UC (11%; p0.0001), with no differences between
stricturing, fistulizing, inflammatory CD (39% vs 27% vs 34%; pns). IMM and
anti-TNFs were used in a comparable proportion of IBD-K and IBD-C pts
(IMM 39% vs 45%; Anti-TNFs 28% vs 35%;pns both).
CONCLUSION: In a prospective multicenter match-pair study, incident cases of
cancer were more frequent in CD vs UC, with a high frequency of GI and
genitourinary cancers in IBD. CCR was more frequent in UC, lymphoma and
ileal carcinoma in CD. CD phenotype and UC extent may influence the fre-
quency of any cancer, while IMM and/or anti-TNFs the frequency of specific
cancer histotypes (lymphoma, skin cancer).
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP211 SERRATED POLYPS IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASE (IBD): ENDOSCOPIC CHARACTERISTICS
DIFFER FROM SERRATED POLYPS IN NO-IBD POPULATION
D. Moussata1,*, G. Boschetti2, M. Chauvenet3, K. Stroeymeyt3, S. Boyer3,
S. Nancey3, F. Berger4, B. Flourie3
1 Groups
Lyon Sud Hospital, Pierre Benite, 2Gastroenterology, Lyon Sud Hospital, Lyon,
3
Gastroenterology, 4Pathology, Lyon Sud Hospital, Pierre Benite, France
Contact E-mail Address: driffa.moussata@chu-lyon.fr
INTRODUCTION: Serrated polyps (SP) include hyperplastic polyp (HP), sessile
serrated adenoma (SSA) and traditionnal serrated adenoma (TSA). Endoscopic
characteristics of these lesions are well-known in general population, but whether
they have specific aspect in patients with inflammatory bowel disease (IBD) is
unknown.
AIMS & METHODS: To compare endoscopic characteristics of SP between
IBD and non-IBD patients. Prospectively, 229 patients were included. A chro-
moendoscopy with indigo carmin (0.2%) was performed (H180, Olympus,
Japan) under sedation. All the lesions were described according to Paris classi-
fication; the size (mm), localization and histology were reported.
RESULTS: 154 IBD patients (77 men, 53  13.5 yrs, mean  SD) and 75 non-
IBD patients (38 men, 58  15 yrs) were included. We detailed for each group the
characteristics of HP and SSA polyps which are summarized on table1. No
patient presented TSA. A total of 349 SP were detected by chromoendoscopy:
195 in 56% (42/75) of patients in non-IBD and 154 in 13.6% (21/154) of IBD
patients. Among patients with SP, the HP polyps were more frequent in non-IBD
group (26/42, 62% vs 11/21, 52.3%, NS) and presented the same macroscopic
aspect (IIa) in the 2 populations. Whereas, among patients with SP, SSA tended
to be more frequent in IBD patients (10/21, 47.6% vs 16/42, 38%, NS) and
presented more often dysplasia than in non-IBD patients (6/21, 28.6% vs 8/42,
19%, p50.05). Their macroscopic aspect was different with IIb of Paris classi-
fication in IBD patients. In IBD patients, SSA tended to be larger (10.3 /- 12.7
vs 4.7 /- 2.1 mm, p50.01). In IBD group, SSA were localized all along the
colon, whereas in non-IBD the SSA were preferentially localized in the right
colon.
Nb of pts with SP Non-IBD (42/75, 56%)IBD (21/154, 13.6%)p
Total nb of SP lesions 195 154 - Hospital, APHP, Paris, 11Rennes University and Hospital, Rennes, 12Institut
Nb of pts with HP 26 (26/42, 62%) 11 (11/21, 52.4%) NS
Nb of pts with SSA 16 (16/42, 38%) 10 (10/21, 47.6%) NS
Nb pts with SSA with dysplasia8 (8/42, 19%) 6 (6/21, 28.6%) 50.05
Total nb of SSA 37 (37/195, 19%) 37 (37/154, 24%) NS
Total nb of SSA with dysplasia 13 (13/37, 35%) 14 (14/37, 37.8%) NS
Mean size of SSA 4.7 /- 2.1 10.3 /- 12.7 50.01 surgical resection because of the fear of associated dysplasia/cancer. The risk of
Paris classification of SSA 25 IIa, 12 Is 23 IIa, 10 IIb, 4 Is -
Localization of SSA 24 RC, 13LC 20 RC, 17 LC - colitis (UC) and Crohns disease (CD) is unknown.
CONCLUSION: In IBD patients, the size, Paris classification and localization of
serrated polyps differ from those of non-IBD patients. IBD patients presented
more often SSA with dysplasia, suggesting that SSA could be involved in cancer
pathway. This hypothesis has to be verified by following prospectively the cohort
of IBD patients.
Disclosure of Interest: None declared
OP212 INVESTIGATION OF DIFFERENTIALLY EXPRESSED
MICRORNAS IN COLITIS ASSOCIATED DYSPLASIA AND
ADENOCARCINOMA
M. Patel1,2,*, M., I. Aslam1,2, A.M. Verma1,2, K. West2, J. Jameson2,
J.H. Pringle1, B. Singh2
1
Cancer Studies & Molecular Medicine, University of Leicester, 2University
Hospitals of Leicester, Leicester, United Kingdom
Contact E-mail Address: maleene@doctors.org.uk
INTRODUCTION: A number of recent studies have identified microRNA
(miRNA) expression profiles associated with Ulcerative Colitis (UC). Our
study aimed to discover miRNAs related to disease progression in order to
identify dysplasia and colitis associated cancer (CAC) in patients with UC.
AIMS & METHODS: Total RNA was extracted from archived paraffin
embedded tissue and allocated to 4 discovery groups: UC (n4), CAC (n4), high-grade dysplasia in one patient (0.4%) and cancer in 2 patients (0.8%). In
low grade dysplasia (n4) and high grade dysplasia (n4). MiRNA expression
profiling was performed using Applied TaqMan human miRNA array cards
v2.0. Quantitative RT-PCR using individual miRNA assays was subsequently
used to validate the results in a further independent cohort: normal (n21), UC
(n 22), Dysplasia (n7) and CAC (n12). CONCLUSION: In this cohort of 293 IBD patients undergoing intestinal resec-
RESULTS: Intergroup comparison of the initial array data identified a progres-
sive increase in the differential expression levels of miR-10b, 18a, and 32 from
dysplasia to CAC.
The validation cohort showed a significant differential expression of miR-18a, 21
and 135b (table 1.0).
A69
Table to abstract OP212
MiR-18a MiR-21 MiR-135b
Combined Tissue Fold Fold Fold
P Value Change P Value Change P Value Change
Normal vs. UC 0.092 2.8 0.0358* 1.4 5 0.0001* 6.6
Normal vs. CAC and Dysplasia 5 0.0001* 6.4 5 0.0001* 3.9 5 0.0001* 11.4
UC vs. CAC and Dysplasia 0.022* 3.6 0.0002* 2.4 0.0008* 4.8
Table 1.0: MiR expression in different tissue groups.
Furthermore mir-31 appeared to be increased in the acute phase of UC and
combining selected miRNA profiles (mir18a and 21) showed significant variance
(p50.05).
CONCLUSION: Several miRNAs were increased in dysplastic and CAC tissues
and may contribute to pathological processes, such as dysregulation of apoptosis
and impairment of epithelial barrier dysfunction. Further investigation of these
miRNAs may enable clinicians to monitor disease progression in patients with
UC and distinguish those at increased risk of developing CAC.
Disclosure of Interest: None declared
OP213 RISK OF DYSPLASIA AND CANCER COMPLICATING
COLONIC STRICTURES IN INFLAMMATORY BOWEL DISEASE: A
GETAID STUDY
M. Fumery1,*, G. Pineton de Chambrun2, C. Stefanescu3, A. Buisson4,
A. Bressenot5, L. Beaugerie6, A. Amiot7, R. Altwegg8, G. Savoye9, V. Abitbol10,
G. Bouguen11, M. Simon12, J.-P. Duffas13, X. Hebuterne14, S. Nancey15,
X. Roblin16, J. Lefevre6, J.-P. Le Mouel1, J. Moreau13, Y. Bouhnik3, L. Peyrin-
Biroulet5 on behalf of GETAID
1
Amiens University and Hospital, Amiens, 2Lille University and Hospital, lille,
3
Beaujon Hospital, APHP, Clichy, 4Clermont-Ferrand Hospital and University,
Cmernont Ferrand, 5Nancy University and Hospital, Nancy, 6Saint Antoine
Hospital, APHP, Paris, 7Creteil Hospital, APHP, Creteil, 8Montpellier University
and Hospital, Montpellier, 9Rouen Hospital and University, Rouen, 10Cochin
Mutualiste MontSouris, Paris, 13Toulouse University and hospital, Toulouse,
14
Nice University and Hospital, Nice, 15Lyon University and Hospital, Lyon, 16St
Etienne University and Hospital, St Etienne, France
Contact E-mail Address: mathurinfumery@gmail.com
INTRODUCTION: Management of colonic strictures complicating inflamma-
tory bowel disease (IBD) is a challenge in clinical practice and leads frequently to
intestinal dysplasia or cancer complicating colonic strictures in both ulcerative
AIMS & METHODS: We aimed to determine the frequency of dysplasia and
cancer among adult patients with IBD undergoing intestinal resection for a color-
ectal stricture without dysplasia or cancer known at the time of surgery. The
GETAID conducted a nationwide retrospective study. Only centers having a
database of all consecutive IBD patients who underwent intestinal resection
for IBD during a given period could participate in this study. All patients with
preoperative evidence of dysplasia/cancer were excluded. Demographical, clini-
cal, endoscopic, surgical, and histopathological data and outcomes were
collected.
RESULTS: Among 12 013 IBD patients operated for IBD in 16 GETAID cen-
ters between August 1992 and January 2014, we identified 293 patients operated
for a colonic stricture, including 248 CD, 39 UC and 6 IBD unclassified. 51%
were males and the median age at stricture diagnosis was 38 years (Q125-
Q351). All patients underwent preoperative colonoscopy. The stricture was
not passable in 66% of cases. The median disease duration at stricture diagnosis
was 8 (3-14) years. Strictures presented a median length of 6 cm (4-10), and were
symptomatic in 73% of patients. They were located in the right colon, transverse,
or left or rectal in respectively 16%, 14%, 64% and 6% of CD patients, and
respectively 6%, 13%, 62% and 19% in UC. The median stricture duration
before surgery was 6.3 (1.6-20) months in CD and 3 (0.6-9.6) months in UC.
Surgical procedure was segmental, subtotal colectomy and coloprotectomy in
respectively 79%, 19% and 10% of CD patients and in respectively 18%, 28%
and 54% in UC. In CD, low-grade dysplasia was observed in 3 patients (1%),
UC, cancer was observed in 2 (5%) patients, high-grade dysplasia in 1 (2%) and
low-grade dysplasia in 1 patient (2%). The median follow-up after strictures
resection was 4.3 years (1.4-8.1). All patients with dysplasia or cancer received
a curative surgery, but one patient died of colorectal cancer.
tion for colonic stricture, dysplasia or cancer were observed in 3% of cases. These
findings should be taken into account to guide decision in IBD patients with
colonic strictures in clinical practice.
Disclosure of Interest: None declared
A70
OP214 FORTY-YEARS OF ULCERATIVE COLITIS SURVEILLANCE
FOR COLORECTAL CANCER: PREVALENCE OF MULTIFOCAL
NEOPLASIA AND INTERVAL CANCER, TIME TREND IN CANCER
RISK, AND THE NATURAL HISTORY OF PROGRESSION OF EACH
GRADE OF DYSPLASIA
C. H. R. Choi1,*, M. Rutter2, A. Askari1, J. Warusavitarne1, M. Moorghen1,
S. Thomas-Gibson1, B. Saunders1, T. Graham3, A.L. Hart1
1
Academic Institute, St. Marks Hospital, London, 2Gastroenterology, University
Hospital of North Tees, Stockton on Tees, 3Tumour biology, Barts Cancer
Institute, Queen Mary University of London, London, United Kingdom
Contact E-mail Address: pacoblue@gmail.com
INTRODUCTION: The prevalence of multifocal neoplasia and interval cancer
in patients with ulcerative colitis (UC) is unclear. Furthermore, there is a con-
tinuing debate on the change in colorectal cancer (CRC) incidence over time and
the risk of progression from each grade of dysplasia to CRC. This study reports
on data collected from patients with extensive UC between 1971 and 2012 at a
large tertiary center in the UK, with an aim to answer these important questions.
AIMS & METHODS: A retrospective analysis of UC patients enrolled in long-
term surveillance was performed. Data were obtained from medical records,
surgical, endoscopy and histology reports. The primary end point was defined
as death, colectomy, withdrawal from surveillance, or the census date (January 1,
2013). Raised dysplastic lesions arising within a diseased segment were classified
as sporadic adenoma or UC-associated dysplasia according to the clinical con-
sensus made at the time of diagnosis. Cox proportional hazards models and
Kaplan-Meier curves were generated to assess the risk of cancer progression.
RESULTS: A total of 1,375 patients underwent 8,650 colonoscopies (median, 5
per patient; interquartile range (IQR), 3 8 per patient) during 16,037 patient-
years of follow-up (median, 11 years; IQR, 7 17 years). Colorectal cancer was
detected in 72 patients (5% of study population). The rate of interval cancer was
23.8%. Out of 64 CRCs where a surgical specimen was available, 24 (37.5%) had
synchronous cancers or a spatially distinct focus of dysplasia. The cumulative
incidence of CRC by disease duration was 0.07% at 10 years, 2.9% at 20 years,
6.7% at 30 years and 10% at 40 years. Linear regression revealed no significant
change in the overall incidence of CRC during the four decades of the surveil-
lance program (R -0.13; p0.42). However, there was a significant reduction in
incidence of colectomy performed for dysplasia or CRC over time (R -0.43;
p0.007). The risk of developing CRC for each type of neoplasia compared with
patients with no neoplasia was: sporadic adenoma (hazard ratio (HR), 0.50; 95%
confidence interval (CI), 0.15 1.64; p0.25), indefinite for dysplasia (HR, 6.1;
95% CI, 1.721.5; p0.005), low-grade dysplasia (HR, 7.8; 95% CI 2.425.7; permeability has previously been studied in small IBS populations, but findings
p50.001), and high-grade dysplasia (HR, 33.1; 95% CI, 9.7112.9; p50.001).
There was no significant difference in the risk of CRC between indefinite for
dysplasia and low-grade dysplasia group (log-rank; p0.786).
CONCLUSION: The overall risk of CRC was considerably lower than pre-
viously reported. However, there was no significant change in CRC incidence
over time. Multifocal neoplasia and interval cancer was common, highlighting
the importance of careful inspection with advanced imaging technologies to
ensure lesions are not missed. High-grade dysplasia is a strong indication for
colectomy. Indefinite for dysplasia may have a similar risk of CRC compared
with low-grade dysplasia and the differential patient management decisions
should not be made solely on the histological finding.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 14:0015:30
NORMAL AND ABNORMAL CROSS-TALK AT THE MUCOSAL BORDER: RELEVANCE
FOR GI FUNCTION AND DYSFUNCTION HALL L/M_____________________
OP215 ANTIBIOTIC INDUCED DYSBIOSIS AND CORRECTIVE
IMPACT OF SACCHAROMYCES BOULARDII IN HEALTHY
VOLUNTEERS
C.P. Kelly1,2,*, T.A. Kabbani1, K. Pallav1, J.A. Villafuerte-Galvez 1,
R.R. Vanga1, N. Castillo1
1
Gastroenterology, Medicine, Harvard Medical School, 2Gastroenterology,
Medicine, Beth Israel Deaconess Medical Center, Boston, United States
Contact E-mail Address: ckelly2@bidmc.harvard.edu
INTRODUCTION: Interactions between the microbial flora of the intestine and
the human host play a critical role in maintaining intestinal health and in the
pathophysiology of a wide variety of disorders including antibiotic associated
diarrhea, Clostridium difficile infection and inflammatory bowel disease.
Antibiotics disrupt the normal intestinal microflora whereas probiotics, such as
Saccharomyces boulardii, have the potential to reduce these harmful effects and
to restore a more healthy and balanced intestinal microbiota.
AIMS & METHODS: The aim of this study was to evaluate the effects of an
antibiotic (Amoxicillin/Clavulanate), a probiotic (Saccharomyces boulardii),
Florastor) and the combination on the microbiota of healthy adult volunteers.
Healthy subjects were randomized to one of four study groups (n12 for each):
1) S. boulardii (SB), 500 mg twice daily for 14 days, 2) Amoxicillin/Clavulanate
(AC), 875/125 mg twice daily for 7 days, 3) Amoxicillin/Clavulanate plus S.
boulardii (each dosed as above), 4) Control (no treatment).
Seven stool samples were collected from subjects in the active groups (groups 1, 2
& 3) and 3 stool samples from controls. Gastrointestinal symptom questionnaires
were also completed by the participants. 16S rRNA gene pyrosequencing was
used to identify the predominant bacterial genera in stool samples and to monitor
changes in the microbiota in each study group.
RESULTS: Subjects showed a complex microbiome at study entry that appeared
to segregate into groupings or enterotypes as previously described. Antibiotic
treatment (AC group) was associated with marked microbiome changes and
these persisted for some time after treatment ended. Antibiotic treatment led to
United European Gastroenterology Journal 2(5S)
a markedly reduced prevalence of the genus Ralstonia and parallel increases in
Parabacteroides and Escherichia / Shigella. S. boulardii treatment alone did not
substantially modify the microbiome. However, when S. boulardii was adminis-
tered in combination with Amoxicillin/Clavulanate the antibiotic-induced
changes in the genera Ralstonia, Parabacteroides and Escherichia / Shigella
were significantly attenuated (P50.05 for each). Diarrhea scores (measured
using the Gastrointestinal Symptom Response Score (GSRS)) increased during
antibiotic treatment in parallel with increases in the prevalence of Escherichia /
Shigella in the stool (R2 0.9993 by Linear regression, P50.001). S. boulardii
treatment in combination with the antibiotic prevented the increase in
Escherichia/shigella prevalence and also prevented antibiotic associated diarrhea
(P50.05 for each).
CONCLUSION: The microbiomes of healthy individuals show substantial diver-
sity but remain stable over time. Antibiotic treatment is associated with marked
microbiome changes with both reductions (Ralstonia) and increases
(Parabacteroides, Escherichia / Shigella) in different genera. S. boulardii treat-
ment can prevent some antibiotic-induced microbiome changes and, in parallel,
can reduce antibiotic associated diarrhea. Future studies are warranted to
explore whether the strong correlation between an increased prevalence of
Escherichia / Shigella and increased symptom scores for antibiotic associated
diarrhea represent a cause and effect association that is positively influenced
by S. boulardii.
Disclosure of Interest: C. Kelly Financial support for research from: Biocodex
Inc, Other: Travel support, T. Kabbani Other: Travel support, K. Pallav: None
declared, J. Villafuerte-Galvez: None declared, R. Vanga: None declared, N.
Castillo: None declared
OP216 GUT PERMEABILITY IN IBS IS SITE SPECIFIC, SUBTYPE
DEPENDENT AND AFFECTED BY CONFOUNDING FACTORS
Z. Mujagic1,*, S. Ludidi1, D. Keszthelyi1, M.A. Hesselink1, J.W. Kruimel1,
K. Lenaerts2, N.M. Hanssen3, J.M. Conchillo1, D.M. Jonkers1, A.A. Masclee1
1
Division Gastroenterology-Hepatology, Department of Internal Medicine -
NUTRIM School for Nutrition, Toxicology and Metabolism, 2Department of
Surgery - NUTRIM School for Nutrition, Toxicology and Metabolism,
3
Department of Internal Medicine - CARIM School for Cardiovascular Diseases,
Maastricht University Medical Center, Maastricht, Netherlands
INTRODUCTION: Altered intestinal barrier function is one of the assumed
pathophysiological mechanisms of irritable bowel syndrome (IBS). Intestinal
were contrasting and difficult to compare due to differences in methodology.
AIMS & METHODS: Objectives of the present study were 1) to assess intestinal
permeability at different sites of the GI tract, in a large group well characterised
IBS patients and healthy controls (HC) and investigate differences between sub-
types, and 2) to assess potential confounding effects of multiple patient-related
factors.
IBS patients (all according to ROME III criteria) and HC of a large IBS cohort
underwent a validated multi-sugar test to assess intestinal permeability on four
sites of the GI tract. Sucrose excretion and the lactulose/rhamnose (L/R) ratio in
0-5 h urine indicated gastroduodenal and small intestinal permeability, respec-
tively. Sucralose/erythritol (S/E) ratio in 0-24 and 5-24 h urine was used as
indicators of whole gut and colonic permeability, respectively. Linear regression
analysis was used to assess the association between IBS and IBS subtypes and
intestinal permeability and to adjust for possible confounding factors, i.e. demo-
graphics (age, sex, BMI), psychological symptoms (anxiety or depression), life-
style factors (smoking history, (defined as current or previous smoker) and
alcohol intake of 415 units/week), and use of medication in the 2 weeks prior
to inclusion (NSAID, PPI, SSRI and medication that affects motility).
RESULTS: 91 IBS patients, i.e. 37% diarrhoea predominant (IBS-D), 23%
constipation predominant (IBS-C), 33% with mixed (IBS-M) and 7% with
unspecified stool pattern (IBS-U), and 94 HC were enrolled. Sucrose excretion
was significantly increased in the total IBS group versus HC (median [Q1; Q3] in
mmol: 5.26 [1.82; 11.03] vs. 2.44 [0.91; 5.85], p50.05), as well as in IBS-C (7.40
[2.37; 18.29], p50.01) and IBS-D (4.22 [2.12; 8.03], p50.05) versus HC.
However, the differences attenuated when adjusting for confounders. Factors
with significant confounding effects were higher BMI, smoking history and use
of drugs that positively affect motility.
Furthermore, the L/R ratio was increased in IBS-D patients compared to HC
(0.023 [0.013; 0.038] vs. 0.014 [0.008; 0.025], p50.05), which remained significant
after adjustment for confounders.
There was no significant difference between groups in 0-24 and 5-24 hour S/E
ratio.
CONCLUSION: Small intestinal, but not gastroduodenal, colonic and whole gut
permeability is increased in patients with IBS-D when compared to HC, irrespec-
tive of possible confounding factors. Adjustment for possible confounders is
necessary when studying intestinal permeability, especially in a heterogeneous
disorder as IBS.
Disclosure of Interest: Z. Mujagic: None declared, S. Ludidi: None declared, D.
Keszthelyi: None declared, M. Hesselink: None declared, J. Kruimel: None
declared, K. Lenaerts: None declared, N. Hanssen: None declared, J.
Conchillo: None declared, D. Jonkers: None declared, A. Masclee Consultancy
for: Pentax medical, Grunenthal GmbH, Ferring
United European Gastroenterology Journal 2(5S)
TUESDAY, OCTOBER 21, 2014 14:0015:30
UPDATE ON CAPSULE ENDOSCOPY HALL N_____________________
OP217 THE USE OF SMALL BOWEL CAPSULE ENDOSCOPY IN THE
INVESTIGATION OF IRON DEFICIENCY ANAEMIA. ADHERENCE
TO BSG GUIDELINES AND IMPACT ON DIAGNOSTIC YIELD
G.H. Bain1,*, V. F. P. Ritchie1, S.S. Salunke1, J.M. Thomson1
1
NHS GRAMPIAN, Aberdeen, United Kingdom
Contact E-mail Address: gillianbain@nhs.net
INTRODUCTION: Iron deficiency anaemia (IDA) occurs in 2-5% of adult men
(M) and postmenopausal women (F) in the developed world1 and is a common
reason for referral to Gastroenterology2. Small bowel (SB) capsule endoscopy
(CE) has revolutionised investigation of SB disorders. British Society of
Gastroenterology (BSG) guidelines suggest considering CE if the Haemoglobin
(Hb) cannot be restored or maintained with iron therapy3. The few studies exam-
ining diagnostic yield (DY) of CE in IDA alone have demonstrated a wide
variability in positive findings (30%5-71%6).
AIMS & METHODS: To determine if use of CE in IDA adhered to BSG guide-
lines, and the effect of adherence to guidelines on DY. A retrospective audit of
CEs performed in our institution over 5 years from 2009-2013 was performed. All
patients with the indication of IDA were identified and their CE reports exam-
ined. Data were collected on blood indices from the laboratory system. IDA was
defined, according to local laboratory indices, as: Hb in M of 5140g/l (if
570yrs) or 5116g/l (if 70yrs) and in F of 5120g/l (570yrs) or 5108g/l
(70yrs), along with a serum ferritin in M of 520mg/l and in F of 57mg/l
(550yrs) or 510mg/l (50yrs).
RESULTS: From 2009-2013, 391 CEs were performed. 131 (33.5%) had IDA as
the recorded indication. Following review, 22 were excluded (5 as indication was
overt bleeding, 7 no CE report, 10 no blood results available). 10 were incomplete
(poor bowel prep): 6 were not repeated and therefore excluded, 4 were repeated
and the incomplete study excluded. Therefore a total of 99 patients were included
in the study. The capsule was retained at a stricture in 4 patients- these patients
were included. Retention was confirmed with abdominal x-ray at 2 weeks in 2
patients (2%). Combined with the incomplete studies, this gives a completion rate
of 87.2%.
The number of CE performed per year for IDA increased over the study period.
The mean age was 60 (17-90) of which 46.5% (n46) were M and 53.5% (n53)
were F.
In 71.7% (n71) CE was performed according to BSG guidelines: 38.4% (n38)
Hb not restored with iron therapy and 33.3% (n33) Hb restored but not main-
tained. In the remaining 28.3% (n28) CE was performed out with BSG guide-
lines: 14.1% (n14) Hb restored and maintained, 7.1% (n7) Hb checked once
and was restored but not checked again to determine if maintained and in 8.1%
(n8) no bloods were checked after initial blood tests before CE.
46 studies had positive SB findings giving a DY of 46.5%. Findings were angio-
dysplasia 23.2% (n23), inflammation/ulceration/stricture 15.2% (n15), angio-
dysplasia and inflammation 3% (n3), active bleeding 2% (n2), polyp/mass
2% (n2) and blunted villi 1% (n1). In addition to this, 12 studies had sig-
nificant findings outside the SB giving a DY of 12.1% and an overall DY of
58.6%.
Overall DY was higher when CE was performed in accordance with BSG guide-
lines [64.8% (46/71) versus 42.9% (12/28) (p0.07)].
CONCLUSION: Adherence to BSG guidelines for use of CE in IDA was 71.7%.
Overall DY was high at 58.6% but improved to 64.8% when guidelines were
adhered to.
REFERENCES
1. WHO. 2008.
2McIntyre and Long. 1993.
3. SG. 2011.
4Koulaouzidas, et al. 2012.
5Holleran, et al. 2013.
Disclosure of Interest: None declared
OP218 SMALL BOWEL CAPSULE ENDOSCOPY IN CLINICAL
PRACTICE: PROSPECTIVE DATA FROM A REGIONAL REGISTRY
2011-2013 (REGISTRO LOMBARDO DELLE COMPLICANZE)
M. Soncini1, E. Rondonotti2,*, C.M. Girelli3, A. Russo4, D. Moneghini5, L. Elli6,
R. Schalling7, M. Maino8, P. Cesari9, N. Mantovani10, D. Conte6, R. de
Franchis11 on behalf of AIGO, SIED and, SIGE Lombardia
1
Gastroenterology, A.O. San Carlo Borromeo Milano, Milano, 2Gastroenterology,
Valduce Hospital, Como, 3Internal Medicine, A.O. Busto Arsizio, Varese,
4
Epidemiology, ASL Milano1, Milano, 5Gastroenterology, A.O. Spedali Civili
Brescia, Brescia, 6Gastroenterology, IRCCS Policlinico Milano, Milano, 7Internal
Medicine, A.O. Vimercate, Monza-Brianza, 8Gastroenterology, A.O. Sa Gerardo,
Monza, 9Gastroenterology, Congregazione Ancelle della carita`, Brescia,
10
Gastroenterology, A.O. Poma, Mantova, 11Gastroenterology, A.O. L. Sacco,
Milano, Italy
Contact E-mail Address: soncini.marco@sancarlo.mi.it
INTRODUCTION: Data on small bowel capsule endoscopy (SBCE) mostly
come from retrospective studies
AIMS & METHODS: The primary outcome was to prospectively describe the
extent of use, indications, results, complications, and practical issues of SBCE in
clinical practice. The secondary outcome was to compare the distribution of the
VCE in the different districts of the region.All the 32 centers performing capsule
endoscopy in Lombardia region were invited and agreed to participate in the data
collection. In January 2011 a dedicated registry has been set up to collect data on
diagnostic yield, practical issues and complications for each performed proce-
dure. Each center was asked to update the registry every three months.
A71
RESULTS: Between January 2011 and December 2013, 93.7% (30/32) centers
accessed the registry, recording 3191 procedures. The main indications for SBCE
were: obscure gastrointestinal bleeding (OGIB) / unexplained anemia 76.1%,
suspected Crohns disease 4.5%, known Crohns disease 1.0%, chronic diarrhea
3,0%, suspected small bowel tumor 1.5%, others 13.9%. Overall, SBCE was
positive in 48.2 % of patients, negative in 41.8% and undefined in 10.0%. In
37.0% of the cases SBCE was performed as an inpatient procedure, 61.9% as an
outpatient procedure and in 1.1% in a day hospital setting. Patients who
performed the VCE as outpatients were younger: mean 60.217.2 vs.
65.917.3 yrs respectively (p50.001), whereas there was no difference for
gender, indications, results and prescriber. 86.7% of patients were evaluated
directly by the physician at his own medical center before performing the
VCE, 10 .7% came from other hospitals and only 2.6% directly from the general
practitioner. Of 3191 patients, 27 (0.84%) experienced capsule complications; 18
(0.56%) of them required endoscopic or surgical retrieval. Acute obstruction
occurred in 5 (0.15%) patients. The distribution of the centers and activity of
VCE is however not homogeneous in 11 district of Lombardia.
CONCLUSION: Our prospective data confirm that OGIB is still the leading
indication for SBCE. VCE is a safe outpatient procedure, usually performed
by local district hospitals. Its distribution among the regional district is however
not homogeneous.
Disclosure of Interest: None declared
OP219 IRON DEFICIENCY ANEMIA DESPITE EFFECTIVE GLUTEN-
FREE DIET IN CELIAC DISEASE: DIAGNOSTIC ROLE OF VIDEO-
CAPSULE ENDOSCOPY
K. Efthymakis1,*, A. Milano1, F. Laterza1, M. Serio1, M. Neri1
1
Department of Medicine and Ageing Sciences, "G. DAnnunzio" University and
Foundation, Section of Internal Medicine and Center for Excellence on Ageing
(Ce.S.I.), Chieti, Italy
Contact E-mail Address: mneri@unich.it
INTRODUCTION: Iron deficiency anemia (IDA) is frequently associated with
celiac disease (CD). Although gluten free diet (GFD) and adequate oral or
parenteral iron supplementation is an efficient treatment for IDA, iron deficiency
remains a relatively frequent finding during follow-up and it is usually correlated
to both clinical and serological lack of response to GFD. Little is known on
patients with persistent IDA despite effective GFD treatment, a finding observed
in approximately 8% of patients[1].
AIMS & METHODS: To evaluate the role of video-capsule endoscopy (VCE) in
CD patients with IDA non-responsive to adequate GFD.
We evaluated consecutive patients affected by CD undergoing GFD for at least
24 months with persistent concomitant IDA. All patients were assessed for IgG
and IgA transglutaminase (t-TG) and endomysium (EMA) antibodies and, if
negative, underwent complete endoscopic evaluation.
RESULTS: We evaluated 32 consecutive female patients (mean age 43.18.9
years) on GFD for a mean of 6.24.9 years and concomitant IDA with negative
antibody work-up. Six were excluded for gynecological disorders or major recent
surgery. None of the patients presented signs of overt gastrointestinal bleeding.
Twenty six patients were eventually included in the study and underwent gastro-
scopy, colonoscopy and VCE. Altogether, eleven patients resulted positive at
endoscopy. Gastroscopy showed mucosal lesions potentially causing anemia in
seven (27%): erosive duodenitis (n1), active CD (n3), erosive gastritis (n2),
esophagitis (n1). Colonoscopy showed only 2 potentially associated finding
(hemorrhoids). At VCE we documented small bowel involvement in 6 cases
(23%): 3 erosive jejunitis (1 eventually diagnosed as refractory CD, 2 Crohns
disease), 2 jejunal teleangectasias, 1 diffuse jejunal lymphangectasia. Some over-
lap was observed between endoscopic procedures since in four subjects EGDS
and VCE produced significant findings. However, in three cases VCE was suc-
cessful in unraveling a more severe/extensive disease that could not have been
picked up or correctly assessed by gastroscopy. Low albumin levels were signifi-
cantly associated with a positive outcome at VCE in celiac disease (p50.009). No
correlation was found for vitamin B12, vitamin D, folate, or transferrin serum
levels.
CONCLUSION: VCE allows the identification of significant clinical findings in
approximately 23% of CD patients with IDA despite adequate GFD. These are
associated to hypoalbuminemia, indicating their occurrence at more severe stages
of the disease.
REFERENCES
[1]Rubio-Tapia A, et al. Am J Gastroenterol 2013.
Disclosure of Interest: None declared
OP220 BULGES ON SMALL BOWEL CAPSULE ENDOSCOPY:
INNOCENT LESIONS WE SHOULD TAKE WITH A PINCH OF SPICE
G. Hatem1,*, A. Buda2, R. Caccaro1, A. Ugoni1, R. DInca`1, M. De Bona2,
M. De Boni2, F. Galeazzi1, A. DOdorico1, E., V. Savarino1, G.C. Sturniolo1
1
Department of Surgery, Oncology and Gastroenterology, University of Padova,
Padova, 2Department of Oncology, Gastroenterology Unit, S. Maria del Prato
Hospital, Feltre, Italy
Contact E-mail Address: giorgia.hatem@gmail.com
INTRODUCTION: A drawback of Small Bowel Capsule Endoscopy (SBCE) is
represented by the difficulty to distinguish submucosal masses from innocent
bulges, in particular when alarm signs are lacking (e.g. bleeding, irregular surface,
polyp-like appearance). A correct interpretation of the endoscopic images is
necessary in order to avoid patients unnecessary investigations.
AIMS & METHODS: Aims of our study were 1. to evaluate prospectively the
prevalence of bulges on SBCE and 2. to discriminate innocent bulges from sub-
mucosal tumours with a previous validate score (SPICEa) in a large cohort of
A72
patients referred to a teaching hospital. Consecutive patients undergoing SBCE
from January 2010 to December 2013 were considered eligible. All SBCE data
were analysed by expert readers (4 200 SBCE analysed). Patients with a pro-
truding lesion as the main finding of SBCE were included and the SPICE score
applied. All these patients were either investigated by Computed Tomography
Enterography or Magnetic Resonance Enterography and clinically followed-up
in the long period.
RESULTS: 640 consecutive patients (male/female 330/310, median age 55)
underwent SBCE between January 2010 and December 2013. Patients had a
median follow-up period of 26 monthes (range 4-48). 30 patients (4.7%)
showed at least one bulging area without alarm signs. Out of them three patients
(10%) had a SPICE score 4 2 and in 2 a neoplastic lesion was diagnosed (1
carcinoid and 1 ovarian cancer). Among the 27 patients with a SPICE score 5 2,
seven (26%) had peritoneal adhesions whereas in 20 (74%) all investigations
showed normal findings.
CONCLUSION: Bulges represent a rare finding (4.7%) when SBCE is evaluated
by experienced physicians. SPICE score can predict the presence of malignant
lesion and identify low risk patients in whom further invasive investigations can
be avoided. Indeed, in our large cohort 2/3 of suspected lesions were eventually
diagnosed as innocent bulges.
REFERENCES
Girelli CM et al. Gastrointestinal Endoscopy 2011; 74: 1067-1074.
Disclosure of Interest: None declared
OP221 CORRELATION BETWEEN FAECAL CALPROTECTIN AND
LEWIS SCORE IN SMALL-BOWEL CAPSULE ENDOSCOPY; A
MULTICENTRE STUDY
A. Koulaouzidis1,*, T. Sipponen2, E. Toth3, R. Makins4, U. Kopylov5,
L. Bartzis1, A. Nemeth3, G. Wurm Johansson3, M. Nadler 6, A. Eliakim6,
E.G. Seidman5, J.N. Plevris1
1
Centre for Liver & Digestive Disorders, The Royal Infirmary of Edinburgh,
Edinburgh, United Kingdom, 2Clinic of Gastroenterology, Department of Medicine,
Helsinki University Central Hospital, Helsinki, Finland, 3Department of
Gastroenterology, Skane University Hospital, Malmo, Sweden, 4Gastroenterology
Department, Cheltenham General Hospital, Gloucestershire Hospitals NHS
Foundation Trust, Cheltenham, United Kingdom, 5Division of Gastroenterology,
McGill University Health Center, Montreal, Canada, 6Department of
Gastroenterology, Chaim Sheba Medical Center, Tel Hashomer, Israel
INTRODUCTION: Faecal calprotectin (FC) remains an invaluable, non-inva-
sive biomarker of gut inflammation. Small-bowel capsule endoscopy (SBCE) is a
prime imaging modality for the small-bowel. The Lewis score (LS) has been
developed to standardize inflammation reporting of in SBCE. Previously, we
showed that LS shows only moderate correlation with FC levels, although this
seems to improve for FC levels 5100g/g.[1]
AIMS & METHODS: To check the validity of the above observation across
other SBCE centres. Retrospective study; 6 centres (5 university hospitals and
1 district general hospital), offering SBCE, in Canada, Finland, Israel, Sweden,
and UK; 2 SBCE systems (PillCamSB; GivenImaging Ltd, Israel and
MiroCam; IntroMedic Co, Seoul, Korea) and 2 types of FC assays (quantita-
tive and semi-quantitative). An interval of 43 months between FC measurement
and SBCE was considered exclusion criterion. Spearmans rank correlation coef-
ficient (rs) was employed as non-parametric measure of statistical dependence
between two variables. A two-tailed P value of 50.05 was considered statistically
significant.
RESULTS: In the aforementioned period, a total of 333 SBCE have been per-
formed fulfilling the inclusion criteria. Of those, 283 were attached to an ELISA
quantitative estimation of FC and the remainder to semi-quantitative assays. In
the former group, by convention, FC levels below the detection threshold (i.e.
undetectable) were considered as 0. The mean FC, LS and the time interval
between FC measurement and SBCE was 100.36 190.67 g/g, 435.96 970,
and 28.3 39.3 days, respectively. In this subgroup, the correlation between FC
and LS was only moderate (rs0.385), as previously showed [1].
Although 2 different SBCE systems were used (PillCamSB: 132 and
MiroCam: 151), there was no statistically significant difference between FC
levels (100.37 191.24 g/g vs 90.71 166.1 g/g; P0.649), time interval
between FC/LS (28.4 39.4 days vs 20.63 29.5 days; P0.059), prokinetic
(P0.547) or bowel prep used (P0.717). Eventually, no LS/FC correlation
difference was recorded between the 2 SBCE systems, despite the fact that LS
calculator is only available in the proprietary review software from
GivenImaging Ltd, (P0.1188). In the group of semi-quantitative FC measure-
ment (n50), the interval between SBCE and FC was 40.1 58.4 days (i.e. not
different to the quantitative FC group; P0.07) and the rs between LS and FC
was 0.092, P0.126.
When the 2 FC thresholds of 100 g/g and 250 g/g where used, irrespective of
FC assay, no difference in the time interval between FC and LS was noted
(P0.945), while the rs between FC and LS for the 2 threshold levels was
0.247 and 0.337, respectively (P0.307).
CONCLUSION: This multicentre study confirms that LS low to moderate cor-
relation with FC levels.
Acknowledgement: We would like to thank Endoscopy nurses Pirkko Tuukkala
and Virpi Pelkonen for their invaluable help with data collection.
REFERENCES
Koulaouzidis A, et al. Lewis score correlates more closely with fecal calprotectin
than Capsule Endoscopy Crohns Disease Activity Index. Dig Dis Sci 2012; 57:
987-993.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
ESGE-GivenImaging Research grant 2011, Lecture fee(s) from: Dr
FalkPharma UK, Other: Travel support: Dr FalkPharmaUK, Almirall,
Abbott, MSD, T. Sipponen: None declared, E. Toth: None declared, R.
United European Gastroenterology Journal 2(5S)
Makins Lecture fee(s) from: SynMed UK, U. Kopylov: None declared, L.
Bartzis Other: grant from the Hellenic Society of Gastroenterology, A.
Nemeth: None declared, G. Wurm Johansson: None declared, M. Nadler:
None declared, A. Eliakim Other: Speaker for Given Imaging Ltd, E. Seidman
Other: Speaker for Given Imaging Ltd, J. Plevris: None declared
OP222 ASSESSMENT OF THE PERFORMANCE OF THE COLONIC
PILLCAM PCCE-2 IN PATIENTS WITH ACTIVE COLONIC
CROHNS DISEASE: A PILOT STUDY
M. Lowenberg1,*, M.A. Samaan1, D. Franchimont2, C. Ponsioen1, P. Bossuyt3,
L. Amininejad2, E.M. Lensink1, A. M. Van Gossum2, G.R. DHaens1
1
Inflammatory Bowel Disease Unit, Academic Medical Centre, Amsterdam,
Amsterdam, Netherlands, 2Gastroenterology, Hospital Erasme, Brussels,
3
Gastroenterology, Imelda Ziekenhuis, Bonheiden, Belgium
Contact E-mail Address: markasamaan@gmail.com
INTRODUCTION: Treatment goals in Crohns disease (CD) have evolved in
recent years from symptom control to mucosal healing, usually visualized by
optical ileocolonoscopy. The Pillcam colon capsule endoscope (PCCE-2, Given
Imaging, Israel), an ingestible capsule equipped with a video camera at both
ends, was designed for visualization of the colon. This multicenter pilot explora-
tory study was designed to investigate and validate the value of the PCCE-2 in
patients with active CD.
AIMS & METHODS: A cohort of 39 patients with active CD was prospectively
studied with serial PCCE-2 and optical colonoscopy. The primary aim of the
study was to compare the assessment of CD activity using the PCCE-2 with
colonoscopy, which was used as the gold-standard technique.
Inclusion criteria: patients with a CDAI 4 200, an elevated serum CRP (4 5 mg/
L) and faecal calprotectin (FC 4 200 mg/g) in whom a colonoscopy was clinically
indicated and with prior documentation of involvement of at least 2 colonic
segments by CD. Exclusion criteria: any contraindication for optical colonoscopy
or colon capsule examination. Evaluation: CDEIS & SES-CD, serum CRP & FC
levels, CDAI, PCCE-2 passage time and side effects. Independent investigators
reviewed recordings of colonoscopy and PCCE-2 procedures. Statistics:
Pearsons correlation coefficient was used to calculate correlations.
RESULTS: Thirty-nine patients were enrolled with ages ranging from 18 to 60
years. The mean baseline CDAI was 292 (/- 94); serum CRP 51 (/- 76) mg/L;
FC 1201 (/- 725) g/g. The average capsule passage time through the entire
gastrointestinal tract was 7:11 (/- 5:52) hours. In 65% of the cases, the capsule
was expelled from the rectum in less than 6 hours. No episodes of capsule reten-
tion were reported.
The mean CDEIS and SES-CD were 8.0 (/- 5.6) and 10.9 (/- 7.1) for PCCE-2,
and 11.0 (/- 7.0) and 15.9 (/- 9.5) for colonoscopy, respectively. A strong
correlation was found between the two techniques when assessing CDEIS
(Pearson 0.75, p 0.01) and a moderate correlation was found for SES-CD
(Pearson 0.65, p 0.01).
PCCE-2: PCCE2: Colonoscopy: Colonoscopy:
CDEIS SES-CD CDEIS SES-CD
PCCE-2:CDEIS 1 .904** .749** .704**
PCCE-2:SES-CD 1 .653** .648**
Colonoscopy:CDEIS 1 .929**
Colonoscopy:SES-CD 1
Table 1: Showing Pearsons correlation coefficients for the techniques used to
assess CD activity.
When comparing the PCCE-2 scores with CDAI and CRP measurements, a poor
correlation was seen. FC measurements showed slightly better correlation with
PCCE-2 CDEIS but the correlation remained weak and did not reach statistical
significance (Pearson 0.27, p 0.11).
CONCLUSION: This pilot study comparing PCCE-2 to standard colonoscopy
in patients with active colonic CD has shown a strong correlation for assessing
CDEIS and moderate correlation for SES-CD. No capsule retention was
observed. The present data should encourage further large trials to confirm the
utility of PCCE-2 in assessing colonic CD activity.
Disclosure of Interest: M. Lowenberg: None declared, M. Samaan: None
declared, D. Franchimont: None declared, C. Ponsioen Financial support for
research from: Abbott Laboratories, Schering-Plough Corp., Falk Pharma,
Tramedico, Consultancy for: Abbott Laboratories, Glaxo Smith Kline, P.
Bossuyt Lecture fee(s) from: Abbott, Consultancy for: Falk pharma Belgium,
L. Amininejad: None declared, E. Lensink: None declared, A. Van Gossum:
None declared, G. DHaens Financial support for research from: Falk
Pharma, MSD, Lecture fee(s) from: MSD, UCB Inc., Abbott, Ferring
Pharmaceuticals Inc., Consultancy for: Abbott, Jansen Biologics, TEVA,
Glaxo Smith Kline, Shire Pharmaceuticals Inc., Nova Nordisk A/S, Pfizer Inc,
MSD, UCB Inc.
United European Gastroenterology Journal 2(5S)
TUESDAY, OCTOBER 21, 2014 14:0015:30
FROM RISK STRATIFICATION TO ABLATION IN BARRETTS OESOPHAGUS HALL
O_____________________
OP223 IMPACT OF SURVEILLANCE FOR BARRETTS ESOPHAGUS
ON SURVIVAL OF PATIENTS WITH NEOPLASTIC
PROGRESSION: RESULTS OF A LARGE MULTICENTER
PROSPECTIVE COHORT STUDY
F. Kastelein1,*, S. van Olphen1, M. Spaander1, E. Steyerberg2, M. Bruno1 on
behalf of ProBar-study group
1
Gastroenterology and Hepatology, 2Public health, ERASMUS UNIVERSITY
MEDICAL CENTER, Rotterdam, Netherlands
Contact E-mail Address: f.kastelein@erasmusmc.nl
INTRODUCTION: Surveillance is recommended for Barretts esophagus (BE)
to detect esophageal adenocarcinoma (EAC) at an early stage. However, the
value of BE surveillance is under discussion given the overall low incidence of
neoplastic progression, large screening base, and lack of discriminative tests for
risk stratification.
AIMS & METHODS: The aim of this study was to evaluate the impact of BE
surveillance on the survival of patients with neoplastic progression. 783 patients
with BE of at least two centimeter were included in a multicenter prospective
cohort study and followed during surveillance according to the ACG guidelines.
Incident cases of high-grade dysplasia (HGD) and EAC were identified during
follow-up. Patients with neoplastic progression were treated with intensive sur-
veillance or endoscopic treatment for HGD or early EAC, and esophagectomy
for advanced EAC. Survival data were collected for all patients in the study,
cross-checked using death and municipal registries and compared to survival
data from patients with EAC in the general population based on data from
the Dutch cancer registry. Information on cause of death was obtained from
the general practitioner or gastroenterologist and was compared to cause of
death in age and gender matched controls in the general population based on
data from the Dutch central statistical office. Cox-regression models were used to
calculate hazard ratios (HR) and 95% confidence intervals (CI).
RESULTS: During follow-up 53 patients developed HGD or EAC with an
incidence rate of 1.2 per 100 person-years. Thirty-five patients (66%) were clas-
sified as stage 0 disease, 14 (26%) as stage 1, and 4 (8%) as stage 2. EAC was
diagnosed at a significantly earlier stage during BE surveillance than in the gen-
eral population (P50.001). The survival of BE patients with neoplastic progres-
sion during surveillance was worse than those of BE patients without neoplastic
progression during surveillance (HR 2.98, 95% CI 1.62-5.50), better than those of
patients with EAC in the general population (HR 0.16, 95% CI 0.09-0.29), and
comparable to those of patients with stage 0 or stage 1 EAC in the general
population. The overall 5-year survival was 74% in BE patients with neoplastic
progression during surveillance, 94% in BE patients without neoplastic progres-
sion during surveillance and 17% in patients with EAC in the general population.
The majority of BE patients died due to malignancies (36%) or cardiovascular
diseases (29%). Four percent of BE patients died due to EAC. The cause of death
for BE patients was comparable to those of age and gender matched controls in
the general population.
CONCLUSION: BE surveillance enables the detection of EAC at an early and
curable stage when endoscopic treatment is still feasible. The 5-year overall
survival of patients with neoplastic progression during surveillance is 74%
which corresponds to the survival of patients with stage 0 or stage 1 EAC in
the general population.
Disclosure of Interest: None declared
OP224 SEX HORMONES AND BARRETTS OESOPHAGUS - A FUTURE
THERAPY OR JUST A HOT FLUSH?
H.N. Haboubi1,*, E. McAdam1, P. Griffiths2, G. Jenkins1
1
Cancer Biomarker Group, Swansea University, 2Department of Histopathology,
ABM University NHS Board, Swansea, United Kingdom
Contact E-mail Address: h.n.y.haboubi@swansea.ac.uk
INTRODUCTION: The presence of Barretts Oesophagus (BO) and subsequent
development of Oesophageal Adenocarcinoma (OA) is up to four-times more
common in male patients compared to females. The reasons behind this gender
difference remain unclear, and whilst hormones have been an attractive area for
investigation, the results have been quite variable, probably owing to the multi-
factorial mechanisms underlying carcinogenesis.
The pro-inflammatory transcription factor, NF-kB has been implicated in a
number of infectious and malignant processes. Given that Barretts
Oesophagus arises in an inflammatory environment associated with the reflux
of acid and bile, it has not been surprising to note increased NF-kB activity in
these tissues during the progression of Barretts metaplasia through the dysplastic
sequence to OA. In-vitro studies have demonstrated activation of NF-kB p65 and
nuclear localisation following exposure to bile and acid. In other cell lines, NF-
kB has also been demonstrated to be under the influence of hormonal control,
both directly as well as through the inhibition of alternate immunomodulatory
pathways.
AIMS & METHODS: We aimed to investigate the effects on nuclear localisation
of NF-kB p65 following hormone therapy in oesophageal cell lines to attempt to
explain the observed gender differences in BO and OA.
We investigated the possible protective effects of 17B-Estradiol on OE33 cell lines
through ELISA analysis of activated NF-kB p-65 levels. We subsequently inter-
rogated members of the NF-kB pathway to better understand the mechanisms
underlying observed effects using western blotting and RT-PCR of in-vitro trea-
ted cells, as well as immunohistochemical staining of endoscopically obtained
oesophageal biopsies. Analysis of the effect of estradiol on immortalised
A73
normal squamous epithelium HET1A cell line through ELISA analysis as well
as Western Blotting was also undertaken.
Finally, the effect of Estrogen blockade through Tamoxifen treatment on the
effect on the NF-kB pathway was evaluated.
RESULTS: Pre-incubation with estradiol at physiological concentrations reduces
baseline nuclear NF-kB p-65 levels (p50.05). Furthermore, this treatment abro-
gated the NF-kB inducing effect of deoxycholic acid.
Immunohistochemical staining of endoscopically retrieved biopsies of Barretts
metaplasia, OA and squamous tissue adjacent to cancer revealed that female
patients have higher levels of inactive cytoplasmic p-65 than men (p0.006), as
well as lower levels of activating pIKK than their male counterparts (non-
significant).
Finally, the inhibitor of NF-kB, ikB was significantly increased in both OE33 and
HET1A cell lines exposed to Estradiol (p50.01).
CONCLUSION: Given that female patients have higher cytoplasmic p65 levels
than males, it is possible that the mechanisms underlying this could be through
reduced nuclear localisation following exposure to sex hormones. This is sup-
ported by the in-vitro demonstration that 17B-Estradiol reduces nuclear p65
levels.
It is plausible therefore that estrogen could have a role in reducing inflammation
in the oesophageal mucosa following exposure to noxious chemicals present in
refluxate, and this protective effect may be through its activity on the NF-kB
pathway.
Disclosure of Interest: None declared
OP225 ACTIVATED METABOLIC PATHWAYS IN BARRETTS
OESOPHAGUS ACCORDING TO BODY COMPOSITION OR BMI
AND PROGRESSION TO CANCER
S. Di Caro1,*, W.H. Cheung2, L. Fini3, R. Haidry1, M. Keane1, L. Lovat1,
R. Batterham2, M. Banks1
1
Gastroenterology, 2Centre for Obesity Research, UNIVERSITY COLLEGE
HOSPITAL, LONDON, UK, London, United Kingdom, 3Gastroenterology, Busto
Arstizio Hospital, Milan, Italy
Contact E-mail Address: Simona.DiCaro@uclh.nhs.uk
INTRODUCTION: Barretts oesophagus (BE) remains the strongest risk factor
for oesophageal adenocarcinoma (OAC). Several studies describe an association
between BE and obesity through mechanical and metabolic consequences.
Visceral fat is a recognised endocrine organ. Adipokines and insulin resistance
have an impact on obesity related diseases and cancer pathways.
AIMS & METHODS: In sequential patients (pts), undergoing upper gastroin-
testinal endoscopy, we assessed BMI, waist-hip ratio (WHR) and presence of
metabolic syndrome, to evaluate the correlation between BMI and body compo-
sition with metabolic indexes and adipokines in BE compared to controls. A
blood sample was obtained to test fasting insulin, glucose, lipids, HbA1c and
serum adiponectin and leptin. All pts were classified to overweight, obese and
abdominally obese (by WHR). Biopsies were obtained from BE and histological
progression to cancer was correlated with metabolic indexes. Chi square, Fisher,
t-Student test and logistic analysis were used for comparison.
RESULTS: 480 patients (250 cases; F/M: 193/287; mean age: 58.0815.51) were
enrolled. Insulin levels (10.2 vs 7.2IU/ml; p0.001), Hba1c (5.8 vs 5.1%;
p50.01), metabolic syndrome (33.2 vs 20%; OR 1.95; p 0.0017), insulin resis-
tance (47 vs 27%; OR 1.54; p50.01), dyslipidaemia (72.8 vs 53.9; OR 2.3;
p50.0001) and hypertension (37.4 vs 21.3%; OR 2.4; p50.001), were higher in
BE compared to controls.
MS was present in 39.7 vs 34.2% (OR 3.05; p50.001), 43.7 vs 21.9% (OR 5.2;
p50.001), 92.1 vs 54.9% (OR 8.08; p50.0001), in overweight, obese, abdominal
obese pts with BE and controls, respectively.
Insulin resistance was present in 39.2 vs 33.8% (OR 1.3; p50.05), 38 vs 22.3%
(OR 1.7; p50.01) and in 82.5 vs 54.5% (OR 1.5; p50.001) in overweight, obese
and abdominal obese pts, respectively.
A trend was observed for decreased adiponectin levels in BE vs controls while
leptin showed no correlation.
In BE pts, the presence of dysplasia was associated with MS (42 vs 25%;
p0.005) and and insulin resistance (51.4 vs 34.0%; p0.005).
CONCLUSION: BE association with dyslipidaemia, insulin resistance, MS and
hypertension suggests activation of specific metabolic pathways in pts with
altered body composition or BMI. The strongest risk factor is abdominal obesity.
Progression to cancer appears modulated by metabolic dysfunction in MS and a
carcinogenic insulin pathway.
REFERENCES
1. Ryan AM, Healy LA, Power DG, et al. Barrett esophagus: prevalence of
central adiposity, metabolic syndrome, and a proinflammatory state. Ann Surg
2008; 247: 909-915.
2. Kendall B, Macdonald G, Hayward N, et al. The risk of Barretts oesophagus
associated with abdominal obesity in males and females. Int J Cancer 2013; 132:
2192-2199.
3. Rubenstain J, Kao J, Madanick R, et al. Association of adiponectin multimers
with Barretts oesohagus. Gut 2009; 58: 1583-1589.
Disclosure of Interest: None declared
A74
OP226 OUTCOMES OF ENDOSCOPIC SURVEILLANCE IN BARRETTS
OESOPHAGUS: A POPULATION BASED COHORT STUDY IN THE
UK
M. Solaymani-Dodaran1,2,*, J. West2, T. Card2
1
Minimally Invasive Surgery Research Center, Iran University of Medical
Sciences, Tehran, Iran, Islamic Republic Of, 2Division of Epidemiology and Public
Health, University of Nottingham, Nottingham, United Kingdom
Contact E-mail Address: Masoud.Solaymani-Dodaran@nottingham.ac.uk
INTRODUCTION: The impact of endoscopic surveillance in patients having
Barretts oesophagus (BO) is not clear. We compared oesophageal cancer inci-
dence and mortality in a cohort of patients with BO undergoing surveillance and
another of those not being surveyed.
AIMS & METHODS: We used linked UK Clinical Practice Research Datalink,
Hospital Episode Statistics, Office of National Statistics Death records, and
Cancer Registry Data. We identified cases with Barretts oesophagus and cate-
gorized them as surveyed or not surveyed based on subsequent endoscopic exam-
ination(s) starting at least 1 year after Barretts diagnosis. We estimated
oesophageal cancer incidence and mortality as well as all cause mortality after
excluding the first year of follow-up and compared them in the two groups. Cox
proportional hazard regression models were used to estimate hazard ratios and
their 95% confidence intervals.
RESULTS: In total 15704 subjects with Barretts oesophagus were identified of
which 3499 were surveyed. Mean ages were 61 and 65 in those surveyed and not
surveyed respectively. While risk of occurrence of oesophageal cancer (HR3.89
95%CI 1.91-7.92) and oesophageal adenocarcinoma (HR4.04 95%CI 1.88-
8.70) in those undergoing surveillance was four times higher compared with
those not being surveyed after adjusting for age, sex, smoking, alcohol and
BMI, their risk of death due to oesophageal cancer showed only a 26% non-
significant excess (HR1.26 95%CI 0.68-2.36) and their risk of death due to all
causes was significantly lower (HR0.81 95%CI 0.68-0.98).
CONCLUSION: At present less than a quarter of those with BO in the UK are
surveyed. Those who are surveyed have a lower risk of death overall, suggesting a
rational targeting of surveillance resources. If the increased incidence of carci-
noma in the surveyed is real (rather than just representing earlier diagnosis due to
surveillance) then the far lower excess of death than occurrence might suggest
surveillance is of benefit.
Disclosure of Interest: None declared
OP227 SOX2 AS A NOVEL MARKER TO PREDICT NEOPLASTIC
PROGRESSION IN BARRETTS OESOPHAGUS
S. H. Van Olphen1,2,*, K. Biermann2, M. Spaander1, F. Kastelein1, B. Hansen1,
H. Stoop2, L. Looijenga2 on behalf of on behalf of the ProBar-study group
1
Department of Gastroenterology & Hepatology, 2Department of Pathology,
Erasmus University Medical Center Rotterdam, Rotterdam, Netherlands
Contact E-mail Address: s.vanolphen@erasmusmc.nl
INTRODUCTION: The value of surveillance for patients with Barretts oeso-
phagus (BO) based on histological diagnosis of low-grade dysplasia (LGD)
remains debated given the lack of discriminative power to stratify BO patients
at high risk for neoplastic progression of those at low risk. The use of biomarkers
in addition to histological assessment improves risk stratification and has the
potential to improve cost-effectiveness of BO surveillance. SOX2 plays a pivotal
role in the development of oesophageal and gastric epithelium and is down
regulated in intestinal metaplasia and gastric cancer.
AIMS & METHODS: The aim of this study was to investigate the value of SOX2
in BO patients to predict neoplastic progression and to combine the results with
our previously reported p53 immunohistochemical data within the same. We
conducted a case-control study within a large prospective cohort of 720 BO
patients, with a total follow-up time of more than 5600 years. In total 44 BO
patients with neoplastic progression defined as development of high-grade dys-
plasia (HGD) or oesophageal adenocarcinoma (OAC)(cases) and 44 BO patients
without neoplastic progression (controls) were selected and matched for age and
gender. SOX2 protein was detected by immunohistochemistry in more than 3000
biopsies and was scored independently by two investigators blinded for long-term
outcome. The results were combined with p53 immunohistochemical data.
Hazard ratios (HRs) were calculated by Cox-regression models adjusted for
age, gender, BE length and esophagitis.
RESULTS: Normal BO epithelium showed homogeneous strong nuclear expres-
sion of SOX2, while expression of SOX2 was progressively lost in dysplastic
epithelial cells. Loss of SOX2 expression was seen in 9% of biopsy series without
dysplasia, in contrast to 37% of biopsy series with LGD and 70% of biopsy series
with HGD or OAC. Multivariate analysis showed that loss of SOX2 expression
(HR 2.3; 95% CI:1.1-4.6) and aberrant p53 expression (HR 3.7; 95% CI:1.8-7.8)
were independent predictors for neoplastic progression (multiplied HR of 8.5),
whereas presence of LGD was no longer predictive. The positive predictive value
for neoplastic progression increased from 47% with histological diagnosis of
LGD, to 83% with LGD and concurrent aberrant SOX2 expression, to 87%
with LGD and concurrent aberrant p53 expression and to 91% with aberrant
SOX2 and p53 expression.
CONCLUSION: SOX2 is lost during transition from non-dysplastic BO to
HGD/OAC. Loss of SOX2 and aberrant p53 expression are independent pre-
dictors for neoplastic progression in patients with BO and more powerful than
the histological diagnosis of LGD. SOX2 and p53 immunohistochemistry may be
useful as a discriminative test to improve risk stratification of Barrett
surveillance.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP228 THE SURF TRIAL PRE-ASSESSMENT COHORT: SPATIAL
EXTENT OF LOW-GRADE DYSPLASIA AND EXTENT OF
AGREEMENT BETWEEN EXPERT PATHOLOGISTS ARE
ASSOCIATED WITH RISK OF MALIGNANT PROGRESSION
L.C. Duits1,*, K.N. Phoa1, T., V. Pham1, F.J. Ten Kate2, C.A. Seldenrijk3,
G.J. Offerhaus2, M. Visser1, S.L. Meijer1, K.K. Krishnadath1, R.C. Mallant-
Hent4, J.G. Tijssen1, J.J. Bergman1
1
Academic Medical Centre, Amsterdam, 2University Medical Centre, Utrecht, 3St
Antonius Hospital, Nieuwegein, 4Flevoziekenhuis, Almere, Netherlands
INTRODUCTION: Low-grade dysplasia (LGD) in Barretts oesophagus (BO) is
an accepted risk factor for progression to high-grade dysplasia (HGD) or oeso-
phageal adenocarcinoma (OAC). However, the diagnosis of LGD is subjective
and it is unclear which additional factors can help identify LGD patients at
increased risk of progression. For the purpose of this study, all patients screened
for the SURF trial were separately reviewed by 3 expert pathologists. The SURF
trial is a randomized study showing that prophylactic ablation of BO with con-
firmed LGD reduces progression to HGD/OAC.1
AIMS & METHODS: We aim to investigate predictors of malignant progression
in BO patients diagnosed with LGD. 234 LGD patients (78% male; mean 63
years 10.7) underwent histology review by 3 expert pathologists, who separately
evaluated each available level of biopsies from the BO segment. Confirmed LGD
was defined as a majority diagnosis from the expert pathologists. Primary out-
come was neoplastic progression (HGD/OAC) during endoscopic follow-up
(FU). Median duration of FU was 41 months (IQR 22-61). Cox regression
analysis was performed on the risk of malignant progression.
RESULTS: 36/61 patients (59%) with confirmed LGD at baseline developed
HGD/OAC. 10/173 patients (6%) who were downstaged at baseline to non-
dysplastic BO (NDBO) demonstrated malignant progression. The hazard ratio
(HR) for baseline confirmed LGD was 15.1 (95% CI 7.4-30.5). The number of
expert pathologists confirming the presence of LGD and the number of levels
within the BO segment with confirmed LGD predicted progression, as shown in
the table below.
No of events Hazard ratio (95% CI)
Pathologists confirming LGD:None 4.1% (5/122) -
1/3 9.8% (5/51) 2.6 (0.77-9.14)
2/3 51.5% (17/33)17.4 (6.39-47.24)
3/3 67.9% (19/28)28.6 (10.60-77.29)
Extent of LGD*: No LGD 5.8% (10/173)-
1 level LGD 58.3% (21/36)13.8 (6.49-29.39)
2 levels LGD50% (5/10) 14.6 (4.90-43.52)
3 levels LGD83.3% (5/6) 26.4 (8.84-78.98)
15/173 patients who were downstaged to NDBO at baseline developed confirmed
LGD at a subsequent FU endoscopy, of whom 5 patients had malignant pro-
gression. Time-dependent Cox regression yielded a HR of 20.8 (95% CI 8.80-
49.07) for occurrence of confirmed LGD at any time during follow-up.
CONCLUSION: A consensus LGD diagnosis is the most important predictor of
malignant progression. Multilevel LGD and extent of agreement between expert
pathologists were strongly associated with risk of HGD/OAC. These character-
istics might help select BO patients with LGD for prophylactic ablation therapy.
REFERENCES
1. Phoa et al. JAMA 2014; 311: 1209-1217.
Disclosure of Interest: L. Duits: None declared, K. Phoa: None declared, T.
Pham: None declared, F. Ten Kate: None declared, C. Seldenrijk: None declared,
G. Offerhaus: None declared, M. Visser: None declared, S. Meijer: None
declared, K. Krishnadath: None declared, R. Mallant-Hent: None declared, J.
Tijssen: None declared, J. Bergman Financial support for research from:
Covedien GI Solutions
TUESDAY, OCTOBER 21, 2014 14:0015:30
CHALLENGES IN THE TREATMENT OF PANCREATIC AND BILIARY TRACT CANCER
LOUNGE 5_____________________
OP229 CLINICOPATHOLOGICAL CHARACTERISTICS OF
PANCREATIC RESECTION SPECIMENS OF INHERITED/
FAMILIAL VERSUS SPORADIC PANCREATIC DUCTAL
ADENOCARCINOMA
F. Harinck1,*, F. Boersma1, I. Konings1, P. Fockens2, J. van Hooft2,
M. Dijkgraaf2, W. Dinjens1, K. Biermann1, M. Bruno1 on behalf of On behalf of
the Dutch Research Group of Pancreatic Cancer Surveillance in High-Risk
Individuals
1
ERASMUS MC UNIVERSITY MEDICAL CENTER ROTTERDAM,
Rotterdam, 2Academic Medical Center Amsterdam, Amsterdam, Netherlands
Contact E-mail Address: f.harinck@erasmusmc.nl
INTRODUCTION: There is a growing interest towards pancreatic cancer screen-
ing in individuals with an increased inherited or familial risk for this disease.
When designing screening programs aiming to identify high-risk lesions for early
resection, knowledge of the pathology of the disease is essential. In this current
study we focus on the clinicopathological characteristics of pancreatic resection
specimens of patients with inherited or familial pancreatic cancer in comparison
to sporadic cases.
AIMS & METHODS: Pancreatic intraepithelial neoplasia (PanIN) and intra-
ductal papillary mucinous neoplasm (IPMN) were quantified in surgical
United European Gastroenterology Journal 2(5S)
resection specimens of patients with inherited/familial pancreatic cancer and
patients with sporadic pancreatic cancer. Inherited/familial pancreatic cancer
was defined as patients with at least one first degree relative with pancreatic
cancer and/or carriers of a pancreatic cancer prone gene mutation.
RESULTS: Pancreatectomy specimens were evaluated from 16 patients with
inherited/familial PDAC (mean age 63, SD 8.9) and 19 patients with sporadic
PDAC (mean age 69, SD 8.9). PanIN lesions were the most common precursor
lesions for both groups, IPMNs were seldom detected. A significant difference
was observed in the mean number of precursor lesions (9.3 vs. 2.7, p0.04). The
number of patients in whom at least two high-grade precursors were detected was
significantly higher in the inherited/familial group. More patients within the
inherited/familial group had PanIN-3 lesions and the number of PanIN-3 lesions
found in these patients was significantly higher compared to the sporadic group.
Furthermore, in significantly more patients within this group multiple PanIN
lesions were detected.
CONCLUSION: This study shows that the number of high-grade PanIN-lesions
in patients with inherited or familial PC are higher than in patients with sporadic
PC. These high-grade precursor lesions are an important target for screening and
surveillance of high-risk individuals for which the most suitable test has yet to be
identified.
Disclosure of Interest: None declared
OP230 EXPLORING THE EFFECTS OF FACTORS ASSOCIATED WITH
THE OUTCOME OF PANCREATIC CANCER SCREENING IN HIGH-
RISK INDIVIDUALS
I. Driesprong-de Kok1, F. Harinck1,*, I. Konings1, I. Vogelaar1, P. Fockens2,
M. van Ballegooien1, M. Bruno1
1
ERASMUS MC UNIVERSITY MEDICAL CENTER ROTTERDAM,
Rotterdam, 2Academic Medical Canter Amsterdam, Amsterdam, Netherlands
Contact E-mail Address: f.harinck@erasmusmc.nl
INTRODUCTION: There are several disease-related aspects of pancreatic cancer
(PC) that indicate that screening for this cancer type among high-risk individuals
(HRI) could be worthwhile. However, we currently lack scientific evidence to
recommend screening for PC in HRI outside research protocols. By using an
established simulation model, we aimed to analyse which parameters have the
highest impact when estimating the effects of a pancreatic cancer screening
program.
AIMS & METHODS: The Microsimulation Screening Analysis (MISCAN)
model (Habbema JD, 1985) was used. The majority of the model assumptions
were based on the recommendations as stated in the consensus paper of the
international Cancer of the Pancreas Screening (CAPS)-consortium (Canto
MI, 2013). By performing sensitivity analyses we explored which parameters
had the highest impact on the effects of screening.
RESULTS: The mortality reduction (MR) was 35% and 58% (436 and 722 cases
per 10,000 persons) for 5 yearly and annual screening, respectively. In the base
case situation for 5 yearly screening, the number needed to screen (NNS) was
117.1 and number needed to treat (NNT) was 2.5 to prevent one cancer death.
The NNT was lowest in case all screen positives with preinvasive stage 3 or
cancer are treated (2.4, MR 32%). If only persons are treated who are already
in an (early) invasive stage of disease, the NNT was 5.3 (MR 10%). Results were
sensitive for PDAC risk (risk doubled: NNS 64.3, NNT 2.7, MR 38%) and
duration of the preclinical stage of the disease (increased to 30 years: NNS
92.6, NNT 3.2, MR 46%). Results were less sensitive for test characteristics.
CONCLUSION: By building a comprehensive microsimulation model, we iden-
tified which parameters potentially have the highest impact on the outcome of a
PC screening program. FU strategy of screen positives and duration of the pre-
clinical stage are important as is inclusion of patient populations that are exposed
to a certain risk to develop PC. To identify these risk groups and to assess their
risk level, more epidemiological research needs to be done. The true effect of the
PC surveillance including the impact of various FU strategies can only be derived
from clinical trials with long term follow up. The present study provides some
guidance as to which choices could be made.
Disclosure of Interest: None declared
OP231 REPEATED PANCREATIC SURVEILLANCE IN HIGH RISK
INDIVIDUALS FOR PANCREATIC CANCER: THE
PSYCHOLOGICAL BURDEN
I. Konings1,*, G. Sidharta2, F. Harinck1, C. Aalfs3, J.W. Poley1, E. Smets4,
A. Wagner5, P. Fockens6, A. van Rens7, J. van Hooft6, M. Bruno1, E. Bleiker2,7
on behalf of the Dutch research group on pancreatic cancer surveillance in high
risk individuals
1
Department of Gastroenterology and Hepatology, Erasmus MC University
Medical Center Rotterdam, Rotterdam, 2Division of Psychosocial Research and
Epidemiology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek
Hospital, 3Department of Clinical Genetics, 4Department of Medical Psychology,
Academic Medical Center Amsterdam, Amsterdam, 5Department of Clinical
Genetics, Erasmus MC University Medical Center Rotterdam, Rotterdam,
6
Department of Gastroenterology and Hepatology, Academic Medical Center
Amsterdam, 7Family Cancer Clinic, The Netherlands Cancer Institute, Antoni van
Leeuwenhoek Hospital, Amsterdam, Netherlands
Contact E-mail Address: i.konings@erasmusmc.nl
INTRODUCTION: Pancreatic cancer (PC) is one of the most fatal human malig-
nancies with a median survival of 56 months. There is great interest in PC
surveillance for high risk individuals to detect PC or precursor lesions in an
earlier, potentially curable stage. Studies assessing the feasibility of such PC
surveillance programs have, however, not addressed the psychological burden
for participants. The aim of this ongoing, prospective study is therefore to
A75
evaluate the psychological burden of repeated pancreatic surveillance of indivi-
duals at genetically high risk to develop PC.
AIMS & METHODS: Individuals with a lifetime risk of developing PC410%,
who are offered yearly pancreatic surveillance with MRI and endoscopic ultra-
sound (EUS) in a Dutch ongoing prospective multicenter cohort study (FPC-
study), were invited to complete a questionnaire each year to assess their experi-
ence with MRI and EUS, and their psychological distress (assessed with the
Cancer Worry Scale (CWS) and the Hospital Anxiety and Depression Scale
(HADS)). The questionnaires were sent after intake for participation but
before the first MRI and EUS (T1), after the first MRI and EUS (T2), and
after the MRI and EUS one (T3), two (T4) and three years (T5) after initial
intake.
RESULTS: A total of 477 out of 512 questionnaires were returned (93%) by 141
participants: 36, 69, 128, 108, 85 and 51 T0, T1, T2, T3, T4 and T5 questionnaires
respectively. The mean age of participants was 52 years. An average of 90%
experienced the MRI as not or a little burdensome (86%, 92%, 90% and
94% at T2, T3, T4 and T5 respectively) versus an average of 89% in case of
an EUS (91%, 94%, 95% and 94% at T2, T3, T4 and T5 respectively). Prior to
the first MRI and EUS (T1), 34% of individuals dreaded the EUS while only 3%
of individuals dreaded the MRI. However, after their first MRI and EUS, the
percentage of individuals dreading their next EUS decreased significantly to 5-
9% (T2-T5); the percentage of individuals dreading a next MRI remained stable
(0-8%, T2-T5). The mean CWS-score (13) remained stable and low as surveil-
lance progressed. An average of 7% showed clinical relevant anxiety levels
(HADS-A-score 11) and an average of 5% clinical relevant depression levels
(HADS-D-score 11).
CONCLUSION: The psychological burden of repeated pancreatic surveillance
seems tolerable with an average of 90% of high risk individuals experiencing no
or little burden of the yearly MRI and EUS. Participants also have few worries
about cancer and the percentage of individuals with clinical relevant levels of
anxiety and depression is comparable to that of the general population.
Therefore, from a psychological point of view, yearly pancreatic surveillance of
high risk individuals seems feasible.
Disclosure of Interest: None declared
OP232 EFFICACY OF NEOADJUVANT THERAPY IN BORDERLINE
RESECTABLE PANCREATIC CANCER WITH ABUTMENT OF THE
SUPERIOR MESENTERIC ARTERY
D. Satoh1,*, Y. Shiozaki1, H. Araki1, K. Yoshida1, H. Matsukawa1,
M. Okajima1, M. Ninomiya1
1
Department of Surgery, Hiroshima city hospital, Hiroshima, Japan
INTRODUCTION: Neoadjuvant therapy may be beneficial for patients with
borderline resectable pancreatic cancer (BRPC) due to selection of the patients
likely to experience the most favorable surgical outcome. Such selection excludes
patients who develop distant metastasis during treatment, precludes delayed
postoperative adjuvant therapy that results from surgical complication or
delayed recovery, and reduces the risk of margin-positive resection. Until now,
few reports have demonstrated that the outcome of patients with BRPC treated
with neoadjuvant therapy was directly comparable to that of patients with BRPC
who initially underwent resection without neoadjuvant therapy. In actuality,
patients with severe superior mesenteric-portal vein (SMPV) impingement or
occlusion of the short segment, defined as one of the criteria of BRPC, initially
have undergone resection with considerable frequency. The aim of this study was
to compare the outcome of patients with BRPC treated with and without neoad-
juvant therapy.
AIMS & METHODS: We retrospectively reviewed 27 patients with BRPC,
according to the National Comprehensive Cancer Network (NCCN) classifica-
tion system, who underwent resection with or without neoadjuvant therapy, and
53 patients with locally advanced but resectable pancreatic cancer (LAPC) who
initially underwent resection between 2001 and 2012. We divided the patients
with BRPC into three groups: 1) the patients with severe SMPV impingement or
occlusion of the short segment, pathologically confirmed as invasion, treated
without neoadjuvant therapy (BRPC-P(-); n10); 2) the patients with superior
mesenteric artery (SMA) abutment 5180 degrees, treated without neoadjuvant
therapy (BRPC-S(-); n9); and 3) the patients with SMA abutment 5180
degrees, treated with neoadjuvant therapy (BRPC-S(); n8). We evaluated
the outcome of these three groups, and that of the LAPC patients.
RESULTS: The R0 resection rates were 50% in the BRPC-P(-) group, 56% in
the BRPC-S(-) group, and 88% in the BRPC-S() group. Although the R0
resection rate of the BRPC-S() group was higher than that of the other two
groups, the difference was not statistically significant. The median overall survi-
val in the BRPC-S() group was 52 months, which was significantly better than
that of the BRPC-S(-) (27 months, P0.0345) and BRPC-P(-) (8 months,
P0.0192) groups.
The LAPC group had a significantly more favorable median overall survival
compared with the BRPC-P(-) group (29 months and 8 months, respectively,
P0.0345).
CONCLUSION: BRPC patients with SMA abutment should be treated with
neoadjuvant chemotherapy. When SMPV invasion is very suspicious, such as
radiological findings of SMPV deformity or occlusion, initial resection may be
avoided.
Disclosure of Interest: None declared
A76
OP233 SECOND-LINE CHEMOTHERAPY FOR ADVANCED BILIARY
TRACT CANCER AFTER FAILURE OF GEMCITABINE PLUS
PLATINUM: RESULTS OF AN AGEO MULTICENTER
RETROSPECTIVE STUDY
B. Brieau1,*, L. Dahan2, Y. De Rycke3, T. Boussaha4, P. VASSEUR5,
D. Tougeron5, T. LECOMTE6, R. CORIAT1, J.-B. Bachet7, P. Claudez8,
A. ZAANAN9, P. Soibinet10, J. Desrame11, A. Bidault12, I. Trouilloud13,
F. Mary14, C. Locher15, L. Marthey16, W. Cacheux3, A. LIEVRE17
1
Hopital Cochin, PARIS, 2Hopital La Timone, MARSEILLE, 3Institut Curie,
4
Hopital Saint Antoine, PARIS, 5CHU Poitiers, Poitiers, 6CHU Tours, TOURS,
7
Hopital La Pitie Salpetrie`re, PARIS, 8CHU Saint Etienne, Saint Etienne,
9
Hopital Europeen Georges Pompidou, PARIS, 10CHU Reims, Reims, 11Hopital
Jean Mermoz, Lyon, 12Hopital Kremlin Bicetre, Kremlin Bicetre, 13Hopital
Ambroise Pare, Boulogne-Billancourt, 14Hopital Avicenne, Bobigny, 15Centre
hospitalier de Meaux, Meaux, 16Hopital Beclere, Clamart, 17Hopital Rene
Huguenin, Saint Cloud, France
INTRODUCTION: First-line chemotherapy (CT1) with the combination of
gemcitabine platinum has become a new standard in advanced biliary tract
cancer (ABTC) but data on second-line CT (CT2) are lacking. The aim of this
study was to evaluate the efficacy and tolerability of CT2 in patients with ABTC
who received gemcitabine-platinum in CT1.
AIMS & METHODS: We retrospectively reviewed data of consecutive patients
who received CT2 for ABTC after failure to gemcitabine-platinum in 17 French
institutions from November 2002 to December 2013. Progression-free survival
(PFS) and overall survival (OS) were estimated from the start of L2 CT using
Kaplan Meier method. Cox models were applied for multivariate analyses.
RESULTS: Among 603 patients who were treated by gemcitabine-platinum in
CT1, 196 patients (median age, 63 years, range: 28-82; male, 51.5 %) received a
CT2. CT1 included gemcitabine cisplatin (7%) or oxaliplatin (93%), with a
median PFS of 9.7 months and an ORR of 31%. Characteristics at the beginning
of CT2 were: metastatic disease, 94%; 1-2 metastatic sites, 68%; ECOG PS 0-1,
68%. CT2 CT was 5FU-irinotecan (n62), 5FU-oxaliplatin (n17), 5FU-cispla-
tin (n37), 5FU/capecitabine (CAP) (n39) or other various regimens (n41).
Among the 186 evaluable patients, there were 22 partial response (12%) and 70
stable disease (38%). After a median follow-up of 26.4 months, median PFS and
OS were 3.2 and 6.7 months respectively. There was no significant difference
between CT regimens in terms of PFS (5FU-irinotecan, 2.6 months; 5FU-oxali-
platin/5FU-cisplatine, 4.0 months; 5FU/CAP, 3.2 months and others, 3.7
months; p0,27) and OS (6.0 months, 6.3 months, 5.6 months and 9.7 months
respectively; p0.27). There was no significant difference between 5FU/CAP
monotherapy and 5FU-based doublet chemotherapy (5FU-irinotecan, 5FU-cis-
platin and 5FU-oxaliplatin), in terms of PFS (3,0 months and 3,3 months;
p0,91) and OS (5,6 months and 6,3 months; p0,93). In multivariate analysis,
PS 2-3, bilirubine 4 17 mmol/L and CA19.9 4 400 UI/mL were significantly
associated with a shorter PFS while PS 2-3, CA19.9 4 400 UI/mL and non-
response to CT1 with a shorter OS. A grade 3-4 toxicity was observed in 32% of
patients (neutropenia, 33%; diarrhea, 17%) and a toxic death occurred in 1.4%
of patients.
CONCLUSION: CT2 is associated with a disease control in a half of patients
with ABTC who received gem-platinum in CT1. Nevertheless, the short median
PFS observed in this study should encourage the evaluation of new treatments in
patients with good clinical conditions and an adequate biliary drainage.
Disclosure of Interest: None declared
OP234 TEMOPORFIN PHOTODYNAMIC THERAPY IN LOCALLY
ADVANCED BILIARY TRACT CARCINOMA: A MULTICENTER
PROSPECTIVE PHASE II STUDY
A. Wagner1,*, U.W. Denzer2, D. Neureiter3, T. Kiesslich4, F. Berr1,
A. Puspoeck5, K. Emmanuel6, A.W. Lohse2, U. Beuers7, E.A. Rauws8,
N. Degenhardt9, G.W. Wolkersdorfer1
1
Department of Internal Medicine I, Paracelsus Medical University / Salzburger
Landeskliniken (SALK), Salzburg, Austria, Salzburg, Austria, 2I. Department of
Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany,
3
Institute of Pathology, 4I. Department of Medicine, Paracelsus Medical University
/ Salzburger Landeskliniken (SALK), Salzburg, 5Department of Internal Medicine
IV, Medical University of Vienna, Vienna, 6Department of General and Visceral
Surgery, Krankenhaus Barmherzige Schwestern, Linz, Austria, 7Department of
Gastroenterology & Hepatology, 8Academic Medical Centre, Amsterdam,
Netherlands, 9University Medical Center Hamburg-Eppendorf, Hamburg,
Germany
Contact E-mail Address: f.berr@salk.at
INTRODUCTION: Photodynamic therapy using porfimer (P-PDT) is estab-
lished local tumor ablative therapy in non-resectable hilar bile duct cancer
(hBDC) improving palliation and survival time. In a pilot trial, temoporfin
PDT (T-PDT) showed improved tumoricidal penetration depth, if compared
with P-PDT.
AIMS & METHODS: We investigated clinical effectiveness and safety of T-PDT
in a single-arm phase II study (NCT01016002; from 2005 to 2011). In respect of
previous publications on P-PDT, results were compared concerning OS, local
tumor control (TTP), and adverse events (ADE). Twenty-nine patients with
unresectable hBDC received median 1.0 (range 1-4) T-PDT plus stenting and
were followed up at three-month intervals.
RESULTS: OS after treatment was median 17.3 (12.6 22.0, 95% CI) months
for 19 patients of category M0, and 15.4 months for all patients (M0 M1, 11.7-
19.1, 95% CI). Median time to local tumor progression was 6.5 months (3.6-9.4,
95% CI). Cholestasis improved significantly in patients with initially elevated
bilirubin levels and 74% of patients with occluded segments at baseline
showed local response with reopening of median 3.0 segments. A significant
United European Gastroenterology Journal 2(5S)
improvement of palliation could be achieved (Karnofsky performance status,
median 10%, range -20% - 40%). PDT was technically successful in all
cases and was generally well tolerated; there was no grade 4 toxicity and no
treatment-associated mortality. Adverse events were phototoxic skin reactions
(n9), three late phototoxic skin reactions (at T-injected vein), cholangitis
(n4), and liver abscess (n1).
CONCLUSION: T-PDT can be delivered safely to patients with biliary tract
cancer and shows improved time to treatment patency and prolonged survival
compared to P-PDT. It is statistically not inferior to P-PDT concerning improve-
ment of cholestasis and palliation. It is highly tumoricidal and associated with
similar rates of infectious complications, but with an elevated rate of skin photo-
toxicity, which could have been possibly avoided, taking specific precautions.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 14:0015:30
COLORECTAL CANCER: NOVEL MECHANISMS, NOVEL TARGETS LOUNGE
6_____________________
OP235 ZINC FINGER PROTEIN 545 IS A NOVEL TUMOR SUPPRESSOR
THROUGH INHIBITING RIBOSOMAL RNA TRANSCRIPTION IN
COLON CANCER
S. Wang1,*, X. Zhang1, J. Yu2
1
School of Chemistry and Biological Engineering, University of Science and
Technology Beijing, Beijing, China, 2Institute of Digestive Disease and Department
of Medicine and Therapeutics, State Key Laboratory of Digestive Disease, Li Ka
Shing Institute of Health Sciences, CUHK Shenzhen Research Insititute, The
Chinese University of Hong Kong, Hong Kong, Hong Kong
Contact E-mail Address: wangshiyan9885@hotmail.com
INTRODUCTION: Zinc finger protein 545 (ZNF545) is a member of Kruppel-
associated box containing Zinc-finger proteins.
AIMS & METHODS: We aim to clarify its biological function as a tumor
suppressor in colon cancer. ZNF545 methylation was evaluated by bisulfite
genomic sequencing. The biological function of ZNF545 was determined by
apoptosis and autophagy assays. ZNF545 target pathway was identified by pro-
moter luciferase assay, immunofluorescence, electrophoretic mobility shift assay
(EMSA) and co-immunoprecipitation assays.
RESULTS: ZNF545 was silenced or downregulated in all 8 colon cancer cell
lines by promoter hypermethylation. Partial and dense promoter methylation of
ZNF545 was detected in 41.7% (25/60) of cancer tissues. Restoring ZNF545
expression in colon cancer cell lines induced apoptosis as well as autophagy.
These effects were attributed to inhibition of ribosomal RNA (rRNA) transcrip-
tion. To elucidate the binding sites of ZNF545 on rDNA promoter, two deletion
mutants in rDNA promoter were constructed based on pHrD-IRES-Luc con-
struct containing the human rDNA promoter (from -410 to 81). pHrD-IRES-
Luc-deletion-1 is from -268 to 81 containing far upstream control element
(UCE), UCE and rDNA core promoter element and pHrD-IRES-Luc-dele-
tion-2 is from -172 to 81 containing UCE and rDNA core promoter element.
We found that ZNF545 significantly suppressed the promoter transcriptional
activity on both rDNA promoter reporter deletion constructs, indicating that
the binding site(s) of ZNF545 should be at least present within the minimal
rDNA promoter region. To further refine the binding site(s) of ZNF545,
EMSA was performed using six overlapping biotinylated DNA probes spanning
minimal rDNA promoter region (60bp). Our results showed that two regions in
rDNA promoter exhibited strong binding to Flag-tagged ZNF545 proteins
derived from nuclear extracts. One was within the linking region between UCE
and core promoter element (from -97 to -62), and the other was located down-
stream of the transcription start site (from 41 to 78). Bioinformatic analysis
demonstrated that ZNF545 protein contains twelve C2H2 zinc fingers arranged
in two distinct clusters which are separated by a degenerate zinc finger motif (Z5).
The first cluster, referred to as Hand1, contains zinc fingers 1 to 4, and the second
cluster, in the carboxyl terminus, referred to as Hand2, contains zinc fingers 6 to
13. To explore which part of the multiple adjacent zinc fingers participate in
promoter DNA interaction, ZNF545 Hand1 and Hand2 were individually
cloned and fused at the N-terminal end to GFP protein or its KRAB domain.
Fluorescence microscopy imaging and EMSA assay indicated that both Hand1
and Hand2 were capable of binding to rDNA promoter independently.
Luciferase reporter assay demonstrated that transcriptional repression KRAB
domain coupled Hand1 and Hand2 still exhibited significant negative influence
on rDNA promoter activity, albeit to a lesser extent compared with the full-
length ZNF545, suggesting that ZNF545 needed both Hand1 and Hand2 for
firmly binding to rDNA promoter for rRNA transcription inhibition.
Moreover, KRAB domain of ZNF545 was responsible for recruiting KAP1, a
scaffold corepressor for recruiting other co-repressors as evidenced by co-
immunoprecipitation.
CONCLUSION: ZNF545 acts as a functional tumor suppressor in colon cancer
through inhibiting rRNA transcription.
Disclosure of Interest: None declared
OP236 SEPT9 AND SFRP1 DNA HYPERMETHYLATION IN
COLORECTAL CANCER: RESTRICTION TO A SINGLE CPG
ISLAND AND EXPANSION TO THE GATEKEEPER
MYOFIBROBLASTS
A. Kalmar1,2,*, R. Wasserkort3,4, S. Spisak2,5, G. Valcz2, B. Wichmann1,2,
K. Toth1, K. Leiszter1, B. Bartak1, T. deVos6, B. Molnar1,2, Z. Tulassay1,2
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary,
3
Extracorporeal Immune Modulation Unit, Fraunhofer Institute of Cell Therapy
United European Gastroenterology Journal 2(5S)
and Immunology, Rostock, 4Epigenomics AG, Berlin, Germany, 5Dana-Farber
Cancer Institute, Harvard Medical School, Boston, 6Epigenomics Inc, Seattle,
United States
Contact E-mail Address: alexandra.kalmar@gmail.com
INTRODUCTION: Several genes are regulated by DNA methylation and the
aberrant alteration of this mechanism can lead to cancer formation. Septin 9
(SEPT9) and secreted frizzled-related protein 1 (SFRP1) are known to play
role in colorectal cancer, however, the DNA methylation pattern of these
genes in the epithelial and stromal cells in colorectal cancer remains unknown.
AIMS & METHODS: Our aim was to analyse DNA methylation patterns in
DNA methylation-regulated genes in healthy and diseased colonic epithelial and
stromal cells. Colonic epithelial and stromal cells were collected separately using
laser capture microdissection (LCM). Microdissected samples were subjected to
bisulfite treatment and direct bisulfite sequencing was used to analyze the methy-
lation status of ten regions within SEPT9, SFRP1 genes in tissue samples
obtained from normal (n3), adenomatous (n3) and colorectal cancer (n3) OP239 ECTOPIC COLORECTAL FAT ACCUMULATION ASSOCIATES
samples. In addition SEPT9 and SFRP1 protein expression was assessed using
immunohistochemistry on independent healthy (n10), adenomatous (n14)
and CRC (n13) samples. Stromal myofibroblast cells were detected by alpha-
SMA immunohistochemistry, the immunopositive cells were LCM separated and
SFRP1 DNA methylation was assessed by high resolution melting analysis
(HRM).
RESULTS: The regions analysed in SEPT9 were unmethylated in normal tissues
except for a methylation boundary detected downstream of the largest CpG
island within SEPT9. In adenoma and tumor samples, the epithelial cells dis-
played markedly increased methylation levels (480%, p510-4), but only within
one of the CpG islands investigated. In stromal cells increased methylation (up to
50%, p510-4) was only seen in tumor patients and in histologically normal tissue
close to the tumor, but not in adenoma. The analyzed region of SFRP1 also
showed remarkable increase in the adenoma and tumor epithelial cells. Protein
level of SEPT9 and SFRP1 showed significant (p50.05) decreasement in ade-
noma and tumor tissue samples compared to the healthy controls. Alpha-SMA
immunopositive myofibroblast cells were identified as the main source of stromal
SFRP1 protein, that was found to be downregulated by DNA hypermethylation
only in carcinoma, but not in adenoma.
CONCLUSION: Hypermethylation of SEPT9 and SFRP1 could be detected in
the analysed adenoma and cancer samples compared to the healthy control
samples. According to the results of the laser microdissected samples, the
DNA methylation alterations originated in epithelial cells, while stromal cells
appear to acquire hypermethylation only subsequently via field effects. The
DNA hypermethylation of the analyzed genes result in decreased protein level,
that can contribute to colorectal cancer formation and invasion.
Disclosure of Interest: A. Kalmar: None declared, R. Wasserkort Shareholder of:
Epigenomics AG, Other: former employee of Epigenomics AG, S. Spisak: None
declared, G. Valcz: None declared, B. Wichmann: None declared, K. Toth: None
declared, K. Leiszter: None declared, B. Bartak: None declared, T. deVos Other:
employee of Epigenomics Inc., B. Molnar: None declared, Z. Tulassay: None
declared
OP238 IS MEASURING THE DEPTH OF SUBMUCOSAL INVASION A
MEANINGFUL APPROACH IN MANAGEMENT OF T1
COLORECTAL CARCINOMAS AFTER ENDOSCOPIC TREATMENT?
Y. Kouyama1,*, S.-E. Kudo1, H. Miyachi1, K. Ichimasa1, S. Matsudaira1,
H. Oikawa1, T. Hisayuki1, K. Wakamura1, T. Hayashi1, K. Kodama1, T. Kudo1,
Y. Mori1, M. Misawa1, A. Katagiri1, M. Kaga1, E. Hidaka1, F. Ishida1,
S. Hamatani1
1
Showa University Northern Yokohama Hospital, Tsuzuki-ku Yokohama-shi,
Japan
Contact E-mail Address: kouyuta1101@gmail.com
INTRODUCTION: According to the current Japanese guideline, additional sur-
gical colectomy with lymph node (LN) dissection should be considered after
endoscopic treatment even for cases where the depth of SM invasion is
1000m or more. However, many patients who underwent additional colectomy
did not have LN metastasis. This over-surgery problem has become a major
issue.
AIMS & METHODS: The aim is to investigate the necessity of measuring the
depth of submucosal invasion in T1 colorectal carcinomas after endoscopic
treatment.
A total of 21060 colorectal neoplasms excluding advanced cancers have been
resected endoscopically or surgically at our unit from April 2001 to September
2013. Of these, 902 SM-invasive cancers were included. Initial or additional
surgical colectomy with LN dissection was performed in 568 cases, and of
which LN metastasis was found in 54 cases (9.5%). There are two ways to
measure the depth of SM invasion. One is to directly measure the vertical dis-
tance from the line of muscularis mucosae. The other is, when the line of mus-
cularis mucosae is not easily identified due to cancer invasion, the surface layer of
the lesion is used as a baseline. According to this rule, a pathologist in our unit
categorized 816 lesions and measured each depth of SM invasion. Then, we
analyzed the correlations between the depth of SM invasion and the other patho-
logical factors including LN metastasis.
RESULTS: Of these 568 lesions, the muscularis mucosa could be identified in
180 lesions (31.7%), and 60 lesions were invaded SM 1000m, 120 lesions
showed SM =1000m. For the other 388 lesions (68.3%), the muscularis
mucosa was recognized broken or disappeared and the depth of SM invasion
was measured from the surface layer. All the results turned out to be =1000m.
Once the muscularis mucosae was judged to be unclear and the surface layer was
applied as the baseline, all the cases would be considered =1000m. It indicates
that there is no need to measure the invasion depth in this case. In some lesions, it
A77
is hard to decide the baseline. Because the muscularis mucosae sometimes split up
and both of them or their surface can be considered as the baseline. The depth of
SM invasion is associated with the morphology of the lesion to some extent.
Many of depressed-type lesions invade downward, but protruded types often
grow upward. Sometimes the depth of SM invasion becomes shorter after
being more massively invaded. Some lesions collapse in tumor development.
LN metastasis was found in 4 (6.7%) out of 60 lesions with SM 51000m
and in 50 cases (9.8%) out of 508 lesions with SM =1000m (p0.49). The
depth of SM invasion was not a statistically significant risk factor for LN
metastasis.
CONCLUSION: There are several problems in measuring the depth of SM
invasion. The reconsideration should be needed concerning the depth of SM
invasion.
Disclosure of Interest: None declared
WITH ABDOMINAL OBESITY AND INSULIN RESISTANCE IN
JAPANESE COLORECTAL POLYP PATIENTS
S. Kawata1,2,*, S. Wada1, Y. Yasunaga1, K. Oka1, N. Dan1, H. Matsumoto1,
S. Yoshioka3, Y. Inui1
1
Gastroenterology, Hyogo Prefectural Hospital, Nishinomiya, 2Gastroenterology,
Yamagata University Hospital, Yamagata, 3Surgery, Hyogo Prefectural Hospital,
Nishinomiya, Japan
Contact E-mail Address: sumio_kawata@pref.hyogo. lg.jp
INTRODUCTION: Several lines of epidemiological evidence have suggested that
obesity and insulin resistance are independent risk factors for the development of
colorectal adenoma and cancer (Ref. 1, 2). Obesity is known to be associated with
ectopic fat accumulation in the liver and skeletal muscle. However, obesity-
related accumulation of fat in the colorectal tissue has not been reported.
AIMS & METHODS: We conducted the present study to seek evidence of
obesity- or insulin resistance-related colorectal accumulation of fat in patients
with colorectal polyps. For the 27 patients (15 males and 12 females) with color-
ectal polyps enrolled in this study, we measured the triglyceride, total cholesterol,
and phospholipid contents of non-tumorous tissues surrounding the polyps
which were resected by endoscopic mucosal resection (EMR) or endoscopic
submucosal dissection (ESD). Non-tumorous colorectal tissues of 32 patients
(13 males and 19 females) with colorectal cancer, obtained from surgical resec-
tion, were used for immunohistochemistry examination using anti-perilipin
(PLIN1) antibody to examine the location of lipid droplets. The contents of
lipid droplets were divided into three grades (0 to 2), and then the grades of
the lipid contents were compared with visceral fat areas assessed by CT scan.
RESULTS: The tissue triglyceride/phospholipid value was significantly corre-
lated with serum triglyceride, fasting plasma insulin (FPI), and HOMA-IR (P
5 0.01, P 5 0.01, and P 5 0.01, respectively; Spearman rank test). Tertile
analysis of the triglyceride/phospholipid value to assess factors associated with
higher triglyceride/phospholipid values showed that serum triglyceride (P
0.025), FPI (P 0.041), and HOMA-IR (P 0.013) were significantly higher
in the highest tertile than in the lowest tertile. Serum adiponectin level (P 0.046)
was also significantly lower in the highest tertile. Lipid droplets were observed in
the submucosal region of non-tumorous colorectal tissue in 27 of 32patients
(grade 1 in 13 and grade 2 in 5), and the grades of fat droplet correlated
with BMI, abdominal circumstance and visceral fat area (P 0.04, P 5 0.01, and
P 5 0.01, respectively; Kruskal-Wallis test).
CONCLUSION: Triglyceride content of colorectal tissue was increased in color-
ectal polyp patients with insulin resistance. Ectopic colorectal fat accumulation
was observed in the submucosal region, correlating with BMI, abdominal cir-
cumstance and visceral fat accumulation. Thus, the results in the present study
suggest an association of the ectopic fat accumulation with abdominal obesity
and insulin resistance.
REFERENCES
1. Otake S, Kawata S, et al. Association of visceral fat accumulation and plasma
adiponectin with colorectal adenoma: evidence for participation of insulin resis-
tance. Clin Cancer Res 2005; 11: 3642-3646.
2. Otake S, Kawata S, et al. Decreased levels of plasma adiponectin associated
with increased risk of colorectal cancer. World J Gastroenterol 2010; 16: 1252-
1257.
Disclosure of Interest: None declared
OP240 RISK OF METACHRONOUS ADVANCED COLORECTAL
NEOPLASIA AFTER POLYPECTOMY OF SMALL AND
DIMINUTIVE ADENOMAS
J.S. Koo1,*, S.Y. Kim1, J.J. Hyun1, B. Keum1, B.J. Lee1, Y.T. Jeen1, S.W. Lee1
1
Division of Gastroenterology Departmemt of Internal Medicine, Korea
Univiversity College of Medicine, Seoul, Korea, Republic Of
INTRODUCTION: As screening colonoscopy is increasing for colorectal cancer
prevention, colorectal polyps 510 mm in diameter are encountered more fre-
quently. Generally, surveillance colonoscopy is recommended considering the
index colonoscopy findings. However, it is not well established what factors
are related with developing advanced neoplasia after polypectomy of small and
diminutive polyps.
AIMS & METHODS: The study was conducted to reveal the risk of advanced
colorectal neoplasia after polypectomy in patients with small and diminutive
adenomas. We enrolled 3,526 patients (mean age 53.9 year, 2,164 male), who
underwent surveillance colonoscopy after index colonoscopy from January 2002
to June 2012 in Korea University Hospital. We reviewed the medical records and
pathology reports to evaluate the risk for the development of advanced colorectal
neoplasm in surveillance colonoscopy. According to the largest size and number
A78
of adenoma in index colonoscopy, the patients were divided into the subgroups
and analyzed.
RESULTS: Among a total 3,526 patients, 1,949 (55.3%) had colorectal adenoma
and 528 (15.0%) of them had advanced adenoma in index colonoscopy. During a
median follow-up period of 46.5 months, colorectal adenoma was diagnosed in
1,401 (39.7%), 115 (3.3%) of whom had advanced neoplasm. In the patients with
polypectomy in index colonoscopy, metachronous advanced neoplasia were
higher among patients with 4 or more baseline adenomas, those with an adenoma
6 mm in diameter or greater. In subgroup analysis, the risk of metachronous
advanced adenoma was increased with the adenoma number and size. However,
the risk in the group with multiple (3) diminutive adenomas was not higher
than the group with 1 or 2 small adenomas. In multivariate analysis, age (OR
1.06, 95%CI 1.03-1.08) was significantly associated with an increasing metachro-
nous advanced neoplasm, as were the number and size of baseline adenomas (p
50.01 and p 50.01, respectively).
CONCLUSION: As risk of metachronous advanced neoplasia is associated with
the number and size of prior adenomas, it will be needed to modify the surveil-
lance interval considering the size and number of previous adenomas.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
VIDEO CASE SESSION HALL A_____________________
OP241 ENDOSCOPIC RESECTION OF A GIANT ESOPHAGEAL
SUBMUCOSAL LIPOMA
F. Baldaque-Silva1,2,*, M. Marques2, E. Sanchez-Hernandez3, R. Coelho2,
F. Vilas-Boas2, J. Lopes4, F. Carneiro5,6, G. Macedo2
1
Gastrocentrum, Karolinska University Hospital, Stockholm, Sweden,
2
Gastroenterology, Centro Hospitalar Sao Joao, Porto, Portugal,
3 1
Gastroenterology, Complejo Hospitalario de Ourense, Ourense, Spain,
4
Pathology, Centro Hospitala Sao Joao, 5Pathology, IPATIMUP, 6Pathology,
Porto Medical School, Porto, Portugal
Contact E-mail address: fbaldaquesilva@gmail.com
INTRODUCTION: Lipomas are extremely rare in the esophagus, constituting
less than 0.5% of esophageal neoplasias. If large enough, esophageal lipomas can
cause symptoms such as dysphagia, bleeding and airway obstruction. If symp-
toms are cumbersome a resection is indicated. The resection of big esophageal
lipomas is usually performed through surgery. To our knowledge there is no
previous description of endoscopic resection of a giant esophageal lipoma.
AIMS & METHODS: A 68-years-old male patient was referred to our clinic
from abroad, due to the presence of a big esophageal submucosal lesion with
endoscopic, radiologic and ultrasonic characteristics of lipoma. The lesion caused
progressive dysphagia and the patient refused surgery. Physical examination on
admission was normal. Upper endoscopy revealed the presence of a 14cm long
esophageal subepitelial, yellow and hard lesion, occupying more than of
luminal circumference and causing severe luminal narrowing. The surrounding
mucosa was normal. Endoscopic ultrasound shown the presence of an avascular,
hyperecogenic, regular and homogeneous lesion in the submucosal layer, with
32x42mm of transverse diameters.
RESULTS: After multidisciplinary discussion, discussion with the referring
doctor and informed consent, an endoscopic resection was performed at our
endoscopy unit under general anesthesia. First, a submucosal tunnel was created
and the tumor was completely enucleated in one piece using endoscopic submu-
cosal dissection (ESD). Although the use of different techniques and instruments,
it was not possible neither to retrieve the lesion en bloc, nor to fragment it using a
snare, due to its hardness and size. The lipoma needed to be fragmented inside
the luminal esophagus using a combination of ESD knife and a conventional
snare, being completely removed. There were no major complications such as
bleeding or perforation during or after the procedure. The patient started oral
diet the day after the procedure and was discharged at day 6. The pathological
analysis confirmed the presence of a well differentiated lipoma with negativity for
MDM2 immunohistochemistry. On the follow-up there were no signs of stric-
ture, remaining the patient asymptomatic 4 months after the procedure.
CONCLUSION: Esophageal lipomas are rare. Endoscopic resection can be a
safe, feasible, and effective alternative to surgery even in cases of giant esopha-
geal lipomas.
Disclosure of Interest: None declared
OP242 PURELY ENDOSCOPIC REMOVAL OF A GIANT, DOUBLE-
HEADED ESOPHAGEAL FIBROVASCULAR POLYP
E. Fedorov1, E. Ivanova1,*, D. Seleznev1, A. Kasimsev2, O. Yudin1
1
MOSCOW UNIVERSITY HOSPITAL 31, Moscow, 2Volgograd Regional
Oncological Center, Volgograd, Russian Federation
Contact E-mail address: katendo@yandex.ru
INTRODUCTION: The surgical approach is generally recommended for the
excision of giant esophageal fibrovascular polyps to ensure adequate hemostasis
and clear resection of the base. Only single cases of merely endoscopic removal of
this rare benign tumor have been described in the literature.
AIMS & METHODS: To demonstrate possibilities of successful resection of a
giant fibrovascular polyp of the esophagus via an endoscope. A 50-year-old man
was admitted to our hospital with a 6-month history of globus sensation, mild
intermittent dysphagia during swallowing, occasional heartburn and epigastric
pain. In a barium swallow and repeated EGDs a giant double-headed polyp with
smooth overlying mucosa, arising from the upper esophagus just near the level of
the cricopharyngeus at the pharyngo-esophageal junction and extending from 17
to 34 cm from the incisors settling in the distal esophagus was revealed. It had a
broad 18mm basis, distal head 32 mm at its maximum diameter with 2
United European Gastroenterology Journal 2(5S)
ulcerations on the apex, proximal head 25 mm in diameter and length, with
the ramification at the distance of 45 mm from the stalks base. EUS detected
the lesion originated from the submucosal layer with inhomogeneous echo-tex-
ture with both hyper- and hypoechoic features with a number of vascular struc-
tures within the stalk.
RESULTS: Removal of the polyp was performed under general anesthesia with
elective intubation, started with GIF-H180 following by GIF-2T160, using the
Maxim-402 electrosurgical unit and CO2 insufflation. The equipment for inter-
vention included 4 endo-loops, grasping forceps and large electrosurgical snare.
At first, we applied two loops at the level of ramification, resected the first 75 mm
fragment above the loop and removed it. Then, we placed 2 another loops at the
very base of the pedicle and removed the second fragment, thus performed total
polypectomy, leaving the ligated 10 mm long stalk stump in place. Neither bleed-
ing nor other complications occurred. The total length of the resected esophageal
lesion measured 135 mm. Histology showed the mixture of fibrous and adipose
tissue accompanied by an abundant network of large vessels, covered by a
normal squamous epithelium. The patient was discharged from the hospital on
the 4th day. A month later control EGD was performed, it revealed just tiny scar
at the level of the upper esophageal sphincter and no other changes of the
esophageal wall.
CONCLUSION: The removal of the giant esophageal polyp using modern endo-
scopic equipment can be safely performed without open surgery.
Disclosure of Interest: None declared
OP243 MUCOSAL INJURIES DURING PERORAL ENDOSCOPIC
MYOTOMY: ARE SEVERE COMPLICATIONS JUST AROUND THE
CORNER?
P. Familiari1,*, G. Gigante1, M. Napoleone1, M. Marchese1, I. Costamagna2,
I. Boskoski1, A. Tringali1, V. Perri1, G. Costamagna1
Digestive Endoscopy Unit, Gemelli University Hospital, 2Digestive Endoscopy
Unit, Gemelli University Hospitale, Rome, Italy
Contact E-mail address: pietrofamiliari@tiscali.it
INTRODUCTION: After Peroral Endoscopy Myotomy (POEM) the integrity of
esophageal mucosa is crucial for the safety of the procedure. Nevertheless a
variety of mucosal injuries may occur during POEM
AIMS & METHODS: Between 2011 and April 2014, 156 patients underwent
POEM in a single center. Before oral feeding patients underwent EGD to rule out
for mucosal injuries. Four different types of mucosal injuries occurred: intrao-
perative mucosal perforations, large mucosal tearing, postoperative ulcers and
extended mucosal flap necrosis.
RESULTS: Mucosal perforations occurred in 7 patients (4.5%): in 5 cases,
during the submucosal dissection, the knife inadvertently perforated the
mucosa at the esophagogastric junction (EGJ). In one case the tip of the endo-
scope perforated the mucosal flap. In the last case, during the myotomy, the
operator did not recognize the cleavage between the mucosa and the muscular
layer and cut the mucosa by mistake. In all these cases, the perforation was
immediately repaired with clips and the postoperative course was uneventful.
In one patient (0.6%), despite submucosal dissection seeming to proceed regu-
larly, when the endoscope was almost at the EGJ, a 12 cm long tearing of the
mucosa, likely caused by the shaft of the endoscope, was recognized. The pro-
cedure aborted, and the mucosal tearing was clipped. No complications occurred,
the patient was fed after 24 hours.
In 49 patients (31.4%) an ulceration, more likely related to thermal injury during
dissection, was observed at the EGJ. In 14 cases (16%) ulcers were larger than
1cm. Despite the potential risk of mediastinal infection, none of the patients
experienced fever, pain or symptoms, and they were fed after a median of 2.5
days.
In one patient, a complete necrosis of the mucosal flap, extended from the
mucosal incision to the EGJ was diagnosed. A suspected full thickness perfora-
tion was identified at the EGJ. CT scan was negative for mediastinal and abdom-
inal collections. A conservative treatment, including fasting and antibiotics was
instituted. The patient was fed with a soft diet after a negative EGD and eso-
phageal X-ray, 7 days later. The mucosal necrosis eventually resulted in a eso-
phageal stricture, that is still being dilated using bougies
CONCLUSION: Mucosal injuries are relatively frequent after POEM.
Nevertheless, mucosal injuries are asymptomatic in the vast majority of cases,
and do not usually alter substantially the post-operative course. However, endos-
copists should take particular care of the mucosal flap during submucosal dis-
section, because severe complications may be just around the corner.
Disclosure of Interest: None declared
OP244 FEASIBILITY OF USING THE MASTER TO PERFORM
FLEXIBLE ENDOSCOPIC SUTURING AND KNOT-TYING
P.W. Chiu1,2,*, S.J. Phee3, S. Chung1, K.Y. Ho4
1
Department of Surgery, Yong Loo Lin School of Medicine, National University of
Singapore, Singapore, Singapore, 2Department of Surgery, THE CHINESE
UNIVERSITY OF HONG KONG, Hong Kong, China, 3School of Mechanical and
Aerospace Engineering, Nanyang Technological University, Singapore,
4
Department of Medicine, Yong Loo Lin School of Medicine, National University
of Singapore, Singapore, Singapore
Contact E-mail address: philipchiu@surgery.cuhk.edu.hk
INTRODUCTION: We employed Master and Slave Transluminal Endoscopic
Robot (MASTER) to performed gastric ESD in 5 patients & endoscopic full
thickness resection in animal model [1,2]. Endoscopic closure of a gastrointestinal
defect remained the most challenging task. This is related to complexity of sutur-
ing and lack of instrumental dexterity. The latter could be mitigated with a
flexible 2-arm robotic assisted system. We aimed to investigate the feasibility
United European Gastroenterology Journal 2(5S)
of performing flexible endoscopic suturing and knot-tying using a revised version
of MASTER.
AIMS & METHODS: The MASTER was equipped with a pair of graspers and
needle holder. We used grasper to hold up the tissue and the other to drive the
needle through. The motions for suturing were controlled with external consoles.
Feasibility studies on endoscopic robotic suturing were conducted in a phantom
and a live pig. In phantom experiment, we examine continuous suturing & knot
typing using MASTER with 4-O V-LocTM (Covidien Co Ltd). In live pig, sutur-
ing was performed with 4-O suture (Ethicon Co Ltd) in a rectal incision. The
needle was grasped by the MASTER needle holder introduced through a 6.5 mm
instrument channel. The MASTER endoscope was then inserted into the rectum
without overtube. The timings to complete various stages of suturing in different
environments were recorded.
RESULTS: In phantom experiment, a total of 8 minutes 30 seconds was taken to
complete suturing with 2 knots. The operator took 1 minute 25 seconds to orient
the needle for suturing. Another 1 minute 17 seconds was spent to drive the
needle through the two edges. The needle was then cut, followed by the first
hitch in 1 minute 28 seconds and first knot tightened in 28 seconds. In the live
animal, the operator took 24 seconds to transfer the needle from the grasper to
needle holder with proper orientation. The needle was driven through tissue in 1
minute and 11 seconds. The MASTERs needle driver was able to hold the needle
steadily without rotation during the entire process.
CONCLUSION: We have shown that flexible robotic-assisted endoscopic system
can perform endoluminal suturing and knot-tying using commercially available
sutures and needles.
REFERENCES
1. Phee SJ, Reddy N, Chiu PW, et al. Robot assisted endoscopic submucosal
dissection is effective in treating patients with early stage gastric neoplasia. Clin
Gastroenterol Hepatol 2012; 10: 1117-1121.
2. Chiu PW, Phee SJ, Wang Z, et al. Feasibility of full thickness gastric resection
using master and slave transluminal endoscopic robot and closure by overstitch:
a preclinical study. Surgl Endosc 2014; 28: 319-324.
Disclosure of Interest: P. Chiu Consultancy for: Scientific Advisory Board
member of Endomaster, S. J. Phee Directorship(s) for: Co-founder of
Endomaster, Other: Developer of MASTER robot, S. Chung: None declared,
K. Y. Ho Directorship(s) for: Co-founder of Endomaster, Other: Developer of
MASTER robot
OP245 CLINICAL CASES OF NON-EXPOSED ENDOSCOPIC WALL-
INVERSION SURGERY WITH SENTINEL NODE BASIN
DISSECTION AS A NEW CONCEPT OF MINIMALLY INVASIVE
SURGERY FOR EARLY GASTRIC CANCER
O. Goto1,*, H. Takeuchi1, H. Kawakubo1, M. Sasaki1, A. Fujimoto1, Y. Ochiai1,
T. Uraoka1, Y. Kitagawa1, N. Yahagi1
1
Keio University, School of Medicine, Tokyo, Japan
Contact E-mail address: ogotou-gi@a3.keio.jp
INTRODUCTION: Non-exposed endoscopic wall-inversion surgery (NEWS)
was invented as a novel method of full-thickness resection without intentional
perforation and therefore without the risk of tumor seeding. Especially, NEWS
combined with sentinel node navigation surgery (SNNS) has been expected as a
minimally-invasive, function-preserving surgery for possibly node-positive early
gastric cancer (EGC)1).
AIMS & METHODS: We aimed to verify the feasibility of NEWS with sentinel
node basin dissection (SNBD). After obtaining an approval from the institu-
tional review board of the hospital, NEWS with SNBD was performed in 2
cases. One was 2 cm, diffuse-type mucosal cancer with ulceration, and the
other was a post-endoscopic submucosal dissection (ESD) case (25 mm, slightly
invasive submucosal cancer with lymphatic invasion). Under general anesthesia,
mucosal markings were placed and 0.5 ml of indocyanine green (ICG) solution (5
mg/ml) was injected into the submucosa at 4 quadrants around the lesion. After
10 min of injection, stained lymph nodes were identified as sentinel node (SN)s
and a SN basin including the SNs was dissected. After confirming no metastasis
in the SNs by intraopearative pathological diagnosis, NEWS was performed.
After placing serosal markings laparoscopically and circumferential submucosal
injection endoscopically, circumferential sero-muscular incision was made, fol-
lowed by sero-muscular suturing as the lesion and a surgical sponge inverted
toward the lumen. Subsequently, circumferential mucosal incision was made as
the sponge was picked out. The lesion was retrieved perorally and endoclips were
placed on the anastomosis. The completeness of the procedure and complications
were assessed.
RESULTS: NEWS with SNBD was successfully finished in the both cases. The
operation time and intraoperative blood loss were 270 min and 260 min, and less
than 10 ml and 40 ml, respectively. They were discharged without complications
on the postoperative day 13 and 10, respectively. The primary lesion was com-
pletely resected and final pathological diagnosis was identical with preoperative
one in the former case. No cancer was detected in the resected gastric wall in the
latter case. No cancer cell was identified in the dissected SN basins in the both
cases.
CONCLUSION: We demonstrated that NEWS with SNBD was feasible for
EGC cases. This method might become a new standard of minimally invasive
gastrectomy to cure EGC which is out of indication of ESD and also is a candi-
date of SNNS.
REFERENCES
1) Goto O, Takeuchi H, et al. Gastric Cancer. Epub ahead of print 2014.
Disclosure of Interest: None declared
A79
OP246 FIRST GASTRODUODENAL ANASTOMOSIS WITH PURE
NOTES APPROACH IN HUMAN BEING
M. Barthet1,*, G. Vanbiervliet2, J.-M. Gonzalez1, S. Berdah1
1
Gastroenterology, APHM, Marseille cedex 20, 2Gastroenterology, CHU Nice,
Nice, France
Contact E-mail address: marc.barthet@ap-hm.fr
INTRODUCTION: Pures NOTES gastrointestinal anastomosis with tissue
apposition stent might offer a safe, reliable and efficient procedure. After con-
ducting an experimental study in live pigs with 100 % success (1) following a two
years period research (2), we decided performing this procedure in human being.
AIMS & METHODS: The patient was a 30 years-old man with complete duo-
denal stenosis due to chronic pancreatitis and complicated with severe portal
hypertension related to portal vein thrombosis. Access to the peritoneal cavity
was done under EUS guidance, with 19G FNA needle and guidewire, in front of
the duodeno-jejunal angle (Video1). Then a 20 mm balloon dilatation over the
guide wire was performed to allow the passage of double working chanel gastro-
scope. After passing in the peritoneal cavity, the bowel loop was selected, held
with a twin grasper and the Hot Axios (X Lumena, California, USA) was intro-
duced in the duodenal lumen. The distal flange was deployed and the scope was
pulled back in the gastric cavity, bringing back the duodenal loop to the gastric
serosa. The proximal flange of the stent was released in the gastric lumen, making
a tight anastomosis
RESULTS: The procedure was uneventful. The patient was refed at day 2 with
soft diet and with normal diet ay day 4 without any problem. Ct scan and
endoscopic control were performed at day 5 (Video2) and the patient was dis-
charged from the hospital at day 6. At one month the stent was retrieved without
any difficulty showing an efficient anastomosis.
CONCLUSION: After a long and challenging period in experimental studies, we
believe that NOTES gastrointestinal anastomosis is feasible and safe in human
beings. We planned to start a pilot prospective study.
REFERENCES
1. Vanbiervliet G, Gonzalez JM, Bonin E, et al. Gastrojejunal anastomosis
exclusively using NOTES techniques in live pigs. Surg Innov 2013. Epub ahead
of print.
2. Vanbiervliet G, Garces-Duran R, Garnier E, et al. NOTES gastroenteric
anastomosis using a tissue apposition stent. A reproducible and efficient techni-
que in live pigs. UEGW 2013, October 16th, oral presentation.
Disclosure of Interest: None declared
OP247 SINGLE-SESSION ERCP AFTER ROUX-EN-Y GASTRECTOMY
USING A MODIFIED PERCUTANEOUS-ASSISTED
TRANSPROSTHETIC ENDOSCOPIC THERAPY (PATENT)
APPROACH
I. Penas Herrero1,*, F. Santos Santamarta1, P. Diez Redondo2, H. Nunez
Rodr guez2, P. Gil Simon2, C. De la Serna Higuera2, M. Perez-Miranda2
1
Gastroenterology, 2Endoscopy Unit, Hospital Universitario Ro Hortega,
Valladolid, Spain
Contact E-mail address: mpmiranda5@hotmail.com
INTRODUCTION: ERCP remains challenging following Roux-en-Y.
Transenteric ERCP via PEG or percutaneous jejunostomy tracks is an option
in selected cases. PATENT is a novel technique for percutaneous ERCP that
avoids the need for PEG tract maturation (Law R et al, Endoscopy2013;45:671-
5). The PEG tract is protected by a self-expandable metal stent (SEMS) placed
transmurally to allow immediate, safe percutaneous scope passage into the GI
tract. PATENT has so far being used only through the stomach.
AIMS & METHODS: We report ERCP in a Roux-en-Y gastrectomy patient by
means of a modified PATENT through the jejunum. A biflanged saddle-shaped
lumen-apposing metal stent (LAMS) was used for track protection and Ovesco
clips were used for jejunal closure.
RESULTS: A 76-year-old man with symptomatic common bile duct stones had
failed ERCP because of prior Roux-en-Y total gastrectomy. He had several other
comorbidities, prior abdominal surgeries and relapsing episodes of adhesion-
related bowel obstruction. At the time of failed ERCP, abdominal transillumina-
tion was achieved next to the afferent jejunal limb anastomosis. Two T-tags were
used to hold the small bowel in place prior to insertion of a Russell introducer
into the jejunum. After track dilation, a 15mm diameter LAMS (X-Lumena,
Mountain View, Ca) was placed percutaneously, with the distal flange deployed
in the jejunum under endoscopic monitoring, and the proximal flange deployed
at the skin access site. After forced balloon expansion, a standard gastroscope
was passed through the LAMS into the jejunum up to the papilla. Cannulation,
sphincterotomy and stone removal were performed. Single-scope cholangioscopy
was instrumental to clear cystic duct stones.
After ERCP and cholangioscopy, the gastroscope was withdrown towards the
jejunostomy, then redirected retrogradelly towards the esophagus through the
efferent jejunal limb. Another gastroscope with the Ovesco clip in place was
passed per-orally. Dual scope rendezvous facilitated identification and Clip-clo-
sure of the jejunostomy. Methylene-blue was used to check for leakage. A bal-
loon PEG-tube was left for temporary drainage. No procedural complications
ensued.
CONCLUSION: PATENT is also feasible through the jejunum. LAMS instead
of SEMS and Ovesco-clip closure are technical choices worth considering to
enhance overall PATENT safety. PATENT widens the options for endoscopic
biliary therapy in cases where enteroscopy-based ERCP is not feasible.
Disclosure of Interest: None declared
A80
OP248 EUS-GUIDED HEPATIC INTRA-ARTERIAL
CHEMOEMBOLIZATION
E. L. A. Artifon1, F.O. Carneiro1, C.M. Sakai1,1,*, G. L. R. Silva1, R.N. Moura1,
B.F. Medrado1, C.K. Furuya1, P. Sakai1
1 1
Gastrointestinal Endoscopy, Clinicas Hospital of Sao Paulo University, Sao
Paulo, Brazil
Contact E-mail address: chris_ms@hotmail.com
INTRODUCTION: Intra-arterial chemotherapy is an effective modality to treat
unresectable hepatic metastasis from colorectal primaries if systemic chemother-
apy has failed. This technique has some advantages over systemic chemotherapy,
such as: very high concentrations of agents in a pre-determined region (FUDR
provides 15-fold increase); anoxic damage that increases vascular permeability
and provides better chemotherapy infiltration; cytotoxic effect that leads to vas-
culitis by occlusion/ischemia; and free-radical injury due to toxicity to the tumor
during reperfusion.
AIMS & METHODS: In this presentation, we will demonstrate an EUS guided
fine-needle intra-arterial injection of chemotherapy.
This technique was performed in a 53-year-old woman with an advanced sigmoid
colon cancer who presented with abdominal pain six months after sigmoidect-
omy. CT revealed multiple nodules in segments III, VI, VII and VIII of the liver.
The patient underwent trans-arterial chemoembolization (TACE), with 70%
regression of all nodules, except for one measuring 4cm on segment III.
By a single-step procedure, the EUS linear equipment was positioned at the
proximal gastric wall and the hepatic nodule was identified. With the use of
Doppler imaging, we localized the arterial vessel that supplies the nodule.
After that, it was performed EUS-guided hepatic intra-arterial puncture, with
a 22-gauge needle, confirmed by contrast media injection. With this confirma-
tion, the intra-arterial injection was performed with chemotherapies substances
and lipiodol.
RESULTS: In this patient, the CT showed regression on the tumor size of 20%,
40% and 60% after 7 days, 1 and 3 months.
Our group has demonstrated in a previous study of EUS-guided or
Interventional radiology to hepatic intraarterial chemotherapy: a prospective
trial, that response rate, median survival, and median complication free survival
were similar in both of the treatment modalities, but the median duration of
hospitalization was smaller in the EUS-guided approach patients.
CONCLUSION: EUS-guided intra-arterial chemotherapy appears to be safe and
feasible in a subset of patients with metastatic liver disease. Further studies are
necessary before a formal recommendation is made.
Disclosure of Interest: None declared
OP249 EUS-GUIDED ANASTOMOSES AS CONDUIT FOR
ENDOTHERAPY OF COMPLICATED HEPATOLITHIASIS
A.L. Vargas-Garcia1,*, I. Penas Herrero1, F. Santos Santamarta1, R. Sanchez-
Ocana1, P. Diez-Redondo1, H. Nunez1, C. De la Serna-Higuera1, M. Perez-
Miranda1
1
Gastroenterology, Hospital Universitario Ro Hortega, Valladolid, Spain
Contact E-mail address: mpmiranda5@hotmail.com
INTRODUCTION: EUS-guided anastomoses using covered Self-Expandable
Metal Stents (SEMS) are used for pseudocyst drainage and necrosectomy. This
concept could be applied to stone clearance of hepatolithiasis, shifting from
percutaneous to endoscopic intervention, with potentially improved patient qual-
ity of life.
AIMS & METHODS: We performed EUS-guided hepatico-gastrostomy (HGS)
with a covered SEMS followed by removal of left-sided hepatolithiasis through
the HGS. A right liver lobe abscess was also drained transduodenally under EUS,
and retained stones removed.
RESULTS: A 48 y.o. cholecystectomized female had relapsing biliary colic and
cholangitis. ERCP showed stones filling the left ductal system above a stricture at
the confluence. ERCP-based lithotripsy was not deemed feasible, and plastic
biliary stents were placed. Left hepatectomy was considered and dismissed in
favour of a radical attempt at endoscopic removal. EUS-guided HGS was per-
formed with a covered biliary SEMS. Two-weeks later, a nasobiliary drain was
placed via ERCP into the left hepatic duct, and transgastric cholangioscopy
performed through the HGS for lithotripsy and retrograde stone clearance into
the stomach. Mild postprocedure cholangitis subsided. Retained stone fragments
were cleared at second look cholangioscopy. The HGS SEMS was removed. She
remained well for 8 months but then had severe sepsis caused by liver abscess on
segments VI-VII. After failed abscess resolution and persistent sepsis following
percutaneous drainage, EUS-guided transduodenal abscess drainage was per-
formed. Procedural steps for HGS were replicated: 1) EUS identification and
19G needle puncture of target; 2) 0.035 guidewire passage into the abscess
through needle; 3) Serial over-the-wire puncture tract dilation with a 6.5F cysto-
tome and 4mm balloon; 4) 4cm covered SEMS placement across puncture tract
under combined fluoroscopy and endoscopy. The distal stent end was clipped to
the duodenal mucosa to minimize migration risk. Balloon cholangiography
through the SEMS showed communication with a dilated intrahepatic duct
and retained stones. A7F plastic stent was placed through the SEMS into the
bile-duct. Abundant pus drained from the abscess into the duodenum. Sepsis
improved within hours. Stones were cleared electively through the SEMS 2-
weeks later, once a mature track had developed. The patient recovered
uneventfully.
CONCLUSION: EUS-guided anastomoses using covered biliary Self-
Expandable Metal Stents (SEMS) allowed interval biliary drainage and delayed
treatment of left-sided hepatolithiasis and right-sided liver abscess.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP250 A VERY STRANGE POLYP OF THE SIGMA IN COLO-RECTAL
SCREENING COLONOSCOPY
M. Rossi1,*, G. Ghezzi 2, M. Motter2, R. Nienstedt1, R. Fasoli1, C. Tieppo1,
D. Giacomin1, F. Agugiaro1, G. de Pretis1
Gastroenterology, 21st Division of Surgery, S.Chiara Hospital, Trento, Italy
Contact E-mail address: mauro.rossi@apss.tn.it
INTRODUCTION: Productive colo-rectal lesions observed during a screening
colonoscopy performed in a faecal-occult-blood-test (FOBT)-positive female
patient are sometimes a challenge both for endoscopists and pathologists.
AIMS & METHODS: We describe the case of a 52-year-old asymptomatic
woman who underwent a screening colonoscopy after having being found posi-
tive at FOBT, as well as diagnostic difficulties thereof, subsequent follow-up and
final diagnosis.
RESULTS: During a screening colonoscopy after FOBT, on 16th December
2009, an unusual huge sessile polyp of the sigmoid region was observed.
Biopsies showed a nonspecific chronic inflammation and the pathologist reported
the presence of iron pigment deposits. Follow-up colonoscopy three months later
confirmed the lesion, with macrobiopsies suggestive of deep cystic colitis. On 19th
of April 2011 a CT scan was reported as unremarkable. The patient remained
asymptomatic and we performed a control colonoscopy on 11th October 2011,
which showed an important regression of the lesion. Histological examination in
two of six biopsies showed an incipient tubular adenoma with mild dysplasia and
in the other four biopsies acute and chronic inflammation. At this point the
lesion was considered an adenomatous polyp and the patient was referred to
surgery, due to the judgment of endoscopic unresectability. The patient refused
surgery and we performed a new colonoscopy on the 9th of March 2012, when we
noted a further regression of the lesion.
At a deeper enquiry in her medical history she reported very painful menses
associated with temporary constipation. For this reason she had performed several
pelvic ultrasounds as well as gynaecological examinations, all reported normal.
Moreover, she reported the occurrence of her last menstrual cycle at the time of the
first colonoscopy. On this basis, new biopsies were sent to the pathologist with the
clinical suspect of endometriosis. The reassessment of the CT scan showed a
thickening of the sigmoid wall. An endoscopic ultrasound showed a hypoechoic
thickening of the sigmoid with impairment of the normal wall stratification. The
ultimate histopathological report confirmed the diagnosis of endometriosis.
CONCLUSION: 1) endometriosis can present as an unusual sessile polyp
mimicking colonic carcinoma (1).
2) the presence of iron pigments in the first histological report could suggest the
diagnosis.
3) the regression of the lesion due to menopause facilitated in this case the
diagnosis, which saved an unnecessary surgical resection.
REFERENCES
1. Kelly P, et al. Intestinal endometriosis morphologically mimicking colonic
adenocarcinoma. Histopathology 2008; 52: 510-514.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
HOW TO MANAGE IBD IN 2014 HALL D_____________________
OP251 LONG-TERM OUTCOMES OF TOP-DOWN VERSUS STEP-UP
TREATMENT IN NEWLY DIAGNOSED CROHNS DISEASE
D.R. Hoekman1,*, J.A. Stibbe2, F.J. Baert3, P. Caenepeel4, P. Vergauwe5, M. de
Vos6, A. A. van Bodegraven7, S.A. Vermeire4, G.R. DHaens2
1
(Pediatric) Gastroenterology, 2Gastroenterology, Academic Medical Center,
Amsterdam, Netherlands, 3Gastroenterology, AZ Delta, Roeselare,
4
Gastroenterology, University Hospital Gasthuisberg, Leuven, 5Gastroenterology,
AZ Groeninge Hospital, Kortrijk, 6Gastroenterology, Ghent University Hospital,
Ghent, Belgium, 7Gastroenterology, VU University Medical Centre, Amsterdam,
Netherlands
Contact E-mail Address: d.r.hoekman@amc.uva.nl
INTRODUCTION: Early combined immunosuppression (top-down (TD)) is
more effective than conventional management (step-up (SU)) for induction of
remission and reduction of corticosteroid use in patients with recently diagnosed
with Crohns disease (CD). However, it remains unknown whether short-term
benefits are sustained long-term and if the natural history of CD can be altered.
Therefore, we aimed to investigate the long-term effects of TD (induction IFX
and maintenance azathioprine (AZA)) vs. conventional SU treatment in CD.
AIMS & METHODS: Long-term follow-up data was retrospectively collected
from patients who participated in a randomized controlled trial evaluating TD
vs. SU in patients with newly diagnosed Crohns disease (1). Data collection was
performed in 15 of the 18 participating centers. For 16 semesters following the
original 2-year trial, the following data was abstracted from patients medical
records: clinical disease activity by global assessment, significant flares of CD,
medication use, hospitalization, surgery and the occurrence of new fistulas.
Comparisons were done by intention-to-treat analysis. Time to event data was
evaluated using the Kaplan-Meier and log-rank test. Proportions were compared
using Fishers exact test. Colonoscopy reports were scored as one of the follow-
ing: Normal (0), aphthous ulcers (1), small ulcers (2) or large/deep ulcers (3).
RESULTS: 124 patients (SU n63) were included in the analysis. At the start of
follow-up, 81.8% (60.0% AZA, 21.8% methotrexate (MTX)) vs. 66.0% (50.9%
AZA, 11.3% MTX) of patients used an immunomodulator, and 20.0% vs.
15.1% received IFX in TD and SU, respectively. The number of semesters in
full clinical remission did not differ between between TD and SU (68.0% vs.
68.0%; p1.0). However, patients in the TD group had fewer semesters with a
flare (13.2% vs. 20%; p50.01), and longer flare-free survival (median 9 vs. 5
semesters; p0.03). Mean time to first hospitalization was 13.8 vs. 13.2 semesters
(p0.47), mean time to first new fistula was 15.2 vs. 14.1 semesters (p0.21) and
United European Gastroenterology Journal 2(5S)
mean time to Crohn-related surgery was 15.1 vs. 14.1; p0.19) for TD and SU,
respectively. 157 endoscopy reports of 75 patients were scored. 19.4% of TD and
38.5% of SU patients had at least one endoscopy with large ulcers (p0.08).
66.7% of TD and 56.4% of SU patients had at least one endoscopy with no
ulceration (p0.48).
CONCLUSION: Top-down treatment resulted in a reduction of flares and a
longer flare-free survival compared to step-up treatment. These results suggest
that TD algorithms might be beneficial in newly diagnosed CD. However, TD
treatment did not result in differences in remission rates, surgery, or other out-
comes, although a trend was observed for the presence of large ulcers during
endoscopy.
REFERENCES
(1) DHaens, GR et al. Early combined immunosuppression or conventional
management in patients with newly diagnosed Crohns disease: an open rando-
mised trial. Lancet 2008; 371: 660667.
Disclosure of Interest: D. Hoekman: None declared, J. Stibbe: None declared, F.
Baert Financial support for research from: Abbott, Lecture fee(s) from: Merck,
Abbott, Consultancy for: Merck, Abbott, Falk, P. Caenepeel: None declared, P.
Vergauwe: None declared, M. de Vos: None declared, A. van Bodegraven Lecture
fee(s) from: Abbott, Ferring, Consultancy for: Abbott, MSD, S. Vermeire
Financial support for research from: UCB Pharma, MSD, Abbvie, Lecture
fee(s) from: Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for:
UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, G.
DHaens Financial support for research from: Abbott, Jansen Biologics, Given
Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s) from: Abbott, Tillotts,
Tramedico, Ferring, MSD, UCB Farma, Norgine, Shire, Consultancy for:
Abbott, Actogenix, Centocor, Cosmo, Engene, Ferring, GlaxoSmithKline,
Jansen Biologics, Millenium Pharmaceuticals, MSD, Novonordisk, PDL
Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB Farma
OP252 MANAGING PEDIATRIC ACUTE SEVERE ULCERATIVE
COLITIS ACCORDING TO THE 2011 ECCO-ESPGHAN
GUIDELINES: EFFICACY OF INFLIXIMAB AS A RESCUE THERAPY
G. DArcangelo1, M. Capponi1, F. Nuti1, F. Civitelli1, G. Romano1,
F. Vassallo1, F. Viola1, S. Cucchiara1, M. Aloi1,*
1
Pediatric Gastroenterology And Liver Unit, SAPIENZA UNIVERSITY OF
ROME, Rome, Italy
Contact E-mail Address: marina.aloi@uniroma1.it
INTRODUCTION: Acute severe ulcerative colitis (ASC) is a potentially life-
threatening event. Scarce pediatric data are available about success rates of
Infliximab (IFX) as a second line therapy.
AIMS & METHODS: This study was performed in consecutively observed
pediatric patients with ASC and aimed at assessing the long-term efficacy of
IFX and clinical predictors of poor outcome. Patients had been recruited, after
reporting of the 2011 ECCO-ESPGHAN guidelines on pediatric ASC1. Children
who experienced an episode of ASC, defined as a PUCAI of at least 65 points,
were evaluated. Clinical assessment through PUCAI and laboratory data (ESR,
CRP, hemoglobin, albumin, hematocrit, ferritin) were recorded at admission and
at day 3 and 5. All patients were treated according to the above mentioned
guidelines for ASC and received intravenous (iv) corticosteroids (CS). IFX was
administered as second-line therapy in CS-refractory patients. In a 2-year follow
up we assessed the overall colectomy rate and efficacy of IFX.
RESULTS: Thirty-one patients (age: 10.64.88, 52% female) met the criteria for
ASC: 21 (68%) responded to iv CS, while 10 (32%) received IFX for CS-refrac-
toriness. Among the latter, 2 (20%) underwent urgent colectomy; however, at a
2-year follow up, 5 (50%) needed elective colectomy, while only 3 of the CS-
responders required surgery (14%). Compared to CS-responsive patients, those
CS-refractory showed a significantly shorter interval from the diagnosis of
ulcerative colitis to the episode of ASC (p 0.04) and a higher rate of colectomy
at maximum follow-up (p0.007). Patients needing colectomy differentiated
from those responding to medical therapy for more frequent courses of CS
prior to ASC (p0.02), but not for laboratory values, sex, disease location,
disease extension, therapy, mean PUCAI, serological markers and family history.
CONCLUSION: Although it has short-term effectiveness as a rescue therapy to
avoid urgent colectomy in CS-refractory children, IFX does not modify the long
term colectomy rate in ASC. Frequent courses of CS are predictive of a poor
long-term outcome.
REFERENCES
1 Am J Gastroenterol 2011; 106: 574-588.
Disclosure of Interest: None declared
OP253 IMPACT OF DISEASE DURATION ON CLINICAL OUTCOMES
WITH ADALIMUMAB TREATMENT IN PATIENTS FROM IMAGINE
1 treated with anti-TNF alpha. For most of them with severe lesions unresponsive to
M. Dubinsky1, J.S. Hyams2, J. Rosh3, J. Markowitz4, F. Ruemmele5,*,
S. Eichner6, A. Lazar7, Y. Li6, B. Pappalardo6, R.B. Thakkar6
1
Cedars-Sinai Medical Center, Los Angeles, 2Connecticut Childrens Medical
Center, Hartford, 3Goryeb Childrens Hospital/Atlantic Health, Morristown,
4
Cohen Childrens Medical Center, New Hyde Park, United States, 5Universite
Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, Paris, France, 6AbbVie
Inc, North Chicago, United States, 7AbbVie Deutschland GmbH & Co. KG,
Ludwigshafen, Germany
INTRODUCTION: Adalimumab (ADA) was shown to be an effective treatment
in inducing and maintaining remission in children with moderately to severely
active Crohns disease (CD) in the IMAgINE 1 trial1. The impact of baseline
disease duration on the safety and efficacy of ADA is evaluated in patients (pts)
from IMAgINE 1.
A81
AIMS & METHODS: In IMAGINE 1, pts aged 6-17 years (yrs) with baseline
PCDAI 430 received open-label (OL) induction of ADA at weeks 0/2 according
to body weight (40kg, 160/80mg; 540kg, 80/40mg). At week 4, pts were rando-
mized according to body weight to double-blind higher-dose (HD) ADA (40kg,
40mg every other week [EOW]; 540kg, 20mg EOW) or lower-dose (LD) ADA
(40kg, 20mg EOW; 540kg, 10mg EOW) to week 52. Pts experiencing disease
flare or non-response could move to blinded weekly dosing after week 12, then to
OL weekly HD ADA for continued flare/non-response. Pts with loss of response
or intolerance to infliximab (IFX) could enroll in IMAgINE 1. Remission
(PCDAI10) and response (PCDAI decrease  15 points from baseline) were
assessed in pts, regardless of dose, at weeks 26 and 52 according to disease duration
at IMAgINE 1 baseline: 1, 41-2, 42-3, 43 yrs. The impact of prior IFX use
and disease duration on remission rates was also assessed in the disease duration
subgroups. Data were analyzed using non-responder imputation (NRI), whereby
pts with missing data or that obtained after moving to weekly dosing were con-
sidered not to have efficacy, and a modified NRI (mNRI) whereby only pts with
missing data were considered as non-responders.
RESULTS: Greater rates of remission and response were observed across the
three disease duration subgroups  3 yrs at both weeks 26 and 52 relative to
those with disease duration 4 3 yrs (Table). IFX naive pts had numerically
higher rates of remission relative to IFX exposed pts regardless of disease dura-
tion subgroup. Rates of serious adverse events (AEs) and AEs leading to dis-
continuation were lower in pts with shorter duration of CD ( 3 yrs).
Table. Week 26 and 52 remission and response rates in ADA-treated patients by
baseline disease duration subgroup
1.0 yr 41.0-2.0 yrs 42.0-3.0 yrs 43.0 yrs
N43 N30 N43 N72
NRI mNRI NRI mNRI NRI mNRI NRI mNRI
Remission, n (%)
Week 26 13 (30.2) 16 (37.2) 15 (50.0)* 15(50.0)* 17 (39.5) 17 (39.5) 18 (25.0) 21 (29.2)
Week 52 7 (16.3) 13 (30.2) 14 (46.7)y 15 (50.0) 12 (27.9) 15 (34.9) 20 (27.8) 23 (31.9)
Response, n (%)
Week 26 20 (46.5) 28 (65.1) 21 (70.0)* 23(76.7)* 26 (60.5) 28 (65.1) 34 (47.2) 40(55.6)
Week 52 9 (20.9) 21 (48.8) 17(56.7)*y 20(66.7)* 17 (39.5) 24 (55.8) 23 (31.9) 30(41.7)
CONCLUSION: Higher efficacy rates and lower incidence of serious adverse
events in pts with a shorter duration of CD suggests early treatment with ADA
may be beneficial for pts.
REFERENCES
1. Hyams et al. Gastroenterology 2012; 143: 365-374.
Disclosure of Interest: M. Dubinsky Financial support for research from: Janssen,
Consultancy for: AbbVie, Janssen, Takeda, Pfizer, Prometheus labs, Santarus,
UCD, J. Hyams Lecture fee(s) from: Janssen Orthobiotech, Consultancy for:
Janssen Orthobiotech, AbbVie, TNI Biotech, EnteraHealth, Pfizer, Soligenix,
Takeda, Other: Expert testimony and payment for development of educational
presentations: Janssen Orthobiotech, J. Rosh Financial support for research from:
AstraZeneca, AbbVie, Janssen, UCB, Lecture fee(s) from: Abbott Nutrition,
Prometheus, Consultancy for: AbbVie, Janssen, Soligenex, Other: Board member-
ship: GI Health Foundation, J. Markowitz Consultancy for: AbbVie, Janssen
OrthoBiotech, UCB, Soligenix, F. Ruemmele Lecture fee(s) from: Shering-
Plough, Nestle, MeadJohnson, Ferring, MSD, Johnson & Johnson, Centocor,
Other: Board membership: SAC:DEVELOP (Johnson & Johnson), invited to
MSD France, Nestle Nutrition Institute, invited to Nestle Health Science, invited
to Danone, invited to MeadJohnson, Biocodex, S. Eichner Shareholder of:
AbbVie, Other: Employee: AbbVie, A. Lazar Shareholder of: AbbVie, Other:
Employee: AbbVie, Y. Li Shareholder of: AbbVie, Other: Employee: AbbVie,
B. Pappalardo Shareholder of: AbbVie, Other: Employee: AbbVie, R. Thakkar
Shareholder of: AbbVie, Other: Employee: AbbVie
OP254 PARADOXICAL PSORIASIS IN A LARGE COHORT OF IBD
PATIENTS TREATED WITH ANTI-TNF ALPHA: 5 YEARS-
FOLLOW-UP STUDY
D. Pugliese1,*, P.M. Ferraro2, M. Marzo1, C. Felice1, L. Celleno3,
O.M. Nardone1, G. Andrisani1, F. Pizzolante1, A. Papa1, I. De Vitis1,
G. Rapaccini1, L. Guidi1, A. Armuzzi1
1
IBD UNIT, 2Nefrology, 3Dermatology, Complesso Integrato Columbus Catholic
University, Rome, Italy
Contact E-mail Address: danipug@libero.it
INTRODUCTION: New onset of psoriasiform skin lesions is an emerging para-
doxical side effect in a subgroup of patients with inflammatory bowel disease (IBD),
topical therapy, it is necessary to withdraw from treatment, with relevant impact on
the management of disease. To date the pathogenesis is not fully understood, but
smoking seems to be a risk factor for developing these lesions. Aim of this study was
to estimate the incidence of psoriasiform skin lesions in a large cohort of IBD
patients treated with anti-TNF alpha and to analyze its clinical correlates.
AIMS & METHODS: A retrospective cohort study on all IBD patients who
started anti-TNF alpha at our IBD Center from January 2008 to December
2013 was performed. We recorded clinical characteristics at baseline: sex, type
and duration of disease, extra-intestinal manifestations, smoking habit, type of
anti-TNF alpha and concomitant immunosuppressive therapy. Information on
time-dependent variables was updated at each clinical visit. Baseline character-
istics of patients who did and did not develop psoriasis were compared with t-
test, Mann-Whitney and Fisher exact test as appropriate. Proportional hazards
regression models were used to estimate the association between each predictor
A82 United European Gastroenterology Journal 2(5S)
and time to development of psoriasis. Time-dependent predictors were updated In general, the percentages of patients with individual infection AEs were similar
at each available time point. between the PBO and VDZ subgroups, except for nasopharyngitis, which was
RESULTS: A total of 401 patients started anti-TNF alpha (both infliximab and less common with PBO (range across all PBO subgroups, 4%412%). Also,
adalimumab) between January 2008 and December 2013. There was preponder- percentages of patients with individual infection SAEs across all PBO subgroups
ance of Crohns disease (60%) and infliximab treated patients (60%), with a were similar to or nominally lower than those across all VDZ subgroups.
mean age at diagnosis of 40  14 years. The median duration of disease was 6 CONCLUSION: These data suggest that the infection AE and SAE profiles in
years (range 0-29 years). Thirty-one percent of patients had also concomitant patients with UC or CD are similar whether VDZ is used as monotherapy or with
extra-intestinal manifestations and 21% were started on concomitant immuno- concomitant IM and/or CS therapy. Infection rates were generally similar among
suppressive therapy. Participants contributed a total of 738 person-years of the VDZ and PBO groups, although length of exposure tended to be longer for VDZ
follow-up, during which 42 incident cases of psoriasis were recorded, all of than for PBO. The rarity of individual infection SAEs limits the interpretation of
them confirmed by punch biopsies, with an incidence rate of 5.7 per 100 these data.
person-years. Comparing IBD patients with and without skin lesions, we REFERENCES
found higher rate of smokers in the subgroup of patients who developed psoriasis 1. Feagan BG, et al. N Engl J Med 2013; 369: 699-710.
(18% vs 36%, p 0.01). Cox-regression survival analysis confirmed smoking as 2. Sandborn WJ, et al. N Engl J Med 2013; 369: 711-721.
independent predictor of psoriasis (HR 2.52, 95%CI 1.33, 4.76, p 0.01). Disclosure of Interest: J.-F. Colombel Consultancy for: Abbott, Amgen, Biogen,
Conversely, concomitant immunosuppressive therapy was inversely related to M. Boehringer-Ingelheim, BMS, Cellerix SL, Chemocentryx, Centocor, Cosmo
psoriasis (HR 0.34, 95% CI 0.12, 0.95, p 0.04). The association with other Tech Ltd, Elan, Genentech, Giuliani SPA, Given Imaging, GSK, Immune
predictors was not statistically significant. Pharmaceuticals, Merck & Co, Millennium Pharmaceuticals, Neovacs SA,
CONCLUSION: New onset of psoriasis is a relevant side effect of anti-TNF Ocera Therapeutics, Pfizer, Prometheus, Sanofi, Schering, Shire, Synta,
alpha therapy, with an incidence rate of 5.7 per 100 person-years. Smoking is Takeda, Teva, Tikvah Therapeutics, Inc., Therakos, TxCell, UCB Pharma,
confirmed as the main risk factor for developing lesions. The combination ther- Wyeth, C. Siegel: None declared, B. Abhyankar Other: Employee of Takeda
apy with anti-TNF alpha plus immunosuppressants was associated with a Global Research & Development Centre Ltd., E. Loftus, Jr. Financial support
reduced risk for psoriasis. for research from: AbbVie, UCB Pharma, Janssen, Takeda, Amgen, Pfizer,
Disclosure of Interest: D. Pugliese: None declared, P. Ferraro: None declared, M. Genentech, Santarus, Shire, Bristol-Myers Squibb, GlaxoSmithKline, Robarts
Marzo: None declared, C. Felice: None declared, L. Celleno: None declared, O. Clinical Trials, Consultancy for: AbbVie, UCB Pharma, Janssen, Takeda,
Nardone: None declared, G. Andrisani: None declared, F. Pizzolante: None Immune Pharmaceuticals, J. Lewis Financial support for research from: Bayer,
declared, A. Papa: None declared, I. De Vitis: None declared, G. Rapaccini: Shire, Centocor, Nestle, Takeda, Consultancy for: Takeda, Rebiotix, Amgen,
None declared, L. Guidi Financial support for research from: AbbVie, MSD, Millennium Pharmaceuticals, Prometheus, Lilly, Shire, AstraZeneca, Janssen
A. Armuzzi Lecture fee(s) from: AbbVie, MSD, Chiesi, Ferring, Nycomed, Pharmaceuticals, Merck, AbbVie, Other: Served on a Data and Safety
Takeda and Otsuka, Consultancy for: AbbVie, Lilly, MSD and Takeda Monitoring Board for clinical trials sponsored by Pfizer, S. Sankoh Other:
Employee of Takeda Pharmaceuticals International Co., M. Smyth Other:
Employee of Takeda Global Research & Development Centre Ltd., C. Milch
OP256 SAFETY OF VEDOLIZUMAB ALONE OR WITH Other: Employee of Takeda Pharmaceuticals International Co.
CONCOMITANT CORTICOSTEROIDS AND/OR
IMMUNOSUPPRESSANTS IN PATIENTS WITH ULCERATIVE
COLITIS OR CROHNS DISEASE TUESDAY, OCTOBER 21, 2014 15:4517:15
1, 2 3 4 5 NOVEL APPROACHES FOR THE TREATMENT OF LIVER METASTASES HALL
J.-F. Colombel *, C.A. Siegel , B. Abhyankar , E., V. Loftus, Jr. , J.D. Lewis ,
B_____________________
S. Sankoh6, M. Smyth3, C. Milch6
1
Icahn School of Medicine at Mount Sinai, New York, 2Dartmouth-Hitchcock
Medical Center, Lebanon, NH, United States, 3Takeda Global Research & OP257 INCREASED COLORECTAL CANCER RISK IN FIRST-DEGREE
Development Centre Ltd, London, United Kingdom, 4Mayo Clinic, Rochester, MN, RELATIVES OF PATIENTS WITH SERRATED POLYPS WHO DO
5
Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, NOT FULFIL WHO CRITERIA FOR SERRATED POLYPOSIS
6
Takeda Pharmaceuticals International Co., Cambridge, MA, United States SYNDROME
Contact E-mail Address: jean-frederic.colombel@mssm.edu C. Guarinos1,*, C. Egoavil1, M. Juarez1, M. Rodriguez-Soler1, E. Hernandez-
Illan1, P. Zapater1, R. Jover1 on behalf of EPIPOLIP group
INTRODUCTION: Safety and efficacy of vedolizumab (VDZ) in treating ulcera- 1
Hospital General Universitario Alicante, Alicante, Spain
tive colitis (UC) and Crohns disease (CD) were established in the GEMINI 11 Contact E-mail Address: rodrigojover@gmail.com
and 22 trials, respectively, wherein rates of some infections (eg, nasopharyngitis)
were higher with VDZ therapy than with placebo (PBO). This analysis evaluates INTRODUCTION: Diagnosis of serrated polyposis syndrome (SPS) is made by
infection rates in patients treated with VDZ alone or with concomitant corticos- the fulfillment of any of the WHO criteria. These criteria have been considered to
teroids (CSs) and/or immunosuppressants (IMs) in GEMINI 1 and 2. be very stringent. Patients with multiple serrated polyps can also show high risk
AIMS & METHODS: The randomized PBO-controlled GEMINI 1 and 2 studies of colorectal cancer (CRC) without fulfilling these criteria.
each consisted of a 6-wk induction phase (VDZ 300 mg or PBO at wks 0 and 2) AIMS & METHODS: 1) To determine if patients with multiple serrated polyps
followed by a 46-wk maintenance phase (VDZ 300 mg or PBO every 4 or 8 wks). non-fulfilling WHO criteria show a similar clinical and molecular profile to SPS
Data from both phases of both studies were pooled, and percentages of patients cases. 2) To determine the risk of cancer in patients with multiple serrated polyps
with adverse events (AEs) and serious adverse events (SAEs) in the Infections and and their relatives.
Infestations System Organ Class (MedDRA version 15) were determined for Patients from the EPIPOLIP study, a multicenter nationwide project that aimed
those who received VDZ or PBO during both induction and maintenance. Data to investigate causes of multiple colonic polyps, were included. A total of 54
were analyzed by baseline concomitant CS and IM use. patients fulfilling WHO criteria for SPS were included. As well, 64 patients
RESULTS: In GEMINI 1 and 2, 1434 patients received VDZ and 297 received with more than 10 polyps throughout the colon, more than 50% of them ser-
PBO during both the induction and maintenance phases. Percentages of patients rated, without fulfilling WHO criteria for SPS (SPS-like group) were also
with infection AEs and infection SAEs were similar among subgroups, regardless included for comparison. Clinical and pathological characteristics of patients
of whether VDZ was used as monotherapy or with a CS and/or IM (Table). with SPS and SPS-like were compared. Moreover, mutation analysis of KRAS
Table to abstract OP256 and BRAF was performed in a total of 1504 polyps of all the patients from both
groups and also from a third group of 73 patients with sporadic serrated polyps.
No. (%) of Patients Age- and sex-adjusted standardized incidence ratios (SIRs) of CRC in first-
degree relatives were calculated in SPS and SPS-like pedigrees. SIR from a
VDZ Only VDZ CS VDZ IM Only VDZ CS IM random sample of 115 families with sporadic CRC was used for comparisons.
Event Preferred Term (n445) Only (n506) (n247) (n236) RESULTS: Patients with SPS-like show a lower number of polyps (mean 46 vs
26; p50.001), higher number of adenomas (median 1 vs 3; p0.002) and an older
Infection AEsa age at diagnosis (49 vs 53years; p0.03). There were no differences in family
Any infection AE 196 (44) 214 (42) 112 (45) 100 (42) history of CRC or polyps (48% vs 46%) either personal history of CRC (20% vs
Nasopharyngitis 67 (15) 52 (10) 27 (11) 34 (14) 17%). KRAS or BRAF somatic mutations have been shown in at least 25% of
Upper respiratory 34 (8) 33 (7) 21 (9) 18 (8) the polyps in all the SPS cases and in 96% of SPS-like patients. In both groups,
somatic mutations of BRAF and KRAS share a very close profile in sessile
tract infection serrated adenomas (SSA) and hiperplastic polyps (HP) (BRAF: SSA SPS 89%;
Bronchitis 20 (4) 20 (4) 9 (4) 8 (3) SSA SPS-like 78%; HP SPS 69%; HP SPS-like 64%; KRAS: SSA SPS 2.8%;
Influenza 18 (4) 18 (4) 5 (2) 10 (4) SSA SPS-like 8.2%; HP SPS 15.1%; HP SPS-like 9.9%). However, the molecular
Sinusitis 13 (3) 18 (4) 3 (1) 10 (4)
profile in sporadic serrated polyps is very different, with lower frequency of
BRAF mutation and higher of KRAS (BRAF: SSA sporadic 50%; HP sporadic
Urinary tract infection 14 (3) 17 (3) 7 (3) 11 (5)
30%, p50.001; KRAS: SSA sporadic 50%; HP sporadic 28.5%, p50.001). The
Infection SAEsb incidence of CRC was similar in first-degree relatives (FDR) of patients from
Any infection SAE 19 (4) 17 (3) 12 (5) 9 (4) both groups, and significantly higher than in relatives of cases with sporadic
Anal abscess 6 (1) 3 (51) 5 (2) 4 (2) CRC (SPS: 3.12; SPS-like 3.20; sporadic CRC, 0.45; p50.001).
Abdominal abscess 2 (51) 2 (51) 0 1 (51) CONCLUSION: Patients with multiple serrated polyps non-fulfilling WHO cri-
Appendicitis 2 (51) 0 0 0 teria show a clinical and molecular profile very similar to patients with SPS.
Sepsis 0 0 0 2 (51) Moreover, FDR from these patients show a CRC risk also similar to SPS
Wound infection 0 2 (51) 0 0
patients. These patients and their relatives should be considered as high risk
population.
REFERENCES
1. Boparai KS, et al. Gut 2010; 59: 1222-1225.
United European Gastroenterology Journal 2(5S)
2. Guarinos C, et al. 2013.
Disclosure of Interest: None declared
OP258 ANALYSIS OF DNA METHYLATION IN BOWEL LAVAGE
FLUID FOR DETECTION OF COLORECTAL CANCER
E. Yamamoto1,*, T. Harada1, H. Yamano2, Y. Shinomura1, H. Suzuki1
1
SAPPORO MEDICAL UNIVERSITY, sapporo, 2Akita Red Cross Hospital,
Akita, Japan
Contact E-mail Address: e.yamamoto@sapmed.ac.jp
INTRODUCTION: Aberrant DNA methylation could potentially serve as a
biomarker for colorectal neoplasms. In an earlier study, we demonstrated that
DNA methylation is detectable in the mucosal wash fluid from colorectal tumors,
which can be collected during colonoscopy 1. Importantly, wash fluid from inva-
sive cancers exhibited significantly higher levels of methylation of tumor-related
genes than noninvasive tumors. This prompted us to postulate that wash fluid
from invasive tumors contained greater numbers of exfoliated tumor cells, and
that the methylation was a potential biomarker predictive of tumor invasiveness.
AIMS & METHODS: In the present study, we assessed the feasibility of using
DNA methylation detected in bowel lavage fluid (BLF) for colorectal cancer
(CRC) screening. A total of 508 BLF specimens were collected from patients
with CRC (n 56), advanced adenoma (n 53) or minor polyp (n 209) and MYOTOMY: RESULTS OF A CONSECUTIVE SERIES OF PATIENTS
healthy individuals (n 190) undergoing colonoscopy. Methylation of 15 genes
(miR-1-1, miR-9-1, miR-9-3, miR-34b/c, miR-124-1, miR-124-2, miR-124-3, miR-
137, SFRP1, SFRP2, APC, DKK2, WIF1, LOC386758 and ZNF582) was then
analyzed in MethyLight assays, after which receiver operating characteristic
(ROC) curves were analyzed to assess the diagnostic performance of BLF
methylation.
RESULTS: After analyzing BLF specimens in a training set (n 345), we
selected the three genes showing the greatest sensitivity for CRC detection
(miR-124-3, 71.8%; LOC386758, 79.5%; SFRP1, 74.4%). A scoring system
based on methylation of those three genes (M-score) achieved 82% sensitivity
and 79% specificity, and the area under the ROC curve (AUC) was 0.834. The
strong performance of this system was then validated in an independent test set
(n 153, AUC 0.808). No significant correlation was found between M-score
and the clinicopathological features of the CRCs.
CONCLUSION: Our results demonstrate that DNA methylation in BLF speci-
mens may be a useful biomarker for detection of CRC. BLF methylation tests
could potentially improve the diagnostic performance of other screening meth-
ods, including the fecal occult blood test and computed tomographic
colonoscopy.
REFERENCES
1. Kamimae S, Yamamoto E, Yamano HO, et al. Epigenetic alteration of DNA
in mucosal wash fluid predicts invasiveness of colorectal tumors. Cancer Prev Res
(Phila) 2011; 4: 674-683.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
EVIDENCE-BASED TREATMENT OF ACHALASIA HALL C_____________________
OP259 IS GASTROESOPHAGEAL REFLUX DISEASE A MAJOR
DRAWBACK OF PERORAL ENDOSCOPIC MYOTOMY? ANALYSIS
OF CLINICAL, PROCEDURAL AND FUNCTIONAL FACTORS,
ASSOCIATED WITH GERD AND ESOPHAGITIS
P. Familiari1,*, G. Gigante1, M. Napoleone1, M. Marchese1, I. Costamagna1,
S. Greco1, I. Boskoski1, A. Tringali1, V. Perri1, G. Costamagna1
1
Digestive Endoscopy Unit, Gemelli University Hospital, Rome, Italy
Contact E-mail Address: pietrofamiliari@tiscali.it
INTRODUCTION: Per-Oral Endoscopic Myotomy (POEM) combines the long
term efficacy of an esophagogastric myotomy with the benefits of an endoscopic,
minimally invasive, procedure for the treatment of achalasia. An anti-reflux wrap
is usually associated to surgical myotomy. No antireflux procedures are per-
formed after POEM. Previous studies demonstrated that POEM is a safe and
effective procedure at mid-term follow-up. However, incidence of GERD after
POEM has been not satisfactorily analyzed.
AIMS & METHODS: Aim of this study is to evaluate the incidence of GERD
after POEM in a large consecutive series of patients, and to identify the clinical
factors associated with the disease.
A total of 156 patients underwent POEM in a single endoscopy center between
2011 and April 2014. After POEM patients underwent a regular follow-up. Post-
operative GERD was systematically investigated with an esophageal manometry,
EGD, and pH-monitoring (usually between the 6-month and 12-month follow-
up). During a mean follow-up of 11 months, 81 patients had a complete GERD
evaluation and were included in the study. Demographics (sex and age), data on
the clinical history (BMI, medications, alcohol and tobacco consumption), the
esophageal manometry (postoperative basal LES pressureand 4sIRP) and the
procedure (length of myotomy) were prospectively collected and analyzed.
GERD was defined by an altered esophageal acid exposure at pH-monitoring
(total reflux time 4 5%). Esophagitis was classified according to the Los Angeles
classification. Fishers Exact test and ANOVA test were used to identify factors
associated with GERD incidence and esophagitis.
RESULTS: An altered esophageal acid exposure was demonstrated in 44 patients
(54%; mean total reflux time 23% [range 6.6% 69.8%]; mean DeMeester score
82.9, [22.7-224.1]). Twenty patients (24.7%) had reflux esophagitis (10 grade A, 4
grade B, 4 grade C, 2 grade D). Only 38,6% of patients with GERD had heart-
burn, including 45% of patients with esophagitis. All the symptomatic patients,
and those with esophagitis received pantoprazole 40mg /day, with a complete
A83
symptoms relief. No medications were prescribed in case of normal findings at
EGD and/or no symptoms
At univariate analysis, altered esophageal acid exposure was correlated only with
the age of patients (50.477 year (GERD) vs 41.86 years (no GERD), p0.029)
and IRP (8.897 (GERD) vs 12.033 (no GERD), p0.012). Reflux esophagitis
was correlated with 4sIRP (6.821 mmHg (esophagitis) vs 11.524 mmHg (no
esophagitis), p0.001). BMI was substantially higher in patients with esophagitis
(27.1 Kg/m2 vs 24.7 Kg/m2, p0.06). GERD or esophagitis were not associated
with sex, length of myotomy, postoperative basal LES pressure, alcohol con-
sumption or tabagism.
CONCLUSION: GERD is a frequent adverse event after POEM, and may
represent a significant drawback of the procedure. Nevertheless, the majority
of patients with have no symptoms. Heartburn and esophagitis can be easily
managed with standard medications. GERD is significantly correlated with
patients age and a low post-operative 4sIRP. The clinical impact of POEM-
related GERD should be evaluated by larger studies with long term follow-up,
and comparative trials vs. Heller-Dor and vs. pneumodilation.
Disclosure of Interest: None declared
OP260 PERORAL ENDOSCOPIC MYOTOMY (POEM) IS A SAFE AND
EFFECTIVE RESCUE THERAPY AFTER A FAILED HELLER
G. Gigante1,*, P. Familiari1, M. Marchese1, M. Napoleone1, C. Marmo1,
I. Costamagna1, I. Boskoski1, A. Tringali1, V. Perri1, G. Costamagna1
1
Digestive Endoscopy Unit, Gemelli University Hospital, Rome, Italy
Contact E-mail Address: vanni.gigante@gmail.com
INTRODUCTION: Symptoms recurrence occurs in approximately 10% of
patients with achalasia after Heller myotomy. Pneumatic balloon dilation is
the first line treatment in case of recurrence, with only partial benefits at long
term. Peroral Endoscopic Myotomy combines the long term benefits of a surgical
myotomy with the advantages of a less invasive intervention. Differently from
surgery, POEM can be easily performed everywhere in the esophagus, also
including the posterior esophageal wall. POEM can be thus considered as
viable treatment after a failed surgical myotomy.
AIMS & METHODS: We report on a consecutive series of patients who under-
went POEM after a failed Heller. Perioperative data were compared with those of
a standard POEM population.From 2011 to April 2014, 156 patients with acha-
lasia underwent POEM in a single tertiary referral center. Five (3.2%) patients (3
female, mean age 63.6 years [range 5372]) were treated for symptoms recurrence
after surgery. Previous operations included: 1 open Heller/Lortat-Jacob proce-
dure; 2 thoracotomic Heller myotomy without antireflux wrap; 1 laparoscopic
Heller-Dor procedure; 1 laparoscopic Heller-Thal procedure. POEM was per-
formed a mean of 20 years (2-48 years before) after surgery. Data on the clinical
history and the procedure were prospectively collected. Esophageal manometry,
and EGD were performed before POEM and during the follow-up. Esophageal
pH-monitoring was performed 3 months after POEM. The procedural data of
the 5 patients treated after a failed Heller myotomy (FH-group) were compared
with those of the other patients treated with POEM (n151) in our department
(POEM-group).
RESULTS: POEM was successfully completed in all the patients of the FH-
group. POEM aborted in 7 of the 151 patients (4.5%) of the POEM-group.In
the FH-group, mean preoperative basal LES pressure and 4sIRP were 31.3
mmHg (9-50 mmHg) and 23 mmHg (10-45 mmHg), respectively. Mean preo-
perative Eckard score (ECK) was 7(5-9).Operating time was similar in the FH-
group and POEM group (67 minutes [57-161] and 78 minutes [38-161], respec-
tively). Mean length of the submucosal tunnel was 15 cm in the FH-group and 14
in the POEM-group. Mean length of myotomy was 10.8 cm (range 813 cm) in
the FH-group and 12 cm (7-17) in the POEM-group. Mean post-operative hos-
pital stay was similar in the FH-groups and POEM-group, 3.5 days and 3 days
respectively. No perioperative complications occurred in the FH-group. One
patient in the POEM-group (0.6%) experienced a large mucosal-flap ulcer that
resulted in an esophageal stricture. At 3-month follow-up, a significant drop of
the ECK (from 7 to 0.2) was documented in all the cases. Average weight gain
after the procedure was 4.5 kg. Postoperative basal LES pressure and 4sIRP was
20.14 mmHg and 7.5 mmHg respectively. Gastroesophageal reflux was documen-
ted in 3 of the 5 patients (60%). Two patients suffered from esophagitis but only
one patient referred daily heartburn.
CONCLUSION: Our results confirm the feasibility, safety and efficacy of POEM
in patients with symptoms recurrence after Heller myotomy. Additional studies
with a long term follow-up, and comparative trials vs. pneumodilation are neces-
sary to confirm the role of POEM in the treatment of patients after the failure of
a surgical myotomy.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
ENDOSCOPIC MANAGEMENT OF EARLY COLORECTAL NEOPLASIA HALL G/
H_____________________
OP261 COMPLICATIONS AFTER ENDOSCOPIC MUCOSAL
RESECTION OF LARGE COLORECTAL LESIONS. A
MULTICENTER SPANISH EMR GROUP STUDY
E. Albeniz Arbizu1, M. Fraile Gonzalez1,*, D. Mart nez Ares2, N. Pin Vieito3,
P. Alonso Aguirre3, C. Guarner Argente4, J. Cubiella Fernandez5, S. Soto
Iglesias5, J. Rodr guez Sanchez6, B. Lopez Viedma6, F. Mart nez-Alcala7,
F. Mugica8, J. Cobian8, C.J. Gargallo Puyuelo9, M. Gonzalez-Haba Ruiz10,
M.A. Alvarez11, X. Bessa i Caserras11, E. Redondo Cerezo12, J.G. Mart nez
Cara12, L. Lopez-Roses13, J. de la Pena14, H. Leon-Brito1, A. Zuniga Ripa1,
A84
A. Pueyo Royo1, J. Eguaras Ros1, A. Baiges15, M. Lopez Ceron15, E. Saperas
Franch16, O. Garc a17, J. Jimenez Perez1
1
Complejo Hospitalario de Navarra, Pamplona, 2Complejo Hospitalario
Universitario de Vigo, Vigo, 3H. Juan Canalejo, La Coruna, 4H. de la Santa Creu y
Sant Pau, Barcelona, 5Complejo Hospitalario de Orense, Orense, 6H. General de
Ciudad Real, Ciudad Real, 7Centro Andaluz de Gastroenterologa Integral, Sevilla,
8
H. Universitario Donostia, Donostia, 9HCU Lozano Blesa, Zaragoza, 10H. Puerta
de Hierro, Madrid, 11H. del Mar, Barcelona, 12H. Virgen de las Nieves, Granada,
13
H. Xeral, Lugo, 14HU Marques de Valdecilla, Santander, 15H. Clinic, Barcelona,
16
H. General de Catalunya, S. Cugat del Valles, 17H. Moise`s Broggi, Barcelona,
Spain
Contact E-mail Address: edualbeniz@hotmail.com
INTRODUCTION: The main complications of endoscopic mucosal resection
(EMR) of large colonic lesions are delayed bleeding (DB) (2-22%) and perfora-
tion (0.6-1.4%). There are no standardized preventive procedures for these
complications.
AIMS & METHODS: The aim was to describe the complications rate after EMR
of large colorectal lesions and to identify potential risk factors involved. We
analysed data from 881 EMRs of colorectal lesions 20 mm. 660 EMRs were
prospectively registered from February 2013 to March 2014 at 17 hospitals as
part of a Spanish multicenter study. Data were registered on features of patients
and lesions, procedural characteristics and outcomes. DB was defined as a clin-
ical evident bleeding, a decrease of hemoglobin in more than 2 g/dL or of blood
pressure in more than 20 mmHg or an increase of the beat rate in more than 20%
evidenced 24 h or later after EMR.
RESULTS:
DB (n36) p (Vs no DB) All patients (N881)
Size(mm 30/40 77.8/47.2 50.01/0.01 55.9/28.4
Location Proximal transverse/proximal 63.9/72.2 50.01 39.2/49.9
splenic flexure
Age(years) 60/61-74 / 75 17.1/25.7/57.1 0.02 21.3/43.1/35.6
ASA I/II/III/IV 8.3/36.1/52.8/2.8 0.03 15/51.3/30.6/3.1
Aspirin No/ Yes (ceased)/ 66.7/22.3/11.1 0.03 83.2/13.2/3.7
7emsp;Yes (during EMR)
Clips Mucosal defect complete closure 5.6 0.06 17.3
A total of 881 EMR were performed. There were 36 (4.0%) cases of DB and 11
(1.2%) perforations. Factors associated with DB were increasing lesion size,
proximal location, patients older than 75 years, higher ASA classification and
aspirin treatment. Only 2 of the EMR which had their mucosal defect fully
clipped underwent DB (1.3%(2/151) Vs 4.7% not closed, p0.06). Lesions that
had been treated with APC for coagulation did not suffer DB (pNS). All DB
were successfully managed endoscopically with the exception of one patient who
required a vascular interventional radiology treatment. Two patients required
surgery due to perforation (0.2%). No risk factors has been associated to
perforation.
CONCLUSION: DB rate after EMR of large colorectal lesions in our study was
4.0 %. DB occurred most frequently in lesions 30-40 mm located in the prox-
imal colon, in older patients with comorbidities (ASA IIIIV) and in those taking
aspirin (p50.05). Perforation rate in this study was 1.2%. No risk factors has
been associated to this complication.
Disclosure of Interest: None declared
OP262 EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR EARLY STAGE COLORECTAL NEOPLASIA;
RESULTS FROM A NATIONWIDE REGISTRY THROUGHOUT
JAPAN
Y. Saito1,*, M. Fujishiro2, S. Tanaka3, H. Iishi4, T. Miyata5, M. Kaise6,
T. Shimbo7, H. Ishikawa8, N. Uemura7, J. Yoshino9, K. Obara10,
M. Kaminishi11, H. Tajiri12 on behalf of, JGES Colorectal, ESD Study Group
1
Endoscopy Division, NATIONAL CANCER CENTER HOSPITAL, Tsukiji,
Chuo-ku, Tokyo, 2The University of Tokyo Hospital, Tokyo, 3Hiroshima
University Hospital, Hiroshima, 4Osaka Medical Center for Cancer and
Cardiovascular Diseases, Osaka, 5Jichi Medical University, Tochigi, 6Toranomon
hospital, 7National Center for Global Health and Medicine, Tokyo, 8Kyoto
Prefectural University of Medicine, Kyoto, 9Fujita Health University, Nagoya,
10
Fukushima Medical University Hospital, Fukishima, 11Showa General Hospital,
12
The Jikei University School of Medicine, Tokyo, Japan
INTRODUCTION: In the West, when endoscopic polypectomy or mucosal
resection is not possible for early stage colorectal neoplasms, surgery is the
standard of care. Endoscopic submucosal dissection (ESD) can potentially fill
this gap between polypectomy and surgery, giving another endoscopic treatment
option that preserves the native anatomy. However, while high en bloc resection
rates for colorectal ESD have been reported, these earlier reports were limited to
specialized institutions.
AIMS & METHODS: This study is, therefore, aimed to elucidate the efficacy
and safety of ESD for early stage colorectal neoplasms from a nationwide reg-
istry throughout Japan not only in referral centers.
The Japan Gastroenterological Endoscopy Society (JGES) conducted a nation-
wide registry for colorectal ESD. Rates of en bloc resection, en bloc plus R0
(tumor-free margins) resection and ESD related complications were collected
prospectively.
United European Gastroenterology Journal 2(5S)
Registry inclusion criteria were 1) Early colorectal cancer 42 cm not amenable
to EMR; 2) Adenoma with non-lifting sign preventing safe EMR; 3) Residual or
recurrent adenoma after EMR, 41 cm, not amendable to EMR. The registry
protocol was approved by the ethics committee of each participating hospital and
the JGES. The trial was registered with UMIN-Clinical Trials Registry, number
UMIN-CTR 000004040.
RESULTS: From August 2010 to January 2012, 1564 consecutive patients from
69 institutions (561 adenomas, 747 mucosal cancers, 235 submucosal invasive
cancers, 2 cancers with unknown depth, 12 other lesions, 7 lesions with unknown
histology) were entered into this registry. ESD was completed in 1544 (98.7%)
patients. En bloc resection and en bloc plus R0 resection rates were 1484 (94.9%)
and 1278 (81.7%) respectively. Additional surgery was necessary in 133 (8.5%)
patients. Postoperative bleeding, intraoperative perforation, postoperative per-
foration, penetration and peritonitis occurred in 43 (2.8%), 47 (3.0%), 6 (0.4%),
19 (1.2%) and 8 (0.5%) patients, respectively. Emergency surgery was necessary
in 8 (0.5%) patients (4 for intraoperative perforation and the other 4 for post-
operative perforation). Blood transfusion was required in one patient (0.06%)
due to postoperative bleeding. Follow up in one year revealed a 0.90%(11/1217)
rate of local recurrence.
CONCLUSION: This nationwide registry throughout Japan reveals that color-
ectal ESD has matured to a standard treatment for early stage colorectal neo-
plasia based on efficacy, safety and short-term outcome.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
SAFETY IN ENDOSCOPY HALL I/K_____________________
OP263 HOW SAFE AND EFFECTIVE IS ORAL REHYDRATION
THERAPY IN CORRECTING THE METABOLIC DISTURBANCES
POST-COLECTOMY IN PATIENTS WITH FAMILIAL
ADENOMATOUS POLYPOSIS?
S. Mallappa1,*, S. Gabe2, R. Phillips1, M.D. Robertson3, S.K. Clark1
1
The Polyposis Registry, 2Gastroenterology, St Marks Hospital, Harrow, 3Faculty
of Medicine, University of Surrey, Guildford, United Kingdom
Contact E-mail Address: s.mallappa@imperial.ac.uk
INTRODUCTION: There is evidence that colon is an active metabolic organ, the
removal of which leads to chronic activation of the renin-angiotensin-aldosterone
system (RAAS) which in turn results in sodium depletion, hyperaldosteronism
and abnormal glucose tolerance. Previous work has studied patients who have
undergone colectomy for inflammatory bowel disease (IBD)1,2. Patients with
Familial adenomatous polyposis (FAP) undergo prophylactic colectomy with
ileorectal anastomosis (IRA) or restorative proctocolectomy (RPC) or colectomy
with end-ileostomy in their late teens. We have established (60 FAP participants)
that colectomy results in RAAS activation, abnormal glucose tolerance and poor
quality of life.
AIMS & METHODS: To evaluate if oral rehydration therapy (ORT) is safe and
effective in restoring water and electrolyte balance post-colectomy.
Blinded placebo-controlled randomised cross-over trial. 30 patients with demon-
strated hyperaldosteronism from the on-going observational study were
recruited. Patients were randomised to receive either placebo or ORT first in a
cross-over trial for 4 weeks with an intervening washout period of 4 weeks.
Patients attended clinical investigation day (CID) once at the end of each 4
weeks. CID: After fasting, urine and blood samples were collected to measure
sodium loss, hydration status and RAAS activation. Oral glucose tolerance test
was performed. Health related quality of life (HRQoL) was assessed using SF-36
and FACIT-F questionnaires.
RESULTS: Cross-over RCT: Biochemistry results: Data acquired so far in 16
patients (n48 patient CIDs) have demonstrated fasting plasma aldosterone
concentration post-ORT to be significantly lower compared to baseline [189.25
(7.24) vs 536.25 (12.56) pmol/L; p0.05]. HRQoL results: SF 36 Post-ORT,
patients reported improvement in six of the eight dimensions of health as com-
pared to baseline. FACIT-F Post-ORT, patients reported higher scores on four
of the five scales with higher total scores when compared to baseline.
CONCLUSION: ORT forms a safe and effective intervention to correct the
metabolic disturbances post-colectomy resulting in restoration of metabolic
homeostasis and a positive impact on quality of life.
REFERENCES
1. Robertson MD, Bickerton AST, Dennis AL, et al. Enhanced metabolic cycling
in patients following colonic resection for ulcerative colitis. J Clin Endocrinol
Metab 2005; 90: 2747-2751.
2. Robertson MD. Metabolic cross talk between the colon and the periphery:
implications for insulin sensitivity. Proc Nut
Disclosure of Interest: None declared
OP264 INCIDENCE AND RISK FACTORS FOR SEDATION-
ASSOCIATED COMPLICATIONS IN GI-ENDOSCOPY RESULTS
OF OVER 250,000 ENDOSCOPIES: THE PROSPECTIVE,
MULTICENTER REGISTRY OF THE GERMAN WORKING GROUP
OF LEADING HOSPITAL GASTROENTEROLOGISTS (ALGK):
PROSED 2 - STUDY
A. Behrens1,*, C. Ell2 on behalf of, ALGK-ProSed-study group
1
Internal Medicine, Vivantes Klinikum im Friedrichshain, University Teaching
Hospital of the Humboldt University Berlin (Charite), Berlin, 2Internal Medicine
II, Sana Klinikum Offenbach, Offenbach, Germany
Contact E-mail Address: angelika.behrens@vivantes.de
INTRODUCTION: Administering sedation is an established standard practice in
gastrointestinal endoscopy. Sedation is unquestionably associated with a certain
United European Gastroenterology Journal 2(5S)
risk of complications. The data so far published on sedation-associated compli-
cations are limited, in the majority of cases derived from studies including only
small numbers of patients and with clear methodological weaknesses.
AIMS & METHODS: The aim of the present study was to record the incidence
and type of sedation-associated complications. Risk factors were also to be iden-
tified. Sedation-associated complications were recorded and documented with
computer support, using the input template of an endoscopy documentation
system (E&L Ltd., Erlangen, Germany) that only allows an examination to be
entered as complete if the sedation form has been filled out ensuring 100%
data recording.
RESULTS: Data from 34 participating study centers were evaluated. The study
period was from December 2009 to February 2014 (median inclusion period 2
years). A total of 276,764 endoscopies were documented. Of these, 31,267 were
carried out without sedation. Propofol-based sedation was administered in 85%
of the cases; 16,513 endoscopies (6%) were carried out on an emergency basis. A
total of 25 major complications occurred (0.01%; definition: meeting at least one
of the following criteria: admission to intensive care; intubation; resuscitation;
death). Six patients (0.002%) died. Five of these six patients were in American
Society of Anesthesiologists (ASA) class 3 or higher and/or were undergoing
emergency endoscopy (two of six, 33%). Endoscopic retrograde cholangiopan-
creatography (ERCP) was carried out in four of the six patients. The proportion
of ERCP examinations in all endoscopies conducted was 6.6%.
CONCLUSION: The present study is the largest prospective multicenter study to
have been carried out worldwide to document complications of sedation. The
data show that severe sedation-associated complications are rare in gastrointest-
inal endoscopy. Risk factors include ASA class 3 status or higher, emergency
endoscopy, and/or ERCP procedures.
Disclosure of Interest: A. Behrens Financial support for research from: E&L
medical systems GmbH, C. Ell: None declared
OP265 GASTROENTEROLOGIST-ADMINISTERED BALANCED
PROPOFOL SEDATION IS SAFE, EFFECTIVE AND FEASIBLE TO
USE FOR OUTPATIENT COLONOSCOPY EXAMINATIONS
Y. Nathan1, I. Khamaysi2,3, A. Klein2, I. M. Gralnek2,3,*
1
Technion Israel Institute of Technology School of Medicine, 2Gastroenterology,
RAMBAM HEALTH CARE CAMPUS, 3Rappaport Faculty of Medicine
Technion Israel School of Medicine, Haifa, Israel
Contact E-mail Address: i_gralnek@rambam.health.gov.il
INTRODUCTION: Given its rapid onset and short duration of action, Propofol
is an effective and appealing drug for conscious sedation in endoscopy. Current
product labeling dictates its administration only in the presence of personnel
trained in administering general anesthesia. Unfortunately, this significantly
raises the costs of endoscopy by requiring anesthesiology services. Only limited
data have demonstrated that Propofol can be safely and effectively administered
by a Propofol-trained endoscopy team.
AIMS & METHODS: We aimed to evaluate, during outpatient colonoscopy
procedures, the safety of gastroenterologist-administered balanced propofol
sedation (BPS) consisting of fentanyl, midazolam and propofol without an
anesthesiologist or nurse anesthetist present. We performed a retrospective obser-
vational study using prospectively collected endoscopy data from a tertiary care
university hospital endoscopy unit where gastroenterologist-administered BPS is
routine practice. All gastroenterologists undergo standardized conscious sedation
training and testing every two years and are required to have up to date advanced
cardiac life-saving certification. We evaluated patient-level demographic vari-
ables including: age, gender, ASA score, indication for colonoscopy. We also
evaluated clinical and patient outcome variables including: BPS drug dosages,
pre- and post-colonoscopy oxygen saturation levels, pulse, systolic/diastolic
blood pressure, need for mask bag ventilation or endotracheal intubation,
aborted colonoscopy procedure due to sedation, hospital admission post colono-
scopy, and mortality. This study was Helsinki committee approved.
RESULTS: From April 1 to November 30, 2013, n1036 patients (mean age 56.4
years, 570 (55%) males) underwent ambulatory colonoscopy and received gas-
troenterologist-administered BPS from any one of 12 gastroenterologists who
perform endoscopy in the endoscopy unit. Reason for colonoscopy included:
CRC screening / surveillance n352 (34.0%), evaluation of lower GI symptoms
n404 (39.0%), positive FOBT n156 (15.1%), and IBD follow up n124
(11.9%). ASA scores were: ASA I n332 (32.1%), ASA II n611 (59.0%),
ASA III n93 (8.9%). BPS dosages (meanSD) per patient were as follows:
Fentanyl 0.05mg (fixed dose), Midazolam 1.6mg  0.5mg, and Propofol
104mg  62mg. Post-colonoscopy (meanSD) O2 saturation levels were 98%
 4%. Pre and post colonoscopy blood pressures were 133/77 mmHg vs. 118/67
mmHg (p-value 50.001) and pulse 75/min vs.66/min (p-value50.001). No
patient required bag mask ventilation, endotracheal intubation, or hospital
admission. There were no aborted colonoscopies secondary to sedation and no
mortality. All patients were discharged from the endoscopy unit recovery area
directly to home.
CONCLUSION: Gastroenterologist-administered BPS appears safe, effective
and feasible to use, including in ASA II and III level patients, undergoing out-
patient colonoscopy. Although pre-post colonoscopy blood pressures and pulse
rates were found to be statistically significantly different, this difference does not
appear to be clinically meaningful (15 point SBP and 10 point DBP reduction, 9
beats/min pulse reduction). There were no observed adverse events or mortality
associated with gastroenterologist-administered BPS in this study population.
Disclosure of Interest: None declared
A85
OP266 SAFETY OF PROPOFOL ADMINISTERED BY
GASTROENTEROLOGISTS AND TRAINED NURSES IN AN
ENDOSCOPY UNIT. A LARGE PROPECTIVE STUDY
X. Garc a Aguilera1,*, L. Achecar1, M. Del R o1, A. Gonzalez1, G. Arranz1,
A. Vilches1, J. Villalba1, L. Mosquera1, G. Guerrero1, M. Gonzalo1, M.
Van Domselaar1
1
Endoscopy unit, Hospital Universitario de Torrejon de Ardoz, Madrid, Spain
Contact E-mail Address: xagarcia@torrejonsalud.com
INTRODUCTION: Sedation in gastrointestinal endoscopy performed by a spe-
cially trained nurse, guided by endoscopist, is increasingly common in European
countries. Numerous published studies support the efficacy and safety of this
technique, in which propofol is administered during endoscopic procedures,
based on weight, age, and clinical status of the patient. However, there are
controversies on the use of propofol by non-anesthesiologists in gastrointestinal
endoscopy despite the evidence on its safety.
AIMS & METHODS: The aim of our study was to describe our experience on
the safety and effectiveness of propofol administered by medical and nursing staff
of an endoscopy unit. We prospectively recorded all esophagogastroduodenos-
copies (EGDs) and colonoscopies performed in our unit between June 2012 and
March 2014. Sex, age, weight, anesthetic risk, propofol dose, type of examina-
tion, complications, and patient and physician satisfaction data were prospec-
tively collected. We excluded procedures not sedated by endoscopist, and patients
with two endoscopic procedures performed on the same day. Statistical analysis
was performed with the SPSS v20.0 program.
RESULTS: We performed 7,707 procedures, 4148 (53.8%) were colonoscopies
and 3559 (46.2%) EGDs. Propofol was used in all patients at an initial dose of
0.5-1 mg/kg. Colonoscopies also received a fixed dose of 50 mcg of fentanyl.
54.6% of patients had an anesthetic risk ASA I; 41.4%, ASA II; and 4%, ASA
III. The mean age was 54  16.8 (30.4% were 65years). There were 20.7%
therapeutic procedures.
The mean dose of propofol was 129.8  58.06mg. In patients 65years it was
99.2  50.8mg (P 0.001). The mean dose of propofol in EGDs was 124.3 
52.6mg and 134.4  61.9mg in colonoscopies (P 0.0001).
We recorded 125 (2.6%) adverse events, all minor (85 desaturation, 31 brady-
cardia, 5 hypotension and other 4). Most were recovered with chin lift maneuver
(only 3 needed bag-valve-mask ventilation), atropine and volume expansion. 71
adverse events (48 desaturation, 17 bradycardia, 3 hypotension and other 3)
occurred in 65 years (P 0.03), being ASA II in 69.1% (P 0.001). 97.7%
of the procedures were complete, and only 4 (0.1%) were discontinued due to
complications with sedation. Overall satisfaction recorded by the endoscopist
was excellent-good in 99.6% and moderate in 0.3%, being the patient tolerance
excellent in 99.8%.
CONCLUSION: The use of propofol administered by the endoscopist assisted
by nurse is an effective and safe method of sedation, allowing a more comfortable
exploration for both the physician and patient.
Disclosure of Interest: None declared
OP267 SERIOUS ADVERSE EVENTS OF NONANESTHESIOLOGIST-
ADMINISTERED PROPOFOL IN RELATION WITH
GASTROINTESTINAL ENDOSCOPIC PROCEDURE
F. Gonzalez-Huix1, M. Figa1,2, M.A. Alburquerque1,3,*, M. Perez-Contreras2
1
Gastroenterology, Clnica Girona, 2Gastroenterology, Hospital Universitario Dr.
Josep Trueta, 3Gastroenterology, Hospital de Palamos, Girona, Spain
INTRODUCTION: The serious adverse events (SAE) of nonanesthesiologist-
administered propofol (NAAP) would depend on the gastrointestinal endoscopic
procedure.
AIMS & METHODS: To determine the SAE of NAAP rate regarding the gas-
trointestinal endoscopic procedure. Through a prospective database were regis-
tered all consecutives patients that underwent to endoscopic procedure with
NAAP sedation, during the last 5 years. We recorded the SAE: bradycardia
540 bpm, tachycardia 4150bpm, severe systolic hypotension (570mmHg),
severe systolic hypertension (4250mmHg), severe lower oxygen saturation
(SpO2 570%), laryngospasm, aspiration, seizures, cardiac arrest and death.
We had also included the following entries: balloon ventilation requirement,
tracheal intubation, defibrillation and the patients who needed additional sup-
port from anaesthesiologist or critical care specialist.
RESULTS: Between 27971 endoscopic procedures we observed 251 SAE of
NAAP (0.9%). Age: 59.416.4 y; women: 40.6%. Severe bradycardia and tachy-
cardia were more frequent in ERCP: 8(0.4%); p0.000 and 4(0.2%); p0.017,
respectively; as well as hypertension: 4(0.2%); p0.001 and SpO2 570%:
38(1.8%); p0.000. Laryngospasm was most frequent in EUS 2(0.4%);
p0.002. Aspiration was registered only in gastroscopy 4(0.0%) and ERCP
2(0.1%); p0.042. We observed seizures in gastroscopy 3(0.0%), although with-
out statistic significance p0.430. We required balloon ventilation in gastro-
scopy, colonoscopy and ERCP: 23(0.2%), 4(0.0%) y 4(0.2%); p0.017,
respectively. We did tracheal intubation and it was necessary additional support
from anaesthesiologist or critical care specialist mainly in gastroscopy: 4(0.0%);
p0.277 and 8(0.1%); p0.061. In colonoscopy, the complication rate was the
lowest: 63(0.6%); p0.000. We had not needed defibrillation and there were no
deaths.
A86 United European Gastroenterology Journal 2(5S)
for chronic inflammatory responses leading to disease. However it is yet unclear
how this is achieved.
Gastroscopy Colonoscopy EUS ERCP TOTAL AIMS & METHODS: In this study we set out experiments to determine the
n14567 n10787 n559 n2058 n27971 p
physiological triggers that drives ILC1 and ILC3 differentiation. Furthermore,
we aimed to identify the cellular source of the regulators of the ILC1/ILC3
Total Complications 124 (0,9%) 63 (0,6%) 8 (1,4%) 56 (2,7%) 251 (0,9%) 0,000
balance.
Bradycardia 5 40 bpm 16 (0,1%) 31 (0,3%) 1 (0,2%) 8 (0,4%) 57 (0,2%) 0,000
RESULTS: Here we demonstrate that CD127 ILC1 - but not CD103 intrae-
Tachycardia 4150 bpm 10 (0,1%) 2 (0%) 0 4 (0,2%) 16 (0,1%) 0,017 pithelial NK or conventional NK cells differentiate towards ILC3 in response
Hypertension4250mmHg 7 (0%) 0 0 4 (0,2%) 11 (0%)
Sp02 570% 66 (0,5%) 14 (0,1%) 5 (0,9%) 38 (1,8%) 123 (0,4%)
-producing
Laryngospasm 9 (0,1%) 2 (0%) 2 (0,4%) 0 (0%) 13 (0%)
Aspiration 4 (0%) 0 0 2 (0,1%) 6 (0%)
Balloon ventilation 23 (0,2%) 4 (0%) 0 4 (0,2%) 31 (0,1)
Anesthesio.-CCS support 8 (0,1%) 0 0 0 8 (0%)
CONCLUSION: In nonanesthesiologist-administered propofol the serious
adverse events rate is very low (0.9%). The ERCP recorded the highest rate:
more tachycardia, hypertension, severe lower oxygen saturation and aspiration
while the colonoscopy was the lowest.
Disclosure of Interest: None declared
OP268 MULTICENTER RANDOMIZED CONTROLLED STUDY TO
ASSESS THE PREVENTIVE EFFECT OF PROPHYLACTIC
CLIPPING FOR POST-POLYPECTOMY BLEEDING
M. Matsumoto1,*, M. Kato2, N. Sakamoto3
1
Department of gastroenterology, NTT medical center Sapporo, 2Division of
Endoscopy, Hokkaido University Hospital, 3Department of gastroenterology,
Hokkaido University Graduate School of Medicine, Sapporo, Japan
Contact E-mail Address: miosakra@outlook.jp
INTRODUCTION: Prophylactic clipping has been widely used to prevent post-
polypectomy bleeding. However, its efficiency has not been confirmed and so far
there is no consensus on the usefulness of prophylactic clipping.
AIMS & METHODS: To evaluate the preventive effect of prophylactic clipping
for post-polypectomy bleeding.
A multicenter randomized controlled study was conducted from April 2004 to
July 2013 in Japan. Inclusion criteria were patients who were 420 years old and
had polyps 52cm. Patients were divided into the clipping group or the non-
clipping group by cluster randomization. After endoscopic polypectomy, patients
allocated to the clipping group underwent prophylactic clipping, whereas in those
allocated to the non-clipping group, the procedure was finished without clipping.
When spurting bleed occurred shortly after polypectomy, hemostatic treatment
had done and its polyp was excluded from this study. When oozing bleed or
visible vessels were found, coagulation were added by the tip of a snare, the
procedure was continued according to the method in each group.
The occurrence of post-polypectomy bleeding was compared between the two
groups.
RESULTS: Seven hospitals participated in this study. 3365 polyps in 1499
patients were evaluated. The clipping group consisted of 1636 polyps in 752
patients, and the non-clipping group of 1729 polyps in 747 patients. Post-poly-
pectomy bleeding occurred in 1.10 % (18/1636) of the cases in the clipping group,
and in 0.88% (15/1729) of those in the non-clipping group. The difference was -
0.22% (95%CI:-0.96, 0.53). The upper limit of 95%CI was lower than the non-
inferiority margin (1.5%), so we could prove the non inferiority of non-clipping
against clipping. The main risk factor of post-polypectomy bleeding was polyp
size in both groups. Furthermore, additional coagulation was also a risk factor in
the non-clipping group.
CONCLUSION: Prophylactic clipping is not necessary to prevent post-polypect-
omy bleeding. Because additional coagulation was one of the risk factors of post-
polypectomy bleeding, we consider cold polypectomy without high frequency
coagulation as an effective alternate procedure.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
NOVEL INSIGHTS INTO THE IMMUNOPATHOGENESIS OF COLITIS HALL
R_____________________
OP269 HUMAN MONONUCLEAR PHAGOCYTES REGULATE THE
BALANCE BETWEEN INTESTINAL GROUP1 AND GROUP 3
INNATE LYMPHOID CELLS
J. H. J. Bernink1,*, L. Krabbendam2, M. Munneke2, C. Buskens3,
W. Bemelman3, E. de Jong2, B. Blom2, H. Spits2
1
Tytgat Institute, 2Cell Biology and Histology, 3Surgery, Academic Medical Center
Amsterdam, Amsterdam, Netherlands
Contact E-mail Address: j.h.bernink@amc.nl
INTRODUCTION: Recently we identified a human CD127 innate lymphoid
cell (ILC) subset, which produces high amounts of IFN
following activation, 10. In order to gain a deeper understanding of the mechanism of action of
and expresses the transcription factor T-bet. This ILC subset was termed ILC1. It
is likely that these cells are important for the innate immune response against
pathogenic bacteria, as similar ILC1 identified in mice mediate immunity against
Salmonella Enterica. ILC1 may also be pathogenic by itself, as they accumulate in
inflamed intestinal tissues of Crohns patients, whereas the frequency of IL-22
producing ILC3 is diminished.
ILC3 are the predominant ILC subset in the small bowel and maintain the
integrity of the intestinal mucosa. Obviously the balance between the protective
ILC3 and the inflammatory ILC1 should be tightly regulated to reduce the risk
0.001 to IL-23 and IL-1, a process, which is synergistically enhanced by retinoic acid.
0,000 Furthermore, we found that ILC3 differentiate towards IFN
0,002 CD127 ILC1 under influence of the pro-inflammatory cytokine IL-12.
0,042 In experiments aimed to identify the cellular source of the regulators of the ILC1/
0,017 ILC3 balance, we found that tissue-infiltrating monocytes produce IL-12 and
drive ILC1 differentiation, whereas tissue-resident CD103 dendritic cells can
0,061
convert ILC1 towards ILC3.
CONCLUSION: These findings reveal that the balance between pro-inflamma-
tory ILC1 and protective ILC3 is regulated by environmental cues. An efficient
mechanism presents itself by which ILC can quickly adapt to changes inflicted by
pathogens without the need of recruiting new cells from circulation.
Disclosure of Interest: None declared
OP270 INNATE LYMPHOID CELLS TYPE 1 AND TYPE 3 ARE A
SOURCE OF INFLAMMATORY CYTOKINES IN CELIAC DISEASE
I. Marafini1,*, I. Monteleone1, A.O. Paoluzi1, M.L. Cupi1, D. Di fusco1, R. Izzo1,
E. De luca1, S. Vita2, G. Sica1, F. Pallone1, G. Monteleone1
1
University of Rome Tor Vergata, 2Ospedale fatebenefratelli, Rome, Italy
Contact E-mail Address: gi.monteleone@med.uniroma2.it
INTRODUCTION: Innate lymphoid cells (ILCs) are an emerging family of
hematopoietic cells involved in host defence, immune homeostasis and tissue
repair. Various subsets of ILCs producing specific repertoires of cytokines
have been identified and implicated in the pathogenesis of immune-mediated
diseases.
AIMS & METHODS: In this study, we have phenotypically characterized ILCs
in celiac disease (CD), a gluten-driven enteropathy, and determined whether
these cells are a source of cytokines in this disease. ILC subpopulations were
analyzed in lamina propria mononuclear cells (LPMCs), isolated from duodenal
biopsies of patients with active CD, patients with inactive CD on a gluten-free
diet and normal controls and jejunal specimens of patients undergoing gastro-
intestinal bypass by flow cytometry. Cytokines, transcription factors and recep-
tors for interleukin (IL)-15, interferon (IFN)-alpha and Toll-like receptors (TLR)
were assessed in ILCs either freshly isolated or following incubation of control
LPMC with IL-15, IFN-alpha and poly I:C, a TLR agonist, by flow cytometry.
RESULTS: The frequency of ILCs in the intestinal lamina propria of patients
with active CD did not differ from that in normal controls and inactive CD
patients on a gluten-free diet. However, the fractions of T-bet-expressing ILCs
type 1 and ROR-gammat-expressing ILCs type 3 were increased in active CD as
compared to controls, and these ILC subsets produced IFN-gamma and IL-17A,
respectively. ILCs expressed IL-15 receptor a and toll-like receptors 2, 3 and 9.
Treatment of normal intestinal lamina propria mononuclear cells with IL-15 and
Poly:IC, a TLR3 ligand, increased production of IFN-gamma, but not IL-17A,
by ILCs.
CONCLUSION: These data indicate that CD mucosa is infiltrated with ILCs
type 1 and ILCs type 3 that produce inflammatory cytokines and suggest that
ILCs could make a contribution to the CD-related inflammatory response.
REFERENCES
Walker JA, Barlow JL and McKenzie AN. Innate lymphoid cells how did we
miss them? Nat Rev 2013; 13: 75-87.
Meresse B, Malamut G and Cerf-Bensussan N. Celiac disease: an immunological
jigsaw. Immunity 2012; 36: 907-919.
Geremia A, Arancibia-Carcamo CV, Fleming MP, et al. IL-23-responsive innate
lymphoid cells are increased in inflammatory bowel disease. J Exp Med 2012;
208: 1127-1133.
Monteleone I, Sarra M, Del Vecchio Blanco G, et al. Characterization of IL-
17A-producing cells in celiac disease mucosa. J Immunol 2010; 184: 2211-2218.
Disclosure of Interest: None declared
OP271 THE TLR-9 AGONIST DIMS0150 DIRECTLY UPREGULATES
INTERLEUKIN-10 POSITIVE CELLS IN THE COLONIC MUCOSA
OF ULCERATIVE COLITIS PATIENTS
U. Billmeier1,*, W. Dieterich1, C. Admyre2, T. Knittel2, A. Zargari2,
M.F. Neurath1, R. Atreya1
1
Medical clinic 1, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen,
Germany, 2InDex Pharmaceuticals, Stockholm, Sweden
INTRODUCTION: The oligonucleotide DIMS0150 is a Toll like receptor 9
(TLR9) agonist and has been shown to be therapeutically efficacious in the
treatment of refractory ulcerative colitis. In cultured PBMCs, DIMS0150
induced a variety of anti-inflammatory cytokines, including Interleukin (IL)-
DIMS0150, we analyzed its effect in cultured LPMCs in vitro and on histological
sections from colon biopsies taken at different time points before and after local
application of DIMS0150 in ulcerative colitis patients during a clinical trial.
AIMS & METHODS: A randomized, double-blinded, multicenter phase II trial
was performed with DIMS0150 in steroid refractory patients with ulcerative
colitis of moderate degree (EudraCT number: 2006-001846-15). Patients were
randomized to a single rectal administration of either 30 mg of DIMS0150 or
placebo. Clinical response at week 1 and 4 was 41.2% and 52.9% in the
DIMS0150 treated group and 9.1% and 36.4% in the placebo treated group.
United European Gastroenterology Journal 2(5S)
Colon biopsies of ulcerative colitis patients were taken before, 7 and 28 days after
DIMS0150 or placebo treatment and its cross sections were stained for cell
apoptosis (TUNEL) and IL-10, respectively. Immunofluorescence microscopy
subsequently allowed quantification of positive intestinal immune cells.
LPMCs were isolated from colonic biopsies or surgical specimen and cultivated
overnight with and without 100 mM DIMS0150. IL-10 expression was deter-
mined with ELISA and flow cytometry.
RESULTS: Analysis of cross-sections from colon biopsies of ulcerative colitis
patients treated with DIMS0150 revealed no induction of apoptosis in LPMCs.
This result was further confirmed by cultured LPMCs, where DIMS0150 treat-
, IL-17 and serum amyloid protein (SAP) levels. IL-12p70
ment similarly did not lead to apoptosis induction. Quantitative analysis of sec-
, IL-17 levels
tions from colon biopsies of ulcerative colitis patients taken before and after
application of DIMS0150 treatment (n11-16) clearly indicated a significant
induction of IL-10 positive mucosal immune cells after DIMS0150 treatment
, IL-17 and SAP levels were signifi-
which was not observed in the placebo group (n5-7). Double staining revealed
that the main IL-10 producers were mucosal CD4 T-cells and CD11b positive
monocytes and macrophages. Correspondingly, it could be shown that
DIMS0150 directly induced IL-10 production in vitro in lamina propria CD4
and CD14 cells.
CONCLUSION: In clinical trials, topical administration of DIMS0150 has
shown promising effects in the treatment of therapy refractory ulcerative colitis
patients. Our data reveal that application of DIMS0150 significantly induced IL-
10 production by T-cells, monocytes and macrophages in the colonic mucosa.
Thus, induction of the anti-inflammatory cytokine IL-10 could be the central
therapeutic mechanism of action of the late stage clinical candidate DIMS0150 in
level was affected. Conversely, addition of IL-12p70 or IL-23 recom-
ulcerative colitis patients.
and IL-17 levels in CD4CD25-T cells conditioned
Disclosure of Interest: U. Billmeier: None declared, W. Dieterich: None declared,
C. Admyre Financial support for research from: Index Pharmaceuticals, T.
Knittel Financial support for research from: Index Pharmaceuticals, A. Zargari
Financial support for research from: Index Pharmaceuticals, M. Neurath: None
declared, R. Atreya: None declared
OP272 FLAVONOID CONFERS COMMUNICABLE PROTECTION
AGAINST COLITIS THROUGH THE NLRP6 INFLAMMASOME
S. Normand1,2, K. Radulovic1,2,*, M. Seillier-Turini3,4, A. Rehman5,
A. Delanoye-Crespin1,2, C. Bondu1,2, P. Rosenstiel5, A. Carrier3,4,
M. Chamaillard1,2
1
U1019, Team 7, Equipe FRM, Institut National de la Sante et de la Recherche
Medicale, 2Center for Infection and Immunity of Lille, Institut Pasteur de Lille,
Lille, 3UMR1068, Institut National de la Sante et de la Recherche Medicale,
4
UMR7258, Centre National de la Recherche Scientifique, Marseille, France,
5
Institut of Clinical Molecular Biology, University Hospital Schleswig-Holstein,
Kiel, Germany
Contact E-mail Address: katarina.radulovic@inserm.fr
INTRODUCTION: NLRP6-inflammasome dictates host-microbiota interac-
tions that are protecting against intestinal inflammation through mechanisms
which remain largely undefined.
AIMS & METHODS: To further understand the signaling pathways down-
stream of NLRP6, we performed a two-hybrid screening with the Pyrin
domain of mouse NLRP6 as bait. Dextran sodium sulfate-induced colitis was
used as an experimental model of inflammatory bowel disease in both single-
housed and co-housed mice. Cell growth was daily measured over a 7 day-period
by Countess device and trypan blue exclusion according to manufacturer
instructions. U0126 was used as a MAPK/ERK kinases (MEK) 1/2 inhibitor.
RESULTS: Herein, we show that flavonoid maintain gut microbial ecology by
regulating NLRP6-mediated regulation of cell proliferation. Our two-hybrid
screening revealed that NLRP6 interacted with casein kinase 2 (CSNK2) that
is a serine/threonine-selective protein kinase involved in maintenance of cell
growth. Consistently, pharmacological inhibition of CSNK2 by apigenin con-
ferred protection against intestinal inflammation. Co-housing experiments
revealed that the protective activity of the microbiota of apigenin-treated mice
is transmissible to adult wild-type mice, but not to NLRP6- and caspase1/cas-
pase11-deficient mice. Mechanistically, NLRP6 deficiency was found to enhance
cell growth and survival through activation of extracellular signal-regulated
kinases 1 and 2.
CONCLUSION: Collectively, our results demonstrate a key role of flavonoid-
microbiota interactions on the NLRP6-mediated control of the renewal of the
intestinal barrier.
Disclosure of Interest: None declared
OP273 CENTRAL MUSCARINIC CHOLINERGIC ACTIVATION ALTERS
INTERACTION BETWEEN SPLENIC CENDRITIC CELL AND
CD4CD25- T CELLS IN EXPERIMENTAL COLITIS
P. Munyaka1, F.A. Rabbi1, E. Khafipour2, K.J. Tracey3, V. A. Pavlov3, J.-
E. Ghia1,*
1
Immunology / internal Medicine, 2Animal Science, University of Manitoba,
Winnipeg, Canada, 3Center for Biomedical Science, The Feinstein Institute for
Medical Research, Manhasset, United States
INTRODUCTION: Inflammatory bowel disease (IBD) patients present dysau-
tonomia with decreased vagus nerve activity, dendritic cell and T cell over-acti-
vation. In experimental colitis, the cholinergic anti-inflammatory pathway (CAP)
is based on VN activity that regulates macrophage and dendritic cell responses in
the spleen through alpha-7 nicotinic acetylcholine receptor (7nAChR) signaling.
However, some controversy exists related to the type of inflammatory model
used. Recently, we have shown that central stimulation of the VN decreases
experimental colitis and is associated with a down regulation of MHC II and
IL-12p40 release by splenic dendritic cell (DC).
A87
AIMS & METHODS: The aim of this study was to investigate whether central
activation of the CAP alters the function of DC and sequential T cell activation
in the context of a T-cell mediated experimental colitis. Groups of C57Bl/6 mice
were subjected to sub-diaphragmatic bilateral vagotomy (VXP), neurectomy
(NRX) or splenectomy (SPX) and i.c.v. cannulation. I.c.v. infusion of the
M1mAChR agonist McN-A-343 (5mg/kg/day) or vehicle were initiated 8 days
later and one day before induction of colitis with 2,4 dinitrobenzen sulfonic acid
(DNBS; 4mg diluted in Ethanol 30%). After 3 days, mice were euthanized and
inflammation was evaluated clinically (macroscopic score, colon length) and by
colonic tissue IFN-
and IL-23 levels in isolated splenic DCs were determined and IFN-
in DC/CD4CD25- T cell co-culture were studied in the presence or absence of
anti p19-mAb, p35-mAb or IL-12p70 or IL-23 recombinant proteins.
RESULTS: Clinical score, colonic IFN-
cantly decreased in McN-A-343-colitic groups. Splenic level of acetylcholine
was increased in McN-A-343 groups. Attenuation of inflammatory markers by
McN-A-343 treatment was not observed in SPX mice. Splenic DC isolated from
McN-A-343-colitic groups showed a significant decrease of IL-12p70 and IL-23
release and a reduced T cell priming capacity reflected by a decrease of IFN-
and IL-17 release from CD4CD25-T cells. VXP or NRX exacerbated serum,
colonic and in vitro markers and abolished the beneficial effect of the McN-A-343
treatment. Addition of anti p19-mAb in the medium abolished the deleterious
effect on IL-17 in CD4CD25-T cells conditioned with splenic CD11cDCs iso-
lated from VXP and NRX colitic mice, whereas, in the presence of anti p35-mAb
only IFN-
binant proteins restore IFN-
with splenic CD11cDCs isolated from colitic mice treated with McN-A-343.
CONCLUSION: Suppression of splenic immune cell activation and altered inter-
action between DCs and T cells are important aspects of the beneficial effect of
brain activation of the CAP in experimental colitis. These findings may lead to
improved therapeutic strategies in the treatment of IBD.
Disclosure of Interest: None declared
OP274 PRIMARY INTESTINAL MYOFIBROBLASTS EXPRESS THE
TNF-LIKE CYTOKINE TL1A/TNFSF15 FOLLOWING
STIMULATION WITH PRO-INFLAMMATORY MEDIATORS
G. Bamias1, E. Filidou2,*, D. Goukos3, V. Valatas4, K. Arvanitidis2,
M. Panagopoulou2, G. Kouklakis5, G.L. Daikos3, S. Ladas1, G. Kolios2
1
Academic Dpt of Gastroenterology, Laikon Hospital, Kapodistriakon University
of Athens, Athens, 2Laboratory of Pharmacology, Faculty of Medicine, Democritus
University of Thrace, Alexandroupolis, 31st Dpt. of Internal Medicine, Laboratory
of Infectious Diseases, Laikon Hospital, Kapodistriakon University of Athens,
Athens, 4Laboratory of Gastroenterology, University of Crete, Heraklion,
5
Endoscopy Unit, Faculty of Medicine, Democritus University of Thrace,
Alexandroupolis, Greece
Contact E-mail Address: gbamias@gmail.com
INTRODUCTION: TL1A belongs to the TNF superfamily of cytokines
(TNFSF15). It provides co-stimulatory signals for activated lymphocytes that
express the functional receptor DR3. TL1A and DR3 are highly upregulated
in intestinal areas with active IBD-related inflammation. Recently it was reported
that transgenic mice with lymphoid- or myeloid-specific overexpression of TL1A
develop colonic fibrosis.
AIMS & METHODS: Our aim was to determine whether primary human intest-
inal myofibroblasts (IM) express TL1A under stimulation with IBD-associated
pro-inflammatory cytokines. IM were isolated from endoscopically-obtained
colonic biopsies from healthy controls (HC) and patients with Crohns disease
(CD). IM were cultured unstimulated or stimulated under various conditions: a.
with rhTNF-a and/or rhIL-1a; b. with supernatants from colonic tissues obtained
from HC and CD patients; and, c. with supernatants from epithelial GS-29-cell
cultures which were unstimulated or stimulated with rhTNF-a and/or rhIL-1a
and/or rhIFN-g). Total RNA was extracted from the cultured IM and the
mRNA expression of TL1A and the receptor DR3 was measured by real-time
RT-PCR.
RESULTS: Stimulation of IM with either TNF- or IL-1 resulted in significant
upregulation of the relative expression for TL1A mRNA at 6h (unstimulated,
2.895.20 averagesdev; IL-1, 93.5817.44; TNF-, 66.5915.53; IL-
1TNF-, 127.0419.40, P50.00001 for any condition vs. control). The aver-
age increase in TL1A expression was 32.8-fold for IL-1, 23-fold for TNF-, and
43.9-fold for their combination. No difference was seen at 1h whereas at 24h only
stimulation with TNF- was significantly higher than the control condition. We
did not detect DR3 mRNA in IM under any of the above conditions. We also
found that supernatants from cultured HT-29 epithelial cells were able to induce
the expression of TL1A in IM when TNF- was used for stimulation of the
epithelial cells either alone or in combination with IL-1a and/or IFN-g
(P50.05 for any combination vs. unstimulated HT-29 cell supernatant).
Finally, supernatants from CD-derived colonic tissue cultures induced a signifi-
cantly higher upregulation of TL1A mRNA expression in cultured IM (45-fold
increase over tissue cultures form healthy controls, P50.01). The soluble TL1A
protein content was also higher in IM cultures stimulated with supernatants from
CD-derived colonic tissue cultures.
CONCLUSION: Pro-inflammatory cytokines that are abundantly expressed in
intestinal areas with active CD (TNF-a, IL-1a, IFN-g) induce the expression of
the co-stimulatory cytokine TL1A in IM either directly or through the induction
of epithelial-derived mediators. Our results raise the possibility that interactions
between IM-derived TL1A and its receptor, DR3 on epithelial cells or lympho-
cytes may participate in the pathogenesis of chronic intestinal inflammation.
REFERENCES
1. Bamias G, et al. Curr Opin Gastroenterol 2013; 29: 597-602.
2. Bamias G, et al. Dig Liver Dis 2012; 44: 30-36.
A88
3. Drygiannakis I, et al. J Crohns Colitis 2013; 7: 286-300.
Disclosure of Interest: None declared
OP275 CULTURED BLOOD T CELLS AS A PROGNOSTIC BIOMARKER
FOR ANTI-TNF THERAPY RESPONSE IN PATIENTS WITH
ULCERATIVE COLITIS
M.K. Magnusson1,2,*, H. Strid2, S. Isaksson1,2, A. Bajor2, A. Lasson3, K.-
A. Ung4, L. Ohman1,2
1
Dept of Microbiology and Immunology, Inst for Biomedicine, 2Dept of Internal
Medicine and Clinical Nutrition, Inst for Medicine, Gothenburg, 3Department of
Internal Medicine, Sodra Alvsborg Hospital, Boras, 4Department of Internal
Medicine, Karnsjukhuset, Skovde, Sweden
Contact E-mail Address: maria.magnusson@microbio.gu.se
INTRODUCTION: Anti-TNF therapy is used for treatment of ulcerative colitis
(UC). However, only 60-70% of UC patients are responders and so far it has not
been possible to predict therapy response. Therefore, it is of clinical interest to
identify biomarkers of therapy response before therapy initiation.
AIMS & METHODS: To identify prognostic biomarkers of infliximab therapy
response in anti-TNF na ve UC patients before therapy start.
Mucosal biopsies and blood cells were obtained from UC patients before therapy
start. Biopsies were cultured for 24h with or without 1g/ml infliximab and used
for quantitative proteomic analysis using mass spectrometry. Blood cells were
stimulated in vitro with influenza vaccine with and without 10g/ml anti-TNF for
7 days. Receptor expression and cytokine release were determined by flow cyto-
metry and the Meso Scale Discovery platform. Linear Discriminant Analysis
(LDA) was used for generation of the prediction model. To assess the accuracy of
the LDA rule, Leave-one-out cross-validation (LOOCV) was used. Therapy
response was assessed by the validated Mayo score 12-14 weeks after treatment
initiation. Response was defined as a decrease in Mayo score of 3.
RESULTS: We have included 34 UC patients into the study. Sixteen patients
responded to anti-TNF therapy, whereas eighteen patients did not respond.
Therapy responders and non-responders showed no significant differences in
gender distribution, age, smoking habits, disease duration, Mayo score, CRP,
fecal calprotectin, TNF levels in serum or use of immunomodulatory therapy
before start. Proteomic analysis of cultured biopsies showed that infliximab
affected protein expression differently in therapy responders and non-responders.
In particular, reduced activity of NF-B and pro-inflammatory cytokine path-
ways were recorded in therapy responders. This was verified in cultured blood
cells where infliximab induced stronger suppression of CD25 (p0.0004), TNF
United European Gastroenterology Journal 2(5S)
RESULTS: - We recorded 303 pregnancies including 95 before diagnosis of UC
and 208 after the disease, and 294 pregnancies including 88 before diagnosis of
CD and 206 after the disease.
- Mean number of pregnancy was 0.84 and 1.85 in UC and 0.76 and et 1.84 in CD
before and after the disease respectively.
- There was no statistical significant difference (SSD) as regards to fetal risk in
UC considered before and after pregnancy.
- In CD, the rate of caesarean (10.7% Vs 4.5%), spontaneous abortion (6.8% Vs
2.5%), Stillborn (1.9% Vs 0%) were significantly higher after the diagnosis of the
disease, than before.
- Comparing UC to CD, we found no statistical significant difference (SSD) as
regards to fetal risk in UC and CD before the disease; however, the rate of
caesarean (10.7% Vs 4.9%) was higher in patients with CD after diagnosis.
- After diagnosis, the rate of caesarean (UC: 19.2% Vs 2.7%; p50.001; CD:
35.7% Vs 6.7%; p50.001), stillborn (UC: 3.8% Vs 1%; p50.8034; CD: 3.6% Vs
1.6%; p50.9426) and congenital abnormalities (UC: 3.8% Vs 0%; p50.2664;
CD: 3.6% Vs 0.5%; p50.6505) were higher in primiparous than in multiparous
patients.
CONCLUSION: Our data suggest that conception should not be discouraged in
patients with IBD. However, CD in the post diagnosis phase and a primiparous
statute have some negative influence on outcome of pregnancy; thus pregnancy in
those IBD patients should be closely monitored.
Disclosure of Interest: None declared
OP277 INCIDENCE RATE OF MICROSCOPIC COLITIS IN THE
NETHERLANDS
G.M. Masclee1,2,*, P.M. Coloma1, E.J. Kuipers2, M.C. Sturkenboom1
1
Medical Informatics, 2Gastroenterology and Hepatology, Erasmus University
Medical Center, Rotterdam, Netherlands
Contact E-mail Address: g.masclee@erasmusmc.nl
INTRODUCTION: Chronic diarrhea is a common problem and affects the
quality of life of patients. Microscopic colitis (MC) is increasingly recognized
as important cause of chronic diarrhea in the elderly. The incidence rate (IR) of
MC, including two entities: lymphocytic (LC) and collagenous colitis (CC),
increased in recent years. This may be due to detection bias because more diag-
nostic colonoscopies are being performed. Up to date incidence studies account-
ing for this are lacking.
AIMS & METHODS: We aimed to estimate the IR of MC in the general popu-
lation in the Netherlands and in relation to the number of colonoscopies.
receptor 2 (p0.02) and 7 (p0.05) expression on T cells, as well as reduced We conducted a cohort study using data from a primary care database contain-
secretion of interleukin (IL)-4 (p0.002) and IL-1 (p0.02), in therapy respon- ing electronic medical records of 1.6 million subjects in the Netherlands. Study
ders as compared to non-responders (Table 1). By the use of LDA, CD25 and IL- period was from January 1st 2003 to May 31st 2013. Microscopic colitis (CC, LC
4 were used to create a rule for classification of therapy response. When perform- and unspecified) cases were identified by free text search and manual validation.
ing LOOCV, correct classification of future therapy response was achieved in Only diagnostic index colonoscopies were counted and validated against the
85% of the cases. national number of colonoscopies per capita in the Netherlands. Standardized
Table 1. Surface epitope expression on T cells and cytokine secretion in blood software provided age- and sex-specific IR for LC and CC separately.
cells cultured in vitro with and without 10g/ml anti-TNF.Data shown as median RESULTS: The study population of 1,458,410 subjects contributed to 4,158,573
(25-75 percentiles). person-years (PYS). We identified 210 incident MC cases (LC: 122; CC: 88;
unspecified: 54), yielding an overall IR of 5.1/100,000 PYS; 2.1/100,000 PYS
for CC; 1.6/100,000 PYS for LC and 1.3/100,000 PYs for unspecified MC. IR
Responders(%) Non-responders(%) p-value of MC overall, CC and LC separately remained stable from 2003 (IR MC over-
all: 3.5/100,000 PYS) until 2013 (IR MC overall: 2.5/100,000 PYS). IR of LC

CD25 CD4 Tcells 60.6(48.0-65.7) 74.2(67.1-85.3) 0.0004 increased after the age of 50-54 years (3.0/100,000 PYS) until 75-79 years (7.2/
TNFR2CD3Tcells 55.3(47.2-70.4) 70.6(57.3-82.0) 0.02 100,000 PYS), whereas for CC the IR increased already from the age of 45-49
years (1.2/100,000 PYS) until 80-84 years of age (7.9/100,000 PYS). However,
7CD4Tcells 81.0(69.7-82.7) 93.5(82.4-104.3) 0.05 across age groups IRs of CC, and LC were comparable. Across all ages and
IL-4 20.2(1.6-60.2) 73.1(41.4-161.1) 0.002 calendar years, IR was 2-4 times higher for females than males. Accounting
IL-1 33.2(14.9-52.6) 101.8(59.4-185.5) 0.02
CONCLUSION: The effect of infliximab on cultured blood T cells, obtained
before therapy start, differs between therapy responders and non-responders.
The discrepancy in cellular response between responders and non-responders
can be used for prognostic evaluation of infliximab therapy response in order
to tailor treatment.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
IBD: EPIDEMIOLOGY AND DISEASE OUTCOMES HALL N_____________________
OP276 COMPARISON OF FETAL RISKS IN PREGNANCY BEFORE AND
AFTER DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE: A
PROSPECTIVE STUDY
L. Kecili1,*, N. Bounab1, M. Nakmouche1, A. Balamane1, N. Kaddache1,
L. Gamar1, K. Belhocine1, K. Layaida1, T. Boucekkine1
1
Medicine University, algiers, Algeria
Contact E-mail Address: keli_002000@yahoo.fr
INTRODUCTION: Inflammatory bowel disease (IBD) commonly affect young
women during the reproductive years. The fetal prognosis of pregnancy occur-
ring in IBD is generally considered as good.
AIMS & METHODS: To evaluate the impact of IBD on pregnancy (P), we
studied the fetal outcome in 112 patients suffering from ulcerative colitis (UC)
and 112 with Crohns disease (CD), who have been pregnant before and / or after
onset of disease.
In this prospective study we have compared during a 5 year period (1/1/2005 to
31/12/2009) outcome of the pregnancy which occurred before or after onset of
disease.
Statistic study used Student Fishers t test and Mann Whitneys U test.
for possible detection bias: IR of MC decreased from 5.6/1,000 colonoscopies
in 2003 to 2.4 in 2012.
CONCLUSION: Incidence rates of microscopic colitis remained fairly stable
during a 10-year period from 2003-2013 in the Netherlands, taking into account
the increase in the total number of colonoscopies over this period. IR of MC
increased with advanced age, starting at 50 years for collagenous colitis and at 60
years for lymphocytic colitis. IR was 2-4 times higher for females than males
across all ages.
Disclosure of Interest: None declared
OP278 DEVELOPMENT OF A PREDICTION MODEL TO ASSESS THE
RISK OF CHRONIC GASTROINTESTINAL ISCHEMIA IN
REFERRED PATIENTS
J. Harki1,*, Y. Vergouwe2, J.A. Spoor1, E.J. Kuipers1,3, P.B. Mensink 1,4,
M.J. Bruno1, D. van Noord1, E.T. Tjwa1,5
1
Gastroenterology and Hepatology, 2Public health, 3Internal Medicine, Erasmus
MC University Medical Center, Rotterdam, 4Gastroenterology and Hepatology,
Medisch Spectrum Twente, Enschede, 5Gastroenterology and Hepatology, Jeroen
Bosch Hospital, s Hertogenbosch, Netherlands
Contact E-mail Address: j.harki@erasmusmc.nl
INTRODUCTION: Chronic gastrointestinal ischemia (CGI) is a challenging
disease entity. Clinical symptoms may differ amongst patients.
AIMS & METHODS: We analyzed data of a prospective cohort study. Between
2006 and 2013 self-reported symptoms were collected by a structured question-
naire of 431 consecutive patients referred to an academic hospital for evaluation
of possible CGI. All patients received the standard work-up of CGI, consisting of
radiological imaging of the gastrointestinal arteries, and functional testing for
detection of mucosal ischemia by means of visible light spectroscopy (VLS) or
tonometry. The results were discussed in a multidisciplinary expert panel leading
to a consensus diagnosis, which was monitored during follow-up. Predictors for
United European Gastroenterology Journal 2(5S)
the diagnosis of CGI were obtained by comparing the self-reported symptoms in
the questionnaire to the diagnosis of CGI. Multivariable logistic regression ana-
lysis was used to combine the strongest predictors in a prediction model. We
aimed to establish predictors for CGI based on self-reported variables and to
combine these in a prediction model in order to distinguish low, intermediate and
high risk patients for CGI.
RESULTS: Postprandial pain, exercise-induced pain or weight loss was present
in more than 90% of patients. The diagnosis of CGI was established in 192
(45%) patients. Clinical variables showing strong association with CGI were
age 60 years (OR1.4, 95%CI 0.99-1.9), female gender (OR2.5, 95%CI 1.6-
3.8), concomitant cardiovascular disease (OR1.4, 95%CI 0.9-2.2), smoking
(OR1.4, 95%CI 0.95-2.0), severe postprandial pain (OR1.3, 95%CI 0.9-2.0),
weight loss (OR1.2, 95%CI 0.99-1.5) and no use of analgetics (OR1.7, 95%CI
1.1-2.5). Ongoing symptoms of 46 months (OR0.9, 95%CI 0.8-1.0) did not
favor CGI. A c-statistic for the prediction model was obtained of 0.64. Based
on the scoring system patients were categorized as low (30%), intermediate
(47%) or at higher risk (64%) for CGI.
Predictors Score
Age, years 560 60 01
Gender Male Female 03
Cardiovascular comorbidity No Yes 01
Severe postprandial pain No Yes 01
Weight loss, kg/month 53 3 01
Smoking, packyears 525 25 01
Use of analgetics No Yes 20
Duration of symptoms, months 6 46 10
Scorepoints 0-4 5-8 9 Risk of CGI 30% 47% 64%
CONCLUSION: We present a scoring system for the presence of CGI on clinical
features and risk profiles alone for patients suspected of CGI. This tool may be
useful for clinicians to assess the risk of CGI and to decide whether further
diagnostic work-up by means of radiological imaging of the gastrointestinal
arteries and functional testing is indicated and worthwhile.
Disclosure of Interest: None declared
OP279 CLINICAL AND RADIOLOGICAL OUTCOMES PRE AND POST
THE ANTI-TNF ERA FOR PERIANAL CROHNS FISTULAS
N.A. Yassin1,*, A. Askari1, L. Ferrari1, J. Warusavitarne1, O. Faiz1, R. Phillips1,
A. Hart1
1
St Marks Hospital and Academic Institute, London, United Kingdom
Contact E-mail Address: nayassin@gmail.com
INTRODUCTION: Anti-tumor necrosis factor (TNF) therapies are used to treat
fistulising perianal Crohns disease (CD). We evaluated the clinical and radiolo-
gical outcomes of patients with perianal Crohns fistulas in the pre anti-TNF and
in the post anti-TNF era.
AIMS & METHODS: A local database of 263 consecutive patients with Crohns
disease treated at our institution between 2000 and 2014 was established. Data on
patient demographics and relevant outcomes were collated from medical, elec-
tronic and radiological reports. Chi Squared analysis was carried out to deter-
mine differences between the anti-TNF and non-anti-TNF groups. Cox
regression analysis was undertaken to compare difference in time to clinical
and radiological response between the two patient groups. Binary logistic regres-
sion was carried out to determine independent predictors of clinical remission
and response. At the univariate level, variables that reached a p value of 50.10
were included into a multivariate regressional model. At multivariate analysis, a
p value of 50.05 was considered to be significant.
RESULTS: Ninety patients were in the non-anti-TNF group and 173 were trea-
ted with anti-TNF therapy (Infliximab or Adalimumab). Clinical response rates
were significantly higher in the anti-TNF group compared with the non-
anti_TNF group (74% vs 62%, p0.04). Similarly, radiological response rates
were higher in the anti-TNF group (56% vs 28%, p50.01).
Cox Regression analysis demonstrated fistula duration (p0.01) and biologic
therapy (p50.01) to be significant at the univariate level. Factors such as
sex, age, smoking status, diabetes status, Montreal classification, the presence
of proctitis and the use of other immunosuppressive agents were not significant.
At the multivariate level, patients on anti-TNF therapy had a faster radiological
response over a 6 year follow up period as compared with the non-anti-TNF
group (OR2.25, CI 1.14-4.46, p0.02). A short duration of Crohns disease
(less than 5 years) contributes to a faster time to clinical response (OR1.77,
CI1.03-3.05, p0.04) compared with patients who were diagnosed with the
disease for longer.
Multivariate binary logistic regression revealed treatment with anti-TNF therapy
to be an independent predictor of radiological response (OR 3.55, CI 1.59-7.91,
p50.01). Patients with L1 luminal disease are 3 times more likely not to go into
clinical remission on both univaraite and multivariate analyses (OR3.08,
CI1.47-6.46, p0.01). The duration of Crohns diagnosis is also a poor pre-
dictor of clinical response to therapy (p50.01).
CONCLUSION: Patients on anti-TNF therapy have improved clinical and radi-
ological response rates compared with patients without anti-TNF treatment.
Anti-TNF therapy is a positive predictor of radiological response to therapy.
Montreal classification of L1 ileal disease is a poor predictor of clinical healing
of perianal fistulas in both groups of patients.
Disclosure of Interest: None declared
A89
OP280 FAMILIAL RISK OF INFLAMMATORY BOWEL DISEASE: A
POPULATION-BASED COHORT STUDY 1977-2011
F.T. Mller1,2,*, V. Andersen2, T. Jess1
1
Dep of. Epidemiological research, Statens Serum Institute, Copenhagen, 2Institute
for Regional Health services Research, University of Southern Denmark, Odense,
Denmark
Contact E-mail Address: frtm@outlook.com
INTRODUCTION: The inflammatory bowel diseases (IBD) ulcerative colitis
(UC) and Crohns disease (CD) - are caused by complex gene-environment inter-
actions. This study provides updated familial aggregation patterns in a large
population-based Danish IBD cohort.
AIMS & METHODS: Our cohort study was based on the entire Danish popula-
tion during 1977-2011 (n8,295,773). Through a unique personal identification
number assigned to each Danish citizen, sex, date and location of birth, identity
of parents, and information on vital status and emigration were available. This
information was used to establish kinship in the entire population. Individuals
receiving at least 2 diagnoses of IBD during the time period (n45,780) were
identified using the Danish National Registry of Patients. Risk of IBD in family
members to individuals with IBD was assessed by Poisson regression analysis.
RESULTS: The overall proportion of familial CD cases was 12.2% of all CD cases,
whereas familial UC accounted for 8.8% of all UC cases from 2007-2011. The ratio
of CD was 9.36(6.75-12.99) increased in 1st degree relatives to at least two indivi-
duals with IBD, 7.78(7.07-8.57) fold increased in 1st degree relatives to one family
member with CD, and 2.82(2.51-3.16) increased if the 1st degree relative had UC.
The same pattern was observed for the ratio of UC with a risk ratio of 6.92(5.28-
9.06) in 1st degree relatives to at least two individuals with IBD, 2.57(2.28-2.90) in 1st
degree relatives to one family member with CD, and 4.09(3.81-4.38) if the 1st degree
relative had UC. Furthermore, the risk was influenced by an interaction with age
resulting in rate ratios above 20 among infants and young adults belonging to
families with more than one IBD affected member. Second-degree relatives to
patients with CD or UC were also at significantly increased risk not only of the
same but also the other subtype of IBD, whereas the risk of IBD was less pro-
nounced in third degree relatives to individuals with IBD. The overall pattern
described above was stable across several sensitivity analyses.
CONCLUSION: This large-scale population-based study provides updated num-
bers of familial aggregation of IBD. Familial exposure to CD not only increases
the risk of CD but also of UC markedly and vice versa, and the ratio rises with
closer familial ties and in families with multiple affected members. Also we found
that individuals belonging to IBD affected families had particularly high risk of
IBD in early life.
Disclosure of Interest: None declared
OP281 A PROSPECTIVE OBSERVATIONAL COHORT STUDY TO
EVALUATE MUCOSAL HEALING IN ULCERATIVE COLITIS:
HAVE MAYO 1 AND MAYO 0 SCORES REALLY THE SAME
PROGNOSTIC VALUE?
M. Barreiro-de Acosta1,*, N. Vallejo-Senra2, D. De la Iglesia-Garc a1,
L. Uribarri-Gonzalez1, I. Baston-Rey1, R. Ferreiro-Iglesias1, A. Lorenzo-
Gonzalez3, J.E. Dominguez-Munoz1
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, 2Gastroenterology, Unversity Hospital of Santiago
de Compostela. Foundation for Research in Digestive Diseases, 3Gastroenterology,
University Hospital of Santiago de Compostela, Santiago de Compostela, Spain
INTRODUCTION: Mucosal healing has become a common endpoint in most
therapeutic trials and an important objective to be reached in patients with
ulcerative colitis (UC). Despite important differences between endoscopic
Mayo sub-scores 0 and 1, most important trials consider both as mucosal heal-
ing. We hypothesized that only an endoscopic Mayo score of 0 should be defined
as mucosal healing.
AIMS & METHODS: The aim of this study was to evaluate the differences between
endoscopic Mayo-0 and Mayo-1 scores in the clinical course of UC patients.
A prospective observational cohort study was designed. All UC patients who
presented mucosal healing in a colonoscopy were consecutively included and
classified according to the Montreal Classification. Mucosal healing was defined
as an endoscopic Mayo sub-score of 0 or 1. In order to minimize potential
interpretation bias, all colonoscopies were performed and scored by the same
endoscopist. Mayo-0 was defined as normal or inactive disease and Mayo-1 as
the presence of erythema, decreased vascular pattern or mild friability. Clinical
relapse was defined as the need for remission induction treatment, any treatment
escalation, hospitalization or colectomy. In order to assess the clinical course of
UC, all clinical relapses were evaluated at months 6 and 12 after inclusion colo-
noscopy. The influence of demographic variables in the clinical course was also
evaluated. Results are shown as odds ratio (OR) and 95%CI and analyzed by the
chi-squared test and multiple regression whenever appropriate.
RESULTS: 187 UC patients with mucosal healing [127 (67.9%) Mayo-0 and 60
(32.1%) Mayo-1] were included. 94 were male (50.3%), mean age 52 years, range
22 to 85 years. UC was classified as E1 in 31.3% of patients, E2 in 42.2% and E3
in 26.5% according to the Montreal Classification. 9.4% of patients with Mayo-0
score and 36.6% with Mayo-1 score presented with a relapse during the first 6
months of follow up (p50.001). Patients with Mayo 1 score suffered more fre-
quently from a relapse than those with Mayo 0 score in all three Montreal groups
(E1, E2 and E3). The disease relapsed in patients with Mayo 0 and 1 scores at a
similar rate during the following 6 months (14.6%vs 16.6%, respectively,
p0.868). The only factor significantly and independently associated with UC
relapse during follow-up in the multivariate analysis was a Mayo-1 endoscopic
sub-score (OR 6.27 CI 95% 2.75-14.30, p50.001).
CONCLUSION: UC patients with Mayo sub-score 1 have a higher risk of
relapse than those with Mayo sub-score 0, regardless of the extension of the
A90
disease. This study demonstrates that mucosal healing should be only defined as
an endoscopic Mayo score of 0.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
CYSTIC PANCREATIC LESIONS: A CLINICAL DILEMMA HALL O_____________________
OP282 NEEDLE-BASED CONFOCAL LASER ENDOMICROSCOPY
(NCLE) FOR THE DIAGNOSIS OF PANCREATIC CYSTS:
VALIDATION OF THE DESCRIBED CRITERIA
B. Napoleon1,*, A., I. Lemaistre2, B. Pujol1, F. Caillol3, F. Fumex4, C. Lefort1,
V. Lepilliez1, L. Palazzo5, M. Giovannini3
1
Hopital Jean Mermoz, 2Centre Leon Berard, Lyon, 3Institut Paoli Calmettes,
Marseille, 4Hopital Jean Mermoz, Lyon, 5Clinique du Trocadero, Paris, France
Contact E-mail Address: bertrand.napoleon@dartybox.com
INTRODUCTION: Needle-based Confocal Laser Endomicroscopy (nCLE) is an
imaging technique, which enables microscopic observation of the inner wall of
pancreatic cysts, in vivo and in real-time, during an EUS-FNA procedure. A
prospective multicentric French study (CONTACT) aims at evaluating the accu-
racy of nCLE for the diagnosis of lonely pancreatic cysts. Two criteria have been
previously evaluated (INSPECT, CONTACT 1): papillae for IPMN, superficial
vascular network for serous cystadenoma (SCA). Two new criteria have been
highlighted during CONTACT 1 study: a field of bright and black particles for
pseudocyst (PC) and an epithelial border for mucinous cystadenoma (MCN).
The aim of this study is to evaluate retrospectively the yield of nCLE for the
diagnosis of pancreatic cysts based on all these criteria.
AIMS & METHODS: Over 10 months (June 2012 to April 2013), 43 patients
with a lonely pancreatic cyst, 4 2 cm large, without communication with the
pancreatic duct at EUS and MRI were prospectively enrolled. Patients with
calcified chronic pancreatitis were excluded. Following EUS examination, the
AQ-Flex miniprobe was introduced in a 19G needle and real-time video of the
cyst wall was recorded. Fluid obtained by FNA was analyzed. Twelve patients
were excluded of the analysis due to protocol failure or absence of diagnosis
consensus. Final diagnosis of the 31 remaining patients (13 SCA, 7 PCs, 5
United European Gastroenterology Journal 2(5S)
1
Department of Medical Chemistry, Gothenburg University, 2Department of
Gastroenterology and Hepatology, Sahlgrenska University Hospital, Gothenburg,
3
Division of Pathology, Department of Laboratory Medicine, Karolinska Institute,
Karolinska University Hospital, Stockholm, Sweden
Contact E-mail Address: karolina.sjoberg@medkem.gu.se
INTRODUCTION: IPMN and MCN have recently been identified as macro-
scopic precursors of pancreatic cancer. However, our understanding of the mole-
cular backgrounds of these tumors is still incomplete, and their diagnosis remains
challenging. We performed a systematic proteomic analysis of cyst fluid from
different pancreatic cystic neoplasms to further elucidate their pathogenesis and
identify new biomarkers.
AIMS & METHODS: Aspirates from 24 patients with pancreatic cystic lesions
(15 females, median age 63), obtained through EUS-FNA were utilized for the
analyses. Samples were selected to represent triplicates of the most common
cystic tumors: serous cystic tumors, MCN, cystic ductal adenocarcinomas, and
IPMN of the gastric, intestinal and pancreatobiliary type. For comparison, six
pseudocysts were included. 9 samples were characterized as intrinsically benign, 5
as premalignant and 10 as malignant (minimum high-grade dysplasia). Histology
was procurable in 20/24 cases (83%), including 17/18 (94%) cystic tumors.
Pseudocysts were, in the absence of histology, identified by their spontaneous
regress/resolution. Samples were prepared by the filter aided sample preparation
(FASP) method (modified), and digested by trypsin, before analysis by nano-LC
MS/MS on a Q-Exactive instrument. Data were searched against the UniProt/
Swissprot database, using the Andromeda search engine integrated in
MaxQuant. Pathway analyses were performed by Ingenuity Pathway Analysis
(IPA).
RESULTS: A total of 1385 proteins were identified. After filtering out single
occurrences, 541 proteins were found to be unique to lesions with malignant
potential, and 273 to malignant tumors. Pathway analysis revealed the transcrip-
tion factors XBP1 (ER stress response) and NFE2L2 (defense against oxidative
stress) as prominent upstream regulators for proteins that were differentially
expressed in lesions with malignant potential (MCN, IPMN and ductal adeno-
carcinoma). PI3K/AKT and ERK5 were central components of the molecular
networks generated for these tumors. Activation of c-MYC and KRAS were
identified as major events in malignant transformation. Notable predicted
IPMN, and 6 MCNs) was based on histological analysis of the surgical specimen upstream regulators by tumor type were: TGF for serous cystic tumors, c-
(n6), on undoubtedly positive FNA sample using cell blocs (n16), or on MYC for MCN, IL22 for IPMN, and EGFR for cystic ductal adenocarcinomas.
consensus between the 5 investigators (n9). As a first step, the investigators Butyrate (which may be produced by bacteria) and XBP1 were identified as
(5 experts), individually and blindly, reviewed the nCLE records of the 31 cases regulators for intestinal IPMN; KRAS and Catenin beta-1 (Wnt signalling path-
and were asked to give a diagnosis (SCA, PC, IPMN, MCN). When no criteria way) for pancreatobiliary IPMN. Furthermore, the study identified several novel
was evidenced, the diagnosis was indeterminate. Secondly, the investigators biomarker candidates (Table 1).
reviewed together the cases with discrepancies, to assess, if possible, a consensus
diagnosis.
RESULTS: The intial agreement between observers was complete in 35 % of Biomarker Identifies P-value (Fisher-Exact Test, 2-tailed)
cases. For the 65% other cases, a consensus was obtained. Finally a diagnosis
was concluded in 54 % of cases. Inter-observer agreements (IOA) were good TFF2 Malignant potential 0.002
(table 1).Finally the specificity of the nCLE criteria was 100 % for the diagnosis AGR2 Malignant potential 0.007
of SCA, PC and mucinous cyst.
PSCA Malignancy 0.02
Non mucinous Cyst Mucinous Cyst DDAH1 Malignancy 0.03
TXNDC5 IPMN 0.003
SCA PC Mucinous IPMN MCN TFF3 Intestinal-type IPMN 0.0005
(n13) (n7) lesion (n11) (n5) (n6) Total
CONCLUSION: This proteomic study has tentatively identified molecular path-
NCLE diagnosis true 9 2 6 2 2 17 ways/events that have not previously been described in the context of MCN and
wrong 0 0 0 (1) (1) (2) IPMN. Moreover, several new biomarker candidates have been selected for
Indeterminate nCLE diagnosis 4 5 5 2 3 14 further study. Targeted quantitative proteomic studies to define cut-offs and
Diagnostic performances Sensitivity 69 29 55 40 33 validate these markers are underway.
Specificity 100 100 100 67 67
Disclosure of Interest: None declared
per criteria (%)
IOA per criteria 0,77 0,89 0,68 0,77 0,37 0,70
OP284 THE SAFETY OF FOLLOW-UP FOR IPMN OF THE PANCREAS:
A SINGLE INSTITUTION EXPERIENCE
M. Del Chiaro1,*, R. Segersvard2, L. Nilsson2, J. Blomberg2, E. Rangelova2,
CONCLUSION: Based on these four described criteria 46 % of cases remained C. Ansorge2, R. Pozzi-Mucelli3, N. Kartalis3, M. Lohr1, C. Verbeke4
indeterminate. When a diagnosis was proposed the specificity of nCLE was 1
CLINTEC, Karolinska Institutet, 2Gastrocentrum, 3Department of Radiology,
excellent for the diagnosis of SCA and mucinous cysts, with a sensitivity 4 4
Department of Pathology, Karolinska University Hospital, Stockholm, Sweden
50%. This should have a strong clinical impact. An external validation and a Contact E-mail Address: marco.del.chiaro@ki.se
prospective evaluation of the yield of nCLE are both ongoing to confirm these
good results. INTRODUCTION: IPMN of the pancreas is highly prevalent in the general
Disclosure of Interest: None declared population. The strategy of following up the majority of these patients is cur-
rently considered best clinical practice, even though consensus regarding an
appropriate follow-up interval is lacking.
OP283 PROTEOMIC STUDIES ON ASPIRATES FROM CYSTIC AIMS & METHODS: This study analyzes the results of a follow-up program for
NEOPLASMS OF THE PANCREAS PROVIDE NEW CLUES TO patients with IPMN.
THEIR MOLECULAR BACKGROUND AND REVEAL NOVEL From January 2008 to December 2013, 503 patients diagnosed with IPMN were
BIOMARKER CANDIDATES observed at the Pancreas Unit of Karolinska Institute. 452 patients (89.8%) were
K.S. Jabbar1,2,*, C.S. Verbeke3, B. Lindkvist2, L. Eklund2, G.C. Hansson1, followed-up, while 51 (10.2%) underwent surgery. The patients under follow-up
R. Sadik2 represented the study series population.
RESULTS: Overall, 258 (57%) females and 194 males (43%) were analyzed. The
mean patient age was 67.3 yrs, the mean follow-up 932 days. 395 of the patients
(87.4%) were under surveillance according to the prevailing guidelines (group 1),
whereas 57 (12.6%) patients (group 2) were followed-up because of contraindica-
tions for surgery (poor general condition, locally advanced or metastatic IPMN
cancer, synchronous other extrapancreatic cancer. In group 1, 55 patients
(13.9%) required surgery for progression of their IPMN after a median follow-
up of 560 days. In 2 patients (0.5%), a synchronous pancreatic cancer developed
during follow-up. The 1, 3 and 5 years survival rate for the patient series was
96.5%, 92.4% and 87.1%, respectively. In group 1, 33 patients (8.3%) died under
follow-up: 4 (1%) due to IPMN progression, 5 (1.3%) because of extrapancreatic
United European Gastroenterology Journal 2(5S)
cancer and 24 (6%) for other causes. The 1, 3 and 5 years survival rate in group 2
were 74.8%, 48.7% and 40.5%, respectively. In this group 22 patients (38.6%)
died due to IPMN progression (10, 17.5%), extrapancreatic cancer (5, 8.8%), or
for other reasons (7, 12.3%).
CONCLUSION: This study confirms the safety of a surveillance program for
patients with non-surgical IPMN. Incidence of pancreatic cancer and IPMN-
related mortality were low during follow-up. Even if patients with an indication
for surgical treatment were for excluded from surgery for various reasons, survi-
val was acceptable, particularly when compared with pancreatic cancer patients.
Disclosure of Interest: None declared
OP285 ARE IPMN OF THE PANCREAS ASSOCIATED TO AN
INCREASED PREVALENCE OR INCIDENCE OF EXTRA-
PANCREATIC NEOPLASMS? A MULTICENTRE EUROPEAN
OBSERVATIONAL STUDY
G. Marchegiani1,*, G. Malleo1, J. DHaese2, P. Wenzel3, M. Keskin4,
L. Pugliese5, A. Borin1, V. Benning2, N. Oruc4, L. Nilsson6, R. Segersvard6,
M. Lohr7, C. Bassi1, G. Ceyhan2, R. Salvia1, M. Del Chiaro6 on behalf of This
study was conducted as a project of the 6th Pancreas2000, EPC education and,
research program
1
Surgery, Pancreas Institute - Verona University Hospital, Verona, Italy, 2Surgery,
3
Gastroenterology, Klinikum Universitat Munchen, Munich, Germany,
4
Gastroenterology, Ege University, Izimir, Turkey, 5Surgery, IRCCS Policlinico
San Matteo, Pavia, Italy, 6Surgery, 7Gastroenterology, CLINTEC, Karolinska
Institutet at Karolinska University Hospital, Stockholm, Sweden
Contact E-mail Address: giovanni.marchegiani@ospedaleuniverona.it
INTRODUCTION: Although different studies showed an association between
pancreatic IPMN and extrapancreatic neoplasms (EPN), the available data
remain inconclusive.
AIMS & METHODS: This multicentre observational study assessed the preva-
lence and the incidence of EPN in patients with IPMN. Patients diagnosed with
IPMN from 2000 to 2013 were assessed for EPN prevalence. For the incidence
analysis, patients with an EPN previous or synchronous to the IPMN, and
patients with a follow-up 512 months were excluded. Tumor prevalence and
the incidence of EPN that developed during follow-up were compared with
European cancer data. The standardized prevalence and incidence ratios (SPR,
SIR), and the 5- and 10-year incidence rates were calculated.
RESULTS: The study population included 1340 patients. At the time of IPMN
diagnosis, 289 patients developed at least one previous or synchronous EPN
(prevalence of 21.6%). The EPN prevalence was greater than the general popula-
tion (SPR4.04, 95%CI 3.61-5.51). 816 patients were included in the incidence
analysis. At a median follow-up of 44 months, 50 patients developed an EPN
(cumulative incidence of 6.1%). The incidence of EPN was not greater than
expected (SIR1.16, 95% CI 0.85-1.54), with a 5- and 10-year incidence rate
of 5.9% and 20.1%.
CONCLUSION: The prevalence of EPN at the time of IPMN diagnosis is
greater than expected by 4-fold, likely because cancer patients are at increased
medical screening and are diagnosed with IPMN more frequently. This concept is
substantiated by the fact that the incidence of new EPN during the follow-up
period was not greater in comparison with the general population.
REFERENCES
Kawakubo K, Tada M, Isayama H, et al. Incidence of extrapancreatic malig-
nancies in patients with intraductal papillary mucinous neoplasms of the pan-
creas. Gut 2011; 60: 1249-1253.
Disclosure of Interest: None declared
OP286 PANCREATIC SEROUS CYSTADENOMA RELATED
MORTALITY IS ALMOST NIL. RESULTS OF A MULTINATIONAL
STUDY UNDER THE AUSPICES OF THE INTERNATIONAL
ASSOCIATION OF PANCREATOLOGY AND THE EUROPEAN
PANCREATIC CLUB
B. Ja s1,*, V. Rebours1, G. Malleo2, R. Salvia2, R. Moran3, A.-M. Lennon3,
G. Marchegiani4, C. Fernandez del Castillo4, Y. Ha5, M.-H. Kim5, I. Hirai6,
W. Kimura6, J.-Y. Jang7, S.-W. Kim7, C.M. Kang8, W.J. Lee8, S. Crippa9,
M. Falconi10, I. P. Gomatos11, J. Neoptolemos11, A.C. Milanetto12, C. Sperti12,
C. Ricci13, R. Casadei13, M. Bissolati14, G. Balzano15, I. Frigerio16, R. Girelli16,
M. Delhaye17, B. Bernier17, H. Wang18, K.-T. Jang19, D.H. Song19,
M. Huggett20, K. Oppong20, L. Pererva21, K. Kopchak21, M. Del Chiaro22,
R. Segersvard22, L.S. Lee23, D. Conwell23, A. Osvaldt24, V. Campos24, G. Aguero
Garcete25, B. Napoleon25, P. Levy1
1
Service de Pancreatologie Gastroenterologie, Hopital Beaujon, Clichy, France,
2
University of Verona Hospital Trust, Verona, Italy, 3The Johns Hopkins Hospital,
Baltimore, 4Massachusetts General Hospital, Boston, United States, 5Asan
Medical Center, Seoul, Korea, Republic Of, 6Yamagata University Faculty of
Medicine, Yamagata, Japan, 7Seoul National University, 8Yonsei University
Severance Hospital, Seoul, Korea, Republic Of, 9Ospedali Riuniti Academic
Hospital, 10Ospedali Riuniti Academic Hospital, Ancona, Italy, 11The Royal
Liverpool and Broadgreen University Hospitals NHS Trust, Liverpool, United
Kingdom, 12University of Padua, Padua, 13S.Orsola-Malpighi Hospital, Bologna,
14
San Raffaele Scientific Institute, 15San Raffaele Scientific Institute, Milano,
16
Pancreatic Unit, Clinica Pederzoli, Verona, Italy, 17Erasme Hospital, Free
University of Brussels, Brussels, Belgium, 18Southwest Hospital, Third Military
Medical University, Chongqing, China, 19Samsung Medical Center, Seoul, Korea,
Republic Of, 20Freeman Hospital, Newcastle, United Kingdom, 21National Institute
of Surgery and Transplantology named after Shalimov, Kiev, Ukraine,
22
Karolinska University Hospital, Stockholm, Sweden, 23Brigham and Womens
Hospital Harvard Medical School, Boston, United States, 24Hospital de Clinicas de
A91
Porto Alegre, Porto Alegre, Brazil, 25Hopital Prive Jean Mermoz, Lyon, France
Contact E-mail Address: benedicte.jais@gmail.com
INTRODUCTION: Serous cystadenoma (SCA) is a pancreatic cystic neoplasm
which is frequently resected. The purpose of the study was to compare their
related mortality to the perioperative mortality and to examine their natural
history.
AIMS & METHODS: A retrospective multinational study was conducted to
analyze epidemiological and natural history of SCA diagnosed between 1990
and 2014. A questionnaire about clinical and radiological characteristics of
SCA at diagnosis and at the last visit or time of surgery was sent to the partici-
pating centers.
RESULTS: 1786 are presented here. 1357 patients were females (76%, p 5 0.05).
The median age at diagnosis was 57 years [16-91]. Patients were asymptomatic
(62%), had non specific abdominal pain (28%), bilio-pancreatic symptoms (9%)
or diabetes mellitus (4%). SCA was microcystic (45%), macrocystic (31%),
mixed (20%) or solid (4%). There was no predominant location inside the pan-
creas. 48% of patients were operated on during the first year after diagnosis
(median size: 4 cm [0.2-20]), 10% had resection beyond one year of follow-up
(3,1 years [1-20], size: 2,5 cm [0.4-14]), 42% had no surgery (3.6 yr [1-23], size: 2,5
cm [0.5-20]). Surgical indications were: uncertain diagnosis with malignant tumor
(55%), symptoms (29%), increase in size (14%) or adjacent organ compression
(7%). In patients followed beyond one year (n935) size increased in 39% of
cases (growth rate: 4,2 mm / year), were stable in 55%, decreased in 6%. There
were 4 serous cystadenocarcinomas. Post operative mortality was 0.7% (n7),
SCAs related mortality was 0,1% (n1) (NS).
CONCLUSION: SCA related mortality is almost nil, whereas operative mortal-
ity is not. SCA is a benign tumor, exceptionally symptomatic with slow growth.
Uncertainty diagnosis is a too frequent surgical indication even though reliable
diagnostic criteria have been established. SCA without complication should be
followed and not operated.
Disclosure of Interest: None declared
OP287 EVALUATION OF PATIENTS UNDERGOING PANCREATIC
RESECTION: HIGH INCIDENCE OF PANCREATIC CANCER IN
PATIENTS WITH AUTOIMMUNE PANCREATITIS
P. Macinga1,*, A. Pulkertova1, J. Maluskova2, M. Oliverius3, J. Spicak1, T. Hucl1
1
Department of Gastroenterology and Hepatology, 2Department of Clinical and
Transplant Pathology, 3Department of Transplant Surgery, Institute for Clinical
and Experimental Medicine, Prague, Czech Republic
Contact E-mail Address: peter.macinga@ikem.cz
INTRODUCTION: Autoimmune pancreatitis (AIP) is a rare, benign, fibroin-
flammatory disease that may present with signs and symptoms mimicking pan-
creatic cancer (PC). AIP is characterized by a dramatic response to corticosteroid
therapy. Thus, patients diagnosed with AIP can avoid surgery and undergo
immunosuppressive treatment. Despite the availability of well-defined AIP cri-
teria, still a large portion of AIP patients undergoes unnecessary surgery. Only a
few cases of PC in AIP patients have so far been reported worldwide.
AIMS & METHODS: The objective of our study was to assess the proportion of
AIP in all pancreatic resections performed in our center for focal pancreatic
enlargement and to determine clinical characteristics of this subgroup.
We performed a retrospective analysis of data of all patients who underwent
pancreatic resection in our center for suspected cancer/focal pancreatic enlarge-
ment between January 2000 and July 2013.
RESULTS: Two hundred and ninety-five pancreatic resections were performed
in 201 males and 94 females (mean age 60 years, range 36-78 years). Indication
for surgery was tumor suspicion based on clinical symptoms, imaging methods
and laboratory findings. In 19 patients (6.4%, 13 males, 6 females), autoimmune
pancreatitis was diagnosed based on histology of the resected specimen. 10
patients were diagnosed as AIP type 1 (9 males, 1 female), 9 patients had distinct
histopathological features of AIP type 2 (4 males, 5 females). In 6 AIP patients
(31.6%, all males, 3 AIP type 1), pancreatic adenocarcinoma was also present in
the resected tissue. No differences were observed in the preoperative character-
istics of patients with and without cancer (CT, EUS, ERCP, bile duct involve-
ment, laboratory findings including Ca 19-9). In none of the patients the
diagnosis of AIP was made prior to surgery; however the diagnostic algorithm
was not fully completed.
CONCLUSION: A considerable number of resected patients with AIP had syn-
chronous PC in our study. The preoperative diagnosis of AIP in patients with
focal pancreatic enlargement may not always rule out the simultaneous presence
of cancer.
Disclosure of Interest: None declared
A92
TUESDAY, OCTOBER 21, 2014 15:4517:15
VISCERAL SENSITIVITY: CLINICAL AND TRANSLATIONAL SCIENCE ASPECTS
LOUNGE 5_____________________
OP288 CORTICOTROPHIN-RELEASING HORMONE INCREASES
OESOPHAGEAL SENSITIVITY TO MECHANICAL DISTENTION IN
HEALTH
C. Melchior1, C. Broers1,*, T. Vanuytsel1, L. Van Oudenhove1, J. Tack1,
A. Pauwels1
1
Translational Research Center for Gastrointestinal Disorders, KU Leuven,
Leuven, Belgium
Contact E-mail Address: ans.pauwels@med.kuleuven.be
INTRODUCTION: Oesophageal hypersensitivity has been proposed as an
important pathophysiological factor in patients with gastro-oesophageal reflux
disease (GORD) refractory to acid suppressive therapy. Stress is well-known to
affect visceral sensitivity in humans. It has been shown that a real-life stressor is
able to exacerbate heartburn in GORD patients. A recent study from our group
showed that, in humans, an acute psychological stressor increases duodenal per-
meability in a mast cell dependent way and that this effect on barrier function is
mimicked by IV administration of exogenous corticotrophin-releasing hormone
(CRH).
AIMS & METHODS: The aim was to investigate the effect of CRH-adminis-
tration on oesophageal sensitivity in health.This cross-over, randomized, single-
blind study was performed in 10 HV (4m/6f, mean age 31.611.5y) with no prior
history of digestive disease. Oesophageal multimodal sensitivity was quantified
after administration of CRH (100mg IV) and placebo (0.9% NaCl IV), with 1
week interval. After an overnight fast, a multimodal oesophageal stimulation
probe was positioned in the distal oesophagus. Thermal (recirculating a heated
solution), mechanical (increasing balloon volume), electrical (2 stimulation elec-
trodes) and chemical sensitivity (modified Bernstein) were tested. Perception
scores were assessed using Visual Analogue Scale (VAS) and stimulus intensities
corresponding to pain perception threshold (VAS 5) and pain toleration thresh-
old (VAS 7) were assessed. Anxiety and angor were assessed by the State-Trait
Anxiety Inventory (STAI-state) and Profile of Mood Schedule (POMS) ques-
tionnaire before and after the stimulations. Thresholds were compared between
CRH and placebo, and differences in questionnaire data before and after stimu-
lations () were analysed using paired t-tests. A p-value 50.05 was considered
significant.
RESULTS: After CRH administration, VAS 5 levels during mechanical stimula-
tion were significantly lower compared to placebo administration, with a large
size effect (Cohens d1.2; Table 1)). Five HV (50%) did not reach VAS 7 in the
placebo condition at inflation to the maximal volume of the balloon (50ml),
whereas this was only the case in 1 HV (10%) in the CRH condition. CRH
had no significant influence on oesophageal sensitivity to both thermal and
electrical stimulations compared to placebo condition (Table 1). Since both
VAS 5 and VAS 7 were not reached in the majority of the HV at the endpoint
of the chemical stimulation, we were unable to analyse these data. The POMS-
anxious was slightly higher (p0.06) in the CRH condition compared to placebo.
No significant effects on STAI-scores were observed. After CRH administration
5/10 HV had mild transient facial flushing.
Table 1 Results of oesophageal stimulation test (mean  SD).
CRH Placebo p uncorrected Cohens d
Temperature ( C)
VAS 5 43.953.15 45.424.43 0.15 0.4
VAS 7 46.682.61 47.923.95 0.17 0.4
Mechanical (ml)
VAS 5 23.214.39 33.8311.29 0.0057* 1.2
Electrical (mA)
VAS 5 14.579.16 15.377.27 0.43 0.1
CONCLUSION: CRH administration increased oesophageal sensitivity to
mechanical distention in HV and was also associated with a slightly higher
anxiety level. The exact mechanisms of this CRH-induced visceral hypersensitiv-
ity need to be further explored.
Disclosure of Interest: None declared
OP289 MECHANISMS OF THE ADENOSINE A2A RECEPTOR-
INDUCED MECHANICAL SENSITIZATION OF VAGAL C-FIBERS
INNERVATING THE ESOPHAGUS
M. Brozmanova1,*, L. Mazurova1, M. Tatar1
1
Pathophysiology, Jessenius Faculty of Medicine, Comenius University, Martin,
Slovakia
Contact E-mail Address: brozmanova@jfmed.uniba.sk
INTRODUCTION: Studies in patients with noncardiac chest pain indicate that
adenosine acting on esophageal nociceptive pathways contributes to the patho-
genesis of pain originating from the esophagus. Our group has previously
reported that a specific type of esophageal nocieptors, the vagal nodose C-
fibers, express the adenosine A2A receptors that can induce mechanical sensiti-
United European Gastroenterology Journal 2(5S)
the esophagus in the isolated vagally-innervated guinea pig esophagus
preparation.
RESULTS: The selective adenosine A2A receptor agonist CGS21680 sensitized
mechanical response of nodose C-fibers to distention (10-60mmHg) of the eso-
phagus with EC50 of 1-3nM. CGS21680 (3nM) induced (2.40.3)-fold increase
in mechanical response (measured by esophageal distention with 30mmHg,
n10, p50.01). The protein kinase A (PKA) activator forskolin mimicked the
sensitizing effect of CGS21680 by causing a (1.90.3)-fold (n8) and (2.20.2)-
fold (n7) increase in mechanical response at concentrations 1mM and 10mM,
respectively (p50.05). The protein-kinase A (PKA) inhibitor H-89 partially
inhibited the CGS21680-induced increase in excitability. In the presence of H-
89 (30mM), CGS21680 (3nM) caused only insignificant (1.50.3)-fold increase in
mechanical response (n9). The TRPA1 receptor selective antagonist AP18
inhibited the CGS21680 (3nM)-induced increase in mechanical response. In the
presence of AP18 (30mM), CGS21680 (3nM) only caused insignificant (1.30.3)-
fold increase in mechanical response (n8).
CONCLUSION: Our data show that the activation of adenosine A2A receptor in
the vagal nodose C-fibers induces increase in mechanical excitability that is
mimicked by the activation of PKA activator forskolin. Our data indicate that
that the adenosine A2A receptor sensitizes vagal nodose C-fibers via protein
kinase A and TRPA1. The activity of sensitized vagal C-fibers may modulate
perceptions in patients with noncardiac chest pain. Supported by BioMed Martin
(ITMS: 26220220187)
Disclosure of Interest: None declared
OP290 UP-REGULATIONS OF GASTRIC TRPV RECEPTORS AND
DECREASED SERUM CONCENTRATION OF BDNF IN PATIENTS
WITH FUNCTIONAL DYSPEPSIA (FD)
C. K. Y. Cheung1,*, L.L. Lan1, Y. Chan1, J. C. Y. Wu1
1
Institute of Digestive Disease, The Chinese University of Hong Kong, Hong Kong,
Hong Kong
Contact E-mail Address: ckycyn@gmail.com
INTRODUCTION: Immune activation has been implicated in the mechanism of
post-infectious functional dyspepsia. However, the role of immune activation in
FD patients without infection remains unclear.
AIMS & METHODS: To compare the gastric mucosal and serum expression of
brain-derived neurotropic factor (BDNF), transforming growth factor beta
(TGFB) families and transient receptor potential vanilloid type (TRPV) families
between FD patients and healthy controls.
Consecutive adult FD patients (Rome III) with no recent history of gastroenter-
itis and age-and-sex matched asymptomatic healthy controls were recruited for
upper endoscopy. Subjects with GERD and IBS as predominant symptoms,
diabetes mellitus, current or previous H. pylori infection, psychiatric illness and
recent use of NSAID or PPI were excluded. Serum and mucosal biopsies from the
gastric corpus were obtained for quantitative assay of mRNA TRPV1, TRPV2,
TGFB1 by RT-PCR. Serum concentrations of TGFB families and BDNF were
analyzed using immunoassay. The gastric mucosal inflammation was evaluated
using Sydney classification. The associations between these assays and dyspeptic
symptoms were evaluated.
RESULTS: 45 [M:F8:37, mean age: 35.9(9.1)] FD patients were matched with
23 healthy controls [M:F 8:15, mean age: 36.6(10.2)] respectively. FD patients
had PDS as predominant sub-type (PDS: 43, EPS:2). There was no significant
difference in the median inflammation score between FD patients and controls
(FD: 0 (0-1) Vs Control: 0 (0-1), p0.54). However, FD patients had significantly
higher mRNA expression of gastricTRPV1 (FD: 0.0080.002, Control: 0.003 
0.001, p0.03), TRPV2(FD:0.0060.001, Control: 0.0020.001, p0.01)and a
trend of increased gastric TGFB1 (FD: 0.0130.003, Control:0.0050.002,
p0.07) compared to controls.
The serum concentration of BDNF(FD: 240.711.0, Control: 389.622.7,
p50.001) were significantly lower in FD patients. Serum TGFB1 and TGFB2
concentrations were significantly correlated with symptoms of
belching(R0.441, p0.01) and vomiting (R0.378, R0.04) in FD patients.
CONCLUSION: Despite the absence of gastric mucosal inflammation, up-reg-
ulations of gastric mucosal TRPV1, TRPV2, TGFB1 and down-regulation of
serum BDNF were observed in FD patients. The immune activation is associated
with symptoms of belching and vomiting. These findings suggest that mucosal
immune activation also contributes to the development of FD in those without
history of infection.
Disclosure of Interest: None declared
OP291 MODULATION OF GASTRIC VAGAL AFFERENT SATIETY
SIGNALS BY THE MOUSE OESTERUS CYCLE AND 17B-
OESTRADIOL
S. Kentish1,*, C. Frisby1, G. Wittert1, A. Page1,2
1
Medicine, University of Adelaide, 2Gastroenterology and Hepatology, Royal
Adelaide Hospital, Adelaide, Australia
Contact E-mail Address: stephen.kentish@adelaide.edu.au
INTRODUCTION: During oestrus in rodents there is a decrease in meal size and
an overall reduction in food intake1. This occurs immediately after a peak in
plasma oestradiol (E2) levels. Exogenous E2 reduces meal size and overall food
intake in ovariectomized rats2. Whilst E2 can act on the arcuate nucleus to reduce
zation (Am J Physiol Gastrointest Liver Physiol. 300:G485-93).
AIMS & METHODS: The mechanisms underlying the mechanical sensitization
induced by the adenosine A2A receptor are unknown. Here we investigated the
mechanisms of adenosine A2A receptor-induced mechanical sensitization of
nodose C-fibers. Extracellular single unit recordings were made from the vagal
nodose nociceptive afferent nerve fibers with the mechanosensitive terminals in
food intake the E2 receptors, ER, ER and GPR30 are also expressed in vagal
afferent cell bodies located in the nodose ganglia3. Furthermore, E2 has been
shown to increase the excitability of cultured vagal neurons4. Together this sug-
gests there may also be a peripheral E2 site of action on food intake via mechan-
osensitive gastric vagal afferents, the activation of which induces satiety.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We aimed to determine whether E2 can act on gastric
vagal afferents to modulate satiety signals and whether the reduction in food
intake during oestrus may have a vagal component. To investigate this the oes-
trous cycle stage of 8 week old female C57BL/6 mice was determined by vaginal
cell cytometry5 (N3/cycle stage). Single fibre recordings of gastric vagal afferent
mechanoreceptors were made6 in the absence and presence of E2 (10-1000pM).
Recordings were also taken after pre-incubation with the ER selective antago-
nist, fulvestrant. Nodose ganglia were collected, RNA was extracted and ER,
A93
OP293 PRELIMINARY RESULTS FROM THE "GLUTOX" TRIAL: A
RANDOMISED, DOUBLE BLIND, PLACEBO CONTROLLED
CROSSOVER STUDY ON "NON CELIAC GLUTEN SENSITIVITY"
L. Elli1,*, C. Tomba2, F. Branchi2, V. Lombardo2, M.T. Bardella2, F. Valiante3,
L. Fini4, E. Forti5, E. Orzes6, R. Canizzaro6, C. Londoni7, A. Lauri8,
G. Fornaciari9, R. Spagnuolo10, N. Lenoci11, G. Basilisco2, F. Somalvico12,
B. Borgatta13, D. Conte2, E. Buscarini7 on behalf of On behalf of, AIGO "Italian
Society of Hospital Gastroenterologists and Endoscopists"
ER and GPR30 mRNA levels were quantified by QRT-PCR.
RESULTS: Tension receptor response to stretch (3g) was increased by 107% in
mice during oestrus (p50.05 vs. diestrus, one-way ANOVA). There was no
difference in the response of mucosal receptors to mucosal stroking with a von
Frey hair (50mg) at any stage of the oestrous cycle (p40.05, one-way ANOVA).
Exogenous E2 dose-dependently potentiated mucosal and tension receptor
responses to mucosal stroking (10-1000mg, p50.001, two-way ANOVA) and
stretch respectively (15g, p50.05, two-way ANOVA). There was no difference
in the level of potentiation induced by application of exogenous E2 between
oestrous cycle stages (p40.05, two-way ANOVA). The potentiation caused by
E2 on both tension and mucosal receptors was blocked by pre-incubation with
fulvestrant. All three E2 receptors were present within the nodose ganglia, but
1
Center for the Prevention and Diagnosis of Celiac Disease, Fondazione IRCCS Ca`
Granda Ospedale Maggiore Policlinco, 2Fondazione IRCCS Ca` Granda Ospedale
Maggiore Policlinico, Milano, 3Ospedale S.Maria, Feltre, 4Ospedale di Circolo,
Busto Arsizio, 5Ospedale Niguarda, Milano, 6Centro Oncologico, Aviano,
7
Ospedale Maggiore, Crema, 8Ospedale Civile Santo Spirito, Pescara, 9Arcispedale
S.Maria Nuova, Reggio Emila, 10Magna Graecia University, Catanzaro,
11
Ospedale Valduce, Como, 12Alphasearch, Milano, 13Ospedale San Biagio,
Domodossola, Italy
Contact E-mail Address: dottorlucaelligmail.com
INTRODUCTION: Non Celiac Gluten Sensitivity (NCGS) is a recently
described syndrome characterized by gastrointestinal symptoms arising after
there was 60 and 25 times more ER mRNA present than ER or GPR30
respectively (p50.001, one-way ANOVA).
CONCLUSION: Taken together these data suggest that E2 potentiates gastric
vagal afferent activity via an ER pathway, thereby increasing gastric tension
receptor mechanosensitivity which may, at least in part, mediate the reduction in
food intake observed during oestrus.
REFERENCES
1. Eckel LA et al. Physiol Behav 2000; 70: 397-405.
2. Butera PC et al. Physiol Behav 2010; 99: 142-145.
3. Papka RE et al. Cell Tissue Res 2001; 304: 193-214.
4. Qiao GF et al. Am J Physiol Cell Physiol 2009; 297: C654-C664.
5. Byers SL et al. PLos One 2012; 7: e35538.
6. Page AJ et al. J Neurophysiol 2002; 87: 2095-2103.
Disclosure of Interest: None declared
OP292 PHENOTYPES OF THE TRPV1-POSITIVE AND TRPV1-
NEGATIVE VAGAL AFFERENT NEURONS INNERVATING THE
RAT STOMACH
E. Kovacova1,*, F. Ru2, K. Varga1, M. Brozmanova1, M. Tatar1, J. Plevkova 1, 37.911.4, BMI 21.74.2) reported a symptomatic improvement after GFD
M. Kollarik1,2
1
Department of Pathophysiology, Jessenius Faculty of Medicine in Martin,
Comenius University, Martin, Slovakia, 2Department of Medicine, The Johns
Hopkins University School of Medicine, Baltimore, United States
Contact E-mail Address: eva.hanuskova@gmail.com
INTRODUCTION: Gastric afferent nerves regulate the function and mediate
perceptions from the stomach. Although these nerves were extensively studied,
the dependence of their phenotypes on embryonic origin has not been estab-
lished. Primary afferent neurons innervating visceral tissues originate from two
embryonic sources: neural crest (spinal dorsal root ganglia and vagal jugular
neurons) and placodes (vagal nodose neurons). We addressed the hypothesis
that the vagal afferent neurons innervating the stomach express markers consis-
tent with the origin from embryonic placodes.
AIMS & METHODS: Detailed microdissection was performed to identify com-
ponents of the vagal afferent ganglion complex. Vagal primary afferent neurons
innervating the stomach were retrogradely traced by using DiI injection into the
stomach wall (n19). In some studies DiI was selectively injected into the gastric
corpus or fundus (forestomach). Single cell RT-PCR detection of phenotypical
markers and selected receptors was performed in individual labeled neurons.
RESULTS: The nodose and jugular portions of the rat vagal jugular-petrosal-
nodose ganglion complex can be grossly identified by their caudal and rostral
locations, respectively, and their positions relative to branches of cranial nerves.
The vagal afferent neurons labeled from the stomach were localised exclusively in
the nodose portion of the vagal afferent ganglion complex. This location indi-
cates the placodal origin. In single cell RT-PCR analysis we first focused on
neurons positive for the capsaicin receptor TRPV1 because the embryonic mar-
kers have been previously established in the TRPV1-positive population. We
found that the vagal aferent neurons retrogradely labeled from both gastric
fundus and the corpus expressed TRPV1, but the population of neurons inner-
vating the fundus was enriched in TRPV1-positive neurons ( 80%, 16/20) com-
pared with corpus ( 40%, 11/27) (p50.01). TRPV1-positive neurons expressed
placodal markers including the ATP receptor P2X2 (26/27) and neurotrophic
receptor for BDNF - TrkB (23/27), but they rarely expressed neurocrestal mar-
kers, the artemin receptor GFRalpha3 (2/27), preprotachykinin-A PPT-A (2/27).
Gastric TRPV1-positive neurons occasionally expressed the NGF receptor -
gluten ingestion. [1] Although NCGS is thought to be present in a large part
of patients affected by gastrointestinal functional diseases, the lack of diag-
nostic criteria represents a relevant problem.
AIMS & METHODS: Aim of our study was to evaluate the presence of NCGS
in patients reporting different gastrointestinal symptoms. The present study is a
prospective multicenter trial characterized by a double blind gluten challenge,
placebo-controlled with crossover. Patients reporting aspecific gastrointestinal
symptoms or affected by functional disorders (Roma III criteria) have been
invited to follow a 21 day-long gluten free diet (GFD) under nutritional control.
In all the enrolled patients the presence of celiac disease or wheat allergy have
been excluded before starting GFD. Severity of symptoms before and after GFD
was evaluated by means of 10 cm Visual Analogical Scales (VAS). Patients
reporting a significant clinical, VAS-proved improvement after GFD underwent
7 day-long gluten challenge (or placebo with crossover). Gluten was administered
in capsules, 5.6 g per day. Symptoms were always evaluated by VAS also during
challenge. Patients reporting a relevant symptomatic relapse during gluten inges-
tion but not placebo were considered NCGS.
RESULTS: Sixty one patients (6 males, mean age 38.4  11, BMI 21.7  3.9)
were enrolled. After the 21 day-long GFD, 46 subjects (3 males, mean age
(Mean VAS score 7.52.5 vs 3.32.2 before and after GFD respectively,
p0.001). These underwent the double blind, placebo-controlled, gluten chal-
lenge and 16 (1 male, mean age 38.512, BMI 21.92.8) reported a severe
symptomatic relapse after blind gluten ingestion and thus they were classified
as NCGS. No demographic parameters resulted statistically significant between
the investigated groups.
CONCLUSION: Our study identified a 26% of patients as truly NCGS among
functional patients. If these data will be confirmed the proposed algorithm
could be inserted in the diagnostic flowchart of functional diseases.
REFERENCES
1. Catassi C, Bai JC, Bonaz B, et al. Non-Celiac Gluten sensitivity: the new
frontier of gluten related disorders. Nutrients 2013; 5: 3839-3853.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 15:4517:15
LIVER STEATOSIS: THE ROAD FROM INFLAMMATION TO FIBROSIS LOUNGE
6_____________________
OP294 INHIBITION OF KRUPPEL-LIKE FACTOR-4(KLF4) BY MIR-143/
145 PROMOTES ACTIVATION OF HEPATIC STELLATE CELLS
R. Men1,*, M. Wen1, X. Dan1, W. Wang1, X. Liu2, L. Yang1
1
Digestive Diseases Department, 2Laboratory of Cardiovascular Diseases,
Regenerative Medicine Research Center, West China Hospital, Sichuan University,
Chengdu, Sichuan, China
Contact E-mail Address: yangli_hx@scu.edu.cn
INTRODUCTION: Activation of hepatic stellate cells plays a key role in liver
fibrosis/cirrhosis. MicroRNAs (miRNAs) have emerged as pivotal regulator in
HSCs activation. Kruppel-like Factor-4 (KLF4) is a negative regulator of lung
fibrosis, and a target of miR-143 in vascular smooth muscle cells. However, the
potential role of KLF4 and miR-143 in HSCs activation or even liver fibrosis
keeps unclear.
AIMS & METHODS: To characterize miR-143 and KLF4 in activated HSCs
and liver cirrhotic patients, and declare a novel molecular basis by which miR-
143 modulates HSCs.
TrkA (8/27) that is often found in both placodes- and neural crest-derived neu-
rons. TRPV1-positive neurons also expressed the serotonine 5-HT3A receptor
(11/27) and adenosine A1 receptor (13/27) indicative of a chemosensitive func-
tion. Some TRPV1-negative neurons expressed markers found in the placodes-
derived neurons - P2X2 (10/20) and TrkB (5/20), but these neurons did not
express markers found in the neural crest-derived neurons - GFRalpha3 (0/20)
and PPT-A (1/20). Consistent with their putative mechanosensory function
TRPV1-negative neurons did not express 5-HT3A receptor (2/20) and adenosine
A1 receptor (1/20).
CONCLUSION: Our data support the conclusion that the vagal afferent neu-
rons innervating the stomach in the rat originate exclusively from embryonic
placodes. The putive chemosensitive (TRPV1-positive) innervation predominates
in gastric fundus while the corpus is innervated similarly by putative chemosen-
Rat primary HSCs were culture activated or stimulated with TGF-. miRNAs
expression profile on quiescent and activated HSCs were detected by microarray
analysis. miR-143 mimics or inhibitor were transfected to rat primary HSCs for
48 hours. Activated rat primary HSCs or human HSCs line-LX2 were transfected
for 48 hours with KLF4 shRNA or KLF4 overexpression plasmid to loss or gain
function of KLF4. Gene expressions of -SMA, collagen-I, KLF4, miR-143/145
were detected by quantitative RT-PCR (Q-PCR). The protein expressions of-
SMA, collagen-I, KLF4 were evaluated by western blot.
RESULTS: KLF4 were dramatically down-regulated during the process of cul-
tured HSCs activation, while miR-143 and -145 were significantly up-regulated.
Additionally, liver KLF4 level in cirrhotic patients were significantly down-regu-
lated. -SMA and collagen type I were increased after inhibition of KLF4 by
specific shRNA in both rat primary HSCs and LX-2 cell line. Forced KLF4 led a
sors and mechanosensors (TRPV1-negative neurons). reduction of -SMA and collagen type I expression on HSCs. TGF- rapidly
Disclosure of Interest: None declared inhibited KLF4 through induction of miR-143 which negatively regulated KLF4
A94 United European Gastroenterology Journal 2(5S)
expression. Inhibition of miR-143 prevented the activation of HSCs induced by cultured with MCD medium. Lysosomal function was impaired in NASH as
TGF- by targeting KLF4. indicated by reduced cathepsin D cleavage and diminished lysosomal acidifica-
CONCLUSION: KLF4 down-regulated by miR-143 is crucial to HSCs activa- tion. Of interest, we observed that the deficiency in autophagic degradaton trig-
tion and liver fibrosis partially through TGF- signaling pathway.
Disclosure of Interest: None declared
OP295 3-MERCAPTOPYRUVATE SULFURTRANSFERASE
DOWNREGULATION AMELIORATES HEPATIC STEATOSIS AND
OXIDATIVE STRESS INVOLVED IN NONALCOHOLIC FATTY
LIVER DISEASE
M. Li1,*, J. Ding1, X. Wan1, X. Jin1, S. Chen1, C. Yu1, Y. Li1
1
The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou,
China
Contact E-mail Address: lemon2323@126.com
INTRODUCTION: The mitochondrial enzyme 3-mercaptopyruvate sulfurtrans-
ferase (MPST) is a source of endogenous hydrogen sulEde (H2S), a gaseous
signaling molecule implicated in a wide range of physiological processes.
Nonalcoholic fatty liver disease (NAFLD) is currently considered to be the
most common liver disorder in western countries, and is rapidly becoming a
serious threat to public health. The mechanisms of pathogenesis underlying
NAFLD remain unclear at present. The possible role of MPST in the develop-
ment of NAFLD has never been investigated.
AIMS & METHODS: A variety of cellular and molecular approaches were used
to study the effects of MPST on hepatic steatosis and oxidative stress involved in
NAFLD. The NAFLD cell model was established by treating L02 cells with free
fatty acid (FFA) overload. Small interfering RNA (siRNA) was used to knock
down MPST level. The expression of MPST and key enzymes associated with
lipid accumulation and oxidative stress in L02 cells were determined by western
blotting. ATP, hydroperoxide (H2O2), H2S levels, mitochondrial membrane
potential (MMP) and interleukin 6 (IL-6) were measured for potential mechan-
ism exploration.
RESULTS: After culturing L02 cells by FFA for 24h, we detect the increased
protein level of MPST. MPST knockdown in L02 cells resulted in a marked
decrease of lipid accumulation and downregulation of SREBP-1 pathway show-
ing reduced levels of p-SREBP-1 and its downstream proteins including FAS and
ACC. Additionally, administering MPST siRNA exhibited a melioration of
oxdiative stress, embodied in decreased level of H2O2, MDA and IL-6, mean-
while, increased levels of ATP and MMP. Unexpectedly, we observed a sign-
iEcantly increased level of H2S after the siRNA-mediated knockdown of MPST.
The expression of another H2S-synthesizing enzyme namely cystathionine
lyase glycerol in water to produce the mixture of 600 mM EP. This mixture was
(CSE) is enhanced when the MPST is decreased. Further, MPST knockdown in
L02 cells demonstrated weakened of reactive oxygen species (ROS)-related sig-
gers ER stress/UPR in mice with NASH, as evident by the elevated of mRNA
levels of activating transporter factor (ATF6), asparagine synthetase, C/EBP
homologous protein (CHOP) and caspase 12 and increased protein expression
of glucose-regulated protein 78 (GRP78). NASH induction also caused increased
p53 expression and apoptosis of hepatocytes. Immunoreactivity of p53 was colo-
calized with diffused cytoplasmic staining of LC3-I/II. Impairment of lysosomal
function by CQ in mice recapitulated NASH-associated molecular dysfunctions,
including impaired autophagic flux, induction of ER stress/UPR, increased p53
levels, and activation of caspases. However, induction of autophagosome forma-
tion by R or CBZ showed no alleviation of NASH development.
CONCLUSION: This study demonstrates that autophagic function was
impaired at late stage through inhibition of lysosomal acidificiation, thus con-
comitantly inducing ER stress/UPR and p53 followed by hepatic apoptosis in the
pathogenesis of NASH. These findings imply that restoring lysosomal function in
the liver instead of stimulating autophagosome formation is crucial to mitigate
the pathology associated with NASH.
Disclosure of Interest: None declared
OP297 LIPOTOXICITY IN LIVER INDUCED BY PALMITATE IN VIVO
Y. Ogawa1,*, Y. Honda1, T. Kessoku1, W. Tomeno1, K. Imajo1, H. Mawatari1,
S. Saito1, A. Nakajima1
1
Gastroenterology and hepatology, Yokohama city university, Yokohama, Japan
Contact E-mail Address: ogaway@yokohama-cu.ac.jp
INTRODUCTION: Obesity has reached epidemic proportions around the world
due to a modern lifestyle characterized by increased consumption of foods rich in
energy and saturated fatty acids (FAs), combined with reduced physical activity.
Free fatty acid (FFA) levels are elevated in obese subjects and elevated levels of
circulating FFAs are known to be associated nonalcoholic fatty liver disease
(NAFLD). The deleterious effects of FFAs, such as arteriosclerosis1) and exacer-
bation of diabetes2), are termed lipotoxicity. Based mainly on in vitro studies, it
was proposed that palmitate, which is the most abundant saturated FFA in
blood, induces hepatocyte lipoapoptosis3)4). However, the molecular mechanisms
by which FFAs induce liver injury in vivo remain poorly understood. We estab-
lished a method to selectively increase the circulating free palmitate level in mice
and analyzed its effects in liver.
AIMS & METHODS: Ethyl palmitate (EP) was dissolved with lecithin and
then emulsified using a sonicator. The lecithin-glycerol-water solution was used
as the vehicle. The right jugular veins of three-month-old C57BL/6 mice (average
naling pathway that are JNK-1/c-jun signaling as well as IKK/NF-B pathway.
CONCLUSION: Our results show that MPST downregulation ameliorates hepa-
tic steatosis via the decreased activation of SREBP-1 pathway. And MPST
knockdown could stimulate the compensatory process of CSE, thus causing
the increasing of H2S which is recently considered as a novel antioxidant gas.
body weight: 26 g) were catheterized. Following a 5l/g bolus injection of either
emulsified EP solution or vehicle, the mice were continuously infused with the
solutions at 0.01 l/g/min.
RESULTS: Serum ALT levels were significantly increased in mice infused ith EP,
whereas no elevation of serum ALT levels was observed in mice infused for 3 and
Furthermore, the suppression of ROS-related JNK-1/c-jun signaling and IKK/
NF-B pathway synergistically contributes to the improvement of oxdiative stress.
These findings suggest that MPST is implicated in NAFLD and provide new
insight into the pathogenic mechanisms of NAFLD, pointing to potential target
for therapeutic strategy.
Disclosure of Interest: None declared
OP296 DEFICIENT AUTOPHAGOSOMAL-LYSOSOMAL FUNCTION
INDUCED P53 AND HEPATIC APOPTOSIS IN EXPERIMENTAL
NUTRITIONAL STEATOHEPATITIS
X. Wang1,*, W.K. Wu1, F. K. L. Chan1, J.J. Sung1, J. Yu1
1
Institute of Digestive Disease and Department of Medicine and Therapeutics,
State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health
Sciences, Shenzhen Research Institute, The Chinese University of Hong Kong,
Hong Kong, Hong Kong
Contact E-mail Address: wxj0250@gmail.com
12hr with vehicle (control group). Hepatic TNF-, ccl2 (one of monocyte che-
moattractant proteins) and cxcl2 (one of neutrophil chemotactic factors) mRNA
expression levels were significantly higher in mice infused for 3 hr with EP than
control group. The number of neutrophil elastase, F4/80, alpha smooth muscle
actin (alpha-SMA) positive cells in the liver was higher in mice infused EP than
control group. Immunoblot analysis showed that increased phosphorylation of c-
Jun were observed in the liver of mice infused EP than control group. Primary
hepatocyte of wild-type responded to palmitate by expressing ccl2 and cxcl2. By
contrast, cells from Tlr4-/- did not respond to palmitate, indicating that hepato-
cyte sense palmitate via TLR4.
CONCLUSION: The effects of palmitate in liver have never been directly tested
in vivo by selectively increasing circulating palmitate levels. In this study, we
show that the saturated FA palmitate induces expressing chemokines and recruit-
ing macrophages and neutrophils to the liver, in addition, alpha SMA positive
cells indicate palmitate activate hepatic stellate cell. The molecular interactions in
this study could provide novel therapeutic targets for the treatment of NAFLD.
REFERENCES
1) Eguchi K, et al. Saturated fatty acid and TLR signaling link  cell dysfunction
INTRODUCTION: Macroautophagy is an essential cellular pathway mediating and islet inflammation. Cell Metab 2012; 15: 518-533.
the lysosomal degradation of long-lived proteins and damged organelles. During 2) Furuhashi M, et al. Treatment of diabetes and atherosclerosis by inhibiting
the development of nonalcoholic steatohepatitis (NASH), excessive cellular lipid fatty-acid-binding protein aP2. Nature 2007: 959-965.
accumulation impairs autophagic function. Yet the cellular process of autophagic 3) Malhi H, et al. Free fatty acids induce JNK-dependent hepatocyte lipoapop-
dysfunction is not well understood. tosis. J Biol Chem 2006: 12093-12101.
AIMS & METHODS: In this study, we aimed at discovering the underlying 4) Malhi H, et al. Free fatty acids sensitise hepatocytes to TRAIL mediated
mechnism of impaired autophagy and investigating whether pharmacological cytotoxicity. Gut 2007: 1124-1131.
modulation of autopahgy could have beneficial effect on NASH. C57BL/6 Disclosure of Interest: None declared
mice or db/db (C57BL/KsJ-db-/db-) mice were given control or methionine
and choline-deficient (MCD) diet to induce NASH. Liver tissues were analyzed
to determine hepatic triglycerides, lipoperoxide and serum alanine aminotrans-
ferase levels. Markers of autophagy (e.g. LC3 and p62/SQSTM1) and apoptosis
(e.g. p53 and caspases-3/7) were evaluated by Western blots and immunohisto-
chemistry. TUNEL assay was performed to in situ staining of apoptotic cells.
Endoplasmic reticulum (ER) stress/unfolded protein response (UPR) markers
were determined by real-time PCR and Western blots. Autophagy was blocked
in murine hepatocyte cell line (AML12) or C57BL/6 mice using pharmacological
inhibitors bafilomycin A1 and chloroquine (CQ) respectively. Acridine orange
staining was performed to determine the acidic vesicular organelles in vitro.
Autophagy enhancers, namely rapamycin (R) and carbamazepine (CBZ), were
given in control and MCD mice for 21 days.
RESULTS: In both C57BL/6 mice and db/db mice, the development of NASH
by MCD diet impaired the autophagic flux as shown by accumulation of LC3-I/
II and p62. Accumulation of autophagosomes was also present in AML12 cells
United European Gastroenterology Journal 2(5S)
OP298 CELL-SELECTIVE DELIVERY OF INTERFERON GAMMA
PEPTIDOMIMETIC INHIBITS CHRONIC HEPATIC FIBROSIS AND
TUMOR ANGIOGENESIS IN VIVO
R. Bansal1, J. Prakash1,*, K. Poelstra2
1
MIRA institute, University of Twente, Enschede, 2Pharmacokinetics, Toxicology
and Targeting, University of Groningen, Groningen, Netherlands
Contact E-mail Address: r.bansal@utwente.nl
INTRODUCTION: Fibroblasts and myofibroblasts-like cells play a key role in
the pathogenesis of hepatic fibrosis. Thus, pharmacological inhibition of these
cells might lead to an effective therapeutic therapy for liver fibrosis. Among the
potent anti-fibrotics, Interferon gamma (IFN
) is highly efficacious but it failed
in clinical trials due to reduced efficacy and increased adverse effects. Here, we
employed an IFNg peptidomimetic (mimIFNg) that lacks the extracellular recep-
tor recognition sequence but retains the agonistic activities of IFNg. Since plate-
let-derived growth factor receptor beta (PDGFbR) expression is highly over-
expressed on key pathogenic cells, we conjugated mimIFNg to a bicyclic
PDGFbR-binding peptide (BiPPB) for selective delivery.
AIMS & METHODS: The synthesized targeted IFNg peptidomimetic (mimg-
BiPPB) was extensively investigated for anti-fibrotic and adverse effects in acute
or chronic CCl4-induced liver fibrosis mouse models. Furthermore, the construct
was investigated for anti-angiogenic and anti-tumor effects in C26-colon carci-
noma mouse model.
RESULTS: The targeted mimg-BiPPB construct markedly inhibited early and
established hepatic fibrosis in mice. Native IFNg induced only moderate reduc-
tion in fibrosis, while untargeted mimIFNg and BiPPB had no effect. In addition,
untargeted IFNg significantly induced systemic inflammation and MHC-II
expression in brain while mimg-BiPPB did not induce any off-target effects.
Furthermore, in C26-colon carcinoma tumor-bearing mice, mimg-BiPPB exhib-
ited significant reduction in tumor angiogenesis and size via inhibitory effects on
stromal cells, whereas other treatments showed no effect.
CONCLUSION: The present study demonstrates the beneficial effects of cell-
specific targeting of IFNg peptidomimetic to the disease-inducing cells and there-
fore represents a highly potential therapeutic approach to treat chronic diseases.
Disclosure of Interest: R. Bansal: None declared, J. Prakash: None declared, K.
Poelstra Shareholder of: in BiOrion Technologies
OP299 MICROPARTICLES RELEASED BY FAT-LADEN CELLS
ACTIVATE IN A PARACRINE WAY NLRP3 INFLAMMASOME IN
BOTH HEPG2 CELLS AND MACROPHAGES
E. Novo1,*, C. Paternostro1, E. Benetti2, S. Cannito1, C. Bocca1, E. Morello1,
F. Chiazza2, R. Fantozzi2, D. Povero3, A. Feldstein3, M. Collino2, M. Parola1
1
Dept. Clinical and Biological Sciences, 2Dept. Drug Science and Technology,
UNIVERSITY OF TURIN, TURIN, Italy, 3Dept. of Pediatrics, University of
California San Diego(UCSD), La Jolla, CA, United States
Contact E-mail Address: erica.novo@unito.it
INTRODUCTION: Hepatocytes or HepG2 cells overloaded with saturated lipo-
toxic free fatty acids, a condition that mimics lipid accumulation occurring in the
liver in some forms of steato-hepatitis, have been recently reported to release pro-
angiogenic micro-particles (MPs) in a caspase 3-dependent manner, an event
which occurs also in vivo and may have a role in the pathogenesis of NAFLD/
NASH (1).
AIMS & METHODS: In this study we investigated whether MPs released from
fat-laden cells may affect in a paracrine way NLRP3 inflammasome, which is
known to be progressively activated in vivo in NAFLD/NASH conditions.
MPs were collected and purified as released by fat-laden HepG2 (i.e., HepG2
exposed for 24 hr to 0.25 mM palmitic acid or PA), as recently described (1).
HepG2 resting cells were then incubated (15 min-24hrs) with MPs, LPS (100 ng/
mL-1 mg/mL) or PA (150 500 mM), the latter known to induce NLRP3 inflam-
masome in hepatocytes. In other experiments activated human THP1 macro-
phages (48 hrs activation by PMA 25 nM plus 24 hrs in fresh medium) were
exposed up to 24 hrs to MPs released by fat-laden HepG2 cells. Expression of
A95
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
BEST USE OF IMMUNOSUPPRESSANTS IN IBD HALL E_____________________
OP300 LONG-TERM NATURAL HISTORY OF POSTOPERATIVE
RECURRENCE IN PATIENTS ON PREVENTIVE TREATMENT
WITH AZATHIOPRINE
M. Manosa1,2, B. Oller2, Y. Zabana2, L. Marin2, I. Bernal2, J. Boix2, M. Pinol2,
E. Cabre1,2, E. Dome`nech1,2,*
1
CIBEREHD, Barcelona, 2Gastroenterology, Hospital Universitari Germans Trias
i Pujol, Badalona, Spain
Contact E-mail Address: mmanosa.germanstrias@gencat.cat
INTRODUCTION: The postoperative recurrence (POR) in Crohns disease
(CD) occurs in 475% within the first year after intestinal resection if no pre-
ventive treatment is started. Nowadays, azathioprine (AZA) is the most pre-
scribed drug to prevent POR, but its long-term efficacy is unknown and no
recommendations about POR monitoiring beyond the first year after surgery
are available.
AIMS & METHODS: To evaluate the long-term clinical and endoscopic out-
comes of CD after intestinal resection and early preventive therapy with AZA.
From an specific database in which all patients with CD who underwent resec-
tion with anastomosis at our institution since 1998 were prospectively included
and followed, we identified those who initiated AZA (associated or not with
metronidazole or 5-ASA) within the first month after surgery and with at least
a follow-up of 3 years. Endoscopic recurrence (ER) was defined as a Rutgeerts
score 41 and clinical recurrence (CR) as the development of symptoms that
required changes in the treatment for CD. Surgical recurrence (SR) was consid-
ered as the need for surgery. We defined a Combined Outcome as any combina-
tion of the following events: rescue with biological agents, CR or SR.
RESULTS: 189 patients were included of whom 57% male, 64% active smokers
at the time of surgery, 54% penetrating behaviour. 58% of patients had ER after
a median of 22 months (IQR 11.5-44.5). The cumulative probability of ER was
35%, 48% and 59%, the probability of CR was 18%, 27 and 34 % and for SR
was 3% 10% and 16%, at 3, 5 and 10 years, respectively. Only active smoking
after surgery was associated with POR. The risk for the combined outcome was
21%, 23% and 46% at 3, 5 and 10 years. In patients without ER at the first
endoscopic control, the probability at 3, 5 and 10 years of CR was 14%, 22% and
27%; for SR 6%, 9% and 9%; and for the combined outcome of 13%, 26% and
38%, respectively. In the log-rank analysis, the cumulative probability of CR or
SR was significantly higher among those patients with early ER (at the first
control after surgery -p0.044 and p0.05-).
CONCLUSION: The use of AZA after surgical resection in Crohns disease is
associated with a low rate of CR and SR, probably because of early introduction
of rescue therapy with biological in those patients with advanced endoscopic
lesions. Patients without early ER, although at lower risk have a slow but
steady increase in the development of ER and CR upon time, suggesting that
periodical assessment of POR should be kept indefinitely.
Disclosure of Interest: None declared
OP301 ORAL VERSUS SUBCUTANEOUS METHOTREXATE IN
PEDIATRIC CROHNS DISEASE: A MULTICENTER PROPENSITY
SCORE STUDY
D. Turner1,1,*, E. Doveh2, A. Cohen2, M.L. Wilson3, D.C. Wilson3,
A.B. Grossman4, J. Rosh5, Y. Lu6, A. Noble7, R.N. Baldassano8, A. Levine9,
A. Lerner10, A. Bousvaros11, A.M. Griffiths12
1
Shaare Zedek Medical Center, Jerusalem, Israel, Jerusalem, 2Technion Institute,
Haifa, Israel, 3University of Edinburgh, Edinburgh, United Kingdom, 4CHOP,
Philadephia, 5Goryeb Childrens Hospital/Atlantic Health, Morristown, 6Bostons
Children Hospital, Boston, United States, 7Montreal, Montreal, Canada, 8CHOP,
Philadelphia, United States, 9Wolfson Hospital, Holon, 10Carmel Hospital, Haifa,
Israel, 11Boston Childrens Hospital, Boston, United States, 12HSC, Toronto,
Canada
NLRP-3, pro-caspase and cleaved caspase 1, pro-IL-1 and cleaved IL-1 was INTRODUCTION: The question whether methotrexate (MTX) can be effec-
evaluated by Western blot analysis in cell lysates, whereas ELISA assays were tively administered orally has never been addressed systematically in Crohns
used to measure IL-1 and IL-18 levels released by resting HepG2.
RESULTS: MPs were very early (i.e., 1-6 hrs) efficiently internalized by both
HepG2 cells and THP1 macrophages, as revealed by means of confocal micro-
scopy. MPs induced a time-dependent increase in the expression of NLRP3
inflammasome components in resting HepG2 cells starting from 6hr and then
reaching a plateau at 16-24 hrs, with a kinetics that overlapped the one exerted by
PA and was delayed as compared to LPS (1-3 hrs). Interestingly, both MPs and
PA, but not LPS, significantly induced caspase-1 activation and consequent
disease (CD), although avoiding weekly injections can improve quality of life,
especially in children, and reduce costs. In this largest cohort of children receiving
MTX to date, we aimed to use a robust statistical method, propensity score (PS),
to compare effectiveness and adverse events of orally versus subcutaneously
administered MTX in pediatric CD.
AIMS & METHODS: 226 children with established CD treated with oral or SC
MTX, without prior biologics, entered a multicenter, international retrospective
cohort study with follow-up of at least 1-year (62% males, mean age 13.82.8
release in particular of IL-1 in a time-dependent manner. Moreover, MPs years, 88% previously treated with thiopurines, median disease duration 1.9
also up-regulated NLRP3 inflammasome expression in THP1 human macro- (IQR 0.9-4) months, 48% with mild and 45% with moderate-severe disease
phages within 3-6 hrs, resulting in a significantly increased release of IL-1.
CONCLUSION: Fat-laden cells, by releasing MPs in a paracrine way, can effi-
ciently trigger inflammasome activation in surrounding hepatic cells as well as
macrophages, thus identifying an additional new molecular mechanism of
inflammation in NASH pathogenesis.
REFERENCES
1. Povero D et al. Sci Signal 2013; 6: ra88.
Disclosure of Interest: None declared
activity at MTX initiation). 38 (17%) were commenced MTX orally from the
outset (ie PO group), 98 (43%) started SC and switched to PO during the first
year (i.e. SC/PO group), and 90 (40%) were treated with SC only. Matching and
doubly robust regression weighting were based on the PS method, a powerful
tool to control for confounding-by-indication bias in retrospective cohorts. 11/23
pre-treatment basic variables were initially different between the three treatment
groups, but none remained significant after adjustment with the PS weighting,
indicating that PS modeling balanced the treatment groups appropriately.
RESULTS: 76 children (34%) had sustained steroid-free remission (SSFR), 92
(41%) had catch-up growth, 91(40%) required treatment escalation, 40 (18%)
had significant elevated liver enzymes, and 49 (22%) had severe nausea. No
significant differences were found in SSFR between the PO and the SC groups
(OR1.72 (95%CI 0.5-5.9); P0.52) by PS weighted model, but the SC/PO
group was superior to both (P0.0004 and P0.004), likely representing differ-
ences in local practice (most children from this group were from one site). There
A96
were no differences in the need for treatment escalation (P0.24, P0.58 and
P0.13). Height velocity was lower in the PO group vs. the SC group (P0.006)
and the SC/PO group (P0.0004), but in an individual matching of highly homo-
genous 23 pairs, the PO group was not inferior to the SC in this and the other
outcomes. There were no differences between the PO and the SC group in the rate
of elevated liver enzymes (P0.59) and severe nausea (P0.85). According to
Fleming test giving higher weight to long survivors, the time to remission was
delayed in the PO vs the SC group (P0.036), but according to the log-rank test
P0.23.
CONCLUSION: In the largest cohort to date, no significant differences were
found between PO and SC administered MTX in children with CD, suggesting
that it may be reasonable to switch children treated with SC MTX in complete
remission to the oral route while monitoring closely disease activity.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
CHALLENGES IN GORD HALL B_____________________
OP302 MODEL OF TWO IMPORTANT STEPS IN THE PATHOGENESIS
OF GASTROESOPHAGEAL REFLUX DISEASE: IMPACT OF ACIDIC
PH AND PROTEASE-ACTIVATED RECEPTOR-2 (PAR2) ON
MUCOSAL IL-8 SECRETION
L. Winkelsett1, A. Kandulski1,*, P. Malfertheiner1
1
Department of Gastroenterology, Hepatology and Infectious Diseases, OTTO-
VON-GUERICKE UNIVERSITIY MAGDEBURG, Magdeburg, Germany
Contact E-mail Address: arne.kandulski@med.ovgu.de
INTRODUCTION: Activation of protease-activated-receptor-2 (PAR2) is con-
sidered to be a relevant factor for the proposed immuno-pathogenesis of gastro-
esophageal reflux disease (GERD). In esophageal mucosa of patients with
gastroesophageal reflux disease, interleukin-8 (IL-8) and PAR2 were found upre-
gulated when compared to patients without GERD. In vitro studies have shown
increased levels of IL-8-secretion after specifically activating of PAR2.
AIMS & METHODS: To investigate the effects of PAR2-activation upon pH
stimulation in a human esophageal epithelial cell line model.
Normal human esophageal epithelial cells (HEEpiC) have been maintained for 5
days in sixwell plates creating an epithelial monolayer. In a first sequence, cells
were incubated at different pH (7.4; 6.0 or 5.0) sequentially every 7 hours fol-
lowed by 17 hours in basal medium (pH 7.4) for a total of 48 hours. In a second
sequence of 48 hours this monolayer was stimulated with the specific PAR2
agonist SLIGKV-NH2 for 7 hours of at pH 7.4.
RESULTS: After stimulation with different pH, gene expression levels of PAR2
and IL-8 were 4-fold upregulated with decreasing pH (p: 0.015-0.06). However,
there was no upregulation for IL-8 protein in the cell pellets or in the super-
natant. The additional PAR2 activation after sequential pH stimulation led to
IL-8 secretion into the supernatant with increased concentrations after stimula-
tion with lower pH (27.3 /- 2.2 vs. 36.12 /- 4.6 vs. 62.07 /- 6.7 pg/ml,
p0.003), while IL-8 levels in the pellets did not differ.
CONCLUSION: A 2-step-mechanism seems to be involved in the mucosal
immuno-pathogenesis of GERD. Acidic stimulation causes upregulation of
mucosal PAR2 and IL-8. A following activation of the upregulated PAR2
induces the release of IL-8 with a proinflammatory cytokine response of the
esophageal mucosa.
Disclosure of Interest: None declared
OP303 PRESENCE OF BASAL CELL HYPERPLASIA AND DILATION
OF INTERCELLULAR SPACES AND THEIR ASSOCIATION WITH
BASELINE IMPEDANCE VALUES IN PATIENTS WITH POSITIVE
SYMPTOM ASSOCIATION DESPITE NORMAL ACID EXPOSURE
SUPPORTS THEIR ROLE IN SYMPTOMS GENERATION IN NERD
M. Furnari1,*, N. de Bortoli2, P. Zentilin1, L. Mastracci3, E. Marabotto1,
I. Martinucci2, V. Savarino1, E. Savarino4
1
Di.M.I., Gastroenterology Unit, University of Genoa, genoa, 2Dep. Internal
Medicine, Gastroenterology Unit, UNiversity of Pisa, pisa, 3DICMI, Pathologic
Division, University of Genoa, genoa, 4Surgery, Oncology and Gastroenterology,
University of Padua, Padua, Italy
Contact E-mail Address: manuelefurnari@gmail.com
INTRODUCTION: Recently, Microscopic Esophagitis (ME) was positively
related with severity of GERD and negatively with esophageal Baseline
Impedance (BI). Thus, both ME and BI may be helpful to distinguish patients
with GERD from those without. However, several histological features charac-
terize the diagnosis of ME [basal cell hyperplasia (BCH), papillary enlongation
(PE), dilated intercellular spaces (DIS) and epithelial neutrofilic/eosinophilic
infiltration (Neu/Eos)] and few data are available about the role they may play
individually in the pathogenesis of GERD, in particular in well-defined subgroup
of reflux patients.
AIMS & METHODS: To determine frequency and role of histologic features of
ME in different GERD subpopulations and to explore their association with
OP303
BCH PE
BI at 3 cm BI at 5 cm BI at 3 cm BI at 5 cm
Grade 0 -1 2300 (840-4225) 2100 (560-3300) 2415 (560-4225) 2282 (640-3300)
Grade 2 980 (770-4060) 890 (580-2980) 1050 (590-4060) 995 (580-2980)
United European Gastroenterology Journal 2(5S)
mucosal integrity as expressed by BI values. Twenty healthy volunteers (HVs;
11F/9M; mean age 44) and 104 consecutive patients with typical reflux symptoms
underwent upper endoscopy. Biopsies were taken at Z-line and 2cm above it to
assess the presence and severity of BCH, PE, DIS and Neu/Eos [0 (absent), 1
(mild), 2 (marked)]. Within 3 days from endoscopy patients underwent impe-
dance-pH testing off-therapy. We evaluated BI values at 3 and 5cm above the
LES, during the overnight rest, for at least 30 minutes excluding swallows and
reflux induced changes.
RESULTS: We included 20 patients with erosive esophagitis (EE; endoscopy ;
11F/9M; mean age 46yy), 31 with non-erosive reflux disease (NERD; endoscopy
- and abnormal esophageal acid exposure (AET); 10F/21M; 47yy), 34 with hyper-
sensitive esophagus (HE; endoscopy - and normal AET but positive reflux-symp-
tom association; 24F/10M; 45yy) and 19 with functional heartburn (FH;
endoscopy -, normal esophageal AET, negative reflux-symptom association
and negative response to acid suppressors; 11F/8M; 43yy). There were no differ-
ences in terms of frequency of BCH, PE, DIS and Neu/Eos between HVs and FH
(pns). BCH and DIS were more frequent in HE than FH (p50.05), but not PE
and Neu/Eos (pns). NERD had more severe PE and DIS alteration than HE
(p50.05), but not BCH and Eos (pns). Frequency and severity of all lesions
were higher in EE than the other groups (p50.05). Moreover, for each histologic
feature, BI levels at 3 and 5 cm were lower in patients with severe lesions (score 2)
compared to those with mild or no lesions (0-1) (p50.01)[Table].
CONCLUSION: Frequency and severity of BCH and DIS are greater in patients
with positive reflux-symptom association than in HVs and FH, regardless of
AET, whereas PE seems requiring the concomitant presence of abnormal acid
exposure. Thus, the increased frequency of the former lesions and the positive
association between their severity and lower BI values further supports their role
in symptoms generation at least in NERD patients.
Disclosure of Interest: None declared
OP304 IN-VIVO EVALUATION OF MICRO ALTERATIONS IN
PATIENTS WITH EROSIVE ESOPHAGITIS AND NON-EROSIVE
REFLUX DISEASE (NERD) USING PROBE BASED CONFOCAL
ENDOMICROSCOPY (PCLE)
V. Joshi1,*, W. H. S. Ho2, T. Kachaamy3, A.M. Zfass4
1
Gastroenterology, Ochsner Health Center, Kenner, 2Gastroenterology and
Endoscopy Center, Bellingham, 3Mayo Clinic Scottsdale, Scottsdale, 4Virginia
Commonwealth University, Richmond, United States
Contact E-mail Address: vjoshi@ochsner.org
INTRODUCTION: In the US, up to 60 % of patients suffer with GERD.
Unfortunately, the gold standard for the diagnosis of gastroesophageal
reflux disease is still lacking, and the sensitivity of 24-hour pH monitoring for
diagnosing NERD is unsatisfactory. Recent technological advances make the
evaluation of the integrity of esophageal mucosa possible. Previous studies
using confocal endoscope have demonstrated esophageal mucosal breaks and
intrapapillary loops (IPCLs) in patients with gastroesophageal reflux disease.
Confocal laser endomicroscopy is a newly developed endoscopic technique that
allows the observation of living cells, tissue as well as vascular networks of the
mucosal layer in the gastrointestinal tract during ongoing endoscopy. The highly
magnified images of the gastrointestinal tract mucosa can permit real-time his-
tological analysis of the site during endoscopy. Therefore, pCLE can provide
precise assessment of the esophageal squamous epithelial cells and IPCLs without
the need of biopsy. We investigated the use of pCLE for in-vivo evaluation of the
micro alterations of the esophagus not observed by standard endoscopy in
patients with NERD.
AIMS & METHODS: A total of 19 patients with long standing reflux under-
going standard high definition upper endoscopy to evaluate for esophagitis.
Eleven patients were diagnosed with NERD by the absence of endoscopic muco-
sal injury/breaks. At the time of endoscopy 2.5cc of 10% fluorescein was injected.
The confocal probe was placed and optical biopsies obtained within 2 cms above
the gastroesophageal junction (GEJ). Histologic specimens were also obtained
randomly within 2 cm of GEJ. Transmission Electron Microscopy was per-
formed in 7 patients. The endomicroscopy images were interpreted by 2 experi-
enced endoscopists.
CONCLUSION: This is the first pilot study examining the utility of probe based
confocal endomicrosocpy in the setting of NERD. The intercellular spaces and
IPCL size were found to be largest in esophagitis group. They are also larger in
NERD patients in comparison to the normal patients. pCLE could potentially
provide a in-vivo diagnosis via optical biopsy. It may be useful for evaluating
microalterations of the esophagus in real time and assist the diagnosis of NERD.
It could also be used as a marker to demonstrate therapeutic response for tissue
healing in NERD patient and define define the abnormalities at the microscopic
level during endoscopy in pH negative and proton pump inhibitor unresponsive
patients. Further prospective study with a larger cohort is warranted.
Disclosure of Interest: None declared
DIS Neu/Eos
BI at 3 cm BI at 5 cm BI at 3 cm BI at 5 cm
2930 (880-4225) 2850 (560-3540) 2200 (560-4225) 2080 (580-4060)
1045 (830-4060) 1000 (580-3610) 980 (590-2640) 910 (600-2490)
United European Gastroenterology Journal 2(5S)
OP304
Hiatal Microscopic Sex
Number PPI Hernia (n) esophagitis (n) M/F (n)
Normal 3 2 0 0 1/2
NERD 11 4 0 4 5/6
Endoscopic esophagitis 5 3 1 5 4/1
OP305 TASTE MISPERCEPTION AND SENSITIVITY IN SUBSETS OF
GERD PATIENTS
P. Andreozzi1,*, F.P. Zito1, A. Dalessandro1, M. Pesce1, V. Verlezza1, E. Vitale1,
V. Passananti1, F. Turco1, G. Sarnelli1, R. Cuomo1
1
Clinical Medicina and Surgery, UNIVERSITY OF NAPLES " FEDERICO II",
Naples, Italy
Contact E-mail Address: paoloandre.85@gmail.com
INTRODUCTION: Patients with gastroesophageal reflux disease (GERD) may
experience an altered taste perception. However, no studies have explored the
ability of GERD patients to discriminate primary taste. We aimed to investigate
the individual ability to recognize primary tastes in GERD patients.
AIMS & METHODS: Sixty-four clinically diagnosed GERD patients without
known nasal and oral pathologies (27 males, age range 2569 years) and fifty healthy
subjects (HS) (21 males, age range 23-68 years) were studied. Among GERD patients
26 were ON therapy and 38 OFF therapy (with or without proton pump inhibitors
therapy, respectively). All subjects underwent a standardized taste-testing to evaluate
the ability to identify sweet (acesulfame K), bitter (quinine), salty (NaCl), umami
(monopotassium glutamate inosine monophosphate) and sour taste (citric acid),
scoring the intensity of taste perception by using a 100 mm line visual analogue scale
(VAS). In addition, GERD patients underwent pH-impedance 24h monitoring, in
order to measure the pH and the extent of the refluxes.
RESULTS: The percentage of overall taste misperception was significantly
higher in OFF and ON therapy GERD patients than in HS (22.415% and
20.418% vs 13.615%, respectively; p0.028). OFF and ON therapy GERD
patients more frequently failed to correctly identify sweet tastant compared to
HS (10.520.7% and 9.624.5% vs 1000%, respectively; p0.007), whereas a
significant lower perception of salty taste was observed for GERD patients, both
OFF and ON therapy, compared to HS (OFF: 4819.2 and 5325 vs 66.117.2
mm, respectively; p50.001). A negative association was found between both acid
and non-acid reflux extent and umami perception (r-0.45, p0.002; r-0.43,
p0.043), whereas a positive association was found between non-acid reflux
extent and sour perception (r0.32, p0.032).
CONCLUSION: GERD patients, independently of current proton pump inhi-
bitors therapy, showed a lower ability to discriminate and perceive primary
tastes. In particular, GERD patients showed a poor ability to recognize sweet
taste and to perceive salty taste. Interestingly, we found that refluxes extent is
associated to taste impairment with a hypo- and hypersensitivity for humami and
sour tastants, respectively. Given the absence of macroscopic ORL lesions in our
population, the impairment of gustatory function in GERD patients might be
due to refluxes-induced neuro-mediated or microscopic mucosal changes, that
may affect molecular transduction pathways of gustatory signals.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
ADVANCES IN DIAGNOSIS AND MANAGEMENT OF LIVER NODULES HALL
C_____________________
OP306 CANCER STEM-LIKE SPHERE CELLS INDUCED FROM DE-
DIFFERENTIATED HEPATOCELLULAR CARCINOMA-DERIVED
CELL LINES EXERTS LIVER METASTATIC POTENTIAL AND
CHEMORESISTANCE
R. Tsunedomi1,*, K. Yoshimura1, N. Hashimoto1, Y. Watanabe1, S. Hazama1,
M. Oka1
1
Digestive Surgery and Surgical Oncology, YAMAGUCHI UNIVERSITY, Ube,
Japan
INTRODUCTION: Cancer stem cells (CSCs) are thought to play important
roles in carcinogenesis, recurrence, metastasis, and therapy-resistance.
Recently, it was suggested that the possible existence of plasticity between
CSCs and their more differentiated derivative cancer cells. We hypothesized
that poorly-differentiated hepatocellular carcinoma (HCC) has potential that
convert to CSC, which would responsible for metastasis and recurrence.
AIMS & METHODS: To identify molecular tartgets for HCC treatment, we
induced cancer stem-like cells from HCC cell lines using a unique medium, and
examined their potentials. The human HCC cell lines SK-HEP-1, HLE, Hep 3B,
and HuH-7 were used to induce cancer stem-like cells with our sphere induction
medium supplemented with neural survival factor-1. Liver metastatic potential was
examined by injection of the cells to immune-deficient mice spleen. Cell viability was
measured by MTS assay. 9 anti-cancer agents (5-Fluorouracil, Cisplatin,
Carboplatin, Docetaxel, Doxorubicin, SAHA, Irinotecan, Sorafenib, Sunitinib)
were used. The mRNA and protein levels were examined by real-time PCR and
flow cytometry analyses. Reactive oxygen species (ROS) activity was measured with
the cell-permeable fluorogenic probe. Comprehensive analyses were performed by
DNA chip for mRNA and microRNA expressions and by iTRAQ-labeled 2D-LC-
MS/MS analysis for protein expressions. Integrated analysis of those comprehensive
analyses was performed using the Ingenuity Pathway Analysis software.
RESULTS: Poorly differentiated HCC derived SK-HEP-1 and undifferentiated
HCC derived HLE cell lines efficiently formed spheres of cells (SK-sphere and
A97
Size of intercellular
IPCL size Fluorescein channels / DIS
(Mean /range m) leak (mean /range, mm) Reflux disease questionnaire (score)
15.1 (14.5-17) 0 2.5 (1.4-3.5) 0
24.7(12.5-54) 0 4.8 (1.2-7.9) 410
31.2 (25-44) 3 6.53 (5.1-9) 410
HLE-sphere), but well-differentiated HCC-derived HuH-7 and Hep 3B cells did
not. SK-spheres showed increased NANOG, LIN28A, and ALDH1A1 mRNA
levels compared to parental cells. SK-sphere cells showed increased liver meta-
static potential compared to parental cells. As regards epithelial-mesenchymal
transition (EMT), increased expression of Vimentine and Snail were observed in
SK-sphere cells compared to parental cells. The cell viability of SK-spheres was
significantly higher than that of SK-HEP-1 cells in the presence of several anti-
cancer drugs except sorafenib (1.7- to 7.3-fold, each P 5 0.05). Similarly, HLE-
sphere showed increased chemoresistace. Regarding drug efflux, ABCG2 expres-
sion was higher in SK-sphere than in SK-HEP-1 cells. The cell cycle of SK-sphere
was arrested at the G0/G1 phase compared to SK-HEP-1. In addition, SK-sphere
showed induced P21 mRNA. Furthermore, SK-sphere showed higher HIF1A
mRNA expression, more CD44 variant-positive cells, and lower ROS production
compared to parental cells. Integrated analysis with 373 molecules showed that
HIF1A and its downstream genes were up-regulated in SK-sphere (P 5 0.001).
SK-sphere cells was correlated with mitochondrial dysfunction (P 5 0.001) and
was activated in invasion of cells (P 5 0.001).
CONCLUSION: Our novel method successfully induced cancer stem-like cells,
which showed increased metastatic potential and chemoresistace. Moreover, it
was suggested that EMT, cell cycle dormancy, drug efflux, and decreased pro-
duction of ROS were responsible for those SK-sphere characteristics.
Disclosure of Interest: None declared
OP307 SOMATIC LOSS OF ALLELES FROM HEPATIC CYST
EPITHELIUM ALLOW IDENTIFICATION OF CANDIDATE GENES
IN POLYCYSTIC LIVER DISEASE
W.R. Cnossen1,*, A. Hoischen2, R. Woestenenk3, M. Steehouwer2, M. Leenders3,
R.H. te Morsche1, J.A. Veltman2, J.P. Drenth1 on behalf of Genomic Disorders
Group (GDG); Radboud Institute for Molecular LifeSciences (RIMLS)
1
Department of Gastroenterology and Hepatology, 2Department of Human
Genetics, 3Department of Hematology, Radboud university medical center,
Nijmegen, Netherlands
Contact E-mail Address: wybrich.cnossen@radboudumc.nl
INTRODUCTION: Autosomal dominant polycystic liver disease (PCLD) is
characterized by presence of multiple fluid-filled hepatic cysts. Germline muta-
tions in PRKCSH or SEC63 underlie 20% of PCLD cases, but despite wide-
spread presence of the encoded protein(s), the phenotype is restricted to the liver.
We hypothesized that the second allele of these genes is somatically deleted in
cyst epithelium, and that this may also occur for other, as yet unknown PCLD
genes. Loss of somatic allele copies in cystic fluids, which can be detected by
genome-wide SNP microarrays, may therefore directly point to the location of
the germline mutation (the first hit).
AIMS & METHODS: We collected 50 cyst fluid samples from patients with
isolated hepatic cysts. Cyst fluid samples were obtained by aspiration sclerother-
apy and subjected to centrifugation, cytokeratin-19 staining and fluorescent-acti-
vated cell sorting of cholangiocytes. Flow-sorted cells were lysed and DNA was
amplified using whole-genome-amplification (WGA, Repli-G single cell kit,
Qiagen). Genome-wide SNP analysis on a CytoScanHD array (Affymetrix) fol-
lowed to identify regions with loss of heterozygosity (LOH).
RESULTS: Hundreds to thousands of cytokeratin-19-positive cholangiocytes
were sorted. We isolated and amplified DNA from these cells in 8 PCLD
patients. Cyst fluid with a clear content was eligible to process for further ana-
lysis. Genome-wide SNP analysis identified multiple somatic deletions from 0.5
to 12.5Mb. Therefore, genome-wide SNP microarrays of genomic DNA were
simultaneously conducted.
Our experiment was confirmed in a PCLD patient with heterozygous germline
mutation PRKCSH c.2921G4C which is present in a homozygous state in
hepatic cyst epithelium. In addition, a PCLD patient without a known
PRKCSH or SEC63 germline mutation harbored the largest (12.5Mb) homozy-
gous region on chromosome 3 in hepatic cyst epithelium. Subsequently, whole-
exome sequencing of genomic DNA identified candidate genes for PCLD.
CONCLUSION: Cyst epithelium in PCLD is characterized by multiple somatic
loss of genomic regions. These regions may contain genes that contribute to the
phenotype.
Disclosure of Interest: None declared
OP308 PRP19 FACILITATES TWIST1-INDUCED EPITHELIAL-
MESENCHYMAL TRANSITION AND PROMOTES INVASION OF
HEPATOCELLULAR CARCINOMA
J. Yin1,*, J. Zhu1, X. Shen1
1
Department of Gastroenterology, Zhongshan Hospital, Fudan University, shang-
hai, China
Contact E-mail Address: wellyoudiandian@gmail.com
INTRODUCTION: A large body of evidence demonstrates abnormality of ubi-
quitination contributes to the development of various cancer including hepato-
cellular carcinoma (HCC). In our previous work, deubiquitinating enzyme
A98
UCH37 promoted invasion and postoperative recurrence of HCC, and decreased
ubiquitin/proteasome-dependent degradation of pre-mRNA processing factor 19
(Prp19), making Prp19 a potential downstream effector to mediate invasion of
HCC. As one member of protein-ubiquitin ligase, Prp19 participates in activation
of mRNA splicesome, DNA damage response, and ubiquitin/proteasome depen-
dent degradation of proteins.Although dysfunction of aforementioned activities
is closely correlated with oncogenesis, the role of Prp19 in the development of
HCC is less understood.
AIMS & METHODS: We investigated the expression of Prp19 and underlying
mechanisms linked to its pro-invasive role in HCC. rp19 expression in tumor and
paratumor tissues from 169 HCC patients was detected by immunochemistry
staining and western blot, and its correlation with clinical features was analyzed.
Biological behaviors of HCC cell lines with ectopic Prp19 expression were then
assessed ex vivo and in vivo.
RESULTS: Prp19 expression was up-regulated in most HCC tissues and cell
lines, which was positively correlated with vascular invasion, absent tumor cap-
sule and poor prognosis. Prp19 knockdown significantly attenuated migratory
and invasive capacity of HCC cells both ex vivo and in vivo, whereas Prp19
overexpression had the opposite effects. Moreover Prp19 promoted epithelial-
mesenchymal transition (EMT) of HCC cells via sustaining Twist1stability,
which was dependent on p38 mitogen-activated protein kinase (p38 MAPK)
mediated Ser68 phosphorylation within Twist1. Prp19 interacted with transform-
United European Gastroenterology Journal 2(5S)
P. Kaye: None declared, M. Novelli: None declared, B. Disep: None declared, R.
Ostler: None declared, B. Aigret: None declared, B. North: None declared, P.
Bhandari: None declared, A. Haycock: None declared, D. Morris: None
declared, S. Attwood: None declared, A. Dhar: None declared, C. Rees: None
declared, M. Rutter: None declared, P. Sasieni: None declared, R. Fitzgerald
Other: Since this study was conducted the CytospongeTM-TFF3 technology
has been licensed to Covidien GI solutions by the Medical Research Council.
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
NOVEL APPROACHES TO RECTAL CANCER HALL G/H_____________________
OP310 INCIDENCE OF RECTAL ADENOCARCINOMA AND IMPACT
OF NEOADJUVANT TREATMENTS ON PATIENTS SURVIVAL
BETWEEN 1990 AND 2009 IN THE DISTRICT OF FINISTERE
(FRANCE)
M.C. Deniel1,*, M. Cariou2, J.-B. Nousbaum1,2, M. Robaszkiewicz1,2
1
Gastroenterology, 2Registre des Tumeurs Digestives du Finiste`re, University
Hospital, Brest, France
INTRODUCTION: During the past decades, total mesorectal excision techni-
ques and neoadjuvant treatments have been applied in order to improve the
ing growing factor- activated kinase 1 (TAK1) and facilitated k63-linked poly-
ubiquitination of TAK1 in HCC cells, leading to strengthened activation of p38
mitogen-activated protein kinase (p38 MAPK). Prp19/p38 MAPK/Twist1 regu-
latory axis was further attested in orthotopic xenografts models of HCC in nude
mice and human HCC specimens.
CONCLUSION: Increased Prp19 expression promotes HCC invasion by facil-
itating EMT via p38 MAPK/Twist1 pathway. These studies imply that gain of
Prp19 is a pivotal oncogenetic event during HCC progression, rendering it a
promising therapeutic target for advanced HCC.
REFERENCES
Fang Y, Fu D, Tang W, et al. Ubiquitin C-terminal Hydrolase 37, a novel
predictor for hepatocellular carcinoma recurrence, promotes cell migration and
invasion via interacting and deubiquitinating PRP19. Biochim Biophys Acta 2013;
1833: 559-572.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
NEW FRONTIERS IN BARRETTS OESOPHAGUS HALL F2_____________________
OP309 PROSPECTIVE, MULTI-CENTRE, CASE-CONTROL STUDY TO
EVALUATE A NOVEL CYTOSPONGETMTFF3 TEST FOR
DIAGNOSING BARRETTS OESOPHAGUS
C. Ross-Innes1, I. Debiram1, M. ODonovan1, E. Walker1, S. Varghese1, P. Lao-
Sirieix1,*, L. Lovat2, M. Griffin3, K. Ragunath4, R. Haidry2, S. Sami4, P. Kaye4,
M. Novelli2, B. Disep3, R. Ostler5, B. Aigret5, B. North5, P. Bhandari6,
A. Haycock7, D. Morris8, S. Attwood9, A. Dhar10, C. Rees11, M. Rutter12,
P. Sasieni5, R. Fitzgerald1 on behalf of BEST2 Study Group
1
University of Cambridge, Cambridge, 2University College London Hospital,
London, 3Royal Victoria Infirmary, Newcastle upon Tyne, 4Nottingham Queens
Medical Centre, Nottingham, 5Cancer Prevention Trials Unit, London, 6Queen
Alexandra Hospital, Portsmouth, 7St Marks Hospital, London, 8QEII and Lister
Hospitals, Hertsfordshire, 9North Tyneside General Hospital, North Tyneside,
10
County Durham and Darlinton NHS Foundation Trust, Durham, 11South
Tyneside NHS Foundation Trust, Tyne and Wear, 12North Tees and Hartlepool
NHS Foundation Trust, North Tees, United Kingdom
Contact E-mail Address: rcf29@mrc-cu.cam.ac.uk
INTRODUCTION: Barretts oesophagus (BE) is a common condition which is
often undiagnosed and predisposes to oesophageal adenocarcinoma. A mini-
mally-invasive cell sampling device, the CytospongeTM, coupled with an immu-
nohistochemical marker, trefoil factor 3 (TFF3), has shown promise as a
diagnostic tool.
AIMS & METHODS: A multicentre, prospective study was performed to eval-
uate the safety, acceptability and accuracy of the CytospongeTM-TFF3 test in
patients with reflux and dyspepsia symptoms without BE (controls) and cases
with BE ( 1cm circumferential BE or 3 cm tongues). The data were compared
with endoscopy.
RESULTS: 1,110 individuals took part comprising 463 controls (median age 56
years (interquartile range (IQR) 44-66), Male:Female ratio 1.0:1.3) and 647 cases
(median age 66 years (IQR 58-73), Male:Female ratio 4.0:1.0). 1,042 (93.9%)
patients successfully swallowed the CytospongeTM and no serious adverse
events were attributed to the device. Using a visual analogue scale, the
CytospongeTM was rated favourably compared with endoscopy (p0.0003) and
patients who were not sedated for endoscopy were more likely to rate the
CytospongeTM higher than endoscopy (Mann-Whitney test, p50.001). The over-
all sensitivity of the test was 79.9% (95% confidence interval (CI) 76.4-83.0%)
increasing to 87.2% (95%CI 83.0-90.6%) for BE segments with 3 cm of cir-
cumferential BE. There was no loss of sensitivity in patients with dysplasia. The
specificity for diagnosing BE was 92.4% (95%CI 89.5-94.7%).
CONCLUSION: The CytospongeTM-TFF3 test is safe, acceptable and has very
good accuracy for diagnosing BE. This test warrants consideration as an alter-
native to endoscopy for diagnosing BE with potential applicability to screening in
primary care.
Disclosure of Interest: C. Ross-Innes: None declared, I. Debiram: None declared,
M. ODonovan: None declared, E. Walker: None declared, S. Varghese: None
declared, P. Lao-Sirieix Other: Pierre Lao-Sirieix is now employed partly by
Covidien GI Solutions, L. Lovat: None declared, M. Griffin: None declared,
K. Ragunath: None declared, R. Haidry: None declared, S. Sami: None declared,
prognosis of rectal cancer.
AIMS & METHODS: The aim of this study performed in the district of Finistere
(France) between 1990 and 2009, was to analyze the variations in incidence of
rectal adenocarcinoma, as well as access to neoadjuvant treatments and their
impact on patients survival.
All cases of rectal adenocarcinoma diagnosed between January 1, 1990 and
December 31, 2009, recorded in the datbase of the digestive cancer registry of
Finistere, were included in the study. Four 5-years periods were compared. The
studied variables were gender, age, cancer stage at diagnosis (UICC) and first
type of treatment applied. Qualitative variables were compared using the Chi 2
test; survival curves were established using the Kaplan-Meier method and com-
pared with the log-rank test.
RESULTS: 2838 patients were included in the study. The incidence of rectal
cancer did not change significantly during the study period (1990-1994: 7.51 
0.33; 2005-2009: 7.97  0.32 per 100 000 inhabitants). A significant change in the
distribution of cancer stages was noted over time (p 0.04): the proportion of
stage 4 cancers increased from 16.4% to 21.6% between the first and last period.
The proportion of patients who received a neoadjuvant treatment with radiation
therapy or chemoradiotherapy, increased over time for stage 2 and stage 3 can-
cers (23% between 1990 and 1994, 55% between 2005 and 2009.) The proportion
of patients with a stage 4 cancer and treated by chemotherapy increased from 17
to 65%. Overall 5 years survival rates are presented in the table. The variation of
survival was statistically significant (p 10-5). The highest variation in 5-year
survival was noted for patients with stage 3 cancer (29.3% to 65.4%).
Survival
Period 1 year 2 years 3 years 4 years 5 years Total
1990-1994 75% 59,9% 49,3% 41,3% 37,3% 630
1995-1999 76,3% 64,2% 54,9% 48,2% 43,8% 716
2000-2004 77,9% 64,7% 55,7% 51,3% 45,8% 706
2005-2009 81,9% 70,5% 61,5% 54,3% 49,8% 780
Table: survival (in %) at 1, 2, 3, 4 and 5 years, for each period
CONCLUSION: The incidence of rectal adenocarcinoma has not changed in the
Finistere district between 1990 and 2009. Despite a significant increase in the
proportion of advanced stages, there was a significant increase in survival rates
with time, to be compared with the increase in the proportion of patients who
received neoadjuvant treatment or exclusive medical treatment with chemotherapy.
Disclosure of Interest: None declared
OP311 ADDITIONAL SURGICAL RESECTION AFTER ENDOSCOPIC
REMOVAL OF T1 COLORECTAL CARCINOMA IS ASSOCIATED
WITH IMPROVED OVERALL SURVIVAL
T.D. Belderbos1,*, F. N. van Erning2, I. H. de Hingh3, M. G. van Oijen1,
L.M. Moons1, V. E. Lemmens2, P.D. Siersema1
1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht,
2
Eindhoven Cancer Registry, Comprehensive Cancer Centre The Netherlands,
3
Surgery, Catharina Hospital, Eindhoven, Netherlands
Contact E-mail Address: t.d.g.belderbos@umcutrecht.nl
INTRODUCTION: Controversy exists on the adequate management of patients
with pathologically confirmed T1 colorectal carcinoma (pT1 CRC) after initial
endoscopic removal. It is currently not well known whether additional surgery
following endoscopic resection of a pT1 CRC indeed improves the prognosis of
patients. Moreover, it is unknown in which subgroups of patients additional
surgery is actually performed in clinical practice.
AIMS & METHODS: We collected data on current treatment strategies in a
cohort of patients with pT1 CRC to compare the overall survival between
patients undergoing additional surgery versus endoscopic resection only and to
identify factors associated with the decision to perform additional surgical resec-
tion after endoscopic resection. All patients diagnosed with pT1 CRC between
1995 and 2011 in the area of the Eindhoven Cancer Registry (southern part of the
Netherlands) were included. The Cochrane-Armitage Trend test was used to
evaluate trends over time in endoscopic resection of pT1 CRC. Multivariable
United European Gastroenterology Journal 2(5S)
logistic regression was used to assess patient and tumour characteristics asso-
ciated with additional surgical resection. Crude 5-year overall survival was based
on Kaplan-Meier curves and Cox regression analysis was used to discriminate the
independent effect of additional surgical resection on the risk of death after
adjusting for relevant patient and tumour characteristics.
RESULTS: A total number of 1965 patients with pT1 CRC were identified, of
whom 827 (42%) were treated with endoscopic resection (with (n567, 69%) or
without (n260, 31%) additional surgery) and 1138 with primary surgical resec-
tion. The rate of endoscopic resection in pT1 CRC patients remained stable over
time (41% in 1995 and 43% in 2011, p0.45). Patients in whom additional
surgical resection was performed were younger (mean age 65 vs. 69 years,
p50.01), more often had no comorbidities (34% vs. 25%, p50.01) and more
often had a colon than a rectum tumour (71% vs. 63%, p0.017), compared to
patients undergoing endoscopic resection only. In multivariable analysis,
younger patients (OR for patients 550 years versus 70 years 1.95, 95%CI
1.05-3.59) and patients with a tumour in the colon (OR for colon versus
rectum tumours 1.54, 95%CI 1.11-2.15) were more likely to undergo additional
surgery. Crude 5-year overall survival was higher in patients with additional
surgical resection after endoscopic resection compared to patients with endo-
scopic resection only (82% versus 75%, p50.01). The association remained sig-
nificant after adjusting for patient and tumour characteristics (adjusted HR 0.68:
95% CI 0.50-0.93). Female gender, younger age, higher socioeconomic status and
absence of comorbidity were all independently associated with lower mortality.
CONCLUSION: In a large cohort of pT1 CRCs, one third of patients, particu-
larly younger patients with a colon tumour, undergoing endoscopic resection,
underwent additional surgical resection, which was independently associated
with an improved overall survival rate.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
COLORECTAL CANCER SCREENING: STRATEGIES AND OUTCOMES HALL I/
K_____________________
OP312 GETTING OLD WITH LYNCH SYNDROME IN
NORTHEASTERN ITALY
M. Fornasarig1,*, M. Tabuso1, R. Talamini2, A. Viel3, E. Orzes1, V. Canzonieri4,
R. Cannizzaro1
1
Gastroenterology, 2Epidemiology, 3Experimental Oncology I, 4Pathology, Centro
di Riferimento Oncologico, Aviano, Italy
Contact E-mail Address: mfornasarig@cro.it
INTRODUCTION: Lynch Syndrome (LS) is an inherited cancer predisposition
bringing about 2-3% of all new cases of ColoRectal Cancer (CRC), caused by
mutation in mismatch repair (MMR) genes. LS patients have a lifetime risk to
develop a CRC up to 75% in men and 52% in women and an Endometrial
Carcinoma (EC) up to 71%. The cancer spectrum involves other organs
(ovary, stomach, urinary tract and small bowel), but with a lower risk.
AIMS & METHODS: We report our experience of a hospital LS registry collect-
ing cases mainly from Northeastern Italy focusing on the clinical history of
patients through aging. Families included in the study were registered in the
Registro Tumori Ereditari del colon-retto, settled since 1992 at our Correale Other: Dr. Correale is employed bu I-m3d spa. The company developed
Institution. Pathogenic mutations in MSH2, MLH1 and MSH6 were identified
in 37 unrelated families. We tested 251 members of the families including the
probands: 113 (45%) were gene carries (44M and 69F) and 138 were wild-type.
25 families displayed mutation in MSH2, 11 families in MLH1 and one in MSH6.
Surveillance program included colonoscopy from age 22 with an interval of 1-2
years, abdominal ultrasound, urine cytology every two years and upper GI endo-
scopy every 4 years from age 35. For women, the gynecological work out
included transvaginal ultrasonography and endometrial biopsy every two years
from 30-35 years.
RESULTS: The first cancer diagnosed was CRC in almost all males. EC and
CRC were equally diagnosed in women. The number of CRC increased abruptly
until age 40 and decreased slowly with aging. Extra-colonic cancers (EXC),
instead, increased from age 50. 78 (69%) patients developed at least one
cancer: 57 (50.4%) CRC and 32 female patients (46.4%) EC. However, cancer
of any type occurred in all patients over age 60. 66 (56.4%) had multiple primary
cancers related to aging. A progressive increase of CRC and EXC was seen and
patients with six EXC had a mean age of 74 years. The deaths registered were 11
(9.7%): 2 (1.7%) for pancreatic cancer and 9 (7.9%) for other diseases between
69 and 83 of age. Colonic surveillance lasted for an average period of 10.5 years
(2-22 years). 5 patients (4.4%) out of 113 had CRC at stage T1 (2 pts), T2 (2 pts)
and T2N1 (1 pt) and 38 (33.6%) patients had 121 advanced adenomas.
CONCLUSION: Getting old, all LS patients displayed at least one cancer and
more than 50% had multiple primary cancers. Colectomy with ileo-rectum ana-
stomosis is the therapy of choice at first CRC diagnosed to avoid any further
surgical procedures for that disease. Surveillance of organ targets (pancreas,
small bowel, duodenum, urinary tract and stomach) should be included in long
survivors from CRC.
Disclosure of Interest: None declared
A99
OP313 SCREENING FOR COLORECTAL CANCER: A RANDOMIZED
TRIAL COMPARING PATIENT RESPONSE OF SIGMOIDOSCOPY
VS. CT COLONOGRAPHY
C. Senore1,*, N. Segnan1, L. Correale2, G. Iussich3, C. Hassan4, D. Regge3
1
CPO Piemonte, AOU Citta` della Salute e della Scienza, 2I-m3d S.p.a.,
3
Radiology, IRCC Candiolo (TO), Torino, 4Gastroenterology, Osepedale Nuovo
Regina Margherita, Rome, Italy
Contact E-mail Address: carlo.senore@cpo.it
INTRODUCTION: CT colonograpphy has been proposed as non invasive,
potentially acceptable, primary screening test for colorectal cancer (CRC).
Only one randomised trial (1) has been conducted in a population base program,
comparing CT colonography and colonoscopy.
AIMS & METHODS: The aim of the study is to compare the participation rate
of people invited to perform a Flexible Sigmoidoscopy (FS) to the response rate
to the invitation to performa a CT Colonography (CTC), in the context of a
population-based screening program.
A sample of 58 years olds in the general population living in Turin, Italy were
randomly allocated (1:1) to be invited by mail for primary screening with FS or
CTC. Those with a history of CRC, adenomas, inFammatory bowel disease,
recent colonoscopy, or two Erst-degree relatives with CRC were ineligible.
Non-responders to invitation for FS screening were re-invited to attend for
screening with CTC or immunological Fecal Occult Blood Test (FOBT). The
primary outcome was screening participation rate, defined as numbers of invitees
undergoing to the screening relative to the total number of invitees. Participation
rates were also compared in a multivariate model to assess the effect of covariates
(gender and screening arm). We conducted also a survey of a sample of partic-
pants and of refusers to compare screenee experience with the two tests and to
study reasons for non-participation.
RESULTS: Of the 1984 eligible subjects included in the study, 995 and 989 were
randomly assigned to CTC and FS arm, respectively. After excluding 27 people
who could not be traced (1.4% across intervention groups), the participation rate
following the first invitation and mail remainder was 27.1% (265/977) for FS and
30.5% (299/980) for CTC (P0.09).
Participation in screening with CTC was significantly better than with FS (34%,
95% CI: 30-39% vs. 26%, 95% CI: 22-31; OR, 1.6; 95% CI: 1.1-2.3; P0.01)
among men, while no difference between CTC and FS screening was observed
among women (OR, 0.91; 95% CI: 0.7-1.2; P0.53). Invitation for FS non-
responders to undergo screening with CTC or FOBT increased participation
(80-100 days after invitation) by 5% (18 of 330 invitees) and 4.8% (16 of 330
invitees), respectively.
CONCLUSION: A trend toward increased participation in CTC vs. FS screen-
ing was seen. Moreover, men were significantly more likely to adhere to screening
with CTC than with FS. Additional effort may be needed to improve participa-
tion of women in CRC screening.
REFERENCES
1) Stoop EM, de Haan MC, de Wijkerslooth TR, et al. Participation and yield of
colonoscopy versus non-cathartic CT colonography in population-based screen-
ing for colorectal cancer: a randomised controlled trial. Lancet Oncol 2012; 13:
55-64.
Disclosure of Interest: C. Senore: None declared, N. Segnan: None declared, L.
the CAD system used for the study and it contributed to the funding of the study
together with the Piedmont Region Health Authrority, G. Iussich: None
declared, C. Hassan: None declared, D. Regge: None declared
OP314 OUTCOMES OF THE FRENCH COLORECTAL CANCER
POPULATION-BASED SCREENING PROGRAMME USING GUAIAC
FAECAL OCCULT BLOOD TEST
F. Assogba1,*, D. Jezewski-Serra1, D. Lastier1, C. Quintin1
1
1Department of Chronic Diseases and Injuries, INVS, Saint-Maurice, France
Contact E-mail Address: f.assogba@invs.sante.fr
INTRODUCTION: With more than 42 000 new cases and more than 17 000
deaths each year, colorectal cancer is the third most common cancer and the
second most common cause of cancer-related death in France. Due to its large
and growing burden, an organized biennial population-based on a guaiac Fecal
Occult Blood Test (g-FOBT) screening programme has been launched, and gen-
eralized since 2008 in 46 French districts, and progressively spread throughout
the country and now covers all (99) French districts.
AIMS & METHODS: Biennially, all average-risk men and women aged 50 to 74
years are invited to perform a g-FOBT. Individuals with positive g-FOBT were
referred to a gastroenterologist to undergo a total colonoscopy. Early perfor-
mance indicators for the third round (January 1, 2012 to December 31, 2013)
were evaluated according to European guidelines, and then compared with those
of the second round (2010-2011), when available. The TNM classification of
malignant tumours, (7th edition 2009) has been used.
RESULTS: More than 18 million people were invited for this third-round and
5.1 million people performed a g-FOBT. Participation rate was 31% (- 3.4%
since the previous-round). It increased with age and was higher in women than
in men (33% vs 29%). Positive rate was consistent with the expected (2.2%, men
2.5% vs women 1.9%), and varied widely with age and across the districts.
Compared to the previous-round, the positive rate decreased from 2.6% to
2.2%, a decrease of 15.4%. During the period 2010-2011, follow-up colonoscopy
compliance rate was 87%, and varied across the districts from 17% to 98%.
Advanced adenoma detection rate was 4% (men: 5.9% vs women 2.5%), that
of colorectal cancer was 1.5% (men: 2.1% vs women 1.0%). A total of 3949
colorectal adenocarcinomas were detected (in situ: 27% vs invasive: 73%). Stage
I was 39.5% (resp., 38.1%), stage II 26.2% (resp., 26.3%), stage III 22.1% (resp.,
25.6%) and stage IV 12.2% (resp., 10%) for men (resp., women). As expected,
A100
cancers detected at subsequent screening are more often diagnosed at earlier
stages (stage I and II) then those diagnosed during a first screening (68% vs
63%).
CONCLUSION: Five years after the generalization of the French population-
based screening programme throughout the country, participation rate fail to
achieve the European minimum recommended goal (45%). More efforts
should be done to identify the profile of non-adherent to the programme for
developing most effective communication strategies for these targeted people.
One can hope that the next implementation of fecal immunochemical tests to
replace g-FOBT tests might contribute to enhanced the adherence to screening.
Disclosure of Interest: None declared
OP315 COLORECTAL CANCER SCREENING PILOT IN NORWAY -
COMPARATIVE EFFECTIVENESS RESEARCH OF FLEXIBLE
SIGMOIDOSCOPY (FS) AND FECAL IMMUNOCHEMICAL TEST
(FIT)
T. de Lange1,*, A. Jrgensen1, O.P. Brmer2, P. Sandvei3, C.B. Steen1, G. Ursin1,
G. Hoff1
1
Cancer Registry of Norway, 2Oslo University Hospital, Radiumhospitalet, Oslo,
3
Department of Internal Medicine, stfold Hospital, Fredrikstad, Norway
Contact E-mail Address: t.d.lange@medisin.uio.no
INTRODUCTION: Although several modalities are being used in colorectal
cancer (CRC) screening, only fecal occult blood testing (FOBT) and FS have
been subjected to randomized trials and long-term follow-up. Both have been
found to reduce CRC mortality compared to no screening (18% and 28%,
respectively), but a direct comparison between the two has never been done
with end-point CRC incidence and mortality. It is also not clear which modality
is the most cost-effective in any given population. In Norway, a country with
high colorectal cancer incidence and little prior CRC screening, the government
decided to start a comparative effectiveness research pilot in 2012.
AIMS & METHODS: The pilot aims to randomize 1x1 the entire population
aged 5074 in a defined geographical area in South-East Norway (approximately
140 000 individuals) to one of two screening modalities, FIT (OC-Sensor Diana,
Eiken Ltd) or once only FS. The enrollment will take six years and the pilot
includes a number of sub-studies to determine how the screening is perceived in
the target population. We report the results from the enrollment in the main trial
after the first 24 months.
RESULTS: A total of 51500 women and men have been invited so far, 33.373 to
FIT and 18.127 to FS. Participation rates have been 49% in the FS arm, and
57% in the FIT arm, with slightly higher rates among women than men. Positive
FS was defined as advanced neoplasia or three or more adenomas. A total of
10.3% of the FS patients have been referred to colonoscopy. The cut-off value
for positive FIT was set to 75 ug/L, and 1287 patients (6.9%) have so far tested
positive and referred to colonoscopy.
Forty-three cases of CRC have been detected in the FS group so far, at a rate of
5/1000 examined, somewhat higher in men (5.7/1000) than in women (4.3/1000).
Forty-nine cancers have been found in the FIT group after first screening round
(2.6/1000 examined), with 3.7/1000 in men and 1.7/1000 in women. Overall the
adenoma detection rate at sigmoidoscopy is 14.4 %. A total of 853 high-risk
adenomas (adenomas 410 mm, or with high-grade dysplasia or villous features)
have been detected. Adenoma detection rate in the population referred for colo-
noscopy is 59%. One perforation has occurred due to the enema installation
prior to sigmoidoscopy. At colonoscopy the rate of serious adverse events need-
ing hospitalization is currently 8/1000, the main ones being reported are burned
serosa and bleeding, while no perforation has occurred.
CONCLUSION: Participation rates in both arms are slightly below the expected
50% for FS and 60% for FOBT. Cancer rates among those screened are higher in
the once-only FS than after first round of biennial FIT screening, but rates are
within the expected range.
Disclosure of Interest: None declared
OP316 IMMUNOCHEMICAL FECAL OCCULT BLOOD TESTING TO
SCREEN FOR COLORECTAL CANCER: CAN THE SCREENING
INTERVAL BE EXTENDED?
U. Haug1,*, E. Grobbee2, I. Lansdorp-Vogelaar2, M. Spaander2, E. Kuipers2
1
German Cancer Research Center, Heidelberg, Germany, 2Erasmus MC University
Medical Center, Rotterdam, Netherlands
Contact E-mail Address: u.haug@dkfz.de
INTRODUCTION: Colorectal cancer (CRC) screening programs based on fecal
immunochemical testing for hemoglobin (FIT) typically use a screening interval
of 2 years. Studies have shown that the diagnostic yield of the first re-screening
round (reSR) is significantly lower as compared to the initial screening round
(inSR), which raises the question whether the first reSR could be skipped. This
would lead to a longer screening interval that could be advantageous regarding
adherence and organizational effort. Given the quantitative nature of FIT, the
skipped round could be compensated for by lowering the cutoff level (CL) of FIT
at the initial round (i.e., increasing sensitivity at the cost of decreasing specificity).
We aimed to explore how such alternative FIT strategies compare to conven-
tional ones in terms of CRC detection and positivity rate.
AIMS & METHODS: We analyzed longitudinal data of 4523 Dutch individuals
(5074 years) participating in the inSR of a 1-sample FIT screening program, of
which 3427 individuals also participated in the first reSR after 1-3 years. FIT50
was used in both rounds (i.e., a CL of 50 ng haemoglobin (Hb)/ml, correspond-
ing to 10 mg Hb/g faeces). The cohort was followed up until 2 years after the first
reSR. We determined the cumulative number of (screen-detected) CRCs for the 2
FIT50 rounds and compared it to the number of CRCs that would have been
detected at a hypothetical, single inSR with a lower CL. For the latter, we
United European Gastroenterology Journal 2(5S)
considered persons who were diagnosed with CRC (screen-detected or interval
CRC) until the end of the follow-up period and examined whether their FIT level
at the inSR was beyond a certain value. We first looked at FIT11 (i.e., a CL of
11 ng Hb/ml, corresponding to 2 mg Hb/g faeces). This CL is - according to
published literature on diagnostic performance - expected to yield a similar
number of advanced adenomas as detected in the 2 FIT50 rounds combined.
We also compared positivity rates for the different scenarios.
RESULTS: In the 2 FIT50 rounds, 28 CRCs were detected, of which 22 (79%)
were at an early stage (UICC stages I-II). The cumulative positivity rate was
14%. In a hypothetical inSR with FIT11, 27 CRCs would have been detected. Of
these, 19 (70%) would definitely have been detected at an early stage. Two of the
27 CRCs were detected at UICC stage III 9 months and 2 years after the inSR,
respectively, and thus might have been at an early stage if detected at the inSR.
The positivity rate of a hypothetical inSR with FIT11 would have been 18%. All
CRCs detected with FIT11 would also have tested positive with CLs up to 24ng/
ml. The positivity rate of a hypothetical inSR with FIT24 would have been 12%.
CONCLUSION: We provide first empirical evidence regarding alternative FIT
strategies using extended screening intervals in combination with a lower than
usual positivity threshold. The findings remove concerns that such strategies
would go along with a significant increase in the rate of interval cancers or in
the overall positivity rate. Although the approach taken here to lower the posi-
tivity threshold (i.e., CLs below 50 ng/ml) would require careful consideration
regarding test-retest reliability, the findings suggest that, in principle, such alter-
native FIT strategies could be interesting options and provide the basis for
planning next research steps in this direction.
Disclosure of Interest: None declared
OP317 THE 10 YEARS EVALUATION OF THE CZECH COLORECTAL
CANCER SCREENING PROGRAM EFFICACY BASED ON THE
LONG-TERM IMPACT INDICATORS
S. Suchanek1,*, O. Majek2, L. Dusek2, B. Seifert3, M. Zavoral1
1
Department of Gastroenterology, 1st Faculty of Medicine of Charles University
and Military University Hospital, Prague, 2Institute of Biostatistics and Analyses,
Masaryk University, Brno, 3Institute of General Medicine, 1st Faculty of Medicine,
Charles University, Prague, Czech Republic
Contact E-mail Address: stepan.suchanek@uvn.cz
INTRODUCTION: In the Czech Republic, there is 3.75 million inhabitants aged
over 50. The Czech Colorectal Cancer (CRC) Screening Program was introduced
in 2000 based on guiac fecal occult blood testing (gFOBT). In the last decade, the
program has continuously evolved. Currently the annual immunochemical
FOBT (FIT) is offered at the age 50 54, followed by FOBT colonoscopy, if
positive. In age of 55, there is a choice of either FIT biannually or screening
colonoscopy in 10 years interval.
AIMS & METHODS: Three main quality control long-term impact indicators
recommended by the European Guidelines (published in 2010) have been com-
pared in 10 years interval (decrease of CRC incidence and mortality and the
increase of the proportion of early stage cancers) to assess the CRC screening
program efficacy. The data from the Czech National Cancer Registry have been
used.
RESULTS: The CRC incidence in years 2000 and 2010 reached the level of 42.23
and 39.19 (the world standard, ASR-W) and 7,553 and 8,265 (absolute numbers,
712, 9.4%). The CRC mortality recorded in the same years was 23.79 and 17.20
(ASR-W) and 4,508 and 3,991 (absolute numbers, -517, -11.5%). The compar-
ison of CRC stages in years 2000 and 2010 is shown in the table.
Stage 2000 2010 Change
Stage I 16 % 23 % 7%
Stage II 27 % 24 % -3%
Stage III 17 % 24 % 7%
Stage IV 23 % 23 % 0%
Stage unknown 18 % 6% -12%
CONCLUSION: The ten years results show that the Czech CRC screening pro-
gram is effective. All three main long-term impact indicators are fulfilled, the
incidence and mortality are decreasing and the ratio of stage I cancers diagnosed
is rising.
This project has been supported by the Czech Ministry of Health grant No. NT
13673
REFERENCES
von Karsa L, Patnick J and Segnan N. European guidelines for quality assurance
in colorectal cancer screening and diagnosis. First EditionExecutive summary.
Endoscopy 2012; 44 (Suppl. 3): SE1-SE8.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP318 LONG-TERM IMPACT OF THE DUTCH COLORECTAL
CANCER SCREENING PROGRAMME ON CANCER INCIDENCE -
EXPLORATION OF THE SERRATED PATHWAY
M. Greuter1, J.-B. Lew2, J. Berkhof1, K. Canfell2, E. Dekker3, G. Meijer1,
V. Coupe1,*
1
VU University Medical Center, Amsterdam, Netherlands, 2Lowy Cancer Research
Centre, The University of New South Wales, Sydney, Australia, 3Amsterdam
Medical Center, Amsterdam, Netherlands
Contact E-mail Address: mj.greuter@vumc.nl
A101
AAd and 6% CRC miss rate. The IC rate over the 2-year period after the initial
negative FIT was 2.5 (N10) and 7.2 (N25) x 10,000 women aged 50-59 and 60-
69 respectively; the corresponding figures for men were 3.6 (N12) and 8.3
(N24) x10,000; the Hb level at the preceding FIT was 0 in 39.4% of the
cases. Among people with 2 negative FITs the IC rate was 3.9 (N19) and 3.9
(n16) x 10,000 women and men respectively; no Hb was detected in the previous
2 FITs in 34.3% of these cases.
Age 50-59 N examined FIT TC PPV AAd PPV CRC DR AAd DR CRC NNScope

INTRODUCTION: The Netherlands has recently started with the stepwise 1 FIT 88935 4,3% 91,5% 35,3% 4,2% 1,40% 0,17% 2,5
implementation of a colorectal cancer (CRC) screening programme consisting 2 FIT 46692 3,3% 93,0% 25,0% 2,5% 0,77% 0,08% 3,6
of biennial faecal immunochemical test (FIT) screening in individuals aged 55 to 3 FIT 24009 3,0% 93,3% 22,7% 2,8% 0,64% 0,08% 3,9
75 years.
4 FIT 3569 2,9% 94,3% 33,3% 1,0% 0,92% 0,03% 2,9
AIMS & METHODS: 1) To evaluate the impact of the Dutch screening pro-
Age 60-69 N examined FIT TC PPV AAd PPV CRC DR AAd DR CRC NNScope
gramme on the long-term CRC incidence and colonoscopy demand. 2) To
explore the impact of assumptions concerning the serrated pathway on these 1 FIT 76934 6,6% 88,7% 34,6% 7,1% 2,01% 0,41% 2,4
long-term predictions. 2 FIT 61922 4,6% 91,3% 26,7% 3,5% 1,13% 0,15% 3,3
The Adenoma and Serrated pathway to Colorectal CAncer (ASCCA) model was 3 FIT 41882 4,2% 91,6% 24,0% 3,2% 0,93% 0,12% 3,7
set up to simulate the Dutch CRC screening programme between 2014 and 2044. 4 FIT 19166 4,0% 90,2% 23,3% 3,0% 0,84% 0,11% 3,8
Based on pilot studies, we assumed a participation rate of 62% for FIT testing.
We adopted an open-model approach by simulating multiple birth cohorts and
combining the results while accounting for the ageing of the population. Besides
a no screening scenario, we evaluated three screening scenarios differing in the CONCLUSION: The high DR of AAd over several screening rounds is sugges-
contribution of the serrated pathway to the CRC incidence (0%, 15% and 30%). tive for a larger impact of FIT screening on CRC incidence, as compared to
Model-predicted outcomes were CRC incidence and the colonoscopy demand guaiac-FOBT. Gender, age and stool Hb at previous tests could be used to
per year from 2014 until 2044. In addition to the contribution of the serrated modulate the cut-off at subsequent tests, to reduce TC workload. Apparently a
pathway to the CRC incidence, we assessed the impact of other natural history substantial proportion of ICs may not bleed.
assumptions regarding the serrated pathway. Disclosure of Interest: None declared
RESULTS: Due to ageing, the model-predicted CRC incidence in the no screen-
ing scenario increased from 77/100,000 in 2014 to 109/100,000 in 2044. In the
screening scenarios, the predicted CRC incidence first increased compared to no OP320 COLONPREDICT STUDY: DEVELOPMENT AND VALIDATION
screening due to the detection of asymptomatic, prevalent tumours. In 2014, the OF A PREDICTIVE MODEL FOR COLORECTAL CANCER
CRC incidence was predicted to peak between 105/100,000 (under the assump- DETECTION IN SYMPTOMATIC PATIENTS
tion that all CRCs arise from adenomas) and 109/100,000 (under the assumption J. Cubiella1,*, P. VEGA1, M. T. ALVES1, M. SALVE1, M. DIAZ-ONDINA2, P.
that 30% of CRCs arises from serrated lesions). After this peak, the predicted MACIA2, I. BLANCO2, L. BUJANDA3, J. FERNANDEZ-SEARA1,
incidence under screening gradually decreased. In 2044, the estimated CRC inci- E. SANCHEZ1
dence under screening reached a new equilibrium between 65/100,000 and 71/ 1
GASTROENTEROLOGY, 2CLINICAL ANALYSIS, COMPLEXO
100,000 under the assumption that 100% versus 70% of CRCs originate via the HOSPITALARIO UNIVERSITARIO DE OURENSE, OURENSE,
adenoma-carcinoma pathway, respectively. Due to the stepwise implementation, 3
GASTROENTEROLOGY, Hospital de Donostia, San Sebastian, Spain
the predicted number of colonoscopies required for the screening programme Contact E-mail Address: joaquin.cubiella.fernandez@sergas.es
increased gradually over time. In 2014, the expected number of colonoscopies
under screening was estimated to be around 38,000 (752,199 invitees) whereas in INTRODUCTION: Predictive models for colorectal cancer (CRC) detection in
2044, the predicted colonoscopy demand was estimated to be around 117,000 symptomatic patients are based on subjective clinical criteria and have low diag-
(2,154,875 invitees). Except for the contribution of the serrated pathway to the nostic accuracy.
CRC incidence, model predictions were robust for other assumptions regarding AIMS & METHODS: We designed a prospective blind diagnostic tests study
the natural history of the serrated pathway. aimed to develop and validate a CRC predictive model in symptomatic patients
CONCLUSION: The Dutch screening programme will markedly decrease the based on clinical and laboratory variables. We compared its diagnostic accuracy
CRC incidence. With the results of this study, decision-makers on health care with the National Institute for Health and Care Excellence (NICE) referral cri-
planning can anticipate the expected change in CRC-related health care use and teria for the detection of colorectal cancer in symptomatic patients. We included
colonoscopy demand. Although the natural history of the serrated pathway has consecutive patients with gastrointestinal symptoms referred for colonoscopy. In
not yet been fully clarified, different assumptions for these unknown parameters each patient, the symptoms were collected in a structured protocol; fecal calpro-
have limited impact on model predictions. However, the estimate of the propor- tectin (Buhl Quantum Blue ) and hemoglobin (OC-Sensor ) concentrations,
tion of CRCs arising through the serrated pathway does influence the predicted serum carcinoembryonic antigen (CEA) and hemoglobin were determined and
effectiveness of screening. the findings in anorectal examination were described. A predictive model was
Disclosure of Interest: None declared developed based on a binary logistic regression and was internally validated using
the split-sample technique. To compare COLONPREDICT model with NICE
criteria, we used ROC curves and AUC to detect differences in overall diagnostic
OP319 REPEATED FIT SCREENING: THE INFLUENCE OF SUBJECTS accuracy and McNemar test to determine differences in sensitivity and specificity
CHARACTERISTICS AND SCREENING HISTORY ON THE for CRC detection.
POSITIVE PREDICTIVE VALUE AND NEOPLASIA YIELD RESULTS: Between March 2012 and September 2013, 1572 patients were
R. Sassatelli1, S. Crotta2, C. Senore3,*, C. Campari4, L. Paterlini4, C. Cerrato2, included and were valid for analysis. We detected 215 (13.7 %) CRC. The vari-
R. Lolli2, B. Dagnes2, N. Segnan3 ables included in the predictive model were age (years) (OR 1.04, 95% CI 1.02-
1
Gastroenterology, IRCCS Ospedale S Maria Nuova, Reggio Emilia, 1.06), sex (male) (OR 2.27, 95% CI 1.5-3.44), fecal hemoglobin 100ng/ml (OR
2
Gastroenterology, Ospedale Beauregard, Aosta, 3CPO Piemonte, AOU Citta` della 17.2, 95% CI 10.18-29.03), hemoglobin (5 10g/dL) (OR 4.76, 95% CI 2.19-
Salute e della Scienza, Torino, 4Centro Screening, AUSL Reggio Emilia, Reggio 10.37) (10-12g/dL) (OR 1.8, 95% CI 1.09-2.96), CEA ( 3ng/mL) (OR 4.52,
Emilia, Italy 95% CI 3-6.9), treatment with acetylsalicylic acid41 year (yes) (OR 0.42, 95%
Contact E-mail Address: carlo.senore@cpo.it CI 0.24-0.74), colonoscopy in the last 10 years (yes) (OR 0.12, 95% CI 0.06-0.25),
mass on digital rectal examination (yes) (OR 17.19, 95% CI 10.18-29.03), benign
INTRODUCTION: There is limited experience of colorectal cancer (CRC) anorectal disease (yes) (OR 0.27, 95% CI 0.17 to 0.44), rectal bleeding (yes) (OR
screening with fecal immunochemical tests (FIT) over several screening rounds. 2.27 95% CI 1.5-3.44) and change in bowel habits (yes) (OR 1.7, 95% CI 1.14-
AIMS & METHODS: To assess FIT screening performance among people per- 2.51). The AUC of COLONPREDICT model was 0.92 (95% CI 0.91 to 0.94),
forming consecutive tests in 3 population based programs in Italy and to explore significantly higher than the AUC of NICE criteria (AUC 0.59, 95% CI 0.55-
the impact of modulating positivity cuf-off to account for screenees character- 0.63; p 5 0.001). At a COLONPREDICT model cut-off with a 90% sensitivity
istics and screening history. The participating programs target people aged 50 to for CRC detection, the predictive model is statistically more sensitive (89.3 %,
74 (Aosta), 59 to 69 (Turin) and 50 to 69 (Reggio Emilia), offering single sample 67.9 %; p 5 0.001) and specific (79.3 %, 50.3 %; p 5 0.001) than the NICE
biennial FIT, with 100 ng haemoglobin (Hb)/ml buffer (20 g/mg faeces) posi- criteria.
tivity cut-off. We measured the positive predictive value (PPV), the number CONCLUSION: COLONPREDICT is a predictive model with high diagnostic
needed to scope (NNScope) and the detection rate (DR) for advanced adenoma accuracy for the detection of CRC in symptomatic patients. External validation
(AAd) and CRC, and the interval CRC (IC) rate (ICs x 10,000 subjects with is required for widespread use in the indication and priorization of colonoscopy.
negative FIT), among people aged 50 to 69. We simulated the impact of modu- Disclosure of Interest: None declared
lated positivity thresholds, accounting for age, gender and Hb level at previous
tests, among people undergoing their third screening.
RESULTS: The PPV, the NNScope and the DR for AAd and CRC, stratified by
subjects age at screening, are presented in table 1. The PPV for advanced neo-
plasia (AAd CRC) is higher among older people at the initial (p0.047), but
not at subsequent screening (p0.076). The DR is higher among men than
among women both at the initial and at subsequent tests. Setting the positivity
cut-off at 200 ng/ml for women with 0-49 ng Hb/ml at the 2 previous FITs, and
for men with no Hb at the initial FIT and 0-49 ng Hb/ml at the second FIT,
would result in a 26% reduction in the colonoscopy (TC) workload and in a 17%
A102
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
GENETIC INFORMATION IN UPPER GI CANCER: ALREADY CLINICALLY RELEVANT?
HALL L/M_____________________
OP321 A NOVEL TUMOR SUPPRESSOR MDGA2 ACTIVATES
ANTI-TUMOR DMAP1/ATM/P53 PATHWAY AND IS AN
INDEPENDENT PROGNOSTIC FACTOR IN GASTRIC CANCER
K. Wang1,*, Q. Liang1, X. Li1, H.T. Ho Tsoi1, E.S. Chu1, J. Shen1, M. Y. GO1,
J.J. Sung1, J. Yu1
1
Institute of Digestive Disease and Department of Medicine and Therapeutics,
State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health
Sciences, Shenzhen Research Institute, The Chinese University of Hong Kong,
Hong Kong, Hong Kong
Contact E-mail Address: junyu@cuhk.edu.hk
INTRODUCTION: By using genome-wide promoter methylation screening
assay, we identified that MDGA2 (MAM domain containing glycosylphospha-
tidylinositol anchor 2) was preferentially methylated in gastric cancer (GC).
However, the role of MDGA2 in tumorigenesis remains unexplored.
AIMS & METHODS: This study aimed to elucidate the epigenetic regulation,
clinical significance, biological function and molecular mechanism of MDGA2 in
GC. Promoter methylation was evaluated by bisulfite genomic sequencing and
combined bisulfite restriction analysis. Gene expression was examined by RT-
PCR, western blot and immunohistochemistry. The biological functions of
MDGA2 were examined by MTS assay, colony formation, flowcytometry, Ki-
67 and Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)
stainings in vitro and in vivo tumorigenicity analysis. The molecular mechanism
of MDGA2 was explored by promoter-luciferase activity assay, cDNA array, etc.
RESULTS: MDGA2 was silenced in 90.9% (10/11) GC cell lines, which was
closely related to promoter methylation. After treatment with demethylation
agent, expression of MDGA2 was restored in silenced GC cells. MDGA2 expres-
sion was also significantly lower in gastric tumors as compared to their adjacent
normal tissues (P0.001). Importantly, MDGA2 methylation was detected in
62.4% (136/218) of primary gastric tumors. Multivariate analysis revealed that
MDGA2 methylation is an independent factor for poor survival in GC patients
[P0.005, RR1.85 (1.21-2.84)]. Kaplan-Meier survival curves showed that
MDGA2 methylation was signiEcantly associated with shorter survival of GC
patients (1.59y vs. 4.87y, median; P0.001).
We further tested the biological function of MDGA2. Re-expression of MDGA2
in GC cell lines (AGS and BGC823) significantly suppressed cell viability,
reduced cell proliferation, inhibited clonogenicity, caused cell cycle arrest at G1
phase and induced cell apoptosis. On the other hand, knockdown of MDGA2
promoted cell growth by accelerating cell cycle progress and reducing apoptosis
in MKN1 GC cells. In vivo growth of BGC823 GC cells was markedly inhibited
by MDGA2 transfection in both subcutaneous (P50.001) and orthotopic
(P50.001) xenograft models in nude mice.
The molecular mechanisms of the tumor suppressive effect of MDGA2 were
further characterized. We demonstrated that MDGA2 activated p53 pathway
by p53-luciferase reporter assay. In keeping with this, downstream mediators
of p53 signaling were also upregulated by MDGA2, including p63, p73, caspase
9, p21 and ATM. Moreover, MDGA2 directly upregulated and binded to
DMAP1 (an essential regulator of ATM activity) as evidenced by mass spectro-
metry analysis of immunoprecipitation products and pull-down assays using
MDGA2 and DMAP1 recombinant proteins. MDGA2-DMAP1 subsequently
activated ATM and p53, followed by upregulation/activation of p53 signaling
mediators. Activating of DMAP1/ATM/p53 signaling pathway contributes to
the suppression of tumor growth in gastric cancer.
CONCLUSION: MDGA2 is a novel tumor suppressor inactivated by promoter
methylation in gastric cancer. MDGA2 methylation is significantly associated
with shorter survival of GC patients. MDGA2 exhibits tumor suppressive effect
by directly upregulating DMAP1 to stimulate ATM/p53 signaling pathway.
Disclosure of Interest: None declared
OP322 BIOMARKER ASSESSMENT FROM EUS GUIDED BIOPSY
PREDICTS OUTCOMES AND TREATMENT IN PANCREATIC
CANCER
N.Q. Nguyen1,*, A. Ruzskiewicz2, D. Chang3, C.-P. Tan4, J. Bambrick1,
A. Biankin5
1
Department of Gastroenterology & Hepatology, 2Department of Pathology, Royal
Adelaide Hospital, Adelaide, 3Pancreatic Research Group, Garvan Institute,
Darlinghurst, 4Department of Surgery, Royal Adelaide Hospital, 5Pancreatic
Research Group, Garvan Institute, Adelaide, Australia
Contact E-mail Address: quocnam.nguyen@health.sa.gov.au
INTRODUCTION: Current methods of pre-operative predicting outcome of
pancreatic cancer and related pancreatectomy are limited. Although several prog-
nostic biomarkers, including S100A2 and S100A4, are associated with poor out-
come, currently these can only be assessed in operatively resected specimens. The
amount of tissue from EUS guided fine needle aspiration is often insufficient for
biomarker assessment. Procore needles aim to acquire larger volumes of tissue
that may be suitable for pre-operative biomarker assessment.
AIMS & METHODS: (i) To evaluated the feasibility of S100A2 and S100A4
assessment in EUS guided biopsy specimens using the Procore needle, and (ii) to
evaluate the relationship of these biomarkers with outcomes. METHODS:
Clinico-pathological, treatment and survival data from 138 patients (702yrs;
70M:68F) with pancreatic ductal adenocarcinoma (PDAC) were prospectively
acquired. All subjects had EUS guided biopsy with a 22G Procore needle and
cell-block preparation was performed. Sections of cell-block material were
assessed for S100A2 and S100A4 protein expression using immunohistochemistry
(IHC).
United European Gastroenterology Journal 2(5S)
RESULTS: Pre-operative biomarker assessment from EUS acquired specimens
was possible in 92% (127/138) of patients. IHC stain for the biomarkers was
positive in 59 (46%) patients and co-expressed 31 (56%) patients.
Pancreatectomy was performed in 28 (22%) patients. Overall median survival
was 11 (5-16) months with patients who had (i) S100A2/A4 -ve PDAC on EUS (8
vs. 20 months, P50.0001) and (ii) pancreatic resection (18 vs. 12 months,
P0.002) had a significantly better median survival. Of patients who had pan-
createctomy, patients with S100A2/A4 expressing PDAC had shorter survival
(12.0 vs. 22.0 months; P0.02). In the non-surgical treated patients, the presence
of S100A2/A4 was also associated with poorer survival (7 vs. 19.9 months;
P50001). Amongst patients with S100A2/A4 expressing PDAC, pancreatect-
omy, however, led to a small survival benefit compared with those with non-
surgical treatment (12 vs. 7 months, P0.03). Chemotherapy was given to 86
(68%) patients (3 neo-adjuvant, 17 adjuvant and 66 palliative). Amongst patients
who received palliative chemotherapy, patients who had S100A2/A4 expressing
PDAC had significantly poorer survival (7 vs. 22 months, P50.0001), and were
similar to those who had no treatment (vs. 7months, P0.47).
CONCLUSION: Biomarker assessment from EUS guided biopsy specimens is
feasible and successful in over 90% of cases. In patients with PDAC, the presence
of S100A2 and S100A4 expression predicts both survival, and influences the
responses to both pancreatectomy and palliative chemotherapy. These findings
support the potentially important role of pre-operative EUS guided biopsy for
biomarker determination and guide clinical decision-making, particularly with
regard to selection for operative resection of PDAC.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
DIAGNOSIS AND TREATMENT OF CONSTIPATION AND FAECAL INCONTINENCE
HALL R_____________________
OP323 THE BALLOON EXPULSION TEST: REPRODUCIBILITY AND
AGREEMENT WITH RECTAL MANOMETRY AND PELVIC FLOOR
EMG
G. Chiarioni1,2,*, S.M. Kim2, W.E. Whitehead2
1
Gastroenterology, Azienda Ospedaliera Universitaria Integrata Verona,
VERONA, Italy, 2UNC Center for Functional GI and Motility Disorders and
Division of Gastroenterology and Hepatology, University of North Carolina at
Chapel Hill, NC, Chapel Hill, NC, United States
Contact E-mail Address: chiarioni@tin.it
INTRODUCTION: The balloon evacuation test (BET) measures the time
required to evacuate a 50 ml water-filled balloon. We aimed to assess reprodu-
cibility of the BET, determine the upper limit of normal, and assess concordance
with anorectal manometry (ARM) and pelvic floor surface electromyography
(EMG).
AIMS & METHODS: BET was tested in 286 chronically constipated patients
before and after 30-days of conservative treatment at a tertiary gastroenterology
clinic in Italy. BET was performed with a 16 FR Foley catheter filled with 50 ml
of tepid water. Up to five minutes were allowed to evacuate the balloon while
sitting on a conventional toilet in a private bathroom. BET was tested twice, 7-
days apart, in 40 healthy controls recruited among hospital personnel and Med
students. The 238 constipated patients who did not respond to conservative
therapy (increased fluids and fiber, laxatives no more than twice a week) received
an ARM, EMG, and digital rectal examination (DRE). Forty-seven patients with
conflicting ARM and BET results received defecography.
RESULTS: Patients averaged 44 years and 91% were females; controls averaged
38 years and 92% were females. Balloon evacuation was achieved within 1 min
by 37/40 healthy controls, but 3 (8%) required 1-2 minutes. In constipated
patients, 148/286 passed the balloon within 5 minutes including 110 in 1
minute, 35 in 1-2 minutes, and 3 in 2-5 minutes. BET showed perfect reprodu-
cibility in 280/286 (98%) constipated patients when a BET interval over two
minutes is defined as abnormal. Agreement between BET and ARM for dyssy-
nergia was 78% and agreement between BET and EMG was 83%. In 32 patients,
BET was abnormal but ARM was normal, and 31 of these cases showed inade-
quate straining (n11) or anatomical defects which might explain failed BET
(n20).
CONCLUSION: The optimal upper limit of normal for the BET is two minutes.
Test re-test reproducibility is excellent (98%). The BET shows good agreement
with ARM and EMG. A normal BET almost rule out a disordered defecation
syndrome.
Disclosure of Interest: None declared
OP324 ENDOFLIP: A NEW DIAGNOSTIC MODALITY FOR
MEASURING ANAL CANAL FUNCTION
L. Kumar1,*, F. Zaman1, A. Emmanuel1
1
GI Physiology Unit, UCLH, London, United Kingdom
INTRODUCTION: Anorectal manometry is the most well established and com-
monly used technique for investigating anorectal function but despite its wide-
spread use, it has well established limitations. Functional Lumen Imaging Probe
(FLIP) is a novel technique for measuring anorectal function. Its repeatability
and validity of in anorectal studies has already been established. This study
looked at its utility in establishing dynamic properties of anal canal with and
without rectal distension, in particular to demonstrate the sampling reflex, the
poorly understood physiological mechanism of which remains uncertain.
AIMS & METHODS: To establish dynamic and non-homogenous properties of
the anal canal in healthy volunteers using EndoFLIP. Demonstrate the segmental
differences in anal canal. Methods: 19 healthy volunteers were recruited (9
females), mean age 34 (20-75). Purpose built catheters incorporating rectal and
United European Gastroenterology Journal 2(5S)
anal canal balloon were used. Appropriate sized catheter anal canal balloon (2, 3
and 4cm long) corresponding to the length of subjects anal canal (based on
manometry) was used. 3 cross sectional area (CSA) readings were obtained
with 2cm balloon, 5 with 3cm and 10 with 4cm balloon. In order to obtain
meaningful results, the anal canal balloon was required to be touching the
lumen wall and this was achieved by using different inflation volumes, according
to the balloon size, determined by analysing the pre-study test results. Rectoanal
inhibition reflex (RAIR) was recorded by inflating the rectal balloon while
recording the anal canal CSAs with the anal canal balloon. Participants under-
went standard water-perfused anal manometry followed by FLIP on the same
day. The anal canal was divided into distal, mid and proximal parts based on
anatomy and preliminary data analysis. Paired t-test was done comparing CSA in
the following segments (across all the balloon volumes), distal with mid anal
canal, mid with proximal anal canal and distal with upper anal canal. The para-
meters looked at included CSA at rest, squeeze and during RAIR.
RESULTS: Statistically significant difference was noted in between CSAs of the
three segments both at rest and squeeze (Table 1). In all the three phases of rest,
squeeze and RAIR, distal segment had the lowest mean CSA followed by mid
and proximal segment respectively (Table 1). Analysis of RAIR revealed a sig-
nificant difference in CSAs between proximal and distal segments (p 5.0001)
but not between mid and the proximal segments (p .351).
Segmental cross sectional areas
Rest Squeeze RAIR
Mean CSA Mean CSA Mean CSA
Anal Canal Segment (in mm)(SD) (in mm)(SD) (in mm)(SD)
Distal 13.27 (3.19) 12.04 (2.55) 12.37 (3.38)
Mid 15.25 (3.37) 14.40 (3.14) 13.85 (3.88)
Proximal 15.44 (3.97) 15.18 (3.96) 14.03 (4.14)
p values for intra-segmental comparison of CSA
Measured phase Distal - M id M id - Proximal Distal - Proximal
Resting .000 .013 .000
Squeeze .023 .000 .000
CONCLUSION: EndoFLIP allows detailed segmental description of the anal
canal. CSA differences in three segments of anal canal clearly reveal its dynamic
nature. The distal-most part of anal canal has the lowest distension followed by
mid and proximal part, both at rest and squeeze. This segmental difference in the
anal profile demonstrates the anatomical and physiological basis of the sampling
reflex.
Disclosure of Interest: None declared
OP325 EXPLORING THE POTENTIAL OF GENE THERAPY FOR
HIRSCHSPRUNG DISEASE: STUDIES IN THE MIRET51 MOUSE
MODEL
D. Natarajan1,2,*, J. Dattani3, A.J. Burns1, N. Thapar1,4, V. Pachnis2
1
UCL Institute of Child Health, 2National Institute for Medical Research, London,
3
Department of Mathematics, University of Bath, Bath, 4Great Ormond Street
Hospital, London, United Kingdom
Contact E-mail Address: d.natarajan@ucl.ac.uk
INTRODUCTION: Hirschsprung disease (HSCR) affects 1:4500 births and is
characterized by aganglionosis of the distal bowel, caused by a failure of devel-
opment of the enteric nervous system (ENS) from neural crest cells (NCC). The
RET receptor tyrosine kinase is part of a key signalling pathway for ENS devel-
opment and is implicated in the majority of HSCR cases. In mice and humans,
RET is expressed as two main isoforms, Ret51 and Ret9. Mice expressing only the
Ret51 isoform (monoisoformic-miRet51) have distal colon aganglionosis and are
an established model of human HSCR.
AIMS & METHODS: (i) Characterise ENS development in miRet51 mice in
terms of NCC migration, proliferation and neuronal differentiation by lineage
tracing with YFP. (ii) Label and isolate ENS progenitor cells (EPCs) from
miRet51 and wild type animals using a GFP retroviral vector. (iii) Perform genetic
rescue of miRet51 EPCs by infecting with a retrovirus carrying a Ret9-GFP
cassette.
To label all NCC with YFP, miRet51 mice were crossed with
Rosa26YFPstopWnt1cre mice. Immunolabelling of whole guts and sections of
embryos from miRet51 and control littermates was performed using GFP (to
identify YFP cells) plus antibodies to investigate migration, proliferation
(BrdU) and neuronal differentiation (HuC/D). To generate EPCs, cells were
infected with a GFP retroviral vector and positive cells were isolated via fluor-
escent activated cell sorting (FACS). To rescue the miRet51 defect, cells from
miRet51 gut were infected with a Ret9-GFP retrovirus and neuronal differentia-
tion studied.
RESULTS: Migration of NCC in miRet51 guts was impaired compared to con-
trols at all stages in development as determined by immunolabelling of whole gut
and embryo sections. Proliferation was reduced in miRet51 cells compared to
control littermates both in vitro and in vivo. At E10.5, 6.80.9% miRet51 cells
divided versus 19.050.9% in controls; p50.05. At E14.5, proliferation was
13.953.51% in miRet51 cells versus 25.53.78% in controls; n6, p50.05.
Neuronal differentiation and axonal outgrowth, in vivo, was reduced throughout
development. At E18.5, 17.94% of YFP cells were positive for HuC/D in
miRet51 versus 36.110% in control embryos; n4, p50.05. EPCs isolated from
miRet51 guts also displayed reduced neuronal differentiation in vitro compared to
controls (5.451.4% in miRet51 and 16.94.7% in controls; p50.05). This def-
icit was rescued when miRet51 EPCs were infected with a retrovirus expressing
A103
Ret9-GFP. Here, the percentage of neurons changed from 5.451.4% in miRet51
to 17.34.4% in miRet51;Ret9 EPCs versus 21.63.5% in control EPCs; p0.06.
CONCLUSION: Our results indicate that expression of both RET isoforms,
which underpins normal RET activity, is required for the migration, proliferation
and differentiation of NCC ultimately leading to the formation of a functional
ENS. EPCs from miRet51 animals can be isolated and most importantly, the
neuronal differentiation deficit in these cells restored by introducing the Ret9
isoform into miRet51 cells. The isolation of EPCs and the ability to manipulate
and rescue key HSCR genes such as RET paves the way for generating novel
therapies for gut motility disorders.
Disclosure of Interest: None declared
OP326 LIBERTAS: A MULTICENTRE, PHASE II, DOUBLE BLIND,
RANDOMISED, PLACEBO CONTROLLED INVESTIGATION TO
EVALUATE THE EFFICACY, SAFETY AND TOLERABILITY OF
LOCALLY APPLIED NRL001 IN PATIENTS WITH FAECAL
INCONTINENCE
D.G. Walker1,*, D. Jones1, J. Pilot1, R. Ng Kwet Shing1
1
Norgine Limited, Uxbridge, United Kingdom
Contact E-mail Address: DWalker@norgine.com
INTRODUCTION: Faecal incontinence (FI) affects up to 8% of the general
population, rising to c.50% among nursing home residents. FI is under-reported
and can have devastating effects on quality of life (QoL). Although non placebo-
controlled studies have shown a reduction in Wexner score, FI episodes and the
FIQOL, little is available to inform appropriate management strategies as few
well-designed, placebo-controlled clinical trials of FI treatment have been
conducted.
AIMS & METHODS: The aim of Libertas, a robustly-designed, multicentre,
Phase II, double-blind, randomised, placebo-controlled, parallel-group study
was to investigate the efficacy and safety of 1-adrenoceptor agonist NRL001
(1R,2S-methoxamine hydrochloride) in the treatment of non-retentive FI
(ClinicalTrials.gov: NCT01656720). Patient recruitment was across 55
European study centres. Patients with FI were randomised into four groups
(approximately n110 each) to receive once-daily self-administered doses of
NRL001 (5mg, 7.5mg, 10mg or placebo suppositories) for 8 weeks. Libertas
primary objective was to assess the impact of NRL001 versus placebo on severity
and frequency of FI episodes (Wexner scores) at 4 weeks. Key secondary out-
comes for NRL001 versus placebo include: efficacy at 8 weeks (Wexner score and
FI episodes); safety and tolerability; quality of life (FIQoL) following 4 and 8
weeks therapy; and overall patient satisfaction with the treatment.
RESULTS: Patients (n466) were randomised evenly into each of the 4 arms.
Patient demographics were broadly similar in each group: 84% female, mean age
62 (range 19-91) years, mean study entry score ranged from 12.9 to 13.3 points on
the Wexner score. There was a 2.4-3.0 point reduction from baseline in Wexner
score at Week 4 in all four arms with a non-significant treatment effect
(p0.6867). There was a 3.1-3.6 point reduction from baseline in Wexner score
at Week 8 in all four arms with a non-significant treatment effect (p0.5005).
There was a reduction in FI episodes of between 4.8-7.3 episodes per week at
Week 8 with a non-significant treatment effect (p0.5278). NRL001 tolerability
profile in each of the active treatment arms was comparable to placebo. A similar
increase in FIQOL was seen at week 8 in each arm. Patient satisfaction was high
in all arms; 74.7-85.6% of patients would choose to take a suppository of either
NRL001 or placebo again.
CONCLUSION: Although NRL001 was safe and effective with improvements in
both clinical outcome scores and QoL at the end of 8 weeks treatment compared
with baseline, this improvement was also observed in the placebo arm. This
outcome is of interest to the scientific community in that it demonstrates for
the first time in a robust study design that there is a significant placebo response
in this patient population that should be considered in all future study designs
investigating FI.
Disclosure of Interest: D. Walker Other: Employee of Norgine, D. Jones Other:
Employee of Norgine, J. Pilot Other: Employee of Norgine, R. Ng Kwet Shing
Other: Employee of Norgine
OP327 PRELIMINARY SIGNIFICANT FINDINGS FROM A
RANDOMISED CONTROL TRIAL OF POSTERIOR TIBIAL NERVE
STIMULATION IN SYSTEMIC SCLEROSIS ASSOCIATED FAECAL
INCONTINENCE
S.K. Butt1,*, A. Alam1, A. Raeburn1, J. Liwanag1, V. H. Ong2, C.P. Denton2,
C.D. Murray3, N. Zarate-Lopez1, A. Emmanuel1
1
Gastroenterology, UCLH, 2Rheumatology, 3Gastroenterology, Royal Free
Hospital, London, United Kingdom
Contact E-mail Address: s.butt@ucl.ac.uk
INTRODUCTION: The gastrointestinal tract is affected in up to 90% of
Systemic Sclerosis (SSc) patients with faecal incontinence (FI) being reported
in up to 38%. Passive faecal incontinence secondary to internal anal sphincter
atrophy is the characteristic finding. We have shown that neuropathic changes
are implicated in SSc patients with FI and sacral nerve stimulation has emerged
as a potentially beneficial therapy in SSc. However this is expensive, invasive, not
widely available and we have shown that medium term efficacy is poor. Posterior
tibial nerve stimulation (PTNS) is a potential alternative to modulate the sacral
plexus indirectly, with none of these disadvantages. This is the preliminary data
on a randomized placebo controlled trial of PTNS versus sham PTNS to deter-
mine if nerve modulation is an effective treatment in SSc associated FI.
AIMS & METHODS: We commenced a prospective randomised single-blind
study of SSc patients with FI in February 2013 from a specialist Scleroderma
unit. Baseline symptom scoring (bowel diary, Wexner), manometry and endoanal
A104
ultrasound were completed prior to randomization to PTNS or sham. PTNS was
administered conventionally, by insertion of an acupuncture needle according to
anatomical landmarks, connected to an electrical stimulator. Sham PTNS was
administered in identical fashion but the PTNS surface electrode was not con-
nected and instead separate TENS surface electrodes were connected to a TENS
unit. Each patient underwent blinded intervention for 30 minute periods, once a
week for 12 weeks. The primary endpoints were the percentage reduction in
faecal incontinence episodes and change in Wexner incontinence scores.
RESULTS: A total of 13 SSc patients (11 f), mean age 61 (36-72) completed the
trial by October 2013. Of these 6 (5 f) underwent PTNS and 7 (6 f) patients
underwent sham stimulation. All PTNS patients showed a reduction (5-100%)
in the number of FI episodes in comparison to 0 sham patients at 12 weeks
(p50.01 (CI -81.49-14.34)). This matched an improvement in mean Wexner
scores from baseline to treatment end (14.8 to 10.8 vs 13.4 to 13.6, true vs
sham respectively, p0.03.
CONCLUSION: This pilot data is demonstrating significant effects of PTNS in
Scleroderma-associated FI. We present this significant initial data but anticipate
having at least 25 completed patients by October 2014.
Disclosure of Interest: None declared
OP328 TREATMENT OF SLOW-TRANSIT CONSTIPATION (STC) IN
CHILDREN WITH HOME-BASED TRANSCUTANEOUS
ELECTRICAL STIMULATION (TES)
B.R. Southwell1,2,*, Y.-I. Yik2,3, J. Jordan-Ely1, K. Dobson1, J.M. Hutson1,4
1
Surgical Research, Murdoch Childrens Res Inst, 2Dept Paediatrics, University of
Melbourne, Melbourne, Australia, 3Department of General Surgery Faculty of
Medicine, University of Malaya, Kuala Lumpur, Malaysia, 4Dept of Urology,
Royal Childrens Hospital, Melbourne, Australia
Contact E-mail Address: Bridget.southwell@mcri.edu.au
INTRODUCTION: Slow-transit constipation (STC) is generally resistant to
medical treatments. We have shown that transcutaneous electrical stimulation
(TES) using interferential current given by physiotherapists, sped up colonic
transit 1, reduced soiling 2 and increased defecation 3. Battery-operated machines
allow stimulation at home 3.
AIMS & METHODS: To determine if TES administered at home can improve
STC in children. We tested 2 types of treatment. Group 1) if TES added onto
existing treatment and administered daily at home can improve defecation, soil-
ing, abdominal pain and laxative use in STC children. Group 2) if TES combined
with selected laxatives and bowel education was more effective than TES alone.
Children with treatmentresistant constipation with no palpable faecaloma who
presented to a surgical unit at a tertiary childrens hospital were sent for radio-
nuclear colonic transit study 4. Children with slow motility in the proximal colon
were diagnosed with STC. Parents were trained to give TES. Four sticky electro-
des (4cm x 4cm) were placed, 2 on the belly and 2 on the back at the umbilical
level and connected so currents crossed right front to left back and left front to
right back. A beating interferential current (4kHz carrier frequency, 80-160Hz
beat frequency, 30mAmps3) was given 1 hr/day. Daily continence diaries and
laxative use were recorded for 1 mth before and during TES. Defecation, soiling
and laxative use were compared before (pre) and after 2-6 mth stimulation (post).
In Group 1, 62 children (23 male; 2-16yrs) had TES added onto existing laxatives.
In Group 2, 33 children (17 males, 4-16yrs) were educated on diet and water
intake, best time for toileting and correct toilet posture, transferred to low doses
of polyethylene glycol (PEG) and sodium picosulphate laxatives, then had TES
for 2-3mths.
RESULTS: Gr 1: At the start, 56/62 had 5 3 bowel actions (BA)/wk. 6/62
children (10%) had no improvement. Defecation frequency increased in 54/56
from 1.61.6 to 3.51.9 BA/wk, meanSD, p50.05) with 32/54 (59%) patients
increased 3 BA/wk). Soiling reduced in 56/57 (4.62.4 to 0.71.1 days soiling/
wk, p50.001). Urge to defecate started as nil or weak and developed to moder-
ate/strong in half. Laxative use reduced (15/60 (25%) stopped & 30/60 (50%)
reduced). Gr 2: All started with 53 BA/week. 32/33 (97%) increased to 43 BA/
wk with 29/33 (88%) to 7 BA/wk. Stool output improved from 1 (0-2) cups/wk to
7 (2-10) cups/wk (p50.001). Mean number of soiling episodes decreased from 5
to 0 episodes/wk (p50.001).
CONCLUSION: TES is a painless non invasive treatment and can be adminis-
tered at home. In treatment-resistant patients presenting to a surgeon, home-
based TES added onto existing treatment increased defecation into the normal
range in half. With the addition of selected oral laxatives and education on diet
and toileting prior to TES improvement occurred in more patients, was bigger
improvement and was more rapid than with TES alone.
REFERENCES
1. Clarke MC, et al. J Pediatr Surg 2009; 44: 408-412.
2. Leong LC, et al. J Pediatr Surg 2011; 46: 2309-2312.
3. Ismail KA, et al. J Pediatr Surg 2009; 44: 2388-2392.
4. Sutcliffe JR, et al. Pediatr Surg Int 2009; 25: 465-472.
Disclosure of Interest: B. Southwell Consultancy for: GI Therapies, Other:
Product supplied with no restrictionsby Norgine, Inventor of new TES device
to treat constipation in development by GI Therapies, Y.-I. Yik: none, J. Jordan-
Ely: none, K. Dobson: none, J. Hutson Other: Inventor of new TES device to
treat constipation in development by GI Therapies
United European Gastroenterology Journal 2(5S)
OP329 COMPARISON OF THE EFFECT OF POLYETHYLENE GLYCOL
3350, PRUCALOPRIDE, BISACODYL AND PLACEBO ON COLONIC
MOTILITY ASSESSED WITH INTRALUMINAL COLONIC HIGH-
RESOLUTION MANOMETRY IN HEALTHY SUBJECTS: THE
QUANTITATIVE ANALYSIS
M. Corsetti1,*, G. Pagliaro1, E. Deloose1, I. Demedts1, A. Gevers1, L.
Van Oudenhove1, J. Tack1
1
TARGID, KULEUVEN, Leuven, Belgium
Contact E-mail Address: maura.corsetti@med.kuleuven.be
INTRODUCTION: PEG, bisacodyl and prucalopride were demonstrated to be
superior to placebo for treatment of chronic constipation (Ford AC 2011).
Impaired colonic propulsive motility is considered a major pathophysiological
mechanism underlying constipation. The effect of these treatments on colonic
motility has never been directly compared.
AIMS & METHODS: To compare the effect of PEG, prucalopride, bisacodyl
and placebo on colonic motility and on number of high amplitude contractions
(HAPCs) assessed with high resolution manometry (HRM).
In 10 volunteers (293 ys) four colonic HRM studies were performed, at least 10
days apart, after an overnight fast and tap water enema preparation. During
colonoscopy under conscious sedation the HRM catheter (40 solid state sensors,
2.5 cm spaced) was advanced as far as possible and clipped to the mucosa. After
90 min of basal recording, PEG 13.8 mg, prucalopride 2 mg, bisacodyl 10 mg or
placebo were administered orally in a single-blind, randomized, cross-over fash-
ion, and the recording continued for 180 min before and after a standardized
meal. During the meal, in case of PEG, a second dose (13.8 mg) was adminis-
tered. Colonic motility index (MI; averaged every 15 min in the right and left
colon and in the rectum, and expressed as ratio of the baseline value) of four
periods (180 minutes before meal, first, second and third hour after the meal) was
compared between treatments by means of a mixed models analysis with post-
hoc t-tests and Bonferroni correction. The characteristics of HAPCs were com-
pared by means of Students t test. Data are meanSEM.
RESULTS: The catheter was clipped to the right colon mucosa in 23/40 studies,
and at least to the splenic flexure in the remaining cases, with no difference
according to treatment arm. Baseline MI did not differ between treatments in
the right (2.60.36 for PEG, 3.60.72 for prucalopride, 3.60.87 for bisacodyl,
3.90.26 for placebo, NS), left colon (2.70.49, 3.60.49, 3.20.74, 3.60.41,
NS) and rectum (2.70.53, 4.10.79, 3.20.81, 3.80.50, NS). At mixed models
analysis, a significant treatment effect was found in each region of the colon (all
P0.001). In the right colon, the ratio of the baseline value was significantly
higher after PEG (P0.01) and borderline significant after prucalopride
(P0.05) as compared to placebo for all the time points after the meal. In the
left colon, the ratio was significantly higher after PEG than placebo for all the
time points after meal (P0.01). In the rectum, the ratio was significantly higher
after PEG than placebo during the first hour after meal (P0.01). Bisacodyl
induced HAPCs in a significantly higher number of subjects as compared to
prucalopride (9 vs. 3, Fishers exact test P 0.01), PEG (9 vs. 1, P0.001) and
placebo (9 vs 1, P 0.001). The amplitude of HAPCs was significantly higher
after prucalopride than bisacodyl (29214 vs 20012 mm Hg, P 0.01) while
duration, length and velocity did not differ between treatments.
CONCLUSION: In man, PEG, prucalopride and bisacodyl have distinct effects
on colonic phasic activity. While PEG mainly increases phasic activity, bisacodyl
mainly induces HAPCs. Prucalopride has no major effect on colonic phasic
activity but increases HAPCs amplitude.
Disclosure of Interest: None declared
OP330 ENTERIC NEUROPROTECTION IN HUMAN NEURONS:
EFFECTS MEDIATED BY PRUCALOPRIDE, A SEROTONINERGIC
FULL 5-HT4 SELECTIVE AGONIST
F. Bianco1,*, E. Bonora1, M. Vargiolu1, F. Giancola1, N. Thapar2,
D. Natarajan2, V. Stanghellini1, M. Seri1, R. De Giorgio1
1
DIMEC, University of Bologna, BOLOGNA, Italy, 2Dept of Neurosciences &
Mental Health, UCL Institute of Child Health, London, United Kingdom
Contact E-mail Address: franc.bianco19@gmail.com
INTRODUCTION: Serotonin (5-hydroxytryptamine, 5-HT) and related trans-
porters and receptors are involved in a wide array of digestive functions and
disorders. Specifically, 5-HT4 receptors play a major role in intestinal peristalsis
and among agonists, prucalopride (a full 5-HT4 agonist) is an effective entero-
kinetic agent in the treatment of chronic constipation. In addition, 5-HT4 recep-
tor agonists may evoke enteric neuroprotection. We tested whether prucalopride
exerts protective effects on enteric neuron cell cultures exposed to damaging
factors, i.e. oxidative agents e.g. H2O2. Specifically, we aimed to: i) evaluate
the expression and selective identification of 5-HT4 receptors in human enteric
neurons; and ii) define the 5-HT4 receptor-mediated neuroprotection in human
cell cultures by assessing the anti-apoptotic effect exerted by different doses of
prucalopride.
AIMS & METHODS: Human enteric neurospheres were generated from human
gut tissue*; cells from neurospheres were seeded onto 35-mm Petri dishes coated
with fibronectin (2 mg/cm2) and maintained in Dulbeccos modified Eagle
medium (DMEM)/F-12 medium. Western blotting (WB) analysis were per-
formed using the following primary antibodies: anti-5-HT4 receptor (Abcam,
1:200), anti-HuC/D (Invitrogen, 1:200; a paneuronal marker), anti p75_NTR
(Thermoscientific, 1:200) and anti-vinculin (Sigma-Aldrich, 1:50.000). In addi-
tion to neurosphere-derived cells, the expression of the 5HT4 receptor was also
evaluated in the following cell lines: human embryonic kidney (HEK293); mouse
neural crest-derived N2A; and human neuroblastoma cell line (SH-SY5Y).
SulfoRhodamine B (SRB) assay was used to determine the neuronal survival
of SH-SY5Y cells following H2O2 (200 mM for 30 min) exposure and the neuro-
protective effect exerted by prucalopride on these cells. GR 113808 (10 nM for 30
United European Gastroenterology Journal 2(5S)
min) was applied to SH-SY5Y cells to reverse the protective effect of
prucalopride.
RESULTS: WB analysis demonstrated that all cell lines as well as cells from
human neurospheres expressed the 5HT4 receptor. SRB assay showed that SH-
SY5Y cells previously exposed to prucalopride at different concentrations (10,
100 pM; 1, 10 and 100 nM; 100 mM; 1 and 20 mM) were protected by the noxious
effect induced by H2O2. Specifically, prucalopride at 10 pM to 1 nM concentra-
tions exhibited the best neuroprotective effect compared to neurons exposed to
H2O2 only (476.50.1% of neuronal survival vs. 33.30.1%, respectively)
(P50.05). Prucalopride concentrations applied alone to SH-SY5Y neurons did
not show any toxicity and resulted in 910.1% of neuronal survival. In contrast,
the neuroprotective effect of prucalopride was reversed by the 5-HT4 antagonists
GR 113808 (10nM for 30 min).
CONCLUSION: Prucalopride, a 5-HT4 receptor full agonist, mediated signifi-
cant neuroprotection against oxidative-mediated proapoptotic effects. These
results may pave the way to novel application of 5-HT4 agonists as neuroprotec-
tive agents in enteric neuropathies.
REFERENCES
Metzger et al. Gastroenterol 2009
Disclosure of Interest: None declared
OP331 INTEREST IN A MORPHOLOGICAL EVALUATION OF
INTERSTITIAL CELLS OF CAJAL (ICC) IN PATIENTS WITH
SEVERE COLONIC INERTIA (SCI) REQUIRING SUBTOTAL
COLECTOMY. A CASE-CONTROL STUDY
M. Cohen1,*, D. Cazals Hatem2, B. Coffin3
1
Gastroenterology, AP HP Hopital Louis Mourier, Colombes, 2Pathology, Hopital
Beaujon, Clichy, 3Gastroenterology, APHP Hopital Louis Mourier, Colombes,
France
Contact E-mail Address: benoit.coffin@lmr.aphp.fr
INTRODUCTION: Subtotal colectomy is the last resort treatment in patients
with SCI refractory to a well-conducted and optimized treatment. In this condi-
tion, some studies reported an ICC hypoplasia by using a semi-quantitative
analysis. The aims of this case-control study were (1) to determine the best
technique to quantify colonic ICC, (2) to search a relationship between the
number of ICC and the severity of constipation and (3) to evaluate functional
results 1-year after colectomy
AIMS & METHODS: Clinical and pathological data from patients with SCI
having colectomy with ileo-rectal anastomosis in 3 academic hospitals have been
collected. Quantification of ICC immunostained with CD117 was performed in 3
colonic segments in patients and in sex and age matched controls by 2 indepen-
dent observers using a semi-quantitative technique (muscularis propria on ten
high power field (HPF)) according to Wang et al, followed by a morphometric
quantitative technique (% of ICC/10 HPF). ICC hypoplasia was defined as 57
ICC/HPF using Wang et al method or as a mean percentage of ICC 5 1 % using
morphometry. Functional results were evaluated 1-year after colectomy.
RESULTS: Over a 10-year period, 20 patients (female: 85 %; mean age: 46.2 
11.6 years) had a colectomy for SCI. Constipation had been present since child-
hood or adolescence in 76.4 % of patients. Mean number of stool was 0.9  0.4/
week with optimized treatment and 45 % of patients have been hospitalized at
least once for colonic occlusion related to fecaloma. All patients were in opti-
mized treatment failure. Mean colonic transit time (CTT) was 128.2  11.6 h,
ano-rectal manometry did not show megarectum and small bowel manometry
was normal in all patients. According to Wang et al method, 30 % of patients (n
6) display ICC hypoplasia and all controls had normal ICC. Using morpho-
metry, the percentage of colonic ICC was significantly decreased in patients vs.
controls (1.04  0.16 % vs. 1.97%  0.21 %; P 0.005) with no differences
between the 3 colonic segments (P 0.25) and 60 % of patients (n12) had ICC
hypoplasia 5 1% vs. 20 % (n 4) of controls (P 0.009). ICC hypoplasia was
not significantly associated with CTT or occlusion related to fecaloma. After a
one-year follow-up, 17 patients (85 %) were satisfied with at least 1 stool/d, and 3
still had constipation.
CONCLUSION: In patients with severe colonic inertia requiring surgery, mor-
phometric analysis is more sensitive than semi-quantitative analysis to detect a
defect in ICC In our study, the severity of constipation seems unrelated to the
importance of this defect and ICC evaluation has little clinical interests. Clearly,
patients with SCI are satisfied after colectomy.
REFERENCES
Wang et al. Am J Pathol 2008; 32: 980-985.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
UPDATE ON ENDOSCOPIC RESECTION OF EARLY COLORECTAL NEOPLASIA HALL
N_____________________
OP332 ENDOSCOPIC SUBMUCOSAL DISSECTION VERSUS
ENDOSCOPIC MUCOSAL RESECTION FOR LARGE
COLORECTAL TUMORS: A META-ANALYSIS
M. Liggi1,*, S. Cadoni1, P. Gallittu1, M. Erriu2
1
Digestive Endoscopy Unit, Santa Barbara Hospital, Iglesias, 2Department of
Surgery, University of Cagliari, Cagliari, Italy
Contact E-mail Address: macnol@tiscali.it
INTRODUCTION: Colorectal lateral spreading tumors (LST) 20 mm are best
treated by Endoscopic submucosal dissection (ESD) or Endoscopic mucosal
resection (EMR). EMR is a safe and effective treatment for most colorectal
granular-LST (G-LST) lower than 40 mm. ESD should be preferred for both
greater G-LST and non-granular type LST (NG-LST), especially the pseudo-
A105
depressed type, which has a higher potential for invasion and requires a precise
histological evaluation (GIE 2007;66:966). ESD is technically more demanding
and has a relatively high complication rate; EMR is limited by its inability to
achieve en-bloc resection. Hybrid resection techniques (ESD with snaring, EMR
after circumferential pre-cutting or small incision) have been introduced to make
ESD and EMR easier, safer and quicker (DDS 2013;58:1727).
AIMS & METHODS: To perform the first meta-analysis on colorectal ESD-
EMR to assess their impact on their safety and effectiveness in removing color-
ectal LST 20 mm. Medline, PubMed, and Google searches (June 2009-October
2013) were considered to identify appropriate RCTs that compared ESD with
EMR for colorectal LST 20 mm. Keywords were: ESD, EMR, colorectal
tumors, LST. Reviews, case reports and abstracts were excluded. The existence
of noninvasive pattern, determined by magnification chromoendoscopy, was the
minimum requirement for all lesions candidates for ESD and EMR. Primary
end-points were en bloc resection rate, curative resection rate and local recur-
rence. Secondary end-points: rate of bleeding and perforation. Fixed or random-
effect models were used as appropriate based on homogeneity or heterogeneity of
data according to I2 statistic.
RESULTS: 8 studies (7 retrospective and 1 prospective) were identified. Data are
expressed as odds ratio (OR) and 95% confidence interval (CI) [95% CI]. A total
of 4023 lesions were found: 2104 were treated by ESD, 1919 by EMR, respec-
tively. The tumor size was significantly larger in the ESD group (30.65mm vs
243.1 mm, p50.05). The ESD group had a significantly higher proportion of
NG-LST (38.0% vs 27.3%, p50.001). Adenocarcinomas-sm1 were more fre-
quent in the ESD group than in the EMR group (18.3% vs 9.2%, p50.001).
ESD was associated with a longer procedure time (8933 min vs 227 min,
p50.001). Meta-analysis confirmed that, compared to EMR, ESD achieved
higher en bloc resection OR 9.77 [7.9-12.0], curative resection OR 2.04 [1.6-
2.57], and lower local recurrence irrespective of lesion size OR 0.08 [0.04-0.18].
ESD had higher number of perforations OR 3.6 [2.19-5.93]. Bleeding was similar
between the two groups: OR 1.15 [0.73-1.81].
CONCLUSION: The current meta-analysis shows that ESD has considerable
advantages regarding en bloc resection rate, curative resection rate and absence
of local recurrence, at the expense of a higher perforation rate and longer pro-
cedure time. ESD appeared to be an effective and safe procedure, at least in
expert hands, for lesions otherwise difficult to be radically treated with snare-
based endoscopic resection techniques. Better ESD standardization and a more
widespread and systematic implementation in Western countries are required.
Disclosure of Interest: None declared
OP333 WHICH IS THE STRONGEST PREDICTOR TO MOVE FROM
ESD TO PIECEMEAL EMR (PEMR) WHEN EN BLOC RESECTION
CANNOT BE COMPLETED?
J.C. Mar n-Gabriel1,*, J. D az-Tasende1, P. Cancelas Navia1, S. Rodr guez-
Munoz1, A.J. Del Pozo-Garc a1, A. Gonzalez-Blanco1, P. Hernan-Ocana1,
M. Perez-Carreras1, M. Alonso-Riano2, F. Colina-Ruizdelgado2, A. Dom nguez-
Rodr guez1, G. Castellano-Tortajada3
1
Department of Gastroenterology. Endoscopy Unit., 2Department of
Histopathology, 3Department of Gastroenterology., Hospital Universitario 12 de
Octubre, Madrid, Spain
Contact E-mail Address: josecarlos.marin@salud.madrid.org
INTRODUCTION: Endoscopic submucosal dissection (ESD) allows en bloc
resection of gastrointestinal tumors regardless of their size. However, a high
level of expertise is needed in the early learning curve to perform en bloc resection
by ESD and piecemeal endoscopic mucosal resection (pEMR) is frequently
needed to complete the resection.
AIMS & METHODS: To analyse the factors associated with changing the initi-
ally planned ESD to pEMR in a clinical practice setting where 5 100 procedures
have been performed. We included prospectively the first 85 ESDs performed in
our hospital, from September 2008 to April 2014. All ESD procedures were
performed by two teams with 2 endoscopists in each one (A-team: J.C.M.G. &
J.D.T.; and B-team: S.R.M. & A.P.G.) in equal numbers. We recorded charac-
teristics of the lesions and the procedure to predict the need for pEMR to com-
plete the resection.
RESULTS: Main characteristics of the patients and lesions are shown in table 1.
ESD had to be changed to pEMR in 37 patients (43.5%) to complete the resec-
tion of the lesion. In the univariate analysis, the factors that showed a statistically
significant association with moving to pEMR were: location of the lesion other
than in the stomach (54.7% vs. 25%; p 0.007), procedure duration longer than
180 min (57.9% vs 31.9%; p 0.016) and a maximum diameter more than 30 mm
(63.6% vs. 28%; p 0.001). None of the following factors showed statistically
significant association with moving the therapeutic approach to pEMR:
depressed morphology (28.6% vs. 48.4%; p 0.11), lesions treated after the
first 50 ESDs were performed (48% vs. 37.1%; p 0.32), previous electrosurgery
of the lesion (62.5 vs. 41.6%; p 0.29), team who performed the ESD (41.2% vs.
47.1%; p 0.59) or the presence of deep submucosal invasion in the histological
specimen (66.7% vs. 41.8%; p 0.39). In the logistic regression model, the size of
the lesion with a maximum diameter 4 30 mm, was the only factor indepen-
dently correlated with moving to pEMR (OR: 3.2; CI 95%: 1.1 8.3).
A106
Table 1. Characteristics of the lesions, procedure and patients.
Table to abstract OP333
n 85
Age (mean SD) 68 12
Male / Female n;% 48/37 (56.5 / 43.5)
Mean tumor size, mm (mean SD) 30.4 14.9
En bloc resections (n; %) 48 (56.5)
Snare use (Hybrid ESD) 12 (14.1)
Piecemeal resections (n; %) 37 (43.5)
R0 (n; %) 33 (38.8)
Procedure time (mean SD) 183 87
CONCLUSION: When the experience with ESD is low, with 5 100 procedures
performed, the size of the lesion, with a maximum diameter 4 30 mm, is the
strongest predictor for the need to complete the resection with pEMR.
Disclosure of Interest: None declared
OP334 RETROSPECTIVE COHORT STUDY TO ELUCIDATE LONG-
TERM CLINICAL OUTCOMES OF COLORECTAL ENDOSCOPIC
SUBMUCOSAL DISSECTION
M. Yamada1,*, Y. Saito1, H. Takamaru1, T. Sakamoto1, Y. Otake1,
T. Nakajima1, T. Matsuda1
1
Endoscopy Division, National Cancer Center Hospital, Tokyo, Japan
Contact E-mail Address: masyamad@ncc.go.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) is performed as a
curative treatment for colorectal neoplasms.1-5 Long-term clinical outcomes,
however, are necessary to clarify whether colorectal ESD truly has a favorable
effectiveness beyond lower recurrence rates.
AIMS & METHODS: The aim of this retrospective cohort study is to elucidate
long-term clinical outcomes for colorectal ESD. To allow five-year follow-up data,
out of 418 consecutive patients who were treated by ESD at National Cancer
Center Hospital, Tokyo, Japan, between February 1998 and December 2008, we
conducted a survey on patients followed-up longer than three years. After exclu-
sion criteria of squamous cell carcinoma, carcinoid tumor, coexistence of
advanced cancer, familial adenomatous polyposis and ulcerative colitis, 408
patients were enrolled. Long-term outcome data were collected between March
and September 2013. Incomplete and missing data were retrieved from the referral
hospital by asking their chief physician by letter; including last examination data,
date of recurrence, treatment history of any recurrence and the date of death.
Finally, we had complete data of the outcome of 286 patients (70%) and the
survival analyses were conducted. The primary endpoint was 5-year overall survi-
val rate (OS) and the secondary endpoints were recurrence free survival rate (RFS)
and cause specific survival rate (CSS). R0 resection was defined as cancer-free
resection margins. Curative resection was defined when the pathological findings
revealed R0, irrespective of piecemeal or en-bloc resection, with non of the follow-
ing features: deep submucosal invasion (=1,000 m, T1b), lymphovascular inva-
sion, or poorly differentiated adenocarcinoma component. An adenoma with an
unknown lateral margin also classified curative resection.
RESULTS: The 5-year OS, RFS and CSS were 95%, 91% and 100%, respec-
tively, after the 5.4-year (0.3-11.1) median follow-up period. In 220 curative
patients, the 5-year OS, RFS and CSS were 95% 95% and 100%, while the
CSS was low in 66 non-curative patients as 95%, 80% and 100%, respectively.
In the curative patients, three local recurrences including one intramural recur-
rence were detected in two patients with multiple piecemeal resections and one
with R0 resection for recurrence lesion. Two of these patients were successfully
treated by additional ESD and no recurrence was detected in more than 5 years
after the second ESD, respectively, and the other patient underwent salvage
surgery. In the non-curative patients, 38 patients were followed without addi-
tional surgery and 10 recurrences (26%) including 4 distant metastases were
detected. In contrast, only one distant metastasis (3%) was detected in 28
patients who underwent additional surgery. These patients with recurrence
received salvage surgery and/or chemotherapy.
CONCLUSION: The present study has shown favorable long-term clinical outcomes
of colorectal ESD for patients with intramucosal and submucosal superficial invasive
cancer. Therefore, colorectal intramucosal and superficial submucosal cancer can be
well managed by endoscopic resection when it achieves curative resection.
REFERENCES
1) Lee EJ, et al. Surg Endosc 2013
2) Saito Y, et al. Surg Endosc 2010
3) Repici. A, et al. Endoscopy 2012
4) Probst A, et al. Endoscopy 2012
5) Niimi K, et al. Endoscopy 2010.
Disclosure of Interest: None declared
OP335
SIZE
50mm 450mm
ALL POLYP RECURRENCE 14/106 (13%) 6/78 (7.6%) 8/28 (28.5%)
P 0.009
UNSCARRED POLYP RECURRENCE 8/86 (9.3%) 2/62 (3.2%) 6/24 (25%)
P0.005
United European Gastroenterology Journal 2(5S)
OP335 KNIFE ASSISTED RESECTION (KAR) OF LARGE AND
REFRACTORY COLONIC POLYPS AT A WESTERN CENTRE:
FEASIBILITY, SAFETY AND EFFICACY STUDY TO GUIDE FUTURE
PRACTICE
R. Bhattacharyya1,*, G. Longcroft-Wheaton1, P. Bhandari1 on behalf of
Portsmouth, UK
1
Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, United
Kingdom
INTRODUCTION: ESD enables large lesions to be resected en bloc. This
reduces recurrence rates, but ESD is technically challenging with high complica-
tion rates and hence not widely practiced in the west.
We have used a novel Knife Assisted Resection (KAR) technique.
AIMS & METHODS: We aim to evaluate the outcome of KAR in the treatment
of large and refractory colonic polyps and identify polyp features that can predict
complications and recurrence after KAR.
Cohort study of patients referred to our centre for resection of refractory polyps.
All patients who had knife assisted resection of colonic polyps over 20mm in size
from 2006 to Feb 2013 were included. All procedures were performed by a single
experienced endoscopist.
The technique starts with submucosal (SM) injection followed by mucosal inci-
sion using a dual knife (Olympus KD-650L). This is followed by variable degrees
of SM dissection and completion of circumferential mucosal incision. Finally a
snare assisted resection is performed in an en bloc or piecemeal fashion, depend-
ing on the polyp size and extent of SM dissection.
RESULTS: 127 polyps in 127 patients of mean age 71 years. Mean polyp size
46mm (20-170mm). 27% were 450mm. 27% were scarred from previous
attempted resection. 26% were in the right colon.
En bloc resection: 58/127(46%). Size of polyp 550mm was a significant
(p0.001) predictor of en bloc resection (88% vs. 12%).
The complication rate was 11/127(8.6%) with 5(3.9%) bleeds, 4(3.1%) diathermy
damage to muscle fibres and 1(0.78%) perforation. Complications were not
linked to polyp size, scarring or resection site. A single patient with perforation
required surgery. All other complications were managed endoscopically.
The recurrence rate was 14/106(13%). This was significantly higher for polyps
450mm (p 0.009) and in scarred polyps (p 0.024).
On sub-analysis of the unscarred polyps, polyps 50mm with no scarring had a
very low recurrence rate of 3.2% as compared to 25% in polyps 450mm (p
0.005).
Table: Factors associated with recurrence
CONCLUSION: This is the largest reported western series demonstrating the
feasibility, safety and efficacy of KAR for large and refractory polyps, with or
without scarring, at all colonic sites. Our data demonstrates that complications of
KAR are not related to size but the recurrence rate is. Size 450mm and scarring
seem to be predictors of recurrence.
We propose flat polyps 20 50mm in size as the ideal indication for KAR in the
western setting.
Disclosure of Interest: None declared
OP336 EFFECTIVENESS AND SAFETY OF ENDOSCOPIC
SUBMUCOSAL DISSECTION USING THE BALL-TIP
BIPOLARCURRENT NEEDLE KNIFE WITH WATER-JET FUNCTION
(JET B-KNIFE) FOR THE TREATMENT OFCOLORECTAL TUMORS
K. Hiramatsu1,*, H. Matsuda1, M. Ohtani1, T. Nemoto1, H. Suto1,
Y. Nakamoto1
1
Second Department of Internal Medicine, University of Fukui, Fukui, Japan
Contact E-mail Address: hiramatz@u-fukui.ac.jp
INTRODUCTION: ESD is a technically difficult and time-consuming procedure
for the treatment of large colorectal tumors. In Japan, Ball-Tip Bipolar Current
Needle Knife (BB-knife) has been used as a device for safe treatment in ESD by
minimizing the damage in deeper tissues of colorectal neoplasms. In May 2012, a
BB-knife combined with Water-Jet function (Jet B-knife) was newly developed.
AIMS & METHODS: The aim of this study was to examine the effectiveness and
safety of Jet B-knife, which is the Bipolar Current Needle Knife with a ball tip
and 1.5 mm in length. The endoscope we used was Olympus H260AZI or
PCF260AI. Electorosurgical unit was VIO300D(ERBE) with dry cut mode
(effect 3,60W) or spray coagulation mode (effect 2 60W). Translucent hood
had been always attached to the point of the endoscope. We treated 276 lesions
by ESD using BB-knife between March 2007 and April 2012(group A) and 101
lesions using Jet B-knife between May 2012 and March 2014 (group B). We
retrospectively evaluated including the diameter of resected tumor, the time
required for resection, the rate of en-block complete resection, the rate of per-
foration, and compare these data between two groups.
RESULTS: The median time required for the resection was 103 min. in group A
and 61 min. in group B. The difference was statistically significant (p50.01). And
the median diameter of tumor in group A was 23.1mm and that in group B was
RESECTION TYPE SITE SCARRED
En bloc P meal LC RC yes no
1/42 (2.3%) 7/44 (15.9%) 13/83 (15.6%) 1/23 (4.3%) 6/20 (30%) 8/86 (9.3%)
P 0.001 P 0.15 P 0.024
1/42 (2.3%) 7/44 (15.9%) 8/68 (11.7%) 0/18 (0%)
P0.058 P0.195
United European Gastroenterology Journal 2(5S)
26.6mm. The difference was statistically significant (p50.01). On the other hand,
the en-block complete resection rate was 94% in group A and97% in group B.
The rate of perforation was 1.8% in group A and 2.0% in group B. These
differences were not statistically significant.
CONCLUSION: The resection time was significantly shortened using Jet B-
knife, although the mean size of lesions was significantly larger than the other.
This may be not only due to the improvement of cutting skill but also due to the
efficient water jet function during the procedure of hemostasis and the enhanced
lifting effects of lesions by launching it at the submucosal layer. In conclusion,
the use of Jet B-knife may contribute to time-saving and safe procedure in ESD
for the colorectal tumors.
Disclosure of Interest: None declared
OP337 STRATEGY TO OVERCOME A DIFFICULTY OF THE
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR
COLORECTAL TUMORS ACCOMPANIED BY FIBROSIS IN
SUBMUCOSAL LAYER
Y. Tamegai1,*, T. Kishihara1, H. Ishikawa1, K. Okamoto1, A. Chino1,
J. Fujisaki1, M. Igarashi1
1
Endoscopy Division, Cancer Institute Hospital, Tokyo, Japan
Contact E-mail Address: yoshiro.tamegai@jfcr.or.jp
INTRODUCTION: The safety and curability of one-piece resection of colorectal
tumor using ESD technique sometime depends on the degree of fibrosis in the
submucosal (SM) layer. ESD for the tumors accompanied by hard and tight
fibrosis are thought to be most difficult to complete. The aim of this study is
to establish the strategy to overcome a difficulty of the ESD for colorectal tumors
accompanied by fibrosis in SM.
AIMS & METHODS: ESD was performed for 766 cases of colorectal neoplasm
in 760 patients (male: female 449:311; mean age, 65.7 years). Among these
cases, 190 cases were accompanied by SM fibrosis. These cases were divided into
three groups, absent with fibrosis (type A), fibrosis due to benign causes (type B),
and fibrosis due to submucosal cancer invasion (type C). And these were classi-
fied into mild (grade 1), moderate (grade 2), and severe (grade 3) degree. In this
study, we compared the one-piece resection rate between these three groups
according to the degree of SM fibrosis.
RESULTS: We completed ESD procedure on 758 of 766 colorectal tumors, and
8 cases were abandoned due to severe degree fibrosis relating deep SM cancer
invasion and screen-like fibrosis. Among the 190 cases with SM fibrosis, 59 cases
were considered related to cancer invasion (type C), and 131 cases were related to
benign cause (type B). The fibrosis of non-cancerous origin was caused by prior
inadequate endoscopic treatment, biopsy, and others. We classified the endo-
scopic findings as mild degree (B-1), moderate degree (B-2), and screen-like as
severe degree (B-3). Otherwise, a white or brown hump and rich abnormal vessels
were identified in the cases with SM cancer invasion (C-1 to 3). We performed
one-piece resection for 723 (94.4%) cases of 766 ESD cases. One-piece resection
rate of type A as 97.6% (562/576) and type BC was 84.7% (161/190). And the
one-piece resection rate according to the degree of fibrosis as follows, type B-1;
68/71(95.8%), B-2:27/30(90.0%), B-3:18/30 (60.0%), type C-1;31/31(100%, aver-
age SM depth:822.6m), C-2:7/8(87.5%, average SM depth:2,067.1m), C-3:10/
20(50%, average SM depth:3,078.9m). These dates of B-3, and C-3 were show-
ing unwilling results. We experienced only one case (0.13%) of perforation in
type B. Therefore, in cases accompanied by severe degree fibrosis, onepiece
resection becomes more difficult due to the risk of perforation. We designed
safe technique by using endo-clips to prevent perforation before dissection in 3
type B-3 cases, and successfully completed ESD procedure. And in other type B-3
cses, we have searched a dissection line just above muscle layer carefully. Because
of these results, type B-1, type B-2, type C-1, and type C-2 become standard
indication of ESD, type B-3 becomes relative indication of ESD, and type C-3
was thought to be an indication of laparoscopic surgery. Recently, we established
the laparoscopy endoscopy cooperative surgery (LECS) procedure applied with
ESD technique to complete an one-piece resection for the tumors accompanied
by wide and hard fibrosis(type B-3), and we performed one-piece resection for 4
cases successfully.
CONCLUSION: Endoscopic intra-operative evaluation of the cause and degree
of SM fibrosis is very important to complete safe and curative ESD procedure for
early colorectal cancers.
Disclosure of Interest: None declared
OP338 POLYPECTOMY PRACTICES IN THE ENGLISH BOWEL
CANCER SCREENING PROGRAMME
S. Din1,*, A. Ball1, E. Lunn1, S. Riley1, M. Rutter2, S. Johal1
1
Gastroenterology, Sheffield Teacing Hospitals NHS Foundation Trust, Sheffield,
2
Gastroenterology, University Hospital of North Tees, Newcastle upon Tyne,
United Kingdom
INTRODUCTION: Most polyps are 510 mm in size and a range of polypect-
omy techniques are available with wide variations in practice. We aimed to
examine the techniques employed for removal of 510mm polyps in relation to
polyp characteristics, completeness of excision, safety and changes over time.
AIMS & METHODS: Data relating to removal of polyps 510mm between Jan
2010 and Dec 2012 were retrieved from the national Bowel Cancer Screening
Programme (BCSP) database. Categorical data was compared using x2.
RESULTS: 147174 polyps 510mm were removed during 62679 colonoscopies.
A range of techniques was used (cold biopsy forceps (CBF) 19.7%, cold snare
(CS) 22.1%, hot biopsy forceps (HBF) 12.2%, hot snare (HS) 35.1%, EMR
10.9%). EMR was used more frequently in the right colon compared to the
left (14.3% vs. 8.3%, OR 1.84, 95% CI 1.78-1.90, P 50.01).
A107
Most pedunculated polyps were removed using HS; this proportion was lower in
the right vs. left colon (69.6% vs. 88.3%, OR 0.30, CI 0.28-0.33, p 5 0.01).
CS was most common for non-pedunculated polyps in the right colon (29.8% vs.
19.0% in left, OR 1.81 CI 1.76-1.85, P 50.01); whereas most common in the left
colon was HS (34.8 vs. 22.5% in right, OR 1.84 CI 1.79-1.88, P 50.01).
Surgeons were more likely than physicians to use diathermy irrespective of site or
morphology (65.6% vs. 56.5%, OR 1.46 CI 1.43-1.51, P 5 0.01).
In 60% of polyps removed completeness of excision was not histologically asses-
sable. 21.2% were completely excised, 5.8% incomplete and 13% not stated. For
non-pedunculated polyps, histologically-confirmed complete excision was more
common after EMR (23.4% vs. 6.2%, OR 1.16, CI 1.08-1.25, p 50.01) com-
pared to other techniques (CBF 17.7%, CS 15.1%, HBF 19.1%, HS 21.5%); for
pedunculated polyps it was more common after EMR (42.3%) and HS (42.0%)].
Sub-analysis of colonoscopies where only polyps 510mm were removed (45227),
complications were rare. 12 (0.03%) bleeding episodes required transfusion; the
rates for single and multiple polypectomy cases were 0.01% and 0.04% respec-
tively (OR 5.01, CI 1.10-22.8, P 0.02). The HS technique was most commonly
used. There were 16 (0.04%) perforations; 0.02% for single vs. 0.05% for multi-
ple polypectomies (OR 2.20, CI 0.77-6.34, P 0.13). No technique dominated for
single compared with HS for multiple polypectomies.
Between 2010 and 2012, use of CBF, CS and EMR increased, whereas HBF and
HS decreased (p 5 0.01). Table 1
Table 1 Change in trends according to technique
2010(%) 2012(%) OR, 95% CI
CBF 15.2 23.0 OR 1.67, CI 1.61-1.72
CS 21.3 23.3 OR 1.12, CI 1.09-1.16
HBF 14.1 10.1 OR 0.68, CI 0.66-0.71
HS 41.0 31.1 OR 0.65, CI 0.63-0.67
EMR 8.5 12.5 OR 1.55, CI 1.48-1.62
CONCLUSION: The removal of polyps 510mm within the BCSP is safe, but
histological evidence of complete excision is poor with all techniques. Wide
variations in practice reflect the lack of evidence guiding these decisions,
although use of cold resection techniques has increased over time.
Disclosure of Interest: None declared
OP339 ENDOSCOPIC FULL THICKNESS RESECTION IN THE LOWER
GASTROINTESTINAL TRACT USING A NOVEL OVER-THE-SCOPE
DEVICE
A. Schmidt1,*, M. Damm1, C. Gubler2, K. Caca1, P. Bauerfeind2
1
Gastroenterology, Klinikum Ludwigsburg, Ludwigsburg, Germany,
2
Gastroenterology, Universitatsspital Zurich, Zurich, Switzerland
INTRODUCTION: Diagnostic or therapeutic endoscopic full thickness resection
in the colon may be indicated for non-lifting adenomas and other indications.
However, to date there is a lack effective and safe endoscopic methods and
devices. The FTRD (Full Thickness Resection Device, Ovesco, Tubingen,
Germany) is a novel over-the-scope device developped for endoscopic full thick-
ness resection.
AIMS & METHODS: Between 07/2012 until 03/2014, 21 patients underwent
endoscopic full thickness resection at two tertiary referral centers. All resections
were conducted with the FTRD mounted on a standard colonoscope. Resection
technique: The lesion to resect was pulled into a long transparent cap, a 14 mm
Over-The-Scope Clip (OTSC) was deployed and the pseudopolyp above the clip
was resected with a preloaded snare.
In this study we report our first clinical experience with this novel full thickness
resection technique.
RESULTS: Indications for endoscopic full thickness resection were: recurrent or
incompletely resected adenoma with negative lifting sign (9); untretated adenoma
with high-grade dysplasia and negative lifting sign (1), adenoma involving the
appendix (3), flat adenoma in a patient with coagulopathy (1), diagnostic re-
resection after incomplete resection of a T1-carcinoma (3), adenoma involving
a diverticulum (1), submucosal colonic tumor (2), diagnostic resection in a
patient with suspected Hirschsprungs disease. The lesions were located as fol-
lowed: coecum (3), ascending colon (4), transverse colon (2), descending colon
(4), sigmoid (2), recosigmoid transition (3) and rectum (3). Reaching the target
lesion with the endoscope and the mounted FTRD was possible in 20/21 patients
(95.2%). Having reached the target lesion, macroscopically complete resection
was achieved in 19/20 patients. Full thickness resection was confirmed histolo-
gically in 17/20 cases (85%). Histologically complete resection was achieved in
17/20 cases (85%). No perforations or relevant bleeding was observed during or
after resection. Two patients developed a post-polypectomy syndrome which was
managed with antibiotic therapy.
CONCLUSION: Full thickness resection in the lower GI tract with the novel
FTRD is feasible and effective. Prospective studies are needed to further evaluate
the technique and device.
Disclosure of Interest: A. Schmidt Lecture fee(s) from: Ovesco Endoscopy, M.
Damm: None declared, C. Gubler: None declared, K. Caca: None declared, P.
Bauerfeind: None declared
A108
OP340 ELRR OR TATMR BY TEM FOR TREATMENT OF LOW RECTAL
CANCER
E. Lezoche1,*, A.M. Paganini1, S. Quaresima1, A. Balla1, E. de Werra1,
F. Mattei1, G. DAmbrosio1
1
Sapienza University of Rome, Azienda Policlinico Umberto I, Roma, Italy
Contact E-mail Address: emanuele.lezoche@gmail.com
INTRODUCTION: From the beginning of the 90s, the authors have introduced
an original technique of loco-regional resection by Transanal Endocopic
Microsurgery (TEM) named Endoluminal Loco-Regional Resection
(ELRR). In selected patients, this technique is a valid alternative to traditional
surgery for early (Tis-T1) and for T2N0 rectal cancer after neoadjuvant radio-
chemotherapy (n-RCT). Sphincter-saving procedures in patients with low rectal
cancer are largely successful, but there is no universally adopted standardized
technique. From 2008, the authors have developed a new combined technique:
Transabdominal Transanal Total Mesorectal Resection (TATMR) by TEM in
patients not eligible for ELRR (T2-T3N0/N). Transanal TME is achieved with
a modified original TEM rectoscope. The abdominal part is performed laparos-
copically, followed by colo-anal anastomosis and ileostomy.
AIMS & METHODS: From 2001 to 2014, 135 patients (82 males, 53 females,
median age 65 years) with rectal cancer were selected. All patients were studied
preoperatively with tumor markers assay (CEA, Ca19.9, Ca125), digital rectal
examination, colonoscopy with macrobiopsies, vital staining, peri-tumoral tat-
tooing on histologically normal mucosa, total body CT scan, pelvic MRI and
endorectal ultrasound. One hundred and nineteen patients with T1-T2N0 rectal
cancer underwent ELRR by TEM and sixteen patients with T2-T3N0/N under-
went TATMR. All T2-T3 patients underwent n-RCT.
RESULTS: Mean operative time for ELRR and TATMR was 138 min (range
40-300) and 450 (range 360-600), respectively. No intraoperative complication
was observed. Final staging was pT0N0 (5), pTis (51), pT1 (46), pT2 (24), pT3N0
(5), pT3N1 (4). Mean hospital stay was 4 days for ELRR and 16 days for
TATMR. No late complications were observed in ELRR group. In the
TATMR group, anastomotic leakage occurred in 6 cases. Mortality was
observed in two patients for unrelated causes.
CONCLUSION: In patients with low rectal cancer, quality of life should be a
primary objective, without compromising the oncological results. TME is the
gold standard, but postoperative functional sequelae are often observed.
Several surgical alternative procedures are described, but none has been univer-
sally adopted. In selected T1 or T2 (after n-RCT) patients, ELRR by TEM is a
valid alternative to traditional surgery. The authors described a new technique
named TATMR to treat patients with T2-T3 rectal cancer. The main advantages
are the preliminary identification of the distal margin of the tumor and dissection
of the intact distal mesorectal fascia, in order to detect peri-rectal tumor invasion
and to verify the possibility to perform a sphincter-saving procedure. Adequate
experience in TEM is a pre-requisite.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
PATHOPHYSIOLOGY AND MANAGEMENT OF PAIN AND FIBROSIS IN CHRONIC
PANCREATITIS HALL O_____________________
OP341 RISK OF RECURRENT PANCREATITIS AND PROGRESSION TO
CHRONIC PANCREATITIS AFTER A FIRST EPISODE OF ACUTE
PANCREATITIS
U. Ahmed Ali1,2,*, Y. Issa1, J.C. Hagenaars2, O.J. Bakker2, H. van Goor3,
V. Nieuwenhuijs4, T. Bollen5, B. van Ramshorst6, B.J. Witteman7, M.A. Brink8,
A.F. Schaapherder9, C.H. Dejong10, B.M. Spanier11, J. Heisterkamp12, E. van
der Harst13, C. H. van Eijck14, M.G. Besselink1, H.C. Gooszen15, H. C.
van Santvoort6, M.A. Boermeester1 on behalf of Dutch Pancreatitis Study Group
1
Department of Surgery, Academic Medical Center Amsterdam, Amsterdam,
2
Department of Surgery, University Medical Center Utrecht, Utrecht, 3Department
of Surgery, Radboud university medical center, Nijmegen, 4Department of Surgery,
Isala Clinics, Zwolle, 5Department of Radiology, 6Department of Surgery, St
Antonius Hospital, Nieuwegein, 7Department of Gastroenterology, Gelderse Vallei
Hospital, Ede, 8Department of Gastroenterology, Meander Medical Center,
Amersfoort, 9Leiden University Medical Center, Leiden, 10Department of Surgery,
University Hospital Maastricht, Maastricht, 11Department of Gastroenterology,
Rijnstate Hospital, Arnhem, 12Department of Surgery, St Elisabeth Hospital,
Tilburg, 13Department of Surgery, Maasstad Ziekenhuis, 14Department of Surgery,
Erasmus Medical Center, Rotterdam, 15Department of Evidence Based Surgery,
Radboud university medical center, Nijmegen, Netherlands
Contact E-mail Address: u.ahmedali@pancreatitis.nl
INTRODUCTION: Recurrent pancreatitis (RP) and chronic pancreatitis (CP)
may occur after a first episode of acute pancreatitis. Data on incidence and risk
factors for these events are scarce.
AIMS & METHODS: A cross-sectional survey and retrospective review of a
prospectively collected cohort of patients with a first episode of acute pancreatitis
was performed. Primary endpoints were RP and CP. CP was defined in two way:
1. based on clinical diagnosis by treating physician, and 2. based on the M-
ANNHEIM diagnostic criteria. Both definitions were analysed seperately. Risk
factors were evaluated using regression analysis. The cumulative risk was
assessed using Kaplan-Meijer analysis.
RESULTS: 669 patients were included, with a median follow-up of 57 months.
RP and CP were observed in 117 (17%) and 42 (6%) patients, respectively. Rates
of RP were 12%, 24% and 25% in patients with biliary, alcoholic and idiopathic/
other etiology, respectively. CP developed in 2%, 15% and 7% for these etiol-
ogies, respectively. Etiology, smoking and necrotizing pancreatitis were indepen-
dent risk factors for both RP and CP (Table 1). APACHE-II score on admission
was independently associated with RP only. Cumulative risk for RP over 5 years
United European Gastroenterology Journal 2(5S)
was highest among smokers (40%). Patients with alcoholic etiology and current
smokers had a comparable cumulative risk for CP of about 15%. With both
factors present the risk doubled to 30%.
Table 1. Multivariable analysis of risk factors for progression to chronic
pancreatitis
CP diagnosed CP as defined by
clinically the M-ANNHEIM criteria
odds ratio odds
(95% confidence- ratio (95%
interval) P-value confidence-interval) P-value
Etiology 1 50.001 1 0.001
- Biliary 6.48 (2.53 16.58) - 4.22 (1.83 9.73) -
- Alcohol 4.66 (1.71 12.74) 50.001 3.98 (1.64 9.65) 0.001
- Idiopathic/other 0.003 0.002
Current smoking 2.52 (1.19 5.31) 0.02 2.90 (1.42 5.93) 0.004
Pancreatic necrosis 3.45 (1.68 - 7.09) 0.001 6.65 (3.40 13.01) 50.001
CONCLUSION: Five years after a first AP episode, about 1 out of 6 patients
develop RP and 1 out of 15 patients develop CP. Smoking was the predominant
risk factor for RP, while the combination of alcohol and smoking resulted in the
highest cumulative risk for CP. Based on these results, pancreatic specialist
should not only advise patients to discontinue alcohol use after a first pancreatitis
episode, but should emphasize the importance of smoking cessation as well.
Disclosure of Interest: None declared
OP342 DISRUPTION OF FRACTALKINE/CX3CR1 SIGNALLING
ATTENUATES PANCREATIC PAIN IN EXPERIMENTAL CHRONIC
PANCREATITIS
J.G. DHaese1,*, T.D. DHaese1, H. Sezgin1, T. Kehl1, I. E. Demir1,
F. Bergmann2, H. Friess1, G.O. Ceyhan1
1
Department of Surgery, KLINIKUM RECHTS DER ISAR, Munchen, 2Institute
of Pathology, University of Heidelberg, Heidelberg, Germany
Contact E-mail Address: jan.dhaese@med.lmu.de
INTRODUCTION: Chronic pancreatitis (CP) is a chronic inflammatory condi-
tion of the pancreas leading to severe pain and fibrosis. Fractalkine is a chemo-
kine that chemoattracts inflammatory cells through its highly selective receptor
CX3CR1 and has been suggested to aggravate pancreatic inflammation.
Fractalkine is moreover known to be expressed on spinal neurons and sensory
afferents where it has shown major pain-modulatory effects in different experi-
mental pain states.
AIMS & METHODS: We aimed to investigate the course of experimental
chronic pancreatitis in CX3CR1-/- deficient mice and the potential therapeutic
implications of a CX3CR1 inhibitor. CP was induced in CX3CR1-knockout and
wild-type mice by repetitive intraperitoneal cerulein injections. Treatment groups
received an orally available small molecule CX3CR1 inhibitor. Hyperalgesia was
assessed by systematic behavioural observation, locomotion analysis, and mea-
surement of abdominal mechanical sensitivity. Pancreatic tissue was harvested
after sacrifice for further analyses.
RESULTS: Both CX3CR1-knockout and CX3CR1-blocking treated mice
showed significantly less pain related behaviour (p 5 0.0001) and significantly
less weight loss (p 5 0.01) when compared to their wild-type controls, with a
clear dose-response correlation in the treated mice. This reduction in pain related
behaviour was confirmed in IHC and WB analysis of pain markers.
Unexpectedly, there was no difference in inflammatory cell infiltrations, fibrosis,
Amylase/Lipase levels, and Trypsin/MPO activity.
CONCLUSION: Fractalkine/CX3CR1 signalling seems to be crucial in initiating
chronic pancreatic hyperalgesia. It does however not seem to have a direct effect
on inflammatory cell infiltration and fibrosis. Nevertheless, these novel findings
reveal CX3CR1 as a promising new target for the treatment of chronic pancreatic
pain.
Disclosure of Interest: None declared
OP343 PATHOPHYSIOLOGIC EVENTS IN PANCREATIC ACINAR
CELLS ASSOCIATED WITH PANCREATITIS IN RESPONSE TO
TOBACCO COMPARED TO ALCOHOL
M. Luaces-Regueira1,*, M. Castineira-Alvarino1, J.E. Dominguez-Munoz2
1
Gastroenterology, Foundation for Reserch in Digestive Diseases, 2University
Hospital of Santiago de Compostela. Foundation for Reserch in Digestive Diseases,
Santiago de Compostela, Spain
INTRODUCTION: Pancreatitis is characterized by the development of inflam-
matory process secondary to intracellular premature activation of digestive
enzymes, alteration of intracellular calcium levels and enzyme secretion, reactive
oxygen species (ROS) production and death of pancreatic acinar cell. Tobacco is
generally recognized as a relevant risk factor for pancreatitis, but its effect on
acinar cells is unknown
AIMS & METHODS: To evaluate the role of tobacco compared with alcohol in
the pathophysiologic events associated with pancreatitis in pancreatic acinar
cells.
Acinar cells isolated from Swiss mice pancreas by enzymatic and mechanic degra-
dation were stimulated with different concentrations of alcohol (10-100mM) or
tobacco (0.001-0.4mg/ml) and with CCK (positive control). Intracellular enzyme
activity, ROS production, necrosis and intracellular calcium were evaluated by
United European Gastroenterology Journal 2(5S) A109
fluorescence with rodhamine, DCFDA, propidium iodide and fluo-4 substrates, OP345 SMOKING CESSATION BUT NOT ALCOHOL ABSTINENCE
respectively. Amylase secretion was evaluated with p-nitrophenyl-maltohexao- REDUCES THE MORPHOLOGICAL PROGRESSION OF TOXIC
side as substrate. NFB activation was measured by Western blot. Interleukin- CHRONIC PANCREATITIS: A PROSPECTIVE, LONGITUDINAL
1 and TNF secretion was analyzed by ELISA in the supernatant. Apoptosis
was evaluated by caspase 3 activity (western blot). LDH was quantified as a
marker of cytotoxicity. Statistic analysis was performed by ANOVA.
RESULTS: Neither alcohol nor tobacco induced a significant activation of intra-
cellular enzyme. Tobacco significantly increased intracellular calcium levels
[11.384.89% (0.1mg/ml) - 56.2613.14% (0.5mg/ml)] similarly to alcohol
[14.402.06% (10mM) - 59.82.57% (75mM)]. This was associated to an
increase in amylase secretion only after tobacco (21%, 0.4mg/ml). Tobacco,
but not alcohol, induced activation of NFB (2.691.05 fold increase of p65
translocation at 0.1 mg/ml over negative control). Neither tobacco nor alcohol
COHORT STUDY
J. Iglesias-Garc a1,*, M. Luaces-Regueira2, J. Larino-Noia1, M. Castineira-
Alvarino2, J.E. Dominguez-Munoz1
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, 2Foundation for Research in Digestive Diseases,
Santiago de Compostela, Spain
INTRODUCTION: Smoking and alcohol are recognized risk factors for chronic
pancreatitis (CP). Smoking enhances ethanol-induced pancreatic injury and
accelerates the development and progression of CP. However, the effect of stop-
induces interleukin-1 and TNF release. Moreover, tobacco, but not alcohol,
produced a significant citotoxicity (p50.05) and induced acinar cell necrosis at
0.3 y 0.4 mg/ml (14.3% and 19.4%, respectively). This was associated with ROS
production in a dosis-dependent manner (p50.05). In addition, tobacco stimu-
lated the activation of caspase 3 at 0.01 and 0.1 mg/ml (2.530.38 and 1.770.12
vs negative control).
CONCLUSION: High concentrations of tobacco induce a significant increase of
intracellular calcium levels, amylase secretion, ROS production and necrosis in
pancreatic acinar cells. At lower concentrations, tobacco initiates the inflamma-
tory process through the activation of NFB and induces apoptosis in pancreatic
acinar cells. Alcohol does only induce an increase of intracellular calcium levels
in the same experimental model. These results support the relevant role of
tobacco as an etiological factor of pancreatitis.
Disclosure of Interest: None declared
OP344 IS TOBACCO A TRIGGER FACTOR OF PANCREATIC
FIBROGENESIS? EVIDENCE FROM THE INTERACTION
BETWEEN ALCOHOL AND TOBACCO IN PANCREATIC STELLATE
CELLS
M. Castineira-Alvarino1,*, M. Luaces-Regueira1, J.E. Dominguez-Munoz2
1
Gastroenterology, Foundation for Research in Digestive Diseases,
2
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, Santiago de Compostela, Spain
INTRODUCTION: Alcohol has been associated with the activation of pancrea-
tic stellate cells (PSC) and survival of activated PSC. The effect of ethanol is
partly mediated by the generation of oxidative stress within the cells but other
factors are required for pancreatic fibrogenesis to develop. Tobacco is recognized
as an etiological factor of chronic pancreatitis (CP). Tobacco has been shown to
activate fibrogenesis in tissues such as heart, liver and kidney, but its effect on the
pancreas is unknown. We hypothesized that tobacco alone or in combination
with alcohol stimulates pancreatic fibrogenesis by PSC activation through the
generation of oxidative stress within the cells.
AIMS & METHODS: Our aim was to evaluate the effect of tobacco alone and in
combination with alcohol on the activation of PSC and production of extracel-
lular matrix (ECM) proteins, secretion of proinflammatory molecules and the
generation of oxidative stress within the cells.
PSC were isolated from rat pancreas Sprague-Dawley and exposed to tobacco
(cigarette smoke condensate) alone (0.01mg/ml) or in combination of increasing
concentrations of ethanol (5 to 50mM). PSC activation (-SMA expression) was
measured in both early and primary cell culture by Western blot. Fibronectin-1
(FNT-1) was evaluated by western blot and immunochemistry. Collagen-I was
measured by western blot and Masson trichrome. As proinflammatory mole-
cules, fractalkine secretion was analyzed by Enzyme-linked immunosorbent
assay. Oxidative stress was examined using 2-7-dichlorofluorescin diacetate
(DCF-DA) and was detected by flow cytometry. Results are expressed as
meanSEM. Statistical analysis was carried out one-way ANOVA followed by
Fishers LSD post hoc test.
RESULTS: Tobacco alone (-SMA 1.830.3; p0.003 versus negative control)
or in combination with 50 mM ethanol (-SMA 1.530.2; p0.04 versus negative
control) induced PSC activation in early culture. Tobacco in combination with 50
mM ethanol increased the expression of collagen-I (3.91.2, p50.001 versus
negative control) and FNT-1 (3.60.3, p50.001 versus negative control and
ethanol alone). Tobacco also increased the expression of FNT-1 in combination
of 10mM alcohol (2.230.1, p0.007 versus negative control). Tobacco in com-
bination with 50 mM ethanol induced fractalkine secretion at 48 hours (11.53.3
pg/mL vs 51.25 pg/mL negative control; p0.017). Ethanol (50mM) alone
(3.060.77, p0.008 versus negative control) or in combination with tobacco
(0.01mg/mL) (2.680.49 E50, p0.027 versus negative control) increased the
reactive oxygen species fluorescence emission.
CONCLUSION: Tobacco alone or in combination with alcohol induces the
activation of PSC. Tobacco associated with alcohol increases the expression of
extracellular matrix proteins, fractalkine secretion and it is a potential inducer of
oxidative stress. These results support for the first time the synergistic effect of
alcohol and tobacco in the pathogenesis of chronic pancreatitis.
Disclosure of Interest: None declared
ping the consumption of tobacco and alcohol on the progression of CP has not
been well defined.
AIMS & METHODS: We aimed at investigating the effect of cessation the
consumption of tobacco and alcohol on the morphological progression of CP
as evaluated by endoscopic ultrasound (EUS).
A prospective, longitudinal cohort study was designed. Inclusion criteria were
patients diagnosed of toxic non-calcific CP by EUS. All patients should be active
smokers at inclusion. Minimum follow-up was 2 years. EUS was performed
under conscious sedation by the lineal Pentax echoendoscope and HITACHI
ultrasound at inclusion and at 2-year intervals during follow up. Standard
EUS criteria for the diagnosis of CP were evaluated (5 parenchymal criteria
and 5 ductal criteria). Progression was considered when the total number of
EUS criteria of CP increased during follow-up. Data regarding smoking and
alcohol consumption were recorded at baseline and during follow-up. Data are
shown as mean and 95%CI, and compared by the t-student test. A multivariable
logistic regression analysis was performed to determine the effect of maintained
alcohol and tobacco consumption on the progression of CP.
RESULTS: 68 patients (61 male, 7 female, mean age 48.9 years, range 23-74
years) were finally included. 44 of them (64.7%) were drinkers. Median follow-
up time was 56 months (range 24-123 months). Regarding toxic habits, 24
(35.3%) patients stopped smoking, and 26 (59.1%) stopped alcohol consump-
tion. Morphological progression of the disease was observed in 34 patients (50%)
during follow-up. Eight (8.8%) patients developed calcifications. A morphologi-
cal progression of the disease was observed in 28 out of the 44 patients who
continued to smoke (66.6%) and in 6 out of the 24 patients who stopped smoking
(25%) (p0.005). Morphological progression of CP was observed in 61.5% of
patients who stopped alcohol intake and in 50% of those who continued drinking
(n.s.). The only factor significantly and independently associated with the mor-
phological progression of the disease during follow-up was maintained tobacco
consumption (OR5.25, 95%CI 1.73-15.92). Maintained alcohol consumption
was not associated with the progression of CP (OR1.0, 95CI% 0.34-2.93).
CONCLUSION: Smoking is a major factor in the morphological progression of
toxic CP. Smoking cessation should be strongly encouraged in these patients.
Maintained alcohol intake was not associated with the progression of the disease
in this study.
Disclosure of Interest: None declared
OP346 POTENTIAL MECHANISMS OF THERAPEUTIC CANNABIS
USE IN CHRONIC PANCREATITIS
W.K. Utomo1,*, K. Parikh2, M. de Vries3, H. van Goor3, M.J. Bruno1,
M.P. Peppelenbosch1, H. Braat1
1
Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam,
2
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
3
Surgery, Radboud University Medical Center, Nijmegen, Netherlands
Contact E-mail Address: w.utomo@erasmusmc.nl
INTRODUCTION: Cannabis has been a traditional medicine used for centuries
to treat a broad range of disorders from asthma to multiple sclerosis. Several
studies using cannabinoid receptor agonists show possible anti-inflammatory and
anti-carcinogenic effects in vitro and in vivo. However, the molecular pathways
underlying these effects remain unclear. Chronic pancreatitis is characterized by
an ongoing inflammation leading to irreversible changes, and is associated with
increased risk of developing pancreatic cancer.
AIMS & METHODS: We hope to reveal the signalling pathways that are acti-
vated after ingestion of medicinal cannabis in patients suffering from chronic
pancreatitis.
Cannabis-na ve volunteers drank a medicinal cannabis preparation
(Bedrobinol). Peripheral blood was obtained before and 1 hour after ingestion.
Comprehensive descriptions of signal transduction were obtained in these sam-
ples employing kinome profiling on peptide chips exhibiting 960 different kinase
substrates. We calculated mean phosphorylation levels for all 960 substrates
before and after the treatment with medicinal cannabis. Additionally, we ana-
lyzed peripheral blood from 3 patients enrolled in a phase 2 clinical trial compar-
ing purified 9-Tetrahydrocannabinol (Namisol) against placebo in chronic
pancreatitis patients (clinicalTrials.gov ID: NCT01551511) to confirm our find-
ings in abovementioned kinome array.
RESULTS: As expected there is a great deal of similarity between the two
phosphoproteomes (r20.87). Phosphorylation of 106 substrates on the 960
array differs significantly between the two data sets. Of particular interest was
the strong down regulation of cell cycle kinases: Cdk2, Cdk5, and Cdk7. The
inhibition of the G1 to S phase kinase, Cdk2, is apparently mediated via a ATM/
ATR-p53-p21-dependent pathway. Furthermore, we observed a down regulation
of p38 MAP kinase, suggesting a specific anti-inflammatory effect. Finally, there
was also increased activity of the PI3K-Akt-mTOR signaling pathway, which
was confirmed in flow cytometry. Activation of the mTOR pathway is shown to
inhibit autophagy, possibly leading to enhanced cell death in tumors.
A110
CONCLUSION: The observation that medicinal cannabis impairs activation of
specific components of the inflammatory cellular signal transduction provides a
mechanistic rationale for the use of medicinal cannabis in chronic pancreatitis
patients and selected autoimmune diseases. Furthermore, the inhibition of cell
cycle proteins leading to cell cycle arrest and upregulation of mTOR signaling
may contribute to anti-cancer properties of medicinal cannabis, justifying its use
in terminal cancer patients.
Disclosure of Interest: None declared
OP347 DECREASED CFTR ACTIVITY AFTER ETHANOL
CONSUMPTION AND IN ALCOHOLIC PANCREATITIS
J. Maleth1,*, P. Pallagi1, L., V. Kemeny1, Z. Balla1, B. Kui1, A. Balazs1,
L. Judak2, I. B. Nemeth3, Z. Rakonczay Jr.1, V. Venglovecz2, I. Foldesi4,
A. Somoracz5, K. Borka5, D. Perdomo6, G.L. Lukacs6, M.A. Gray7,
S. Monterisi8, M. Zaccolo8, M.M. Lerch9, M. Sahin-Toth10, P. Hegyi1
1
First Department of Medicine, 2Department of Pharmacology and
Pharmacotherapy, 3Department of Dermatology and Allergology, 4Department of
Laboratory Medicine, University of Szeged, Szeged, 52nd Department of
Pathology, Semmelweis University, Budapest, Hungary, 6Department of
Physiology, McGill University, Montreal, Canada, 7Institute for Cell & Molecular
Biosciences, Newcastle University, Newcastle upon Tyne, 8Department of
Physiology, Anatomy and Genetics, Oxford University, Oxford, United Kingdom,
9
Department of Medicine A, University Medicine Greifswald, Greifswald,
Germany, 10Department of Molecular and Cell Biology, Boston University Henry
M. Goldman School of Dental Medicine, Boston, Hungary
Contact E-mail Address: jozsefmaleth1@gmail.com
INTRODUCTION: Excessive ethanol consumption is one of the most common
causes of acute and chronic pancreatitis. It is also documented that genetic
defects of CFTR can lead to pancreatitis, however the effects of alcohol con-
sumption on CFTR function in the pancreas is not known.
AIMS & METHODS: Our aim was to investigate the role of CFTR in the
pathogenesis of alcohol-induced pancreatitis. The effects of ethanol and ethanol
metabolites (fatty acids and fatty acid ethyl esters) on CFTR function and
expression were examined in human (volunteers, patients and cell lines) and in
animal models (guinea pigs and CFTR-/- mice).
RESULTS: Sweat chloride concentration was increased in alcohol intoxicated
patients but not in healthy volunteers, indicating impaired CFTR function.
Moreover, decreased CFTR expression was found in pancreas specimens from
patients with acute or chronic alcohol-induced pancreatitis. In functional studies,
we detected strong inhibitory effects of alcohol and fatty acids on CFTR activity
and HCO3- secretion in pancreatic ductal epithelial cells. The inhibition was
mediated by intracellular calcium overload, decreased cellular cAMP levels and
ATP depletion. In addition, we reproduced the alcohol-induced decrease in
CFTR expression in cultured pancreatic epithelial cells and in vivo in guinea
pigs, which was caused by a combination of reduced CFTR mRNA levels,
decreased cell surface stability and folding defect of CFTR. Finally, we
showed that genetic deletion of CFTR lead to more severe pancreatitis in
CFTR knock-out mice induced by ethanol and fatty acids.
CONCLUSION: The findings indicate that alcohol-induced loss of CFTR func-
tion is critical in the development of alcoholic pancreatitis; therefore, correcting
CFTR function should offer therapeutic benefit.
Our research was supported by the Hungarian National Development Agency
grants (TAMOP-4.2.2.A-11/1/KONV-2012-0035, TAMOP-4.2.2-A-11/1/
KONV-2012-0052; TAMOP-4.2.2.A11/1/KONV-2012 - 0073; TAMOP-
4.2.4.A2-11-1-2012-0001, TAMOP- 4.2.4.A2-SZJO-TOK-13-0017), the
Hungarian ScientificResearch Fund (OTKA NF100677).
Disclosure of Interest: None declared
OP348 EXPRESSION PATTERN OF IL1R1 AND IL13RA2 IN PATIENTS
WITH CHRONIC PANCREATITIS AND CLINICOPATHOLOGICAL
CORRELATIONS
1, 1 2 3 4
R. Poth *, J.G. DHaese , P. Brohawn , F. Bergmann , K. Tan , A. Lewis , 4
J. Roberts4, H. Friess1, G.O. Ceyhan1
1
Department of Surgery, KLINIKUM RECHTS DER ISAR, Munchen, Germany,
2 IgG4
Translational Sciences, MedImmune, Gaithersburg, United States, 3Institute of
Pathology, University of Heidelberg, Heidelberg, Germany, 4Translational
Medicine, MedImmune, Cambridge, United Kingdom
Contact E-mail Address: jan.dhaese@med.lmu.de
INTRODUCTION: Chronic pancreatitis (CP) is a major inflammatory disease of
the pancreas, characterized by vast inflammatory cell infiltration, pancreatic
fibrosis and severe abdominal pain. IL1 has been shown to have an important
role in the pathogenesis of pancreatitis, where IL1b overexpression in the murine
pancreas was associated with CP. IL13 is a major profibrogenic cytokine that has
recently been shown to promote pancreatic stellate cell proliferation suggesting
its role in pancreatic fibrogenesis. While evidence in animal models is constantly
growing, little is known on the expression status of these cytokines and their
receptors in the chronically inflamed human pancreas. In order to evaluate their
therapeutic potential, we therefore aimed to investigate the expression of the IL1
receptor IL1R1 and the IL13 receptor IL13Ra2 for the first time in human tissue
samples and correlate these with clinicopathological parameters.
AIMS & METHODS: The expression and localization of IL1R1 and IL13Ra2
was investigated in CP (n69), and normal pancreas (NP; n32) by QRT-PCR
and immunohistochemistry analyses. Results were correlated with clinicopatho-
logical parameters including the severity of fibrosis, pain, neuritis, and neural
hypertrophy.
RESULTS: There was no difference in the mean relative expression of the recep-
tor IL1R1 in NP vs. CP. In 16/32 patients with NP, a slight IL1R1
United European Gastroenterology Journal 2(5S)
immunoreactivity was exclusively evident in acinar cells. In CP, a slight immu-
noreactivity in acinar cells was present in 18 out of 60 tested patient samples.
IL1R1 mRNA expression showed a moderate but significant correlation with
neural hypertrophy.
The mean relative expression of IL13Ra2 did not differ between NP and CP. In
17/32 patients with NP, a slight to moderate IL13Ra2 immunoreactivity was
evident in acinar cells, islets, and especially in intrapancreatic ganglia, whereas
intrapancreatic nerves as such did not show any IL13Ra2 immunoreactivity. In
CP, a slight IL13Ra2 immunoreactivity was observed in acinar cells, tubular
complexes and islets and moderate immunoreactivity in intrapancreatic ganglia
in 33 out of 60 tested patient samples. IL13Ra2 mRNA expression correlated
significantly with the presence of pain and showed a significant negative correla-
tion with the severity of fibrosis.
CONCLUSION: Although IL1 and IL13 have been suggested to play major
roles in the pathogenesis of CP in mice models, their receptors IL1R1 and
IL13Ra2 are not overexpressed in human CP. Furthermore, IL13Ra2 expression
was even negatively correlated with the severity of fibrosis. These targets may
therefore not be as promising as therapeutic targets in CP as initially
hypothesized.
Disclosure of Interest: None declared
OP349 SERUM IGG4 IN ACUTE, CHRONIC AND AUTOIMMUNE
PANCREATITIS
J. Buijs1,*, D.L. Cahen1, M. J. Van Heerde1, R.A. Hollemans2, B.E. Hansen1, H.
C. Van Santvoort2, M.G. Besselink3, H. R. Van Buuren1, M.J. Bruno1
1
Erasmus University Medical Center, Rotterdam, 2University Medical Center,
Utrecht, 3Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: j.buijs.1@erasmusmc.nl
INTRODUCTION: Type 1 autoimmune pancreatitis (AIP) is the pancreatic
manifestation of a systemic IgG4-related fibroinflammatory disorder (IgG4-
RD). It may be challenging to distinguish AIP from acute and chronic pancrea-
titis, as they share clinical and radiological features.
AIMS & METHODS: The aim of our study was to evaluate the diagnostic value
of IgG, IgG-subclasses, and IgE, in distinguishing type 1 AIP from other forms
of pancreatitis. Between March 2007 and May 2011, sera were obtained from
consecutive patients presenting with AIP and chronic pancreatitis (CP) in a
Dutch tertiary referral center. Sera from patients with acute pancreatitis (AP)
were selected, stratified for gender and cause of pancreatitis, from a database of
732 patients, who participated in a Dutch multicentre trial between March 2004
and March 2007. Causes of acute pancreatitis were alcoholic, biliary and idio-
pathic. Serum levels of IgG, IgG1-IgG4, and IgE were determined.
RESULTS: A total of 174 patients were included; 32 with AIP, 90 with acute
pancreatitis, and 52 with chronic pancreatitis. Elevated IgG4 levels ( 1.4 g/L)
were found in 27 AIP patients (84%), but also in 7 AP (8%) and 9 CP patients
(17%; p50.001). IgG4 levels 42x the upper limit of normal (ULN) were found
in 66% of AIP patients, compared to none of the AP and 3 CP patients (6%;
p50.001). Median serum IgG4 was higher in AIP than in AP and CP (Table 1).
Total IgG, IgG1, IgG3, and IgE levels were also increased in AIP patients,
compared to the other types of pancreatitis. There was no difference in serum
IgG2 levels between the three groups.
In AP and CP patients with elevated IgG4, none of the other subclasses was
useful in distinguishing them from AIP patients. However, median total IgG and
IgE levels were lower in these patients, as compared to AIP patients (p0.02 and
50.001, respectively). In IgG4-negative AIP patients, serum IgE was higher than
in AP and CP patients (p0.013). Total IgG and the other IgG subclasses were
comparable in IgG4-negative AIP and the other types of pancreatitis.
Table 1 Serum IgG, IgG subclasses and IgE in patients with AIP, AP and CP.
Table to abstract OP349
Variable AIP (n32) AP (n90) CP (n52) p-value1
Total IgG 12.7 (10.5-21.7) 9.5 (7.7-11.1) 10.5 (8.9-12.6) 5 0.001*
IgG1 7.7 (5.9-11.9) 5.4 (4.3-6.9) 6.2 (5.3-7.9) 5 0.001*
IgG3 0.6 (0.4-1.0) 0.4 (0.3-0.7) 0.4 (0.3-0.6) 0.003*
4.5 (1.7-7.7) 0.4 (0.2-0.9) 0.6 (0.3-1.1) 5 0.001*
IgE 302 (50-978) 38 (16-104) 47 (19-102) 5 0.001*
CONCLUSION: IgG4 levels are higher in AIP, but can be elevated in AP and
CP patients as well. Therefore, elevated serum IgG4 does not exclude a diagnosis
of AP and CP, and must be interpreted with caution in patients clinically sus-
pected for AP or CP. Combined IgG4 testing with IgG or IgE, may contribute to
the differentiation between AIP and other types of pancreatitis.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
WEDNESDAY, OCTOBER 22, 2014 8:3010:30
HOT TOPICS IN SMALL INTESTINAL DISEASES LOUNGE 5_____________________
OP350 SAFETY AND EFFICACY OF LONG-TERM TEDUGLUTIDE
TREATMENT FOR PATIENTS WITH SHORT BOWEL SYNDROME
AND INTESTINAL FAILURE: FINAL RESULTS OF THE STEPS-3
STUDY
K. Iyer1,*, K. Fujioka2, J., I. Boullata3, T.R. Ziegler4, N.N. Youssef5, D. Seidner6
1
Mount Sinai Medical Center, New York, NY, 2Scripps Clinic, La Jolla, CA,
3
University of Pennsylvania, Philadelphia, PA, 4Emory University School of
Medicine, Atlanta, GA, 5NPS Pharmaceuticals, Inc, Bedminster, NJ, 6Vanderbilt
University Medical Center, Nashville, TN, United States
Contact E-mail Address: Kishore.lyer@mountsinai.org
INTRODUCTION: Patients with intestinal failure associated with short bowel
syndrome (SBSIF) require parenteral support (PS) because of malabsorption
caused by intestinal resection or dysfunction. Chronic PS is associated with
serious complications and reduced life quality. Teduglutide (TED), a recombi-
nant analogue of human glucagon-like peptide 2, improves absorption by
increasing small bowel mucosal surface area.1 In a 24-week, placebo-controlled,
phase III study (STEPS) and its 2-year, open-label extension (STEPS-2), TED
significantly reduced PS volume requirements and number of infusion days in
patients with SBSIF.2,3 STEPS-3 was undertaken to further evaluate long-term
efficacy and safety of TED in patients with SBSIF and provide prior clinical
trial patients with TED access while awaiting marketing authorisation.
AIMS & METHODS: STEPS-3 was a 1-year, open-label, multicentre study of
subcutaneous TED (0.05 mg/kg/day) conducted in patients who enrolled in
STEPS and completed STEPS-2. Patients randomised to TED in STEPS
(TED/TED group) were exposed to TED for 42 months. Patients randomised
to placebo in STEPS (PBO/TED) and patients who qualified for STEPS but were
not treated because of full enrolment (NT/TED) were exposed to TED for 36
months. Baseline was considered the start of TED treatment in STEPS (TED/
TED group) or STEPS-2 (PBONT/TED group).
RESULTS: 14 patients enrolled (mean age, 56 years [range, 4080 years]; 12/14
[86%] white; 10/14 [71%] women; 8/14 [57%] with colon-in-continuity;
meanSD prescribed PS volume at baseline, 12.98.1 L/week); 13 completed
the study. At the last dosing visit, PS was reduced from baseline by 9.8 L/week
(50%), 3.3 L/week (35%), and 5.2 L/week (73%) in the TED/TED (n5), PBO/
TED (n6), and NT/TED (n3) groups, respectively. Compared with baseline,
mean weekly PS infusions were reduced by 3.0 days/week in the TED/TED
group, 1.7 days/week in the PBO/TED group, and 2.8 days/week in the NT/
TED group. 2 patients achieved independence from PS after 126 and 130
weeks of TED treatment (as of 1st visit off PS); 2 additional patients who
were weaned off PS in STEPS-2 maintained enteral autonomy throughout
STEPS-3. Treatment-emergent adverse events (AEs) occurred in all patients;
the most common were asthenic conditions and diarrhoea (both n3). No malig-
nancies; gallbladder-, biliary-, or pancreatic-related events; episodes of gastroin-
testinal obstruction; or deaths were reported. Furthermore, no patient
discontinued the study because of an AE.
CONCLUSION: Long-term TED treatment for up to 42 months is associated
with sustained efficacy in patients with SBSIF, as shown by continued reduc-
tions in PS requirements and achievement of PS independence in some patients.
The safety profile was consistent with prior studies; no unexpected safety signals
were detected.
REFERENCES
1. Tappenden KA, et al. J Clin Gastroenterol 2013; 47: 602-607.
2. Jeppesen PB, et al. Gastroenterology 2012; 143: 1473-1481.
3. Schwartz L, et al. Am J Gastroenterol. 2013; 108: S101.
Disclosure of Interest: K. Iyer Consultancy for: NPS Pharmaceuticals, Inc, Other:
study investigator and advisory board member for NPS Pharmaceuticals, Inc, K.
Fujioka Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator
for NPS Pharmaceuticals, Inc, J. Boullata Other: study investigator and advisory
board member for NPS Pharmaceuticals, Inc, T. Ziegler Other: study investiga-
tor for NPS Pharmaceuticals, Inc, N. Youssef Shareholder of: NPS
Pharmaceuticals, Inc, Other: employee of NPS Pharmaceuticals, Inc, D.
Seidner Financial support for research from: NPS Pharmaceuticals, Inc,
Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator and advi-
sory board member for NPS Pharmaceuticals, Inc
OP351 SAFETY AND EFFICACY OF LONG-TERM TEDUGLUTIDE
TREATMENT: FINDINGS FROM A 2-YEAR, OPEN-LABEL
EXTENSION TRIAL, STEPS-2
P.B. Jeppesen1,*, K. Fujioka2, N.N. Youssef3, S.J. OKeefe4
1
Department of Medical Gastroenterology CA-2121, RIGSHOSPITALET,
Copenhagen, Denmark, 2Scripps Clinic, La Jolla, CA, 3NPS Pharmaceuticals, Inc,
Bedminster, NJ, 4University of Pittsburgh Medical School, Pittsburgh, PA, United
States
Contact E-mail Address: bekker@dadlnet.dk
INTRODUCTION: Teduglutide (TED), a glucagon-like peptide-2 analogue,
enhances intestinal absorptive capacity and enables reduction of parenteral sup-
port (PS) requirements in patients with intestinal failure associated with short
bowel syndrome (SBSIF). In the pivotal, phase III, placebo-controlled STEPS
study, 63% of patients treated with TED had a 20%100% reduction in PS from
baseline at Weeks 20 and 24 vs 30% of patients receiving placebo (P0.002).1
STEPS-2 was a 2-year, open-label, multicentre, multinational extension study of
STEPS designed to assess the long-term safety and efficacy of TED.
AIMS & METHODS: Enrolled patients included those participating in STEPS
who completed 24 weeks of TED (TED/TED) or placebo (PBO/TED) treatment
or those who qualified but were untreated (NT/TED) owing to full study
A111
enrollment. Patients received subcutaneous TED 0.05 mg/kg/day for 24
months (NT PBO/TED) or 30 months (TED/TED). Clinically meaningful
response was defined as 20%100% reduction from baseline in weekly PS
volume; baseline was determined at enrollment in STEPS (TED/TED) or
STEPS-2 (NT PBO/TED).
RESULTS: Of the 88 patients enrolled (TED/TED, n37; NT PBO/TED,
n51) in STEPS-2, 65 (74%) completed the study. Among patients who com-
pleted the study, clinically meaningful response was achieved in 93% of TED/
TED, 55% of PBO/TED, and 67% of NT/TED patients. PS requirement was
reduced by 7.6, 3.1, and 4.0 L/week in TED/TED, PBO/TED, and NT/TED
groups, respectively. 18 patients in TED/TED, 5 in PBO/TED, and 2 in NT/
TED were able to achieve 3 days/week off PS. Responses to TED were
observed regardless of age, remnant anatomy, underlying disease aetiology, or
baseline PS requirements (subgroup analysis). Patients 545 years of age had a
61% reduction, those between 4564 years had 65% reduction, and those 65
years of age had 76% reduction in PS from baseline. Patients with colon-in-
continuity had a 70% reduction and those without colon-in-continuity had a
57% reduction of PS from baseline. 21/22 patients who were responders with
TED in STEPS and completed STEPS-2 sustained their response after 2 years of
TED treatment. 13/88 patients with varying baseline characteristics were able to
achieve independence from PS with TED treatment. TED was generally well
tolerated. The most common gastrointestinal (GI) adverse events (AEs) were
abdominal pain (34%), nausea (19%), and abdominal distension (16%). The
most common non-GI AEs were catheter sepsis (28%), episodes of weight
decrease (25%), and asthenic conditions (23%). Although 64% of patients
reported serious AEs, only 10% were considered treatment related. The serious
AEs included 3 cases of cancer (2 resulting in death and 1 considered treatment
related) and 1 additional death (not considered treatment related).
CONCLUSION: In patients with SBSIF, long-term treatment with TED was
generally well tolerated and resulted in durable and sustained response as demon-
strated by continued reductions in PS, and, in some patients, independence from
PS. This effect was observed across a range of varying baseline characteristics.
REFERENCES
1. Jeppesen PB, et al. Gastroenterology 2012; 143: 1473-1481.
Disclosure of Interest: P. Jeppesen Financial support for research from: NPS
Pharmaceuticals, Inc, Consultancy for: NPS Pharmaceuticals, Inc, Other: advi-
sory board member and study investigator for NPS Pharmaceuticals, Inc, K.
Fujioka Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator
for NPS Pharmaceuticals, Inc, N. Youssef Shareholder of: NPS Pharmaceuticals,
Inc, Other: employee of NPS Pharmaceuticals, Inc, S. OKeefe Financial support
for research from: NPS Pharmaceuticals, Inc, Consultancy for: NPS
Pharmaceuticals, Inc, Other: study investigator for NPS Pharmaceuticals, Inc
OP352 INDEPENDENCE FROM PARENTERAL SUPPORT DURING
TREATMENT WITH TEDUGLUTIDE AMONG PATIENTS WITH
INTESTINAL FAILURE ASSOCIATED WITH SHORT BOWEL
SYNDROME (SBSIF)
P.B. Jeppesen1,*, J., I. Boullata2, T.R. Ziegler3, U.-F. Pape4, K. Iyer5,
M. Kunecki6, S.M. Schneider7, N.N. Youssef8, K. Fujioka9
1
Department of Medical Gastroenterology CA-2121, RIGSHOSPITALET,
Copenhagen, Denmark, 2University of Pennsylvania, Philadelphia, PA, 3Emory
University School of Medicine, Atlanta, GA, United States, 4Charite University
Medical Center, Berlin, Germany, 5Mount Sinai Medical Center, New York, NY,
United States, 6M. Pirogow Hospital, Lodz, Poland, 7University of Nice-Sophia
Antipolis, Nice, France, 8NPS Pharmaceuticals, Inc, Bedminster, NJ, 9Scripps
Clinic, La Jolla, CA, United States
Contact E-mail Address: Bekker@dadlnet.dk
INTRODUCTION: The intestinotrophic agent teduglutide (TED) was asso-
ciated with clinically significant reductions in parenteral support (PS) in clinical
trials in patients with SBSIF.1-4
AIMS & METHODS: We report the clinical characteristics of patients who
achieved complete independence from PS while receiving TED 0.05 mg/kg/day
in either of 2 phase III randomised controlled trials (RCTs)1,2 or their exten-
sions.3,4 PS was reduced (at 4-week intervals in RCTs and 4- to 12-week intervals
in extension studies) if clinical status was stable and 48-hour urine output was
increased by 10% over baseline (target urine output: 12 L/day).
RESULTS: A total of 134 patients were treated with TED 0.05 mg/kg/day. Of
these, 16 patients achieved independence from PS after 12130 weeks of TED
treatment (as of first visit off PS). The duration of PS dependency at baseline
(start of treatment with TED) ranged from 116 years in these patients. Baseline
demographics and disease characteristics varied widely (Table 1). However, more
patients who achieved PS independence had colon-in-continuity (n12/16) and/
or lower baseline PS requirements (57 L/week, n11/16). Adverse reaction
profile of all treated patients was consistent with underlying cause of SBS, con-
comitant medication use, pharmacologic effect of TED within the gastrointest-
inal (GI) tract, and PS requirements. The most commonly reported serious
adverse event (AE) in all treated patients was catheter sepsis; GI AEs were
common and were the main reason for discontinuation.
A112 United European Gastroenterology Journal 2(5S)
Table 1. Baseline Characteristics of Patients Who Achieved Independence From
PS With TED (0.05 mg/kg/day)
Table to abstract OP335
SIZE RESECTION TYPE SITE SCARRED

50mm 450mm En bloc P meal LC RC yes no

ALL POLYP RECURRENCE 14/106 (13%) 6/78 (7.6%) 8/28 (28.5%) 1/42 (2.3%) 7/44 (15.9%) 13/83 (15.6%) 1/23 (4.3%) 6/20 (30%) 8/86 (9.3%)
P 0.009 P 0.001 P 0.15 P 0.024
UNSCARRED POLYP RECURRENCE 8/86 (9.3%) 2/62 (3.2%) 6/24 (25%) 1/42 (2.3%) 7/44 (15.9%) 8/68 (11.7%) 0/18 (0%)
P0.005 P0.058 P0.195

CONCLUSION: A number of patients with widely varied baseline characteris- TABLE. Analysis Results
tics were able to achieve enteral autonomy and independence from PS with TED
treatment. Ex-PN Intra-PN
REFERENCES Insulin Insulin
1. Jeppesen PB, et al. Gut 2011; 60: 902-914. Variables (n56) (n41) p-value
2. Jeppesen PB, et al. Gastroenterology 2012; 143: 1473-1481.
3. OKeefe SJ, et al. Clin Gastroenterol Hepatol 2013; 11: 815-823. Mean Age 65.91013.369 65.7610.178 0.949
4. Schwartz LK, et al. Am J Gastroenterol 2013; 108: S101. Male (%) 44.6% 43.9% 0.942
Disclosure of Interest: P. Jeppesen Financial support for research from: NPS Mean BMI 23.9184.556 22.5524.894 0.166
Pharmaceuticals, Inc, Consultancy for: NPS Pharmaceuticals, Inc, Other: advi- % hypoglycemia (54.0) by Population 31/1876 (1.7%) 16/1788 (0.9%) 0.042
sory board member and study investigator for NPS Pharmaceuticals, Inc, J. % hypoglycemia (54.0) by Patient-Day 21/438 (4.8%) 12/422 (2.8%) 0.182
Boullata Other: study investigator and advisory board member for NPS
% hypoglycemia (54.0) by Patient 10/56 (17.9%) 9/41 (22%) 0.462
Pharmaceuticals, Inc, T. Ziegler Other: study investigator for NPS
Pharmaceuticals, Inc, U.-F. Pape Other: study investigator and advisory board
member for NPS Pharmaceuticals, Inc, K. Iyer Consultancy for: NPS
Pharmaceuticals, Inc, Other: study investigator and advisory board member CONCLUSION: Protocolized administration of insulin inside PN bag has lower
for NPS Pharmaceuticals, Inc, M. Kunecki Other: study investigator for NPS risk of hypoglycaemia compared to Ex-PN insulin and can be safely
Pharmaceuticals, Inc, S. Schneider Other: study investigator and advisory board administered.
member for NPS Pharmaceuticals, Inc, N. Youssef Shareholder of: NPS Disclosure of Interest: None declared
Pharmaceuticals, Inc, Other: employee of NPS Pharmaceuticals, Inc, K.
Fujioka Consultancy for: NPS Pharmaceuticals, Inc, Other: study investigator
for NPS Pharmaceuticals, Inc OP354 LARGE DELETION IN THE EPCAM GENE RESPONSIBLE FOR
THE MILDER PHENOTYPE OF CONGENITAL TUFTING
ENTEROPATHY
OP353 RISK OF HYPOGLYCEMIA WAS LOWER WITH J. Gerada1, C. Saliba2,*, R. Galdies1, W. Cassar1, V. Mercieca3, J. DeGaetano1,
ADMINISTRATION OF PROTOCOLIZED INSULIN INSIDE E. Gerada1, N.J. Sebire4, S. Hill4, M. Vassallo1, C. Scerri2, G. Grech2,
PARENTERAL NUTRITION (PN) BAG COMPARED TO T.M. Attard1
CONVENTIONAL INSULIN ADMINISTERED SEPARATELY 1
Mater Dei Hospital, 2University of Malta, Msida, 3Gozo General Hospital, Gozo,
DURING TOTAL PARENTERAL NUTRITION (TPN) Malta, 4Great Ormond Street Hospital, London, United Kingdom
J.L. Hartono1,*, S.N. Teoh2, M.Y. Sim3, T.M. Foo3, C.Y. Tong4, L.L. Lim1
1
Gastroenterology and Hepatology, 2Pharmacy, National University Hospital INTRODUCTION: A number of point mutations within the EPCAM gene have
Singapore, 3Yong Loo Lin School of Medicine, National University of Singapore, been found to be responsible for congenital tufting enteropathy (CTE). We pre-
4
Dietetics, National University Hospital Singapore, Singapore, Singapore viously described a milder phenotype of CTE in a cohort of Maltese patients1.
Contact E-mail Address: juanda_leohartono@yahoo.com EpCAM staining was negative in the whole cohort1, suggesting a defective
EPCAM gene in the milder phenotype.
INTRODUCTION: Insulin dose adjustment for diabetic patients with inpatient AIMS & METHODS: To identify the underlying genetic abnormality within the
parenteral nutrition (PN) is required to achieve glycemic control. Route of EPCAM gene responsible for the milder CTE. In the period 1985 2012, eight
administration with concomitant protocolized insulin inside the PN bag is per- Maltese patients with CTE from six unrelated families were retrospectively iden-
ceived to have a higher risk of hypoglycaemia compared to conventional ad-hoc tified. Genomic DNA was extracted from peripheral blood. Primers for all nine
insulin administered separately. exons within the EPCAM gene were designed and optimized. PCR products were
AIMS & METHODS: We aim to compare the rate of hypolycemia between amplified and sequenced. To sequence exon 4 exon 6 region, the PCR product
those who received protocolized intra-PN bag insulin and ex-PN bag ad-hoc was purified from the gel and ligated in a TA Vector. The ligated products were
(sliding scale) insulin (administered separately) among diabetic patients who transformed into DH5 bacteria and cultured on ampicillin-containing agar
received inpatient TPN. plates. The cultured DNA was extracted and sequenced. All DNA sequences
Retrospective analysis was conducted for all inpatient diabetic patients who were compared with controls. Unaffected family members (parents) and healthy
received TPN between April 2008 to August 2012 in National University controls were screened for the deletion.
Hospital Singapore. Demographic data such as age, gender, and body mass RESULTS: Genetic analysis of the EPCAM gene in Maltese CTE patients
index (BMI) as well as glycemic reading was recorded. Hypoglycemia was defined revealed a novel homozygous 1773bp deletion in seven patients, starting from
as blood glucose level of 54.0 mmol/L based on ASPEN guidelines. Besides the 1170bp downstream of exon 4, up to 721bp upstream of exon 6, resulting in
conventional model of using the total number of glucose readings from all complete deletion of exon 5. The remaining patient was a heterozygote for the
patients between the 2 groups (by population), we also analysed other gluco- deletion. The mutant homozygous variant resulted in a frameshift, introducing
metrics using other analytic models by patient-day and by (individual) patient 23 novel amino acids, formation of a premature stop codon, p.Ala164Metfs*24.
as previously proposed (Goldberg PA et al. 2006) in order to have a more loss of the transmembrane domain and complete lack of EpCAM protein within
comprehensive result. By patient-day model was done by grouping the glucose the intestinal epithelium. Three sets of parents of 3 affected patients were all
readings into per single day readings per patient as denominator. By patient heterozygous for this deletion. 98 out of 100 healthy controls tested were homo-
model was done by grouping glucose readings of the entire stay using each zygous wild type and two (2%) were heterozygous for the deletion.
individual patient as denominator. CONCLUSION: This novel large deletion within the EPCAM gene was found to
RESULTS: Total of 97 patients were analysed (56 ex-PN insulin; 41 intra-PN be responsible for the milder phenotype of Maltese CTE patients. The hetero-
insulin) with total 3664 glucose readings. Results were summarised in Table. zygous mutation of the patients parents confirms the autosomal recessive pat-
Demographic characteristics (age, gender, and BMI) were similar between the tern of inheritance of CTE. This genetic deletion present in all patients implies a
2 groups. The hypoglycaemic rate for Intra-PN insulin group was not higher than founder effect and we propose this as the first genotype-phenotype correlation in
Ex-PN insulin group. The rate of hypoglycaemia was not significantly different isolated intestinal TE patients.
between Ex-PN insulin and Intra-PN insulin group using analysis model by REFERENCES
patient (10/56[17.9%] vs. 9/41[22%], respectively; p0.462) and by patient- 1. Gerada J, Scerri C, DeGaetano J, et al. Epithelial EpCAM expression does not
day (21/438 [4.8%] vs. 12/422 [2.8%], respectively; p0.182). In fact, the correlate with intestinal absorptive function in the milder phenotype of tufting
number of glucose reading with hypoglycaemia was significantly higher in Ex- enteropathy Gut 2012; 61(Suppl. 3): A75.
PN insulin group using analysis model by population (31/1876 [1.7%] vs. 16/ Disclosure of Interest: None declared
1788 [0.9%]; p0.042).
United European Gastroenterology Journal 2(5S)
OP355 NON-STEROIDAL ANTI-INFLAMMATORY DRUGS INJURE
THE SMALL INTESTINE THROUGH NLRP3 INFLAMMASOME
ACTIVATION
T. Watanabe1,*, A. Higashimori1, Y. Nadatani1, T. Tanigawa1, K. Tominaga1,
Y. Fujiwara1, T. Arakawa1
1
Department of Gastroenterology, Osaka City University Graduate School of
Medicine, Osaka, Japan
Contact E-mail Address: watanabet@med.osaka-cu.ac.jp
INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) induce
intestinal overexpression of tumor necrosis factor (TNF)- in a Toll-like receptor
4 (TLR4)-dependent manner, causing small intestinal damage (Watanabe et al,
A113
Ferrara JL, Harris AC, Greenson JK, et al. Regenerating islet-derived 3-alpha is
a biomarker of gastrointestinal graft-versus-host disease. Blood 2011; 15; 118:
6702-6708.
Disclosure of Interest: None declared
OP357 THE DIAGNOSTIC YIELD OF THE 75SEHCAT TEST IN
PATIENTS WITH CHRONIC DIARRHOEA
N. Mottacki1,*, M. Simren1, K.-A. Ung2, A. Bajor1
1
Dept. of Internal Medicine & Clinical Nutrition, Sahlgrenska Academy, University
of Gothenburg, Gothenburg, 2Department of Gastroenterology, Institute of
Medicine, Skovde, Sweden
Gut, 2008). Although like TNF-, interleukin (IL)-1 is a potent proinflamma-
tory cytokine, its role in this damage remains unknown. The inflammasome
consists of one of several NOD-like receptors (NLRs) including NLRP3,
NLRP6, and NLRC4, the adaptor protein apoptosis-associated speck-like pro-
tein containing CARD (ASC), and pro-caspase-1. The inflammasome is a large
multiprotein complex whose assembly leads to pro-caspase-1 processing into
Contact E-mail Address: nima.mottacki@vgregion.se
INTRODUCTION: The 75SeHCAT test mirrors the turnover rate of bile acids
and is used to diagnose bile acid diarrhoea (BAD). Retention 510% on day 7 is
considered abnormal. Where this is not due to ileal disease (type 1), or associated
with other pathologies (type 3) it is termed idiopathic bile acid diarrhoea (type 2).
cleaved caspase-1, which promotes the processing of pro-IL-1 into its mature AIMS & METHODS: We aimed to study the distribution of the 75SeHCAT test
active form. values in different conditions with chronic diarrhoea, and to determine if there
AIMS & METHODS: The aim of this study was to investigate the role of are diagnostic groups where the test is unnecessary. The prevalence of idiopathic
inflammasomes and IL-1. Indomethacin (10 mg/kg) was administered orally
to wild-type, NLRP3 knockout (KO), caspase-1 KO, or TLR4 KO mice. The
small intestines were removed 3, 6, 12, and 24 h after administration. Intestinal
damage was assessed by measuring the ulcerated area in the intestinal mucosa;
mRNA expression of inflammatory mediators was assessed using RT-PCR.
BAD was also evaluated. 2112 consecutive 75SeHCAT tests performed at our
university hospital were reviewed. Medical records from the referring clinic were
also investigated. Patients were included if referred for the investigation of diar-
rhoea and excluded if there was insufficient data to establish a cause of referral.
Results in each diagnostic group were then compared to 29 previously published
Protein levels of pro-IL-1 and IL-1 in the small intestine were measured healthy controls using non-parametric tests. Patients were considered to have
using a specific ELISA. NLRP3, cleaved caspase-1, and IL-1 localization was BAD if 75SeHCAT on day 7 (S7) was less than 10%.
determined by immunohistochemistry. Further, to clarify the role of IL-1 in the RESULTS: Median S7 was significantly lower compared to controls in all diag-
damage, wild-type mice were intraperitoneally administered mouse recombinant noses except coeliac disease. The relative risk (RR) for a positive 75SeHCAT test
IL-1 (rIL-1), anti-IL-1-neutralizing antibodies, or vehicles after indomethacin in these patients was 7.2 compared to healthy controls. In those with ileocaecal
administration. Crohns disease and ileocaecal resection in particular RR was 13.5/12.0. Female
RESULTS: Small intestinal damage developed 3 h after indomethacin adminis- gender was more prevalent in all groups referred for testing, except patients with
tration and was accompanied by increases in IL-1B mRNA expression and UC. Though there were more female patients in those witout a predisposing
proIL-1 and IL-1 protein levels in the small intestine. IL-1 immunoneutrali- condition, there was a higher proportion of males testing positive for BAD in
zation attenuated small intestinal damage by 53%, while rIL-1 aggravated the this group of patients (54% vs. 42%, p50.005).
damage. NLRP3 mRNA expression increased after indomethacin administra-
tion, whereas that of other NLRs such as NLRP6 and NLRC4 did not. SeHCAT Median S7 Relative risk
Compared to the wild-type mice, the NLRP3 KO and caspase-1 KO mice Clinical feature (n) retention 510 (perc. 10, 90) %female (95% CI)
showed intestinal damage inhibition by 58% and 87%, respectively, with IL-1
protein level reduction, although pro-IL-1 levels were similar between the wild- All patients (n1602) 49.7% (n796) 10.7* (1.00, 36.0) 66.3 7.2 (1.9-27.3)
type and two types of KO mice. Genetic depletion of TLR4 prevented indo- No predisposing condition (n700) 46.4% (n325) 12.0* (1.86, 34.0) 61.4 6.8 (1.8-25.9)
methacin-induced overexpression of NLRP3 mRNA and IL-1 protein in the Cholecystectomy (n231) 67.5% (n156) 6.50* (1.00, 24.0) 85.3 9.8 (2.6-37.3)
small intestine and inhibited intestinal damage by 78%. Immunoreactivity for Collagenous colitis (n171) 35.1% (n60) 16.0* (3.03, 36.0) 79.5 5.0 (1.3-19.5)
cleaved caspase-1 and IL-1 was mainly observed in inflammatory cells such as
macrophage, while NLRP3 was diffusely expressed on many types of cells includ-
ing inflammatory and epithelial cells.
CONCLUSION: Our results suggest that the NLRP3 inflammasome plays a
crucial role in NSAID-induced small intestinal damage, and the TLR4 signaling
pathway may trigger NLRP3 inflammasome activation.
Disclosure of Interest: None declared
OP356 REGENERATING ISLET-DERIVED 3-ALPHA IS A BIOMARKER
OF ORGANIC ENTEROPATHIES
I. Marafini1,*, A. Di Sabatino2, F. Zorzi1, I. Monteleone1, S. Sedda1,
M.L. Cupi1, P. Biancheri2, P. Giuffrida2, G.R. Corazza2, F. Pallone1,
G. Monteleone1
1
University of Rome Tor Vergata, Rome, 2University of Pavia, Pavia, Italy
Contact E-mail Address: gi.monteleone@med.uniroma2.it
INTRODUCTION: The clinical presentation of organic and functional intestinal
disorders can overlap and clinicians rely often on invasive and time-consuming
procedures to make a final diagnosis. Regenerating islet-derived 3- (Reg3), a
Paneth cell-derived antimicrobial protein, is detectable in the circulation of
patients with intestinal graft-versus host disease (GVHD) and patients with
inflammatory bowel disease.
AIMS & METHODS: The aim of our study was to determine whether serum
Reg3 testing is useful for discriminating patients with structural enteropathies
from those with functional intestinal disorders. We prospectively included 39
patients with active celiac disease (ACD), 11 patients with refractory celiac dis-
ease (RCD), 40 patients with active Crohns disease, 6 patients with common
variable immunodeficiency (CVID), and 14 patients with irritable bowel syn-
drome (IBS)-related diarrhea. Serum samples were also taken from 10 CD
patients before and after 6-12 months of a gluten-free diet (GFD). Sera of 22
healthy volunteers were used to determine the cut-off value. Reg3 levels were
measured by a commercial ELISA kit.
RESULTS: Levels of Reg3a exceeded the cut-off value of the assay in 35/39
(89.7%) ACD patients, 11/11 (100%) RCD patients, 6/6 (100%) CVID patients,
and 34/40 (86.7%) Crohns disease patients. None of the IBS patients had
increased levels of Reg3a. Reg3a levels distinguished organic enteropathies
from IBS with a sensitivity of 89% and a specificity of 100%. Reg3a levels
significantly decreased following a GFD.
CONCLUSION: Reg3 is a serum biomarker of intestinal damage that can be
combined with clinical data to identify patients who should undergo invasive
tests for diagnosing organic enteropathies.
REFERENCES
Bevins CL and Salzman NH. Paneth cells, antimicrobial peptides and mainte-
nance of intestinal homeostasis. Nat Rev Microbiol 2011; 9: 356-368.
Gironella M, Iovanna JL, Sans M, et al. Anti-inflammatory effects of pancrea-
titis associated protein in inflammatory bowel disease. Gut 2005; 54: 1244-1253.
Crohns disease (n58) 93.1% (n54) 1.40* (0.01, 9.12) 56.9 13.5 (3.5-51.5)
Ileocecal resection (n58) 82.8% (n48) 2.40* (0.01, 13.2) 63.8 12.0 (3.1-45.9)
Lymphocytic colitis (n53) 34.0% (n18) 15.0* (1.2, 39.8) 66.0 4.9 (1.2-19.7)
Coeliac disease (n53) 20.8% (n11) 27.0 (3.86, 64.2) 77.4 3.0 (0.71-12.7)
Ulcerative colitis (n38) 28.9% (n11) 20.0* (4.80, 49.7) 28.9 4.2 (1.01-17.5)
CONCLUSION: The 75SeHCAT test is a valuable tool in the diagnostic work-up
of chronic diarrhoea. However, in patients with ileal Crohns disease, or post
ileocaecal resection, it may be unnecessary as the test can be presumed to be
positive. Patients who are referred for the test are predominantly female, how-
ever, the likelihood of finding a positive test appears, if anything, to be greater in
males.
Disclosure of Interest: None declared
OP358 SM22 AS POTENTIAL BIOMARKER FOR THE DETECTION OF
TRANSMURAL ISCHEMIC INJURY OF THE INTESTINES
D. Schellekens1,2,*, K. Reisinger2,3, J. Derikx1,2, K. Lenaerts1,2, W. Buurman2,
C. Dejong1,2
1
Dept. of General Surgery, 2NUTRIM School for Nutrition, Toxicology and
Metabolism, Maastricht University Medical Center, Maastricht, 3Dept. of General
Surgery, Orbis Medical Center, Sittard-Geleen, Netherlands
Contact E-mail Address: D.Schellekens@maastrichtuniversity.nl
INTRODUCTION: Acute mesenteric ischemia is an abdominal emergency
requiring rapid diagnosis and treatment since the duration of ischemia is the
most important determinant of outcome. Current biomarkers only detect
ischemic mucosal injury, whereas differentiation between mucosal and trans-
mural ischemic intestinal damage is imperative because only the latter mandates
emergency surgery. Our previous study showed that SM22 (22-kDa protein
exclusively expressed in visceral smooth muscle tissue) is a potential plasma
biomarker for intestinal transmural injury. The aim of this study was (1) to
investigate whether SM22 could be detected in plasma and urine after intestinal
ischemia in rats, (2) to obtain insight into the organ-specific release and clearance
of SM22, and (3) to provide first data on the diagnostic potential of SM22
plasma levels to detect transmural ischemia in man.
AIMS & METHODS: SM22 release was investigated in 42 rats subjected to
mesenteric ischemia for up to 24 hours (h) by jejunal blood supply ligation.
Blood, urine and tissue was sampled at baseline and after 2, 4, 6, 8, 12 and
24h of ischemia. Six rats were sham-operated. SM22 concentrations were mea-
sured using a newly built ELISA. Organ-specific SM22 release and clearance was
studied in blood drawn from portal, hepatic, renal veins and an artery in rats and
in 10 patients undergoing major upper abdominal surgery. Next, SM22 and
Intestinal Fatty Acid Binding Protein (I-FABP) (a sensitive marker to study
enterocyte damage) were quantified in plasma of 12 patients with proven
A114
intestinal ischemia and 50 healthy volunteers. Tissue sections were stained with
haematoxylin/eosin (HE) and anti-SM22. Data are presented as meanSEM and
analyzed using Kruskal Wallis tests. A P-value 50.05 is considered statistically
significant.
RESULTS: In rats, histological assessment revealed degeneration of the mucosa
and necrosis of the muscular layers of the intestinal wall in jejunum from 6h
ischemia onwards as compared to control or sham. Staining for SM22 revealed a
decrease in staining intensity or even a total absence of SM22 protein in the
muscular layers after 8h ischemia. Baseline plasma SM22 levels were 0.1 ng/
ml in all animals. After 4h ischemia, SM22 plasma concentrations were signifi-
cantly increased compared to baseline (7.301.97 ng/ml vs 0.450.09 ng/ml,
P50.05), and remained elevated until 24h. Urinary SM22 concentrations were
significantly higher in rats with intestinal ischemia compared to sham (0.140.08
ng/ml vs 3.050.67 ng/ml, P5 0.05). Transorgan measurements showed that
SM22 was specifically released from the intestines and removed from circulation
by the kidneys, resulting in a plasma half-life of about 16 minutes in rats and 22
minutes in man. SM22 levels were significantly higher in patients with histo-
pathological proven transmural infarction(n6) compared to patients with
only ischemic mucosal injury (n6) and healthy controls (5.9 ng/ml vs 0.6 ng/
ml and 0.4 ng/ml (P5 0.001), respectively).
CONCLUSION: SM22 is released into the circulation after severe intestinal
ischemic injury and is a potentially useful marker of transmural injury during
intestinal ischemia.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
ADVANCED COLONOSCOPIC IMAGING HALL C_____________________
OP359 SIMPLE NEW DIAGNOSTIC FEATURES OF SESSILE
SERRATED ADENOMA/POLYPS ON MAGNIFYING NARROW
BAND IMAGING: A PROSPECTIVE STUDY OF DIAGNOSTIC
ACCURACY
T. Yamashina1,*, Y. Takeuchi1, N. Uedo1, N. Hanaoka1, S. Yamamoto1,
K. Higashino1, R. Ishihara1, H. Iishi1
1
Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular
Diseases, Osaka, Japan
Contact E-mail Address: take8047@hotmail.com
INTRODUCTION: The narrow band imaging classification system (NICE clas-
sification) classifies colorectal polyps very accurately, including differentiating
adenomatous from hyperplastic polyps (HPs). However, it is often difficult to
discriminate sessile serrated adenoma/polyps (SSA/Ps) from HPs.
AIMS & METHODS: The aim of this study was to establish and evaluate new
simple diagnostic features for SSA/Ps using magnifying narrow band imaging
(M-NBI).
We performed a prospective, single-arm observational study of diagnostic accu-
racy in two stages, as follows: phase 1 (seeking stage), development of simple
diagnostic features for SSA/P and definition of diagnostic criteria based on retro-
spective assessments of M-NBI; and phase 2 (validation stage), prospective vali-
dation and evaluation of the simple new diagnostic criteria. (Trial registration
number: UMIN-CTR 000009808)
RESULTS: In the seeking stage, we identified brownish, oval, expanded crypt
openings and thick branched vessels on the surfaces of SSA/Ps. We named these
expanded crypt openings (ECOs) and dilated and branched vessels (DBVs), by reviewers country, specialty, expertise and experience of pathological train-
respectively. In the validation stage, we enrolled 796 polyps in 261 patients. We
classified 126 polyps as NICE Type 1; all these lesions were endoscopically
removed and assessed histopathologically. The sensitivity, specificity, and accu-
racy of ECOs for SSA/Ps were 82.4%, 84.3%, and 81.1%, respectively; whereas
the sensitivity, specificity, and accuracy of DBVs were 59.2%, 45.1%, and 68.9%,
respectively. M-NBI provided a sensitivity of 98% and specificity of 59.5% for
discrimination of SSA/Ps from other lesions classified as NICE Type 1.
CONCLUSION: Identification of ECOs, supplemented with DBVs, has high
sensitivity for the diagnosis of SSA/P. These findings may facilitate the use of
endoscopic optical diagnosis in clinical practice.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
(p0.012), and who has over 10mm concomitant lesion were 45.7%/19.0% in
IC/NIC (p0.001) respectively.
Regarding the location of tumor, right colon/left colon was 51.4%/48.6% in IC
group and 32.8%/67.2% in NIC group (p0.02).
By analysis of covariance, cumulative incidence of IC were always higher in right
colon during the whole examination period (p0.001).
Percentage of patient whose insertion time over 10min was 60.0%/39.8% in IC/
without IC (p0.001).
CONCLUSION: Characteristics of clinicopathological features of IC were small
size, located mostly in the right colon. Regarding the predictive factors of IC at
the index colonoscopy, three or more tumor co-existence, co-existing of tumor
over 10mm, and over 10min insertion time could be predictive factors.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
ENDOSCOPY MEETS PATHOLOGY: EARLY NEOPLASIA IN THE UPPER GI TRACT
HALL I/K_____________________
OP361 INFLUENCE OF REVIEWERS CLINICAL BACKGROUNDS
OVER INTERPRETATION OF CONFOCAL LASER
ENDOMICROSCOPY FOR SUPERFICIAL GASTRIC LESIONS. AN
INTERNATIONAL MULTI-CENTRIC STUDY
K. Sumiyama1,*, H. Neumann2, M. Kobayashi1, S. Abe3, Y. Nakai 4, M. Vieth5,
K. Nakajima6, R. Kiesslich7, H. Tajiri8
1
Department of Endoscopy, The Jikei University School of Medicine, Tokyo,
Japan, 2Department of Medicine I, Interdisciplinary Endoscopy,
Universitatsklinikum Erlangen, Erlangen, Germany, 3Division of Endoscopy,
National Cancer Center Hospital, 4Department of Gastroenterology, The
University of Tokyo, Tokyo, Japan, 5Institut fur Pathologie, Klinikum Bayreuth,
Bayreuth, Germany, 6Department of Surgery, Osaka University, Osaka, Japan,
7
Internist und Gastroenterologe, Caefarzt Medizische Klinik, St.
Marienkrankenhaus, Frankfurt, Germany, 8Department of Internal Medicine,
Division of Gastroenterology and Hepatology, The Jikei University School of
Medicine, Tokyo, Japan
Contact E-mail Address: kaz_sum@jikei.ac.jp
INTRODUCTION: Confocal laser endomicroscopy (CLE) is a novel endoscopic
technology which provides real-time histological tissue analysis during standard
endoscopic observation. In current endoscopic management strategy for gastric
cancer, substantial discrepancy exists between East and West countries due to
diversity in clnical backgrounds such as prevalence of gastric neoplasias. We
surmised that accuracy of CLE interpretation could vary depending on reviewers
clinical backgrounds.
AIMS & METHODS: Aims of this study were to elucidate the influence of
reviewers clinical backgrounds over the CLE deferential diagnosis for superficial
gastric lesions (neoplastic or non-neoplastic) in collaboration with German and
Japanese institutions. Thirty WLE and 30 fluorescein assisted probe based CLE
movie clips (30sec) of 18 neoplastic and 12 non-neoplastic lesions were reviewed
by 39 reviewers. The reviewers had web-based self-training prior to the video
review. The WLE and CLE review was done back to back for each lesion and
initiated by the WLE interpretation. Each clip was then classified as either neo-
plastic or non-neoplastic. The results of the video reviews were compared with
the final histological diagnosis of the studied sites. The outcomes were analyzed
ing, GI endoscopy and CLE independently.
RESULTS: The table below demonstrated the accuracy of the differential diag-
nosis. The accuracy of CLE was generally higher than the accuracy of WLE
regardless of reviewers clinical background. Outcomes of GI experts and
Japanese were better than outcomes of pathologists and Germans respectively
(GI/Pathologist: p0.038 for WLE, p0.002 for CLE, German/Japanese p.001
for WLE, p50.001 for CLE). There was no significant correlation between the
accuracies, and the experience of CLE and pathological training (Expert with
experience of over 1000 GI endoscopy cases with/without pathological training:
p0.93 for WLE, p0.067 for CLE).
Clinical background of reviewers WLE 95%CI WLECLE 95%CI p-value

OP360 CLINICOPATHOLOGICAL FEATURE AND RISK FACTOR OF Overall (n39) 65.64 62.84-68.36 73.93 71.3-76.42 0.0002
INTERVAL CANCER with CLE experience (n7) 64.29 57.4-70.76 75.71 69.34-81.35 0.0195
K. Matsumoto1,*, A. Nagahara1, E. Sagawa1, Y. Nakagawa1, K. Matsumoto1, without CLE experience (n32) 65.94 62.84-68.93 73.54 70.63-76.31 0.0028
H. Ueyama1, N. Sakamoto1, T. Terai1, S. Watanabe1 GI physians and surgeons (GI) (n33) 66.87 63.84-69.80 75.66 72.86-78.30 50.01
1
gastroenterology, JUNTENDO UNIVERSITY SCHOOL OF MEDICINE, Pathologists (n6) 51.32 51.32-66.15 64.44 56.9-71.42 0.63
Tokyo, Japan German (n7) 55.71 48.72-62.55 64.9 57.40-70.76 NS
Contact E-mail Address: kmatumo@juntendo.ac.jp
Japanese (n32) 67.81 64.75-70.76 73.21 73.21-78.71 50.01
INTRODUCTION: Colorectal cancers diagnosed with a few years after index Expert w pathological training (n14) 67.38 62.66-71.84 73.33 68.83-77.50 p0.002
colonoscopy can arise from missed lesions or development of a new tumor and Expert w/o pathological training (n17) 67.64 63.39-71.69 77.25 73.37-80.82 p0.002
recently such cancers are reported as interval cancer.
AIMS & METHODS: We analyzed 59125 cases out of 43210 patients who
underwent colonoscopy. Patients were defined as having an interval cancer
(IC) if they detected colorectal submucosal invasive or deeper invasive cancer CONCLUSION: The results of this study demonstrated that reviewers clinical
within 36 months from index colonoscopy. Another cancer was defined as a non- backgrounds influenced CLE diagnosis for superficial gastric lesions and the
interval cancer (NIC). We investigated the clinical difference between IC and disease-specific expertise of standard endoscopic observation might benefit the
NIC. And investigated to clarify clinicopathological features and risk factors CLE diagnosis accuracy. The interpretation of unstable en face fluorescein
of IC. assisted CLE image might be more similar to real-time endoscopic diagnosis
RESULTS: We identified 35 cases of IC and 1030 cases of NIC. IC/NIC were than histological analysis of sliced fixed tissues.
male; 82.9%/65.3% (p0.03), diameter (T1stage); 15.9mm/21.1mm (p0.002), Disclosure of Interest: None declared
diameter (T2stage); 30.6mm/51.0mm (p0.002), respectively. Average interval
from index colonoscopy of IC was 18.1month. At the index colonoscopy,
patients which co-exist three or more lesions were 57.1%/36.7% in IC/NIC
United European Gastroenterology Journal 2(5S)
OP362 QUANTITATIVE ANALYSIS OF VOLUMETRIC LASER
ENDOMICROSCOPY IMAGES WITH HISTOLOGICAL
CORRELATION OF EX-VIVO ENDOSCOPIC RESECTION
SPECIMENS OF BARRETTS OESOPHAGUS WITH AND WITHOUT
EARLY NEOPLASIA
A.-F. Swager1,*, D. M. de Bruin2, D.J. Faber2, B.L. Weusten1, S.L. Meijer3,
J.J. Bergman1, T. G. van Leeuwen2, W.L. Curvers1
1
Gastroenterology and hepatology, 2Biomedical Engineering, 3Pathology,
Academic Medical Center, Amsterdam, Netherlands
INTRODUCTION: Early neoplastic lesions in Barretts oesophagus (BO) are
difficult to detect with white-light endoscopy. Volumetric laser endomicroscopy
(VLE) is a new optical coherence tomography (OCT)-based imaging technique
that provides large circumferential sub-surface maps of the superficial oesopha-
geal wall layers at a resolution of low-power microscopy. VLE data can be
quantified by measuring the attenuation coefficient (mOCT), the decay of detected
backscattered light versus depth. mOCT has the potential of providing quantitative
optical diagnosis of interrogated mucosa because it relates to the organization of
tissue.
AIMS & METHODS: To investigate the feasibility of mOCT for identification of
early neoplasia in BO.
Endoscopic resection (ER) specimens from BO patients with and without neo-
plasia were scanned ex-vivo with VLE. Histopathology slides from the specimens
were correlated one-to-one with VLE scans based on in-vivo and ex-vivo placed
electrocoagulation markers. Quantification of VLE signal attenuation (mOCT) was
performed on areas of interest (AoIs) from VLE scans that were matched with
histology in order to differentiate non-dysplastic (NDBO) and dysplastic BO
mucosa.
RESULTS: In this pilot study, 14 endoscopic resection (ER) specimens yielded
14 histology-VLE matches with 25 AoIs consisting of 21 NDBO and 4 dysplastic
BO AoIs (LGD n1, HGD n3). Median mOCT values (mm-1) of the different
mucosa types were compared: NDBO 0.41 (IQR 0.17-1.82) and dysplastic BO
3.31 (IQR 1.43-5.49). A statistically significant difference was observed between
these groups (p 0.04).
CONCLUSION: Quantitative VLE by means of mOCT may potentially differenti-
ate between NDBO and dysplastic BO. Further research in larger sample size is
needed to validate mOCT for the distinction between dysplastic and non-dysplastic
BO.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
THERAPEUTIC DRUG MONITORING IN IBD HALL R_____________________
OP363 TIME SINCE LAST DRUG EXPOSURE IN PREGNANCY
DETERMINES ADALIMUMAB AND INFLIXIMAB LEVELS IN
NEONATES (ERA STUDY)
M. Julsgaard1,2,*, L.A. Christensen1, P.R. Gibson3, J. Fallingborg4, R. Gearry5,
A. Walsh6, J. Kjeldsen7, W. Connell2, M.P. Sparrow3, G. Radford-Smith8,
J.M. Andrews9, S.J. Connor10, I. Lawrence11, S. Wildt12, G.T. Moore13,
L. Svenningsen14, O. Rosella3, A. Grosen1, S.J. Bell2
1
Aarhus University Hospital, Aarhus, Denmark, 2St Vincents Hospital, 3Alfred
Hospital, Monash University, Melbourne, Australia, 4Aalborg University Hospital,
Aalborg, Denmark, 5Christchurch University hospital, Christchurch, New Zealand,
6
St Vincents Hospital, Sydney, Australia, 7Odense University Hospital, Odense,
Denmark, 8Royal Brisbane & Womens Hospital, Brisbane, 9Royal Adelaide
Hospital, Adelaide, 10Liverpool Hospital, Sydney, 11Fremantle Hospital,
Fremantle, Australia, 12Koege Hospital, Koege, Denmark, 13Monash University,
Monash Health, Melbourne, Australia, 14Herning Hospital, Herning, Denmark
Contact E-mail Address: mjn@ki.au.dk
INTRODUCTION: Recent studies suggest no adverse pregnancy outcomes in
babies exposed to anti TNF antibodies (ATA). However, the long term implica-
tions are unknown. This study aimed to examine drug levels of ATA in cord
blood of newborns exposed to ATA in pregnancy, and to correlate these with
maternal levels, the duration of therapy during pregnancy, and time to clearance
of ATA in infants.
AIMS & METHODS: Women with IBD exposed to infliximab (IFX) or adali-
mumab (ADA) during pregnancy were included from 2012-present at 14 hospi-
tals in Denmark, Australia and New Zealand. ATA levels were measured using
an ELISA in cord and maternal blood at delivery (Matriks Biotek). If positive at
birth, the infants were tested every third month until ATA were undetectable.
Demographics, disease phenotype, disease activity in pregnancy, duration of
ATA use in pregnancy, medication and pregnancy outcomes were prospectively
collected by questionnaire and from the treating doctor.
RESULTS: 53 mother-baby pairs have been tested (27 IFX and 26 ADA). An
inverse correlation between duration since last exposure and cord ATA levels at
birth was found (IFX: r 0.58, p 0.002; ADA: r 0.42, p 0.047). This was J.F. Brandse1,*, G. R. van den Brink1, J.M. Jansen2, M. Lowenberg1,
also the case for maternal levels at birth (IFX: r 0.59, p 0.002; ADA:
r 0.52, p 0.01). There was a strong correlation between cord blood and
maternal levels at delivery (IFX: Pearsons r 0.80, p 5 0.0001; ADA: r 0.80, 2
p 5 0.0001). Drug was ceased prior to gestational week (GW) 30 in 15 (28%)
women. In them, mean serum concentrations were 0.81 mg/ml (IFX) and 0.08 mg/
ml (ADA), and the cord blood level at delivery was 53 mg/ml in 11/15 (73%). So
far 30 babies have completed testing for detectable ATA levels, and testing is
ongoing in the remaining 23 babies. Complete clearance of ATA was seen in 7, 5,
12 and 6 babies at birth, by 3, 6 and 9 months, respectively. To date there has
been one detectable ATA level at 9 months. Three women (5.7%) gave birth
preterm (GW 33-35). No congenital malformations were detected and all babies
are developing normally.
A115
CONCLUSION: Maternal and neonatal ATA levels were inversely correlated
with the duration since last exposure. Cord blood ATA levels were strongly
correlated with maternal level at delivery. Maternal cessation of ATA prior to
week 30 successfully reduced fetal exposure to drug in the vast majority of cases.
Follow up will determine whether high neonatal levels have any negative
consequences.
Disclosure of Interest: M. Julsgaard: None declared, L. Christensen Lecture fee(s)
from: Ferring, MSD, AbbVie, Other: Member of the advisory board for MSD A/
S, P. Gibson Financial support for research from: Janssen, AbbVie, Ferring,
Lecture fee(s) from: Janssen, AbbVie, Abbott, Fresenius Kabi, Astrazeneca,
Consultancy for: AbbVie, Janssen, Ferring, Takeda, Nestle, Danone, J.
Fallingborg Financial support for research from: Centocor, Abbvie, MSD,
UCB, Other: Advisory board member for Abbvie and MSD, R. Gearry
Financial support for research from: AbbVie, Ferring, Lecture fee(s) from:
AbbVie, Janssen, MSD, Consultancy for: AbbVie, Janssen, MSD, A. Walsh
Consultancy for: Janssen, AbbVie, J. Kjeldsen: None declared, W. Connell
Lecture fee(s) from: Janssen, Abbvie, M. Sparrow Financial support for research
from: Ferring, Lecture fee(s) from: Janssen, Abbvie, Ferring, Other: Advisory
Board: Janssen, G. Radford-Smith: None declared, J. Andrews Financial sup-
port for research from: Janssen, AbbVie, Abbott, MSD, Ferring, Orphan,
Fresenius Kabi, Shire, Astrazeneca, Nycomed, Lecture fee(s) from: Janssen,
AbbVie, Abbott, MSD, Ferring, Orphan, Fresenius Kabi, Shire, Astrazeneca,
Nycomed, S. Connor Financial support for research from: Abbvie, Ferring,
Orphan/Aspen, Shire, Lecture fee(s) from: Abbvie, Janssen, Shire, Ferring,
Consultancy for: Abbvie, Janssen, Vifor, I. Lawrence: None declared, S. Wildt:
None declared, G. Moore: None declared, L. Svenningsen: None declared, O.
Rosella: None declared, A. Grosen: None declared, S. Bell: None declared
OP364 CROSS-IMMUNOGENICITY: ANTIBODIES TO INFLIXIMAB IN
REMICADE-TREATED IBD PATIENTS SIMILARLY RECOGNIZE
THE BIO-SIMILAR REMSIMA
S. Ben-Horin1,*, M. Yavzori1, E. Fudim1, O. Picard1, B. Ungar1, S. Lee2,
S. Kim2, Y. Chowers3
1
SHEBA MEDICAL CENTER, Tel-Hashomer, Israel, 2CELLTRION, Incheon,
Korea, Republic Of, 3Rambam Health Care Campus & Bruce Rappaport School of
Medicine, Technion Institute of Technology, Haifa, Israel
Contact E-mail Address: shomron.benhorin@gmail.com
INTRODUCTION: Remsima, an infliximab bio-similar, recently received
European approval for use in IBD. However, the cross-immunogenicity of
Remsima with the originator drug Remicade in IBD patients is unknown.
AIMS & METHODS: Sera of Remicade-treated IBD patients with measurable
antibodies to Remicade were tested by anti-lambda ELISA for their cross-reac-
tivity to two batches of Remsima. Sera negative for anti-Remicade antibodies
were tested in parallel as controls. Anti-Remicade antibodies were tested for their
functional inhibition of TNFalpha-binding by either Remsima or Remicade
using a competition assay. Cross-reactivity of anti-adalimumab antibodies with
Remicade and Remsima was also investigated.
RESULTS: In total, 124 sera were tested. All 68 positive anti-Remicade IBD sera
were cross-reactive with Remsima. In negative controls (16 healthy individuals,
40 IBD patients), there was a slightly higher background signal in the ELISA
assay for Remsima compared to Remicade, but all 56 control sera which were
anti-Remicade negative also tested negative for anti-Remsima antibodies.
Moreover, the measured titers of anti-drug antibodies were very similar when
reacted against Remicade or Remsima (rho values between 0.92 to 0.99, p50.001
for all experiments, Spearman correlation test). Anti-Remicade antibodies of
IBD patients (n10) exerted a similar functional inhibition on Remsima and
Remicade TNFalpha-binding capacity (PNS for all points on the inhibition
curves). Antibodies to adalimumab in adalimumab-treated IBD patients (n7)
did not cross-react with neither Remicade nor Remsima.
CONCLUSION: Antibodies-to-Remicade in Remicade-treated IBD patients
recognize Remsima to a similar extent, suggesting shared immuno-dominant
epitopes on these two infliximab agents. In contrast, there is no cross-reactivity
of anti-adalimumab antibodies to Remsima or Remicade.
Disclosure of Interest: S. Ben-Horin Financial support for research from:
CELLTRION, Consultancy for: Abbott, Janssen, Takeda & Schering-Plough,
M. Yavzori: None declared, E. Fudim: None declared, O. Picard: None declared,
B. Ungar: None declared, S. Lee Other: CELLTRION employee, S. Kim Other:
CELLTRION employee, Y. Chowers Consultancy for: Abbott, Janssen, Takeda
& Schering-Plough
OP365 EARLY APPEARANCE OF ANTIBODIES TO INFLIXIMAB
PREDICTS LACK OF RESPONSE TO INFLIXIMAB INDUCTION
TREATMENT IN PATIENTS WITH MODERATE-SEVERE
ULCERATIVE COLITIS
C. Ponsioen1, G.R. DHaens1
1
Department of Gastroenterology & Hepatology, Academic Medical Center,
Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis,
Amsterdam, Netherlands
Contact E-mail Address: j.f.brandse@amc.uva.nl
INTRODUCTION: Antibodies to infliximab (ATI) and low serum concentra-
tions of infliximab (IFX) have been suggested as a cause of lack of response to
this treatment in Ulcerative Colitis (UC). However, the measurement of antibo-
dies with conventional assays is limited in the presence of circulating drug.
Therefore early development of ATI during IFX induction therapy and its rela-
tion to IFX concentrations and response have not been studied to date.
A116
AIMS & METHODS: We aimed to determine serum concentrations of IFX and
ATI during induction therapy in patients with moderate-to-severe UC (endo-
scopic Mayo 2/3) in a multicenter prospective study. Serum samples were col-
lected at 10 serial time points during the first 6 weeks of therapy. IFX serum
concentrations and ATI were measured with a homogeneous mobility shift assay
(Prometheus Laboratories, San Diego, CA). Endoscopic response was defined as
improvement by at least 1 Mayo point at week 6-8.
RESULTS: Twenty patients were included, all but one receiving IFX according
to standard induction regime (5mg/kg at week 0,2,6). 8/19 patients were endo-
scopic non-responders. ATI were detected in 7/20 patients, as early as on day 18
from baseline (4 days after second infusion). In ATI positive patients week 6
median IFX trough level was 0 (0-11) ug/ml compared to 12 (8-15) ug/ml in ATI
negative patients (P50.01). During the induction phase 6/8 endoscopic non-
responders tested ATI positive compared to 1/11 endoscopic responders
(P50.01, OR:30, 95%CI:2.2-406.2). 3/12 patients that used concomitant immu-
nomodulatory treatment developed ATI versus 4/8 without co-immunomodula-
tory treatment (ns).
CONCLUSION: Early development of anti-IFX antibodies impairs IFX drug
concentrations and predicts non-response in patients with Ulcerative Colitis.
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie and Takeda,
G. van den Brink: None declared, J. Jansen: None declared, M. Lowenberg:
None declared, C. Ponsioen: None declared, G. DHaens Financial support for
research from: Abbott Inc, Jansen Biologics, Given Imaging, MSD, DrFalk
Pharma, Photopill, Lecture fee(s) from: Abbott Inc, Tillotts, Tramedico,
Ferring, MSD, UCB, Norgine, Shire, Consultancy for: Abbott Laboratories,
Actogenix, Centocor, Cosmo, Engene, Ferring Pharmaceuticals,
GlaxoSmithKline, Jansen Biologics, Millenium Pharmaceuticals, MSD,
Novonordisk, PDL Biopharma, Pfizer, SetPoint, Shire, Takeda, Teva, UCB
OP366 PERSISTENCE OF ANTIBODIES TO INFLIXIMAB FOR MORE
THAN TWO MONTHS STRONGLY PREDICTS LOSS OF
RESPONSE TO INFLIXIMAB IN INFLAMMATORY BOWEL
DISEASES
M. leclerc1, S. Paul1, H. marotte1, E. deltedesco1, L. peyrin biroulet2, X. Roblin1,*
1
CHU Saint Etienne, saint etienne, 2CHU Nancy, Nancy, France
INTRODUCTION: Antibodies to infliximab (ATI) are frequent and may be
associated with worse outcomes in Inflammatory Bowel Disease (IBD). The
value of ATI (ATI threshold value, duration and kinetics) in predicting loss of
response (LOR) is unknown.
AIMS & METHODS: We have studied, from a prospective cohort, all consecu-
tive IBD patients treated with infliximab (IFX) who had at least 2 blood samples
for ATI measurement. Non primary responders to IFX were excluded. Loss of
clinical response was defined by an increase in clinical symptoms requiring a
therapeutic change (IFX dose intensification, initiation of another IBD-related
medication, or surgery).
RESULTS: 93 patients (mean age 30 years, sex ratio 1.2, 59 Crohns disease,
mean duration of follow up 17.2 months) were included in the study representing
481 blood samples. 32 patients (34.4%) lost clinical response during follow-up: 34
patients (38%) had normal C-reactive protein (CRP), 27 patients (30%) had
positive ATI levels (14/27 only once and 13/27 more than 50% of their samples).
A significant correlation was found between positive ATI level and LOR (p
0.011) and between positive CRP level and LOR (p 0.0003). At time of first
sample, an ATI threshold 4 20 ng/mL predicted LOR with 94% specificity and
22% sensitivity (likelihood ratio 3.39, AUROC 0.59). Presence of positive ATI in
more than 50% of one patients samples was associated with more than 50% of
LOR to IFX during follow up, and with systematic clinical relapse in case of
permanent ATI (p 0.0044). The rate of LOR increased in parallel with the
number of consecutive samples positive for ATI (66.7% of LOR when at least 2
positive samples), whereas transient ATI were not associated with LOR (p
0.01). Concomitant thiopurines, duration and dose of IFX were not associated
with LOR neither with detectable ATI (permanent or transient) (p NS).
Independent predictive factors of LOR were ATI 4 20 ng/mL (p 0.0071)
and CRP 4 5 mg/L (p 0.0046). Their association was a better predictor of
treatment relapse than each one separately: relative risk of maintaining clinical
remission was 0.21 [CI 95%, 0.08-0.55] for CRP 4 5 g/L in association with ATI
4 20 ng/mL, 0.64 [CI 95%, 0.46-0.9] for ATI 4 20 ng/mL alone, and 0.65 [CI
95%, 0.43-0.9] for CRP 4 5mg/mL alone. There was a significant inverse corre-
lation between IFX and ATI levels; the highest association was found between
IFX trough levels at time 0 and ATI levels at time 1 (e.g. next infusion),
indicating that IFX trough level decreases before ATI induction.
CONCLUSION: ATI kinetics has a strong value to predict LOR to IFX therapy.
The presence of more than 50% of samples positive for ATI (4 20 ng/mL) for a
given patient is associated with more than 50% of LOR. Permanent ATI levels
are always associated with treatment relapse. Only one sample positive for ATI
does not predict LOR. Two consecutive samples positive for ATI are associated
with 66.7% of LOR whereas transient ATI were not associated with LOR. ATI
and CRP levels are predictors of LOR. Preventing ATI formation is crucial to
reduce LOR to IFX in clinical practice.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP367 IMPACT OF POSTINDUCTION INFLIXIMAB TROUGH LEVEL
AND DISEASE ACTIVITY ON PRIMARY RESPONSE IN CROHNS
DISEASE
A. Echarri1,*, R. Ferreiro2, R. Fraga1, J. Cid3, M. Barreiro2, D. Carpio4,
S. Pereira5, L. De Castro5, S. Soto6, A. Fernandez-Villaverde7, B. Gonzalez8,
E. Santos9
1
Gastroenterology, Complejo Hospitalario de Ferrol, Ferrol, 2Gastroenterology,
Hospital Universitario de Santiago, Santiago, 3Inmunology, Complejo Hospitalario
de A Coruna, Coruna, 4Gastroenterology, Complejo Hospitalario de Pontevedra,
Pontevedra, 5Gastroenterology, Complejo Hospitalario de Vigo, Vigo,
6
Gastroenterology, Complejo Hospitalario de Orense, Orense, 7Gastroenterology,
Povisa, Vigo, 8Gastroenterology, Complejo Hospitalario de A Coruna, Coruna,
9
Gastroenterology, Complejo Hospitalario de Lugo, Lugo, Spain
Contact E-mail Address: ana.echarri.piudo@sergas.es
INTRODUCTION: Primary non-response to infliximab (IFX) induction therapy
occurs in 10-20% of cases in clinical series. Few data have been reported on the
clinical impact of low serum IFX trough levels after the induction treatment and
their relation with clinical response, disease activity or the development of
immunogenicity.
AIMS & METHODS: There are two primary aims of this study: 1. To assess the
clinical relevance of a low serum IFX level during induction therapy. 2. To
identify possible risk factors associated with reduced serum levels of IFX.
We included 36 Crohns disease patients with moderate to severe disease under
infliximab induction treatment. Patients were treated with IFX 5mg/kg at 0, 2
and 6 weeks as induction dose, followed by 5mg/kg every 8w.
Blood samples were drawn at standardized time points before and after induction
therapy (at 0, 6, 14 and 30w) just before IFX treatment. Serum IFX trough levels
and anti-Infliximab antibodies (ATI) were measured using an enzyme-linked
immunosorbent assay (ELISA). Disease activity was assessed at the same time
points by means of the Harvey-Bradshaw Index (HBI; remission53, mild-mod-
erate disease 4-14, and severe disease 415) and CRP/calprotectin levels.
RESULTS: After IFX induction therapy, the median serum IFX trough level
was significantly higher in patients in clinical remission (IFX: 7.62ug/ml) than in
patients with active disease (IFX 0.032 ug/ml P50.01).
Receiver operating characteristic curve analysis indicated a cut-off value of 3ug/
ml at week 6. The positive predictive value of high postinduction IFX trough
level (IFX43 ug/ml at 6w) for prediciting good response and sustained remission
after IFX induction was 490%.
ATI levels were detected in 26% of IFX treated patients and were significantly
related to low trough levels and infusional IFX reactions. Low postinduction
IFX trough levels were related to primary failure in 80% of patients. The cumu-
lative number of patients with low IFX trough levels were significantly higher in
patients with severe disease activity and ATI detection
CONCLUSION: 1. Low post-induction IFX trough levesl are associated with
primary failure.
2. Optimal predictors of postinduction clinical remission to IFX were week 6
trough level43ug/ml and a low disease activity before treatment.
Disclosure of Interest: None declared
OP368 DEVELOPMENT OF AN ALGORITHM INCORPORATING
PHARMACOKINETICS OF ADALIMUMAB IN INFLAMMATORY
BOWEL DISEASES
X. Roblin1,*, M. Rinaudo1, E. Deltedesco1, L. Peyrin Biroulet2, S. Paul1
1
CHU Saint Etienne, saint etienne, 2CHU Nancy, Nancy, France
INTRODUCTION: Several decision algorithms based on the measurement of
infliximab (IFX) trough levels and antibodies to infliximab (ATI) have been
proposed (1). Whether such algorithms can be extrapolated to the pharmacoki-
netics of adalimumab (ADA) has yet to be determined.
AIMS & METHODS: A prospective study included all consecutive patients with
IBD having a disease flare while being on ADA 40 mg every two weeks mono-
therapy were included. All patients were primary responders to ADA and anti-
TNF naive. ADA trough levels and antibodies to adalimumab (AAA) were
measured in blindly to clinical data (Elisa LISA-Tracker, Theradiag). All patients
were optimized with ADA 40 mg weekly. Four months later, in the absence of
clinical remission (CDAI 5 150 for Crohns disease (CD), and Mayo score 5 2
for ulcerative colitis (UC)), patients were treated with IFX therapy. Patients were
y divided into three groups based on ADA trough levels based on previous
studies:
Group A: ADA44.9 g/mL
Group B: ADA5 4.9 g/mL and undetectable levels of AAA (5 10 ng/mL)
Group C: ADA54.9 mg/mL and AAA 4 10 mg/mL
RESULTS: 82 patients were included (55% CD, mean age 43 years, disease
duration 7.4 years, duration of ADA therapy 17 months). After optimization
of ADA treatment, 29.2% of patients achieved clinical remission in the group A
(N 41), 67% in the group B (N 24), and 12% in the group C (N 17) (p 5
0.01 between groups A/B and B/C). CRP level at the time of relapsee, disease
duration, duration of ADA therapy and type of IBD were not predictive of
clinical remission after optimization by univariate analysis. The response to
ADA optimization was significantly more durable in the group B (15 months)
than in groups A and C (respectively 4 and 5 months). Fifty seven patients who
failed following ADA optimization (69%) were treated with IFX and 31.6% of
them achieved clinical remission. Clinical remission rates following IFX initiation
were 12 %, 25% and 80% in groups A, B and C (p 5 0.01 between groups C/A
and C/B), respectively. Duration of response to IFX was significantly higher in
the group C than in groups A and B (14 vs. 3 and 5 months, respectively, p
50.01).
CONCLUSION: The presence of low ADA trough levels in serum without AAA
is strongly predictive of a favorable clinical response after ADA optimization
United European Gastroenterology Journal 2(5S)
(67%). Conversely low ADA levels with detectable AAA are associated with
failure of ADA optimization and a switch to IFX should be considered. ADA
trough levels 4 4.9 mg/mL are associated with clinical response to two anti- TNF
(optimisation and switch) in only 10% of cases and must provide an other
treatment than anti-TNF (class change).
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
IMPROVING SAFETY OF ERCP HALL N_____________________
OP369 NOVEL ERCP PHANTOM WITH X-RAY SIMULATION
OPTIMIZED AND SAFE TRAINING WITHOUT RADIATION
EXPOSURE
R. Ingenpa1, A. Zipfel1, U. Schweizer1, M. Vietz2, V. Aurich2, K.E. Grund1,*
1
Experimental Surgical Endoscopy, Visceral and Transplant Surgery, University
Hospital Tubingen, Tubingen, 2Institute for Informatics, Heinrich Heine University
Dusseldorf, Dusseldorf, Germany
Contact E-mail Address: chir.endo@uni-tuebingen.de
INTRODUCTION: ERCP is a challenging endoscopic procedure which requires
profound knowledge of anatomy and pathology as well as optimal diagnostic
and therapeutic experience in handling of the equipment as well as a good
manual dexterity.
In the meantime simulator training becomes more and more relevant for learning
how to perform ERCP since MRCP has replaced diagnostic ERCP procedures.
But until now all training concepts neglect the important role of X-ray in differ-
ent aspects (diagnostic yield, adjustment of the equipment and especially expo-
sure to radiation). Measurements, calculations and literature REFERENCES
show high X-ray exposure already in clinical routine in training situations X-
ray doses far exceed all legal levels. This is especially for female trainees and
tutors intolerable and inacceptable.
To summarize, a good training setting should include an anatomically correct
phantom and a possibility for optimal hands-on training as well as training of X-
ray adjustment and learning without X-ray exposure.
AIMS & METHODS: Our established hands-on ERCP phantom ("Tubingen
Biliphant") has been additionally supplemented with a virtual reality module
to eliminate the need of real X-ray exposure. This VR module consists of an
X-ray simulation system which generates the radiologic image virtually, based on
a complex sensor system inside the phantom. The reality-like virtual radiologic
image is depicted simulanteously with the endoscopic pictures on an external "X-
ray monitor". With this system the movements of guidewires and instruments can
be recorded by incorporated sensors, processed as a X-ray image and visualised
realistically and synchronously with the hands-on manoeuvres. The adjustment
of the X-ray system with all its features, e.g. widefield, zoom, pulsed mode,
scatters etc. is controlled on a virtually generated panel displayed on a touch
screen; the virtual X-ray picture changes according to the adjustments.
RESULTS: The Tuebingen training phantom "Biliphant" meets the high require-
ments for a realistic hands-on training of ERCP and in combination with the
virtual reality module for X-ray simulation opens the possibility for an unlimited
training time and repetition rate for all interventional procedures without any X-
ray exposure.
This is an important factor especially for female trainees. This universal ERCP
training system with its reality-like X-ray modules overcomes the disadvantages
of traditional ERCP training phantoms. For the first time both endoscopy and
radiology can be trained in a reality-like clinical setting but without X-ray
exposure. Due to the modular construction of the model individual training
situations can be simulated and each training step in the full range of all diag-
nostic and therapeutical interventions can safely be repeated as often as desired.
CONCLUSION: In conclusion, the virtual X-ray simulation system allows
hands-on ERCP training without X-ray exposure for a safe training session in
a realistic hospital-like setting.
Disclosure of Interest: None declared
OP370 COMPLICATIONS OF PROPHYLACTIC PANCREATIC
STENTING USED FOR THE PREVENTION OF POST-ERCP
PANCREATITIS WITH REGARDS TO STENT TYPES: RESULTS OF A
PROSPECTIVE, CONTROLLED STUDY
Z. Dubravcsik1,*, L. Madacsy1, I. Hritz1, A. Szepes1
1
Gastroenterology and Endoscopy, BACS-KISKUN COUNTY HOSPITAL,
Kecskemet, Hungary
Contact E-mail Address: dubravcsikzs@gmail.com
INTRODUCTION: Post-ERCP pancreatitis (PEP) is the most common compli-
cation of ERCP, which can be severe and life threatening especially in high risk
patients. Prophylactic pancreatic stent (PPS) insertion is suggested to prevent
PEP. Although it is a safe procedure a few complications have been described.
The aim of the study was to analyze these in terms of stent types in our pro-
spectively collected database.
AIMS & METHODS: 317 patients with high risk of PEP were considered for
PPS placement over the past 5 years. PEP was categorized as mild, moderate and
severe according to the Cotton consensus criteria. Three different types of 5 Fr, 3-
5 cm long PPSs were used (straight with or without internal flap, and Freeman
type stent (FTS) with internal flap and outer pigtail end). Complications such as
unsuccessful PPS insertion, early stent dislodgement and proximal migration
were identified.
RESULTS: PPS insertion was unsuccessful in 29 patients (9.15%). PEP devel-
oped in 41.38% of these patients (n12; 7 mild, 4 moderate, 1 severe) compared
to 10.07% of the 288 successfully stented patients (n29; 24 mild, 4 moderate, 1
severe). The complications rate was 2.78% (n8) in the successfully stented
A117
group. We found early stent dislodgement in 5 patients (2 stents without internal
flaps, 3 FTSs), who all developed mild PEP. Of the 3 patients who received FTS 1
had severe postpapillotomy bleeding one day after the ERCP, while the other 2
had papillary balloon dilation which might have contributed to early stent dis-
lodgement. Proximal stent migration into the pancreatic duct occurred in 3
patients, all inserted stents were straight with internal flaps. Stent extraction
was possible in 2 patients, while it was unsuccessful twice in 1 patient, who finally
underwent distal pancreatectomy. We did not observe this complication since the
introduction of FTSs into our practice. Although it has been described earlier we
have not observed pancreatitis due to stent removal.
CONCLUSION: PPS insertion is a safe method however complications may
occur. The most severe is proximal stent migration, which may lead to surgery
in minority of cases when endoscopic removal remains unsuccessful. The use of
FTS might prevent this complication. Other complications are mild and can be
managed conservatively.
Disclosure of Interest: None declared
OP371 PROPHYLACTIC PANCREATIC STENT PLACEMENT AFTER
DUODENAL ENDOSCOPIC SNARE PAPILLECTOMY;
PROSPECTIVE, RANDOMIZED STUDY
Y.D. Cho1,*, S.W. Cha1, P. Ahn1, T.H. Lee,1, H.J. Choi1, S.-H. Park1, S.J. Kim1
1
Internal Medicine, Digestive Research, Digestive Disease Center, Soonchunhyang
University, College of Medicine, seoul, Korea, Republic Of
Contact E-mail Address: ydcho@schmc.ac.kr
INTRODUCTION: Endoscopic snare papillectomy (ESP) is an efficient treat-
ment for benign tumors of the duodenal major papilla. However, acute pancrea-
titis is the most common and serious complication following an ESP.
AIMS & METHODS: The aim of this study was to compare the rate of post-ESP
pancreatitis in patients who did or did not receive prophylactic pancreatic stent
placement.
From March 2010 to March 2014, consecutive patients who were to undergo ESP
were randomized to pancreatic stent placement group (stent group) after ESP or
to no pancreatic stent placement group (no stent group). The overall outcomes
after ESP including complications were compared between two groups.
RESULTS: The 37 patients who received ESP for the treatment of major duo-
denal papillary tumors were enrolled. 19 patients were assigned to the stent group
and 18 patients to the no stent group. Post-ESP pancreatitis developed in 8
patients (21.6 %, 8/37), 5 cases occurred in the stent group and 3 cases occurred
in the no stent group. One case in the stent group was considered moderate grade
pancreatitis and the others were considered mild grade pancreatitis. The overall
incidence of post-ESP pancreatitis were 26.3% (5/19) in the stent group and
16.7% (3/18) in the no stent group (p0.693). Although there was no statistic
significance, post-ESP pancreatitis was higher in the stent group.
CONCLUSION: The development of post-ESP pancreatitis were not signifi-
cantly different in patients with prophylactic pancreatic stent placement com-
pared to those without it. Our data suggest that the effectiveness of prophylactic
pancreatic stent placement after ESP may be doubtful. Therefore, more large
scaled prospective, randomized controlled studies regarding the effectiveness of
pancreatic duct stent placement to reduce incidence of post-ESP pancreatitis are
needed.
Disclosure of Interest: None declared
OP372 PANCREATIC STENTS WITH A DIAMETER EXCEEDING FIVE
FRENCH SEEM TO HAVE A PROTECTIVE EFFECT ON POST ERCP
PANCREATITIS - A NATIONWIDE, REGISTER-BASED STUDY
L. Enochsson1,2,*, G. Olsson2,3, F. Swahn1,2, M. Lohr1,2, U. Arnelo1,2
1
Department of Gastroenterology, Karolinska University Hospital, 2Department of
Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm,
3
Department of Surgery, Ryhov County Hospital, Jonkoping, Sweden
Contact E-mail Address: lars.enochsson@ki.se
INTRODUCTION: The role of pancreatic stenting as a prophylactic measure to
reduce post ERCP pancreatitis (PEP) has yet to be determined. In the literature
there are conflicting views as of the beneficial effects of pancreatic stenting where
some studies advocate that temporary small-caliber pancreatic stenting reduce
the risk of PEP(1) whereas other studies indicate the opposite(2). However, most
studies are either single institution studies(1) or small in numbers(2).
AIMS & METHODS: The present report aims to address the use of pancreatic
stenting in a wider clinical perspective as well as analyzing its effect on the risk of
developing PEP.
We performed a nationwide study of ERCP procedures, with or without pan-
creatic stenting, registered in the Swedish Registry for Gallstone Surgery and
ERCP (GallRiks), between 2005 and 2013. Data were collected from the web-
based registry where ERCP procedures are registered prospectively. The primary
outcomes were pancreatitis and postoperative adverse events.
RESULTS: Data from 47,486 ERCP procedures were analyzed (1163 with pan-
creatic stenting). In this unselected study population pancreatitis (OR 3.03; 95%
CI 2.48-3.67) and postoperative adverse events (OR 1.45; 95% CI 1.25-1.69) were
significantly increased in the group that received pancreatic stents. However, the
main indications for the group that received pancreatic stents significantly dif-
fered from those without pancreatic stenting. One single factor of importance for
the risk of adverse events in ERCP is cannulation of the pancreatic duct. The
risks of pancreatitis (OR 3.37; 95% CI 3.06-3.70) and postoperative adverse
events (OR 1.36; 95% CI 1.28-1.44) were significantly increased when the pan-
creatic duct was cannulated. In order to get a better estimation of the protective
effect of pancreatic stenting we did a subgroup analysis of the ERCP procedures
mainly directed towards cannulating the bile duct and where the pancreatic duct
was accidentally cannulated. In this group the risk of pancreatitis (OR 1.17; 95%
A118
CI 0.73-1.81) and postoperative adverse events (OR 0.98; 95% CI 0.79-1.35) was
not affected by pancreatic stent placement. However, we noted a significantly
increased risk for pancreatitis if the diameter of the pancreatic stent was 5 Fr as
compared to if the diameter was 45Fr (OR 4.08; 95% CI 1.31-18.02).
CONCLUSION: Pancreatic stents with a diameter exceeding 5Fr seems to have a
protective effect on the risk of pancreatitis.
REFERENCES
1. Cotton PB, Garrow DA, Gallagher J, et al. Risk factors for complications
after ERCP: a multivariate analysis of 11,497 procedures over 12 years.
Gastrointest Endosc 2009; 70: 8088.
2. Cheng C-L, Sherman S, Watkins JL, et al. Risk factors for post-ERCP pan-
creatitis: a prospective multicenter study. Am J Gastroenterol 2006; 101: 139147.
Disclosure of Interest: None declared
OP373 THE ROUTINE USE OF RECTAL NSAIDS FOR PREVENTION OF
POST-ERCP PANCREATITIS: A META-ANALYSIS
T. Otsuka1,*, S. Kamachi1, S. Nakashita1, T. Akiyama2, S. Kawazoe2, T. Noda3,
Y. Eguchi1, K. Anzai1
1
Internal Medicine, Saga University Hospital, 2Hepatobiliary and Pancreatology,
Saga-Ken Medical Centre Koseikan, Saga, 3Internal Medicine, Karatsu Red Cross
Hospital, Karatsu, Japan
INTRODUCTION: Acute pancreatitis is a common complication of endoscopic
retrograde cholangiopancreatography (ERCP). Rectal nonsteroidal anti-inflam-
matory drugs (NSAIDs) prevent post-ERCP pancreatitis (PEP); however, it is
not clear whether rectal NSAIDs should be used to prevent PEP prior to routine
ERCP.
AIMS & METHODS: PubMed and Embase were searched to identify rando-
mized controlled trials (RCT), published in English, that assessed the effective-
ness of rectal NSAIDs to prevent PEP. These RCTs were included in a meta-
analysis to evaluate the efficacy of routine rectal NSAIDs for the prevention of
PEP.
RESULTS: Our search identified 6 RCTs (Murray et al., 2003; Sotoudehmanesh
et al., 2007; Montano Loza et al., 2007; Khoshbaten et al., 2008; Otsuka et al.,
2012; Elmunzer et al., 2012), enrolling 1,666 patients, that assessed rectal
NSAIDs in the prevention of PEP. Three trials (Murray et al., Khoshbaten
et al., and Elmunzer et al.) enrolled high-risk patients; the other three exam- Intracellular bacterial number was determined by bacterial invasion assay and
ined all patients undergoing ERCP. A fixed-effects meta-analysis of the six RCTs
showed a pooled odds ratio [OR] for PEP of 0.380 (95% confidence interval [CI]
0.268 to 0.539; P 5 0.001) without heterogeneity (P 0.450; I2 0). The pooled
number needed to treat (NNT) with rectal NSAIDs to prevent one episode of
PEP is 7. A fixed-effects meta-analysis of the three RCTs that enrolled all
patients (Sotoudehmanesh et al., Montano Loza et al., and Otsuka et al.), total-
ing 744 patients, found that the routine use of rectal NSAIDs was associated with
a significant risk reduction, with a pooled OR for PEP of 0.328 (95% CI 0.171 to
0.628; P 5 0.001) without heterogeneity (P 0.578; I2 0). The NNT with the
routine use of rectal NSAIDs to prevent one episode of PEP is 16. There were no
adverse events related to the routine use of rectal NSAIDs.
CONCLUSION: Routine use of rectal NSAIDs prevents PEP.
Disclosure of Interest: None declared
OP374 ENDOSCOPIC FIBRIN GLUE INJECTION AS A RESCUE
THERAPY FOR REFRACTORY POST-SPHINCTEROTOMY AND
POST-PAPILLECTOMY BLEEDING
S. Greco1,*, M. Napoleone1, M. Pizzicannella1, A. Tringali1, P. Familiari1,
I. Costamagna1, I. Bos koski1, V. Perri1, G. Vitale1, G. Costamagna1
1
Digestive Endoscopy Unit, Catholic University of Rome, Rome, Italy
Contact E-mail Address: santi.greco@rm.unicatt.it
INTRODUCTION: Bleeding is the second most common complication after
therapeutic ERCP. Endoscopic hemostasis can be achieved by epinephrine,
hemoclip, thermal coagulation or combining these options1,2. In case of failure,
the last options were radiological or surgical treatment1. Fibrin glue injection has
been proposed for endoscopic hemostasis in this subgroup of patients3. Results of
endoscopic injection of fibrin glue, for refractory post-sphincterotomy and post-
papillectomy bleeding, were analyzed in a large series.
AIMS & METHODS: Between October 2007 and April 2014, all patients with
intraoperative or delayed bleeding following endoscopic sphincterotomy or
papillectomy were collected from a prospective database. Bleeding was initially
treated by diluted ephinephrine injection, hemoclips or thermal coagulation;
when these methods failed, fibrin glue (Tissucol, Baxter, frozen storage;
Beriplast P, CSL Behring, refrigerator storage) was injected using 2 separate
23G needles to avoid lumen clogging. After fibrin glue injection the bile duct
was always drained with a stent or a naso-biliary drain (NBD) to avoid cholan-
gitis due to possible biliary obstruction from clot or glue migration3.
RESULTS: Over a 6 year period, 3224 sphincterotomies (2928 biliary, 154 pan-
creatic major papilla, 50 minor papilla, 12 both major and minor pancreatic
papilla, 80 both biliary and pancreatic) and 80 papillectomies were performed
at our Unit. Bleeding occurred in 256 (7.9%) cases, 208 intraoperative (6.4%)
and 48 delayed (1.5%). Hemostasis was successful in 221 (86.3%) cases by
diluted ephinephrine injection, hemoclips or thermal coagulation. In 35
(13.7%) cases (mean age 59.4 range 19-96) with refractory bleeding, 22 post-
sphincterotomy and 13 post-papillectomy, fibrin glue injection was used as
rescue therapy. Stable hemostasis was reached in 33 (94.3%) patients after one
session. A mean of 3.8 ml of fibrin glue was injected. One patient had re-bleeding
after 48 hours and was successfully retreated by fibrin glue injection. In one case
hemostasis failed after fibrin glue injection and also after fully covered metal
stent insertion; emergency arteriography diagnosed and successfully treated a
gastroduodenal artery pseudoaneurism. After fibrin glue injection 16 patients
United European Gastroenterology Journal 2(5S)
received a biliary stent, 16 a NBD, 3 patients both. Cholangiography through
the NBD showed an intraductal fibrin clot in 2 cases (5.7%) easily removed with
a Dormia basket. No cases of pancreatitis were reported after fibrin glue
injection.
CONCLUSION: Endoscopic fibrin glue injection for refractory post-sphincter-
otomy and post-papillectomy bleeding could represent a safe and effective treat-
ment. Main limitation of this series is the lack of a control group.
REFERENCES
1) Boujaoude J, Pelletier G, Fritsch J, et al. Management of clinically relevant
bleeding following endoscopic sphincterotomy. Endoscopy 1994; 26: 217-221.
2) Ferreira LE and Baron TH. Post-sphincterotomy bleeding: who, what, when,
and how. Am J Gastroenterol 2007; 102: 2850-2858.
3) Mutignani M, Seerden T, Tringali A, et al. Endoscopic hemostasis with fibrin
glue for refractory postsphincterotomy
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
SHEDDING NEW LIGHT ON MICROBIOTA IN IBD HALL O_____________________
OP375 ACTIVATION OF THE GCN2/EIF2ALPHA/ATF4 PATHWAY
TRIGGERS AUTOPHAGY RESPONSE TO INFECTION WITH
CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE
ESCHERICHIA COLI
H. T. T. Nguyen1,*, A. Bretin1, J. Carriere1, G. Dalmasso1, A.-C. Maurin2,
A. Bruhat2, A. Darfeuille-Michaud1
1
UMR 1071 Inserm, University of Auvergne, 2Human nutrition unit (UNH),
INRA Theix, Clermont-Ferrand, France
INTRODUCTION: A high prevalence of the adherent-invasive E. coli (AIEC) in
the intestinal mucosa of Crohns disease patients has been shown. We previously
showed that upon AIEC infection, autophagy is induced in host cells to restrain
AIEC intracellular replication. The underlying mechanism, however, remains
largely unknown.
AIMS & METHODS: Here, we investigated the role of the GCN2/eIF2/ATF4
pathway in autophagy response to AIEC infection. Autophagic activity was
assessed by Western blot and immunofluorescent labelling of LC3.
confocal microscopy. Binding of ATF4 to autophagy gene promoters was
assessed by Chromatin immunoprecipitation (ChIP) assay. Wild type (WT)
and GCN2 knockout (KO) mice were infected with an AIEC reference strain
LF82 by gavage.
RESULTS: Infection of human intestinal epithelial T84 cells with AIEC LF82
strain activated the GCN2/eIF2/ATF4 pathway as shown by increased phos-
pho-GCN2 and phospho-eIF2 levels, enhanced ATF4 protein expression, and
upregulated mRNA expression levels of ATF4 target genes. To explore the role
of this pathway in host responses to AIEC infection, we used GCN2-deficient
mouse embryonic fibroblasts (GCN2-/- MEF). GCN2 depletion suppressed
eIF2 activation and inhibited the increase in ATF4 protein level induced by
LF82 infection. mRNA expression levels of the autophagy genes p62, MAP1lc3,
Beclin1, atg3 and atg7 were significantly increased in WT MEF upon LF82
infection, and this was blocked in GCN2-/- MEF. ChIP assay showed that
GCN2 depletion inhibited the LF82-induced binding of ATF4 to the promoters
of these autophagy genes. Consequently, autophagy induction upon LF82 infec-
tion was suppressed in GCN2-/- MEF, leading to increased LF82 intracellular
replication and elevated pro-inflammatory cytokine production, compared to
WT MEF. In vivo study consistently showed that LF82 infection activated the
GCN2/eIF2/ATF4 pathway in enterocytes from WT mice, but not GCN2 KO
mice. In response to AIEC infection, autophagy was induced in WT mouse-
derived enterocytes, and this was not observed in KO mice. LF82 persistence
in the gut was increased in KO mice, leading to aggravated intestinal inflamma-
tion, compared to that in WT mice.
CONCLUSION: The GCN2/eIF2/ATF4 pathway is activated in host cells
upon AIEC infection, which is served as a defense mechanism to induce a func-
tional autophagy to control the intracellular replication of AIEC.
Disclosure of Interest: None declared
OP376 CHANGE OF INTESTINAL FUNGAL COMMUNITY
COMPOSITION IN THE CHEMICALLY INDUCED INFLAMED GUT
AND THEIR PROTECTIVE ROLE IN THE COLON
X. Qiu1, N. Wu2, W. Jiang1, F. Zhang1, X. Yang3, Y. Liu1,*
1
Department of Gastroenterology, Peking University Peoples Hospital, 2Institute
of Clinical Molecular Biology & Central Laboratory, Peking University Peoples
Hospital, 3CAS Key Laboratory of Pathogenic Microbiology and Immunology,
Institute of Microbiology, Chinese Academy of Sciences, Beijing, China
Contact E-mail Address: qiuxinyun2819@126.com
INTRODUCTION: Increasing studies have reported the important relationships
between gut microbes and the intestinal diseases. However, previous studies paid
much attention on the intestinal bacteria, while neglected the role of many other
microbes (such as fungi, virus and parasites, etc).
AIMS & METHODS: The aim of our study was to investigate the eukaryotic
fungal community distribution in the normal and chemical induced-inflamed gut
as well as the relationship between fungi and colitis. C57B/L6 mice were given
drinking water containing 2.5% (w/v) Dextran sulphate sodium (DSS) ad libitum
for 7 days and water for two additional days, then the mucosa and feces in
different part of the gut (ileum, cecum and colon) were collected when the
mice were sacrificed on the day 9 to isolate the total DNA. The ITS1-2
domain of fungal DNA were amplified and detected by Illumina HiSeq 2000
platform. Bioinformatic analysis was performed with the Quantitative Insight
United European Gastroenterology Journal 2(5S)
Into Microbial Ecology (QIIME) software and a previously described fungal ITS
reference database was used to classify the fungi. Shannon-Weiner biodiversity
index was calculated to represent the diversity of fungi. Quantitation of 18S
rDNA in the mucosa and stool samples were used to represent the amount of
fungi. To compare the role of bacteria and fungi in the intestinal inflammation,
we depleted the intestinal bacteria or fungi by giving mice an antibiotic cocktail
(AB) containing four different antibiotics or fluconazole in drinking water
respectively for 23 days. Sixty mice were randomly divided into six groups:
Normal diet group, DSS group, AB group, fluconazole group, ABDSS
group and fluconazoleDSS group. The AB and fluconazole were provided to
the mice from day 1 to day 23 if these anti-microbial drugs were used. In the DSS,
ABDSS and fluconazoleDSS group, DSS was added into the drinking water
only from the day 15 to day 21 at a concentration of 2.5% (w/v). The body
weight change, colon length and colonic inflammation scoring of the colonic
haematoxylin / eosin-staining paraffin sections were calculated.
RESULTS: Fungi distribution varied and increased from ileum to colon, the
diversity and richness of fungi both decreased in the gut of DSS-treated mice
compared with the Normal control. In the colon of DSS-treated group,
Ascomycota was increased while Basidiomycota was decreased at the phylum
level and the Asperigillus, penicillium and Candida were augmented while the
Cladosporium and Cryptococcus were reduced at the genus level. Although
depleting the intestinal bacteria cannot prevent the happening of colitis, it can
dampen the colitis by a reduced weight loss, colon shortening and colonic inflam-
mation scoring in comparison with the DSS group. On the contrary, depleting
the intestinal fungi caused aggravated intestinal colitis by an increased weight
loss, colon shortening and colonic inflammation scoring.
CONCLUSION: Intestinal fungi are part of the normal enteric microbiota,
which could play a protective role in alleviating the intestinal inflammation.
The fungal community changed in different locations and conditions of the
gut, whereas it remains to be answered which fungi participate in protecting
the gut and whether the fungal community interplay with the bacterial flora in
the intestinal canal or not.
Disclosure of Interest: None declared
OP377 CAUSATIVE ROLE OF THE INTESTINAL MICROBIOTA IN
CROHNS DISEASE-LIKE ILEITIS USING GERM-FREE AND
ANTIBIOTIC-TREATED TNF
ARE MICE
M. Schaubeck1,*, T. Clavel2, D. Haller1, J. Walter3, I. Martinez3, M. Roulis4,
G. Kollias4
1
Nutrition and Immunology, TU Munich, 2ZIEL Research Center for Nutrition
and Food Sciences, Freising, Germany, 3University of Nebraska, Food Science and
Technology, Lincoln, United States, 4Biomedical Sciences Research Center
Alexander Fleming, Vari, Greece
Contact E-mail Address: monika.schaubeck@tum.de
INTRODUCTION: Dysbiosis of the human gut microbiota is associated with
ileal Crohns disease (CD). Functional evidence for the causative role of com-
mensal gut bacteria in the development of chronic inflammation in the small
intestine is lacking. We used the genetically-driven TNF
ARE mouse model of
CD-like ileitis in different housing conditions (including germ-free) and in com-
bination with antibiotic treatments or caecal microbiota transplants (CMT) to
test the disease-conditioning role of intestinal bacteria.
AIMS & METHODS: To compare intestinal disease development, TNF
ARE
and TNF/ wildtype mice were housed in germfree (GF), specific pathogen free
(SPF) or conventional (CONV) conditions until the age of 18 weeks. To change
the intestinal microbial composition, CONV mice were treated between 8 and 12
weeks of age with vancomycin and metronidazole (V/M), V/M and norfloxacin
and neomycin (Mix) or ampicillin (Amp). Recurrence of inflammation after
ending V/M therapy was assessed for 6 weeks. To test transferability of protec-
tive effects, in CMT experiments, the cecal microbiota of V/M-treated or
untreated mice was gavaged (three times in week 12) to untreated and V/M-
treated TNF
ARE mice and inflammation was analyzed 6 weeks after CMT.
Intestinal pathology was assessed by microscopic observation of distal ileal &
proximal colonic tissue sections. Gut luminal and mucosa-associated bacteria
were analyzed by 16S rRNA gene sequencing. For qPCR analysis, RNA was
isolated from total ileal tissue. Plasma cytokine levels were analyzed by ELISA.
RESULTS: While GF TNF
ARE mice had no signs of intestinal inflammation,
SPF and CONV mice developed CD-like ileitis. Inflammation of the proximal
colon was observed only in CONV housing. In SPF housed TNF
ARE mice 16S
rRNA gene sequencing showed separation of caecal microbial composition
according to genotype or ileitis severity.
Antibiotic treatments significantly reduced ileitis in TNF
ARE mice. Relapse was
observed 6 weeks after V/M treatment. Ileal TNF and IL-17 transcript levels
were reduced under conditions of disease protection, suggesting the absence of
pro-inflammatory triggers during antibiotic treatment. Improvement of inflam-
mation following antibiotic treatment was accompanied by a significant drop in
bacterial diversity, but total bacterial load was not affected. Comparative taxo-
nomic analysis identified decrease of Bacteriodales associated with disease pro-
tection in all antibiotic treatments. Interestingly, recurrence of inflammation
after antibiotic treatment was clearly associated with preceding regain of a dis-
ease-conditioning microbiota. Transfer of caecal microbiota from V/M-treated
ileitis-free TNF
ARE or untreated WT mice to antibiotic-treated recipient
TNF
ARE was not sufficient to postpone recurrence of inflammation.
CONCLUSION: A causal role of commensal microorganisms in TNF
ARE mice
is strongly supported by the fact that GF and antibiotic-treated mice were free of
ileitis. Relapse was associated with the resilience of the disease-conditioning
microbiota. The potential of single bacteria or bacterial consortia to modulate
immune responses and induce inflammation after colonization of GF TNF
ARE
mice is currently under investigation.
Disclosure of Interest: None declared
A119
OP378 FAECAL MICROBIOTA IN INFLAMMATORY BOWEL DISEASE
PATIENTS WITH AND WITHOUT ARTHROPATHY
J. Kabeerdoss1,* on behalf of, S Pugazhendhi, A Balekuderu, D Prabavathi,
Ruchika Goel, Debashish Danda and BS Ramakrishna
1
Department of Clinical Immunology and Rheumatology, Christian Medical
College, vellore, India
Contact E-mail Address: jayakanthan@cmcvellore.ac.in
INTRODUCTION: Inflammatory bowel disease (IBD) is considered to result
from an abnormal innate immune response elicited by components of the gut
microbiota in genetically predisposed individuals. The gut microbiota shows
alterations (dysbiosis) in IBD. Joint disease or arthropathy occurs in IBD. We
hypothesized that the gut microbial alterations in IBD patients would be differ-
ent in those with arthropathy compared to those without arthropathy.
AIMS & METHODS: To compare gut microbial phylotypes in IBD patients
with and without arthropathy.
a n
IBD patients were recruited from outpatient departments of Christian Medical
w
College from January 2007 to March 2009. Clinical details, laboratory results,
r
i t h d
and severity of joint involvement (by rheumatologist, RG & DD) were entered
into structured forms. Patients who had received antibiotics in the 60 days prior
W
to study were excluded. This study was approved by Institutional research board.
Fresh samples of stool were collected, DNA extracted and DNA libraries pre-
pared using primers targeting hypervariable regions (HVR) 3 and 4 of the 16S
rRNA gene using multiplex identifier sequence tags. The DNA libraries were
sequenced in a 454 sequencing platform. The metagenomic diversity and phylo-
genetic analysis was assessed using the MG-RAST pipeline. Taxonomic compar-
ison of bacteria between the groups was performed using Kruskal-Wallis test and
pairwise Wilcoxon test in linear discriminate analysis effect size (LEfSe) program.
RESULTS: Twenty four IBD patients (12 with and 12 without arthropathy) were
recruited for study. Arthropathy patients included five each with isolated axial
and peripheral and 2 with mixed type of joint involvement. A total of 800,968
reads were generated for the current study. The median read count of the samples
was 24,884 (range 17,774-48,477). Alpha (Shannon) diversity index was signifi-
cantly different between the groups (21.74.4 Vs 38.414.1; p50.05) with sig-
nificantly higher diversity in IBD with arthropathy. The taxonomic comparison
between the groups revealed that statistically significant differences in the micro-
bial phylotypes were noted from Class to Strain levels. The important observa-
tion noted in the study that Enterococcaceae, Enterococcus and Enterococcus
faecium were increased in IBD with arthropathy compared to IBD without
arthropathy.
CONCLUSION: An increase in the abundance of Enterococcus and its species in
the faeces differentiated IBD patients with arthropathy from those without
arthropathy. Enterococcus may be relevant to the pathogenesis of arthropathy
in IBD.
Disclosure of Interest: None declared
OP379 CARD9 DEFICIENCY LEADS TO A PROINFLAMMATORY GUT
MICROBIOTA
B. Lamas1,*, N. Tessandier1, C. Bridonneau2, G.D. Costa2, T.W. Hoffmann2,
L. Brot1, P. Langella2, M. Lavie-Richard2, H. Sokol1,2
1
Avenir Team Gut Microbiota and Immunity, INSERM U1157/UMR CNRS 7203,
Universite Pierre et Marie Curie 6, Paris, 2Commensal and Probiotics-Host
Interactions Laboratory, UMR 1319 Micalis, Jouy-en-Josas, France
Contact E-mail Address: harry.sokol@gmail.com
INTRODUCTION: The exact pathogenesis of inflammatory bowel diseases
(IBD) is still unknown but a deviation of the gut microbiota composition
called dysbiosis has been reported and several susceptibility loci in genes involved
in the interaction with microorganisms have been identified. Among these genes,
Card9 (Caspase Recruitment Domain 9) is an adapter protein for innate immu-
nity toward a wide range of microorganisms including many intestinal commen-
sals and pathogens. Moreover, we showed that Card9-null mice are more
susceptible to dextran sulfate sodium (DSS)-induced colitis than wild-type mice
as a result of delayed recovery characterized by impaired expression of IL-6, IL-
17, IFN-g and IL-22 in colon1. Moreover, the gut microbiota composition is
abnormal in Card9-null mice. Our aim was to explore the role of the gut micro-
biota in the susceptibility of Card9-null mice to DSS colitis.
AIMS & METHODS: Forty germ-free (GF) C57BL/6 wild-type mice were ran-
domly assigned in two groups and inoculated by oral gavage with fresh stools
from conventional wild-type C57BL/6 (GF FWT) or Card9-null C57BL/6 (GF
FKO) mice and maintained in separated isolators. Three weeks after inoculation,
water containing 2% DSS was administered for 7 days (acute injury), followed by
5 days of water (recovery). Animals were monitored daily for scoring using the
disease activity index (DAI) and for weight loss. Colon tissue was fixed in 4%
paraformaldehyde and embedded in paraffin. Sections (5mm) were stained with
H&E. Tissues were scored blindly using a scoring system as described pre-
viously1. Transcripts of 179 inflammation-associated genes were quantified in
colon using Nanostring technology (Mouse inflammation CodeSet).
Statistical analysis was performed using non parametric tests. Differences with
P value less than 0.05 were considered significant.
RESULTS: Colitis severity was higher in GF FKO mice compared to GF FWT
with greater body weight loss and DAI score during recovery period (p50.05
from day 8 to day 12). Histological score was also significantly higher in GF
FKO mice. Colon transcriptomics analysis showed a different pattern between
the 2 groups. GF FKO mice had a higher expression of Th1 and Th17 cytokines
(IFN-g, IL-22, IL-6, IL-1b, IL-23a, IL-12a) but lower expression of Th2 cyto-
kines (IL-4, IL-5, IL-13). Moreover many chemokines (such as CCL2, CCL3,
CXCL1, CXCL2) were overexpressed in GF FKO mice.
CONCLUSION: GF wild type mice colonized with the microbiota of Card9-null
mice are more susceptible to DSS colitis than GF wild type mice colonized with
A120
the microbiota of wild type mice. Immune response in GF FKO mice is skewed
toward Th1/Th17. This study shows that the gut microbiota plays a role in the
susceptibility of Card9-null mice to DSS-induced colitis. On top of its direct
implication in immune response, Card9 could play a role in IBD pathogenesis
by modulating the gut microbiota.
REFERENCES
Sokol et al. Gastroenterology 2013
Disclosure of Interest: None declared
OP380 RISK OF INVASIVE PNEUMOCOCCAL INFECTION IN
PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A
NATIONWIDE DANISH COHORT STUDY
B. Kants1, J. Simonsen2, S. Hoffmann3, P. Valentiner-Branth4, A.M. Petersen5,
T. Jess2,*
1
Microbiological Diagnostics & Virology, 2Department of Epidemiology Research,
3
Neisseria and Streptococcus Reference Laboratory, 4Department of Infectious
Disease Epidemiology, Statens Serum Institut, Copenhagen, 5Department of
Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
Contact E-mail Address: bjk@ssi.dk
INTRODUCTION: Inflammatory bowel diseases (IBD) such as Crohns disease
(CD) and ulcerative colitis (UC) are a result of an inappropriate immune
response. Therefore, the main purpose of the medical treatment is to moderate
the immune response thus reducing disease activity, leading to a theoretically
increased risk of invasive pneumococcal infection (IPI).
The objective of this study was to examine the impact of IBD on the risk of IPI.
AIMS & METHODS: Patients diagnosed with IBD from 1977 to 2013 were
identified from the Danish National Patient Register. For each IBD patient,
20 individuals matched according to sex, age, and municipalities were selected
from the Danish Civil Registration System. The IBD and control group data
were linked with IPI data from the national laboratory surveillance.
Using Cox regression with time since onset of IBD/date of matching as under-
lying time axis we calculated hazard rate ratios (HRRs) for IPI after IBD.
RESULTS: Among 83,358 IBD cases we found 316 IPI cases giving an incidence
of 38 per 10,000, whereas the controls had an incidence of 26 per 10,000. The
HRRs for CD and UC within the first 6 months after IBD diagnosis were high
(43) and then decreased to a constant level which for CD was significantly
higher (approximately twofold) than for the controls and for UC non-signifi-
cantly just above 1.
CONCLUSION: We found an increased risk of IPI infections among patients
with IBD, which was most pronounced in the first years after diagnosis but
remained increased over time, especially in CD.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 11:0012:30
CLINICAL PERSPECTIVES ON GASTRIC MALIGNANT TUMOURS LOUNGE
5_____________________
OP381 THE INCIDENCE AND SEVERITY OF GASTRIC
PRENEOPLASTIC LESIONS ASSOCIATED WITH GASTRIC
CANCER
D. Lazar1,*, S. Taban2, A. Dema2, M. Cornianu2, I. Ratiu1, I. Sporea1,
A. Goldis1
1
Gastroenterology, 2Pathology, UNIVERSITY OF MEDICINE AND
PHARMACY TIMISOARA, Timisoara, Romania
Contact E-mail Address: lazar_daniela@yahoo.com
INTRODUCTION: Gastric cancers are the result of a cascade of histological
changes or precancerous lesions, such as atrophic gastritis, intestinal metaplasia
and dysplasia.
AIMS & METHODS: Our batch consisted of 61 consecutive patients diagnosed
with gastric cancer that underwent surgery. As witness group we used antral
biopsies taken from 96 patients admitted with dyspeptic syndrome. We followed
the incidence and severity of precancerous lesions and infection with H. pylori in
both the gastric cancer group and the witness group.
RESULTS: There were 43 males and 18 females included (average age 59.34
years). According to the Lauren classification, gastric carcinomas studied were
divided in three categories: intestinal type (62.3%), diffuse type (27.9%) and
mixed carcinomas (9.8%). Intestinal type gastric carcinomas develop most fre-
quently on the background of chronic atrophic gastritis (65.8%), with moderate
(28.9%) or severe (23.7%) atrophy of gastric mucosa, accompanied by intestinal
metaplasia. Chronic atrophic gastritis is observed significantly more often in
intestinal type carcinomas, compared with the diffuse ones (p0.012). Diffuse
type carcinoma is associated significantly more often with chronic superficial
gastritis (41.2%) compared with intestinal type carcinoma (p0.009) and with
the witness group (p0.003). Intestinal metaplasia was observed significantly
more often in intestinal type (68.4%), with moderate and severe extension and
in mixed type (66.7%) compared with diffuse type carcinomas (23.5%)
(p50.001). Type III intestinal metaplasia is much more frequent in carcinomas
in comparison with benign lesions studied (p0.00006). Dysplastic lesions are
noted significantly more often in gastric carcinomas of mixed type (66.7%) and
intestinal type (60.5%) in comparison with the diffuse type (23.5%) (p0.001).
High-grade dysplasia is much more frequent in mixed type (50%) and intestinal
type carcinomas (23.7%) in comparison with the witness group (2.1%). The
incidence of bacterial colonization is significantly greater in patients with intest-
inal type (73.7%) and diffuse type carcinomas (64.7%) in comparison with the
witness group (p0.007).
CONCLUSION: Our observations sustain the different histogenesis of cancers
divided after Lauren classification, the incidence of chronic atrophic gastritis and
United European Gastroenterology Journal 2(5S)
and intestinal metaplasia being significantly higher in the intestinal vs. diffuse
type. Histochemical assessment of type III intestinal metaplasia is very useful in
early diagnosis of gastric cancer, having significance for prognosis and surveil-
lance. The frequent association of H. pylori with gastric carcinomas is equally
expressed for the intestinal type, as well as for the diffuse type carcinomas,
confirming the etiopathogenic role of the bacterium in developing both histolo-
gical types of gastric cancer.
Disclosure of Interest: None declared
OP382 THE IMPLICATION OF ULCER IN EARLY GASTRIC CANCER:
CAN WE PREDICT THE CLINICAL BEHAVIOR OF EARLY GASTRIC
CANCER?
Y.J. Lee1,2,*, J.-H. Kim1,2, J.J. Park1,2, Y.H. Youn1,2, H. Park1,2, J.W. Kim1,3,
S.H. Choi1,3, S.H. Noh1,4
1
Yonsei University College of Medicine, 2Internal Medicine, 3Surgery, Gangnam
Severance Hospital, 4Surgery, Severance Hospital, Seoul, Korea, Republic Of
INTRODUCTION: Although the presence of ulcer in early gastric cancer (EGC)
is important for the feasibility of endoscopic resection, only a few studies have
examined the implication of ulcer on clinicopathologic factors in EGC.
AIMS & METHODS: This study aimed to determine the role of ulcer as a
predictor of clinical behavior in EGC. Medical records of patients with EGC
who underwent surgery between January 2005 and December 2012 were reviewed
retrospectively. The clinicopathologic characteristics were analyzed according to
the presence and stage of ulcer in EGC. The stage of gastric ulcer was categorized
into active (A1, A2), healing (H1, H2) and scar (S1, S2) based on the endoscopic
findings.
RESULTS: Of the 3249 patients who included in this study, the presence of ulcer
was observed in 2317 (71.3%) patients. The proportions of ulcer according to the
stage were 6.9% (A1), 21.4% (A2), 28.9% (H1), 30.0% (H2), 9.8% (S1) and
3.0% (S2). Submucosal invasion, lymphovascular invasion (LVI), perineural
invasion, and undifferentiated-type histology such as poorly differentiated ade-
nocarcinoma or signet ring cell carcinoma were significantly higher in ulcerative
EGC than non-ulcerative EGC. When compared according to the stages of ulcer,
submucosal invasion, LVI, and undifferentiated-type histology were significantly
associated with active ulcer stages (A1 and A2). These features were significantly
common in order from active, healing and scar stage in EGC. However, lymph
node metastasis was not significantly different according to the presence of ulcer
and ulcer stages.
CONCLUSION: Ulcerative EGC showed more aggressive behavior than non-
ulcerative EGC. In addition, the stage of ulcer may predict the clinicopathologic
behavior of EGC. Therefore, endoscopic appearance of ulcer should be carefully
examined for an adequate management strategy in EGC.
Disclosure of Interest: None declared
OP383 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR SUBMUCOSAL SUPERFICIAL EARLY GASTRIC
CANCER
S. Nonaka1,*, I. Oda1, H. Suzuki1, S. Abe1, S. Yoshinaga1, T. Nakajima1,
Y. Saito1
1
Endoscopy Division, NATIONAL CANCER CENTER HOSPITAL, Tokyo,
Japan
Contact E-mail Address: snonaka@ncc.go.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) for early gastric
cancer (EGC) is now widely accepted in Japan based on the absolute and
expanded histopathological criteria for curative endoscopic resection (Table)
[1]. Although EGC with submucosal superficial invasion (5500m; SM1) is
included the curative resection criteria, it is very difficult to diagnose the depth
of invasion of SM1 before ESD and almost SM1 EGCs are evaluated histopatho-
logically in the resected specimen. There are a few reports of recurrence of such
cases [2-3], so our aim is to investigate clinical outcomes for ESD of differentiated
type SM1 EGC.
AIMS & METHODS: Patient/lesion characteristics and short-/long-term out-
comes evaluated for 160 patients/163 EGCs diagnosed histopathologically as
curative resection of SM1 in the resected specimens among 2,429 patients/
2,767 lesions treated by ESD with curative intent from 1999 to 2008. Excluded
cases involved EGCs in remnant stomach/gastric tube; residual/recurrent lesions;
patients with follow-up periods 51 year.
RESULTS: Male/female, 139/21; mean age  SD, 67.18.4; location: U/M/L,
53/60/50; macroscopic type: 0-IIa/IIc/IIaIIc/others, 36/105/17/5; median tumor
size, 15mm (range, 4-30); positive ulcer finding, 37 (22.7%); median procedure
time, 60 minutes (10-300); and perforation/delayed bleeding rates, 0% (0)/1.3%
(2). Curative patients included 1 with local recurrence/regional lymph-node
metastasis (LNM)/distant metastasis detected after ESD at 86 months and died
at 108 months; 1 with regional LNM detected after ESD at 50 months who
underwent surgery and is alive without further recurrence. Metachronous gastric
cancer (MGC) was detected in 11 patients including 7 underwent curative ESDs
for 10 MGCs and 4 received surgeries with 2 resulting non-curative ESDs, and 2
surgical patients died from MGC. The median interval between ESD for SM1
EGC and treatments for first MGC was 74 months (12-142). As a result, there
were 20 deaths including 1 from SM1 EGC, 2 from MGC and 17 from other
causes. Five- and ten-year overall/disease-specific survival rates for curative
patients were 91.1%/99.3% and 77.5%/94.0% (median follow-up period, 74.1
months [13-160]), respectively.
United European Gastroenterology Journal 2(5S)
Table: The absolute and expanded histopathological criteria for curative endo-
scopic resection
Table to abstract OP383
En-bloc resection
Negative horizontal and vertical margin
No lymphovascular infiltration
Absolute indication
- Differentiated type intramucosal cancer 20mm in size without ulceration
Expanded indications
- Differentiated type intramucosal cancer 420mm in size without ulceration
- Differentiated type intramucosal cancer 30mm in size with ulceration
- Differentiated type submucosal superficial cancer (SM1) 30mm in size
- Undifferentiated type intramucosal cancer 20mm in size without ulceration
CONCLUSION: Clinical outcomes of ESD for differentiated type SM1 EGC
30mm were favourable, but one patient resulting curative ESD died from SM1
EGC. The careful attention must be taken for possible metachronous GC and
regional LNM even if more than 5 years passes from ESD for SM1 EGC.
REFERENCES
1. Japanese Gastric Cancer Association. Japanese gastric cancer treatment guide-
lines 2010 (ver. 3). Gastric Cancer 2011; 14: 113-123.
2. Oya H, et al. Gastric Cancer 2012; 15: 221-225. [Please provide 2nd and 3rd
authors names and article title for ref. 2.]
3. Abe S, et al. Gastric Cancer. Epub ahead of print 31 January 2014.
Disclosure of Interest: None declared
OP384 CHARACTERISTICS OF SYNCHRONOUS AND
METACHRONOUS GASTRIC NEOPLASMS AFTER ENDOSCOPIC
SUBMUCOSAL DISSECTION
T. Yamaguchi1,*, T. Kuwai1, S. Iio1, A. Tsuboi1, T. Mori1, K. Boda1,
K. Yamashita1, A. Yamaguchi1, H. Kouno1, H. Kohno1
1
Department of Gastroenterology, National Hospital Organization Kure Medical
Center, Kure, Japan
Contact E-mail Address: toshiki4662@yahoo.co.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has become
accepted as a minimally invasive treatment for gastric neoplasms such as early
gastric cancers (EGC) and gastric adenomas. However, gastric neoplasms found
after initial ESD have become a major problem.
AIMS & METHODS: The aim of this study was to evaluate the clinicopatho-
logical features of synchronous and metachronous gastric neoplasms after ESD.
We studied 345 consecutive EGCs or gastric adenomas from 265 patients who
had undergone ESD between June 2007 and December 2012. They were periodi-
cally followed up with endoscopic examination after 1 year or more. Patients
with remnant stomach or additional surgery were excluded from this study. We
defined a second neoplasm found within 1 year after ESD as synchronous and
a second neoplasm found after more than 1 year as metachronous. In this
study, we investigated the incidence, clinical features and endoscopic findings
associated with synchronous or metachronous gastric neoplasms. In cases with
metachronous lesions, data for the initial lesion were analyzed. In cases with
synchronous lesions, data for the initial or largest lesion were analyzed.
RESULTS: The median period of endoscopic follow up was 34 months (range 12 to
77 months). In total, 199 patients (75.1%) had solitary lesions and 66 patients
(24.9%) had multiple lesions. In patients with multiple lesions, 49 patients had
synchronous multiple lesions, 25 patients had metachronous multiple lesions, and
8 patients had both. No difference existed between age or gender among patients
with solitary, synchronous, and metachronous lesions. Additionally, no significant
differences existed between the three groups in terms of lesion location, macroscopic
type, or tumor size. However, marked atrophy (grading O2-3 according to Kimura
and Takemotos criteria) was significantly more frequent in patients with solitary
lesions than in patients with synchronous or metachronous lesions. Concerning
metachronous lesions, all 28 lesions (25 second and 3 third lesions) in the 25 patients
were underwent re-ESD. Of 28 lesions, 7 adenomas, and 20 mucosal carcinoma were
treated curatively with re-ESD; only one lesion underwent additional surgery
because it invaded the submucosa to a depath into 500m less with ulceration.
CONCLUSION: To detect metachronous gastric neoplasms at a stage early
enough for a curative re-ESD, an annual endoscopic examination is effective
surveillance after initial ESD, especially for patients with marked atrophy of
gastric mucosa.
Disclosure of Interest: None declared
OP385 CLINICOPATHOLOGICAL RISK FACTORS FOR LYMPH NODE
METASTASIS IN EARLY GASTRIC CARCINOMA DIAGNOSED
WITH THE WHO CRITERIA IN 380 CHINESE PATIENTS
X. Zou1,*, C. Fang1, Q. Sun2, J. Shi2, Y. Zhang2, Q. Huang2,3
1
Gastroenterology, 2Pathology, Nanjing Drum Tower Hospital, Nanjing, China,
3
Pathology, Veterans Affairs Boston Healthcare System, Boston, United States
INTRODUCTION: Endoscopic resection is the preferred strategy for patients
with early gastric carcinoma (EGC) because of a minimal risk for lymph node
metastasis (LNM), based on the clinical research results primarily from Japan.
However, it remains unclear as to LNM risk factors in Chinese patients with
EGC diagnosed with the updated WHO criteria.
AIMS & METHODS: We followed the 2010 WHO criteria to diagnose EGC in
resection specimens with nodal dissection and investigated clinicopathologic risk
factors for LNM with the Cox logistic regression analysis.
RESULTS: Over an 8-year period from January 2005 to December 2012, we
identified 380 EGC gastrectomies with lymph node dissection performed at the
A121
Nanjing Drum Tower Hospital in China. The average number of lymph node
retrieved and reviewed was 17 ( 10) per case. LNM was detected in 49 (12.9%)
cases. The patient mean age in the LNM group was significantly younger (54.2 
12.8 years) than that in the non-LNM group (60.7  11.4, p50.05). The M/F
ratio was also significantly higher in the former (1.33) than in the latter (2.28,
p50.05). Univariate analysis of clinicopathologic risk factors showed a signifi-
cantly positive correlation with LNM for the followings: distal gastric cancer
(DGC), tumor size larger than 3.1 cm, ulcerated pattern, invasion into submu-
cosa (SM1, SM2), undifferentiated cancer, poorly cohesive carcinoma, micro-
papillary carcinoma, poor differentiation, and lymphovascular invasion.
Multivariate analysis revealed that lymphovascular invasion (OR 25.891, CI
9.077 73.849, P50.001) and DGC (OR 6.735, CI 1.438 31.532,
P50.05) were significant independent risk factors for LNM.
CONCLUSION: DGC and lymphovascular invasion are the independent risk
factors for LNM include. Therefore, EGC in the proximal stomach appears to be
more suitable than DGC for endoscopic resection.
Disclosure of Interest: None declared
OP386 GASTRIC MALT LYMPHOMA: ANALYSIS OF A SERIES OF
CONSECUTIVE PATIENTS OVER 20 YEARS
J. Moleiro1,*, S. Ferreira1, P. Lage1, D. Pereira1
1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil,
E.P.E., Lisboa, Portugal
Contact E-mail Address: joana_moleiro@hotmail.com
INTRODUCTION: Gastric extranodal marginal zone lymphoma of mucosal
associated lymphoid tissue, gastric MALT lymphoma (GML), is associated
with Helicobacter pylori (HP) infection and characterized by an indolent course.
AIMS & METHODS: To evaluate demographic, clinical and endoscopic char-
acteristics, status HP, stage, response to therapeutic and long-term prognosis of
patients followed in our institution. Data of consecutive patients with GML
(1993-2013) staged by Ann Arbor classification / Musshoff were analyzed.
Statistics: chi2, Kaplan-Meier (SPSS 20).
RESULTS: 144 patients (76 men; 68 women), mean age: 56 years (13-83), 67%
presented with dyspepsia. Most frequent endoscopic appearance and location
were erosions / ulcers (46%) in antrum or antrum-body transitional zone
(57%), respectively. HP infection was detected in 71.5%. 127 patients (88%)
were diagnosed at stage IE/IIE (103/24). Stage IE: 94/103 patients (92%) received
HP eradication regimens, 78 (83%) achieved remission after a mean period of 7
months (1-63) and 67 (86%) were in remission after a mean follow-up time of 105
months. Diffuse and antrum plus body lymphomas were significantly (p0.007)
associated with lower remission rate. Relapse occurred in 11/78 (14%) patients
after a mean period of 21 months. Patients that needed 2 eradication regimens
had higher recurrence rate (p0.008). Stage IIE: eradication was performed in
17/24 patients but only 5 experienced remission (30%). There were no patients
diagnosed at stage III and among 16 patients diagnosed at stage IV, 9 achieved
remission after chemotherapy  surgery and 3/7 without remission died due to
disease progression. After a mean follow-up time of 109 months (4-246), 112
patients are still alive (99 without disease) and 32 died (5 due to disease). 5, 10
and 15-year overall survival rates were 91.8%, 82.8%, 66.9%, respectively.
CONCLUSION: Most patients were diagnosed at stage IE and among them HP
eradication was an effective strategy. The diagnosis at an early stage avoided the
need for aggressive therapies. The overall prognosis is favorable with high long-
term survival rates.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 14:0015:30
TARGETING NEW PATHWAYS IN IBD HALL L/M_____________________
OP387 DOWN REGULATION OF THE MICRORNA 200 FAMILY IN
STRICTURED INTESTINAL RESECTION SPECIMENS FROM
CROHNS DISEASE PATIENTS INDICATES A ROLE FOR
EPITHELIAL TO MESENCHYMAL TRANSITION
S. Mehta1,*, A. Lewis1, A. Nijhuis1, P. Biancheri2, C.L. Bishop3, J.O. Lindsay1,
A. Silver1
1
Digestive Diseases, 2Centre for Immunology and Infectious Disease, 3Centre for
Cutaneous Research, Blizard Institute, London, London, United Kingdom
Contact E-mail Address: a.r.silver@qmul.ac.uk
INTRODUCTION: The development of intestinal fibrosis in patients with
Crohns disease (CD) results in complications which represent a major clinical
challenge for professionals, a significant cause of morbidity for patients and a
considerable cost to healthcare services. Understanding the processes that initiate
and regulate intestinal fibrosis will facilitate the development of effective preven-
tative and therapeutic strategies. Specific microRNAs (miRNAs) have been
shown to have defined roles in fibrogenesis in several organ models. The miR-
200 family has been implicated in the development of murine intestinal fibrosis,
possibly via a process termed epithelial to mesenchymal transition, although
human studies are lacking.
AIMS & METHODS: Our aim was to analyse the expression profiles of
miRNAs in surgical resection specimens from patients with CD between areas
of stricture and non-stricture. From each patient, mucosal and submucosal sam-
ples were harvested from within a stricture as well as the normal surgical resec-
tion margins in order for every patient to serve as their own internal control.
Formal histology reports were checked to ensure that fibrosis was present in the
strictured areas used. Matched paired samples were selected (n4) and sent for
microarray analysis using the miRCURY LNATM microRNA Array platform
(7th Gen, Exiqon, Denmark). The expression of differentially expressed miRNAs
was subsequently validated on eight new paired resection samples (stricture and
A122 United European Gastroenterology Journal 2(5S)
non-stricture). Total RNA including miRNA was extracted from the mucosa and mainly regulated by adhesion molecules which are interesting targets for IBD
submucosa of resection specimens and validation performed by qRT-PCR.
RESULTS: The microarray data revealed 32 distinct miRNAs significantly dif-
ferentially expressed (p value 50.05) between the strictured and non-strictured
samples. These included members of the miR-200 family, all of which were down
regulated in strictured specimens: miR-141 (p0.013), miR-200b-3p (p0.045)
and miR-200c-3p (p0.009). The remaining members were also downregulated,
but not significantly so: miR-200a (p0.135) and miR-429 (p0.053).
QRT-PCR validation confirmed these findings. MiR-200 family members were
downregulated in the strictured samples compared to the non-strictured samples:
miR-141 (fold change 0.361, p0.002), miR-200a (fold change 0.432, p0.001),
miR-200b-3p (fold change 0.721, p0.117) and miR-200c-3p (fold change 0.401,
p0.002).
CONCLUSION: These findings demonstrate for the first time that members of
the miR-200 family are significantly downregulated in strictured fibrotic regions
of intestine compared to non-strictured regions in patients with fibrostenosing
CD. This mirrors findings in other organ systems, where the miR-200 family has
been implicated in the development of fibrosis via epithelial to mesenchymal
transition. Further well-phenotyped human studies are warranted.
Disclosure of Interest: None declared
OP388 CIRCULATING MICROVESICLES IN CROHNS DISEASE:
NOVEL MEDIATORS OF ANGIOGENESIS
E. Gaetani1,*, F. Del Zompo1, L. Laterza1, F. Scaldaferri1, R. Landi1,
A. Gasbarrini1
1
Internal Medicine and Gastroenterology, A. Gemelli University Hospital, Catholic
University School of Medicine, Rome, Italy
Contact E-mail Address: eleonora.gaetani@rm.unicatt.it
INTRODUCTION: Circulating microvesicles (cMVs) are small membrane
bound fragments released by a number of cell types, including endothelial cells
(ECs), platelets, leukocytes, macrophages, and smooth muscle cells. Though
initially dismissed as cellular debris, cMVs are instead important mediators of
cell signaling and molecular communication between cells. Indeed, cMVs are
enriched with nucleic acids and proteins, shuttle specific mRNAs and
miRNAs, and transfer biological information between cells. MVs form through
exocytosis from multivesicular bodies, which leads to the formation of exosomes,
or budding of MVs directly from a cytoplasmatic membrane, which results in the
formation of so-called microparticles (MPs). In recent years, there has been
increasing appreciation of the role played by cMVs in the regulation of angio-
genesis. For instance, platelet-derived MPs (PMPs) induce angiogenesis both
in vitro and in vivo and injection of MVs into the ischemic myocardium improves
revascularization after chronic ischemia. The aim of our study was to assess
number, immunophenotype, and angiogenic content and activity of cMVs in
subjects with active Crohns disease (CD).
AIMS & METHODS: We studied 10 subjects with active CD and 10 healthy
controls (HC). Clinical disease activity was determined by the CD Activity
Index (CDAI). Disease was considered active for CDAI index 4220. Platelet-
free plasma was used for fluorescence activated cell sorting (FACS) studies, to
determine the cellular origin of circulating MPs, in particular whether they were
derived from ECs (EMPs), platelets (PMPs), monocytes (MMPs), or apoptotic
cells (AMPs). Next, we analyzed the angiogenic content of cMVs, in terms of both
mRNAs and proteins, using specific profiler PCR arrays for angiogenic pathways
and specific angiogenic antibody arrays. Finally, we determined the functional
activity of the angiogenic message carried by cMVs, by stimulating human umbi-
lical ECs (HUVECs) with proteins extracted from cMVs isolated from the periph-
eral blood of either subjects with active CD or control individuals.
RESULTS: Activated PMPs, AMPs and MMPs were significantly higher in CD
when compared to HC. The presence of 84 angiogenesis-related mRNAs was
investigated in CD and HC. Data analysis of PCR arrays showed 16 significantly
modulated genes, in particular 14 up-regulated and 2 down-regulated. To deter-
mine whether, in CD subjects, cMVs have the ability to induce neovessel gen-
eration in vitro, we used a tube formation matrigel assay. We found that the
number of branching points was significantly greater when HUVECs were incu-
bated with proteins derived from cMVs of CD patients, compared with HC.
CONCLUSION: In CD, angiogenesis is a hallmark of active disease. Our find-
ings demonstrate that, in active CD, cMVs carry a potent and functionally active
angiogenic message. This novel finding increases our understanding of the
mechanisms that underlie development and progression of the disease, with
potentially important biological, clinical, and therapeutic implications.
REFERENCES
Danese et al. Gastroenterology 2006; 130: 2060-2073.
Hatoum et al. Gastroenterology 2003; 125: 5869.
Leonetti et al. PLoS One 2013; 8: e73088.
Chamouard et al. Dig Dis Sci 2005; 50: 574580.
Andoh et al. Am J Gastroenterol 2005; 100: 20422048.
Disclosure of Interest: None declared
OP389 THE EFFECT OF VEDOLIZUMAB THERAPY ON COLONIC
MUCOSAL GENE EXPRESSION IN PATIENTS WITH ULCERATIVE
COLITIS
I. Arijs1,*, G. De Hertogh2, L. Van Lommel3, J. Van der Goten1, M. Ferrante1,
F. Schuit3, G. Van Assche1, P. Rutgeerts1, S. Vermeire1
1
Clinical and Experimental Medicine, 2Imaging & Pathology, 3Cellular and
Molecular Medicine, KU Leuven, Leuven, Belgium
Contact E-mail Address: ingrid.arijs@med.kuleuven.be
INTRODUCTION: Inflammatory bowel disease (IBD) is characterized by con-
tinuous recruitment of leukocytes towards the inflamed gut. This migration is
therapy. Vedolizumab (VDZ) is an antibody to the adhesion molecule 47-
integrin which is uniquely expressed on gut-homing lymphocytes, and thereby
selectively blocks the lymphocyte trafficking to the gut.
AIMS & METHODS: This study investigated the effect of VDZ therapy on
colonic mucosal gene expression in ulcerative colitis (UC). In total 120 endosco-
pically-derived colonic biopsies from 44 UC patients were collected at protocol-
specified time points [week (W) 0, W6, W12 and W52] during 2 randomized-
controlled studies of VDZ1 (Millenium C13006 and C13008). Biopsies were com-
pared with 12 normal colonic non-IBD biopsies and colonic biopsies before and
4-6 weeks after first infliximab therapy from 23 UC patients. Mucosal healing
(Mayo endoscopic subscore 0 or 1) was assessed at W6, W12 and W52. Total
RNA from biopsies was used to analyze whole genome gene expression via
Affymetrix GeneChip Human Gene 1.0 ST arrays. Data were analyzed using
Bioconductor and Ingenuity Pathway Analysis software.
RESULTS: In VDZ responders showing mucosal healing, no gene expression
differences at W6 and only 5 significant (false discovery rate55% and 42-fold)
gene probe sets (down: IDO1, REG3A, KLK6, SAA2 and up: PCK1) at W12 were
found when compared to W0, while many differences in gene expression were
found at W52. A total of 593 (462 down and 131 up) gene probe sets were
significant in VDZ responders with mucosal healing at W52 vs. W0, and 375
(63%) of these probe sets overlapped with the significant probe sets identified in
infliximab responders at W4-6 vs. W0. The common probe sets encoded genes
mainly involved in immune cell trafficking, cellular movement and inflammatory
response. Interestingly, even in VDZ responders showing mucosal healing at W6,
W12 and W52, many gene probe sets remained significantly dysregulated (266,
566 and 99 probe sets respectively for W6, W12 and W52) when compared with
controls, and a great overlap of these significant genes was observed with the
ones identified in infliximab responders vs. controls. Further, we found only few
genes with significantly increased expression (IGJ, IGK, IGKC, TNFRSF17) in
VDZ responders with mucosal healing vs. infliximab responders.
In contrast with the predictive mucosal gene signature identified for response to
infliximab2, we could not identify genes predictive of response to VDZ by com-
paring the pre-VDZ treatment gene expression array profiles of responders show-
ing mucosal healing with non-responders.
CONCLUSION: VDZ influenced colonic mucosal expression of many genes
involved in immune-related functions at W52, but not yet at W6 or W12. The
observed changes were similar with those seen at W4-6 after first infliximab
therapy, suggesting similar mechanisms of action for both therapies. As also
observed in infliximab responders, the expression of many genes remained abnor-
mal in VDZ responders with mucosal healing, indicating that maintenance ther-
apy is necessary to control the intestinal inflammation.
REFERENCES
Feagan, et al. New Eng J Med 2013.
Arijs, et al. Gut 2009.
Disclosure of Interest: I. Arijs: None declared, G. De Hertogh Consultancy for:
Novartis, Genentech, Galapagos, L. Van Lommel: None declared, J. Van der
Goten: None declared, M. Ferrante Financial support for research from: Janssen
Biologics, Lecture fee(s) from: Merck, Tillotts, Ferring, Abbvie, Consultancy for:
Abbvie, Merck, Janssen Biologics, F. Schuit: None declared, G. Van Assche
Financial support for research from: Abbvie, Ferring, Lecture fee(s) from:
Janssen-Cilag, Merck, Abbvie, Consultancy for: PDL BioPharma, UCB
Pharma, Sanofi-Aventis, Abbvie, Ferring; Novartis, Biogen Idec, Janssen
Biologics, NovoNordisk, Zealand Pharma A/S, Millenium/Takeda, Shire,
Novartis, BMS, P. Rutgeerts Financial support for research from: UCB
Pharma, Abbvie, Janssen Biologics, Merck, Prometheus, Bristol-Meyers
Squibb, Lecture fee(s) from: Abbvie, Merck, Consultancy for: Amgen, Merck,
UCB Pharma, Genentech, BMS, Abbvie, Janssen Biologics, Millenium, Neovacs,
Actogenics, Prometheus, Pfizer, Falk Pharma, Tillotts, S. Vermeire Financial
support for research from: UCB Pharma, MSD, Abbvie, Lecture fee(s) from:
Abbvie, Merck, Ferring, UCB Pharma, Centocor, Consultancy for: UCB
Pharma, AstraZeneca, Ferring, Abbvie, Merck, Ferring, Shire, Pfizer, MSD
OP390 AMELIORATION OF ACTIVE ULCERATIVE COLITIS USING
AN ORALLY AVAILABLE TOLL-LIKE RECEPTOR-9 MODULATOR
(BL-7040): A PROSPECTIVE OPEN-LABEL, MULTI-CENTER PHASE
II TRIAL
I. Dotan1,*, E. Levy-Nissenbaum2, Y. Chowers3, A. Fich4, E. Israeli5, T. Adar6,
S. Shteingart6, H. Soreq7, E. Goldin6
1
IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv
Sourasky Medical Center and the Sackler Faculty of Medicine, Tel Aviv,
2
BioLineRx Ltd., Jerusalem, 3Department of Gastroenterology, Rambam Health
Care Campus Bat Galim, Haifa, 4Department of Gastroenterology, Soroka
Medical Center, Beer Sheva, 5IBD Unit, Institute of Gastroenterology and Liver
Diseases, Hadassah-Hebrew University Medical Center, 6Digestive Diseases
Institute, Shaare Zedek Medical Center, 7Department of Biological Chemistry, The
Hebrew University of Jerusalem, Jerusalem, Israel
Contact E-mail Address: irisd@tasmc.health.gov.il
INTRODUCTION: Current treatment of active ulcerative colitis (UC) may be
associated with significant adverse events and loss of response. Toll-like receptor
(TLR)-9 mediates innate and adaptive immune response towards intestinal
microorganisms. BL-7040 is a novel orally available synthetic oligonucleotide,
which directly modulates TLR-9. BL-7040 has an anti-inflammatory effect in
murine models of colitis as well as in patients with auto immune diseases such
as myasthenia gravis, with a good safety profile.
AIMS & METHODS: We performed a prospective multi-center, open-label
phase IIa, proof-of-concept trial to evaluate the efficacy, safety and tolerability
of BL-7040 in patients with moderately active UC, defined by a Mayo score of 
5 and  9, and having an endoscopic sub-score  2 and rectal bleeding sub-score
United European Gastroenterology Journal 2(5S)
 1. Concomitant mesalamine and steroids ( 10 mg prednisone/day) were
allowed. Patients received BL-7040 12mg/day for 3 weeks, followed by BL-
7040 40 mg/day for 2 weeks. Effect was evaluated using the Mayo score, histol-
ogy, and mucosal cytokines levels. Side effects were registered.
RESULTS: Sixteen of the 22 enrolled patients completed a full five-week treat-
ment course and two-week follow-up. The primary endpoint, i.e. a  3 point
decrease and 30% reduction from baseline in the Mayo score, and a  1 point
reduction in rectal bleeding sub-score, or absolute  1 rectal bleeding sub-score,
was met in 8 (50%) patients. The other 8 patients remained stable. Furthermore,
mucosal healing evaluated by endoscopy sub-score improved. Neutrophil levels
and mucosal interleukin-6 (IL-6) levels were significantly reduced in responders,
and correlated with clinical improvement (p0.002 and p0.046 compared to
non-responders, respectively). BL-7040 was well tolerated with one serious
adverse event (hemoglobin decrease to 5.7gr%) considered unrelated to study
drug, and 29 mild-to-moderate adverse events, mainly UC exacerbation (n4,
18.2%), influenza-like symptoms (n3, 13.6%), and dry mouth, fatigue, and
headache (for each n2, 9.1%).
CONCLUSION: In this prospective, open label phase IIa trial, oral administra-
tion of the TLR-9 agonist BL-7040 was associated with clinical response and
mucosal healing in 50% of UC patients with moderately active disease. The
decrease in mucosal inflammation was reflected by significantly lower neutrophil
counts and decreased IL-6 levels. BL-7040 was safe and well tolerated. The
efficacy and safety of BL-7040 for the treatment of active UC should be further
evaluated.
Disclosure of Interest: I. Dotan Lecture fee(s) from: BioLineRx, Ferring, Falk
Pharma, Janssen, Abbvie, Consultancy for: BioLineRx, Genentech, Pfizer,
Janssen, Abbvie, E. Levy-Nissenbaum: None declared, Y. Chowers Lecture
fee(s) from: Abbvie, Janssen, Consultancy for: Abbvie, Janssen, Takeda,
Pharmacosmos, Vecta, A. Fich: None declared, E. Israeli: None declared, T.
Adar: None declared, S. Shteingart: None declared, H. Soreq: None declared,
E. Goldin Consultancy for: BioLineRx, Immune Pharmaceutical
OP391 RANDOMISED, DOUBLE-BLIND, SINGLE-DOSE, PHASE 2
TRIAL ASSESSING EFFICACY AND SAFETY OF THE NOVEL
ANTI-NKG2D MONOCLONAL ANTIBODY NNC0142-0002 IN
CROHNS DISEASE: INSIGHTS FROM AN EXPOSURE-RESPONSE
ANALYSIS
M. Allez1,*, R. Petryka2, B.E. Skolnick3, M. Wisniewska-Jarosinska4, R.,
V. Overgaard5
1
Hopital Saint-Louis, APHP, Universite Denis Diderot, Paris, France, 2NZOZ
Vivamed, Warsaw, Poland, 3Novo Nordisk Inc., Princeton, NJ, United States,
4
Department of Gastroenterology, Medical University of Lodz, Lodz, Poland,
5
Novo Nordisk A/S, Sborg, Denmark
Contact E-mail Address: matthieu.allez@sls.aphp.fr
INTRODUCTION: NNC0142-0002 (anti-NKG2D mAb) is an antagonising
human IgG4 monoclonal antibody that binds to NKG2D receptors. These recep-
tors are located on T- and natural killer cells, which exhibit inflammatory and
cytotoxic properties, and may be linked to mucosal damage.
AIMS & METHODS: A total of 78 patients (aged 18 and 75 years) with
Crohns disease for 3 months, a Crohns disease activity index [CDAI] 220
and 450, and either C-reactive protein 10 mg/L or endoscopic evidence of
inflammation, were randomised 1:1 to a single subcutaneous (s.c.) dose of 2 mg/
kg NNC0142-0002 or placebo. Primary outcome was change in CDAI (CDAI)
from baseline to Week 4. Secondary outcomes included CDAI through Week
12, NKG2D receptor occupancy, pharmacokinetics and safety. Exposure-
response analysis of CDAI from baseline to Week 4, based on mean
NNC0142-0002 concentrations over Weeks 1, 2 and 4 was performed. Four-
level stratification based on two binary factors was implemented: failure to bio-
logic therapy (yes/no) and baseline CDAI (5330 or 330). Pre-specified signifi-
cance level was 10% (p0.10; two-sided test). Primary efficacy outcome was
analysed via a mixed-effect model, whereas the exposure-response analysis was
based on observed means. Due to slow recruitment a futility analysis was insti-
tuted, resulting in discontinuation of recruitment.
RESULTS: Mean CDAI from baseline to Week 4 (primary outcome) was not
significantly different between NNC0142-0002 and placebo (CDAI 16);
however, there was a significant difference by Week 12 (CDAI 55;
p0.10). Significant improvements were noted in the non-failure to biologics
group (treated with NNC0142-0002 [n28]) from Week 1 onwards. NNC0142-
0002 resulted in a median NKG2D occupancy of 480% for 8 weeks. When
patients with high baseline CDAI (330) were partitioned into placebo or tertiles
based on exposure, larger magnitude CDAI changes were observed with higher
concentrations (see table). No signs of exposure-response at Week 4 were
observed for patients with baseline CDAI 5330.
Table to abstract OP335
TSO250 (N39)
CDAI5150 at wk12 LOCF N(%) 15(38.5%)
[95%CI] -4.4%[-23.6;14.8]
p-value 0.6725
CDAI at wk12 LOCF Mean (SD) -67 (100.6)
% change eos (BL-wk8) Mean (SD) 148 (191)
A123
Table to abstract OP391
Median concentration (g/ml)
Exposure (n) Weeks 04 Mean (SE) CDAI Week 4
Placebo (14) 0 96 (21)
Low (6) 5.9 96 (38)
Medium (5) 7.8 129 (26)
High (6) 10.5 174 (37)
Adverse event frequencies were comparable between NNC0142-0002 and pla-
cebo. Most events were mild (49%) or moderate (43%) and were primarily
gastrointestinal disorders, pyrexia, anemia, arthralgia and nasopharyngitis.
CONCLUSION: A single s.c. dose of 2 mg/kg NNC0142-0002 (anti-NKG2D
mAb) did not reduce disease activity at Week 4 (primary outcome) compared
with placebo, but significantly reduced disease activity at Week 12, and was well
tolerated. Exposure-response analysis in patients with baseline CDAI 330 pro-
vides supportive evidence for a treatment effect of NNC0142-0002 and suggests
that higher doses and repeated dosing may further optimise the effect of
NNC0142-0002 in Crohns disease.
Disclosure of Interest: M. Allez Financial support for research from: Novo
Nordisk, Consultancy for: Novo Nordisk, R. Petryka: None declared, B.
Skolnick Other: Full-time employee of Novo Nordisk at the time of data analy-
sis, M. Wisniewska-Jarosinska: None declared, R. Overgaard Other: Employee
and stock holder of Novo Nordisk A/S
OP392 EFFICACY AND SAFETY OF TRICHURIS SUIS OVA FOR
TREATMENT OF MILDLY-TO-MODERATELY ACTIVE CROHNS
DISEASE: A RANDOMISED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, PHASE II STUDY
J. Scholmerich1,*, K. Fellermann2, F.W. Seibold3, G. Rogler4, J. Langhorst5,
S. Howaldt6, G. Novacek7, A.M. Petersen8, O. Bachmann9, H. Matthes10,
N. Hesselbarth11, T. Klugmann12, J. Wehkamp13, J. Klaus14, C. Ott15,
K. Dilger16, R. Greinwald16, R. Mueller16 on behalf of the International, TSU-
2 Study Group
1
Klinikum der Johann Wolfgang Goethe-Universitat Frankfurt a.M, Frankfurt
a.M., 2Abt. Gastroenterologie, UK-SH Campus Lubeck, Lubeck, Germany, 3Abt.
Gastroenterologie, Spital Netz Bern Tiefenau, Bern, 4Div. of Gastroenterology and
Hepatology, University of Zurich, Zurich, Switzerland, 5Integrative
Gastroenterologie, Internal and Integrative Medicine, Kliniken Essen-Mitte, Essen,
6
Hamburgisches Forschungsinstitut fur CED, HaFCED GmbH&Co.KG,
Hamburg, Germany, 7Universitatsklinik fur Innere Medizin III, Medizinische
Universitat Wien, Vienna, Austria, 8Dept. of Gastroenterology, Hvidovre
University Hospital, Hvidovre, Denmark, 9Medizinische Hochschule Hannover,
Hannover, 10Abt. Gastroenterologie, Gemeinschaftskrankenhaus Havelhohe,
Berlin, 11Arztehaus am Klinikum, Schwalmstadt, 12Gastroenterologische
Gemeinschaftspraxis, Leipzig, 13Abt. Innere Medizin I, Robert-Bosch-
Krankenhaus, Stuttgart, 14Klinik fur Innere Medizin I, Universitatsklinikum Ulm,
Ulm, 15Dept. of Internal Medicine I, University Hospital of Regensburg,
Regensburg, 16Dr. Falk Pharma GmbH, Freiburg, Germany
Contact E-mail Address: aed@kgu.de
INTRODUCTION: Until now only open-label data have been available showing
that a dosing of 2.500 embryonated viable eggs of Trichuris suis (TSO) every 3
weeks for 12 weeks led to clinical remission (CDAI5150) in 19 of 29 patients
(65.5%) with active Crohns disease (CD) refractory to standard CD-therapy
before enrolment (Summers et al., Gut. 2005;54(1):87-90).
AIMS & METHODS: This is the first double-blind, randomised, multicentre
POC study to evaluate the efficacy and safety of different TSO dosages vs pla-
cebo for the treatment of mildly-to-moderately active, ileo-/colonic, uncompli-
cated CD. Patients being neither steroid-dependent/-refractory nor on
immunosuppressants with a CDAI of 220-350 and biochemical signs of inflam-
mation were eligible for this study. Patients received either 250, 2.500, or 7.500
TSO, or placebo at fortnightly intervals for 10 weeks. Primary endpoint was the
rate of clinical remission (CDAI5150) at week 12 (last observation carried for-
ward [LOCF]).
RESULTS: 252 patients (154 females; mean age: 37 yrs; mean CDAI: 269) were
randomised. Efficacy is presented below. Administration of TSO did not result in
any serious adverse drug reaction (ADR). Review of non-serious suspect ADRs
following intake of TSO did not reveal a safety concern.
CONCLUSION: Administration of 250 7.500 TSO fortnightly over 12 weeks
was safe and showed a dose-dependent immunological response, but none of the
TSO dosages could show a clinically relevant effect over placebo for the induc-
tion of clinical remission or response in mildly-to-moderately active, ileo-/colonic
CD.
Disclosure of Interest: J. Scholmerich Lecture fee(s) from: Falk Foundation, K.
Fellermann Lecture fee(s) from: Abbvie, Falk Foundation, F. Seibold: None
declared, G. Rogler Financial support for research from: Dr Falk Pharma
GmbH, Lecture fee(s) from: Falk Foundation, J. Langhorst Financial support
TSO2.500 (N71) TSO7.500 (N72) Placebo (N70)
25(35.2%) 34(47.2%) 30(42.9%)
-7.5%[-23.7;8.4] 4.4%[-12.0;20.7]
0.8240 0.3006
-83 (111.6) -102 (111.4) -83 (127.0)
167 (373) 241 (363) 25 (111)
A124
for research from: Techlab Inc., Lecture fee(s) from: Falk Foundation, Repha
GmbH and Techlab Inc, S. Howaldt: None declared, G. Novacek Lecture fee(s)
from: Abbvie, Merck, MSD, Consultancy for: Abbvie, MSD, A. Petersen: None
declared, O. Bachmann Lecture fee(s) from: Falk Foundation, H. Matthes: None
declared, N. Hesselbarth: None declared, T. Klugmann: None declared, J.
Wehkamp: None declared, J. Klaus: None declared, C. Ott Lecture fee(s)
from: Falk Foundation, K. Dilger Other: Employee of Dr Falk Pharma, R.
Greinwald Other: Employee of Dr Falk Pharma, R. Mueller Other: Employee
of Dr Falk Pharma
WEDNESDAY, OCTOBER 22, 2014 14:0015:30
SYMPTOMS IN PATIENTS WITH FUNCTIONAL GASTROINTESTINAL DISORDERS
HALL R_____________________
OP393 WHICH MEASURE OF FECAL INCONTINENCE SEVERITY IS
THE BEST PREDICTOR OF FECAL INCONTINENCE QUALITY OF
LIFE (FIQL)?
W.E. Whitehead1,2,*, O.S. Palsson1,2, S. Heymen1,2
1
Medicine (Division of Gastroenterology and Hepatology), 2Center for Functional
Gastrointestinal and Motility Disorders, UNIVERSITY OF NORTH
CAROLINA, CHAPEL HILL, Chapel Hill, United States
Contact E-mail Address: William_Whitehead@med.unc.edu
INTRODUCTION: Published measures of fecal incontinence (FI) severity all
assess the frequency of FI, but they differ with respect to whether they discrimi-
nate between types of stool loss, volume of stool loss, urgency preceding FI
episodes, and pad use.
AIMS & METHODS: Our aim was to compare two frequently used FI severity
instruments, the Fecal Incontinence Severity Index (FISI) and the Fecal
Incontinence and Constipation Assessment (FICA) scale, with respect to which
instrument and which items within instruments are best able to predict variations
in FIQL. A nationally representative gender, age and ethnicity stratified sample
of U.S. adults with FI (FIPs) were recruited by market research company Cint
USA, Inc. to complete an internet survey including the FISI, FICA, and FIQL
questionnaires. The study was described as a health survey to minimize selection
bias. Stepwise linear regression was used to identify variables that are indepen-
dently predictive of FIQL. Demographic variables were entered as a block in
Step 1, the FISI was entered in Step 2, the FICA in Step 3, and the Somatization
scale of the Brief Symptom Inventory was entered in Step 4. The Somatization
scale was included to confirm that estimates of the effects of FI severity on FIQL
were not confounded by a general tendency to endorse more symptoms. The
regression analysis was repeated with individual items from each severity scale
to identify which questions explain the separate contribution of each scale.
RESULTS: Out of 234 survey completers, 48 (20.5%) were excluded from ana-
lysis because they gave inconsistent responses to two questions repeated for
quality control, leaving 186 for analysis: 52% were women, mean age was 48.9
years (range 20-91), and race/ethnicity was 9% Hispanic and 8% African
American. Post-bacalaurate education was over-represented (39.2%). The 4 sub-
scales of the FIQL were averaged together because they are highly correlated
with each other (r 0.72 0.88) and it is desirable to have a single dependent
measure for regression analysis. Average scores were: FIQL, 2.57 (95% CI 2.44,
2.69) on a 1-5 scale; FISI, 29.9 (95% CI 27.4, 32.4) on a 0-61 scale; FICA, 8.4
(95% CI 8.0, 8.9) on a 1-13 scale; Somatization T-score 65.6 (95% CI 63.7, 67.5).
In the initial regression analysis, the adjusted R2 for demographic variables alone
was .269. Adding FISI increased the R2 to .608, and adding the FICA increased
the R2 to .666. Adding somatization to the model increased R2 to .690. In the
final model, FICA and FISI both made significant contributions (p5.001) to
FIQL even after adjusting for Somatization. A follow-up regression analysis was
performed to identify individual items in each scale that predict FIQL (all items
from both severity scales plus Somatization: adjusted R2 .711). The significant
independent predictors were FISI frequency of liquid FI and gas leakage in the
past month, and FICA frequency of stool leakage and having to rush to the toilet
in the past year.
CONCLUSION: Four FICA and FISI variables make independent contribu-
tions to FI impact on quality of life: FISI frequency of liquid and gas leakage
and FICA frequency of any FI and of having to rush to the toilet. [Supported by
a grant from Salix Pharmaceuticals]
Disclosure of Interest: W. Whitehead Financial support for research from: Salix
Pharmaceuticals, Consultancy for: Takeda Pharmaceuticals, Ironwood
Pharmaceuticals, Entera Health, O. Palsson: None declared, S. Heymen: None
declared
OP394 IBS AND OVER-REPORTING OF ABDOMINAL PAIN IN
RETROSPECTIVE QUESTIONNAIRES: ADVANTAGES OF
EXPERIENCE SAMPLING METHOD AS NEW DIGITAL TOOL IN
SYMPTOM MEASUREMENT
Z. Mujagic1,*, C. Leue2, L. Vork1, R. Lousberg2, M.A. Hesselink1, J. van Os2,
A.A. Masclee1, J.W. Kruimel1
1
Division Gastroenterology-Hepatology, Department of Internal Medicine,
2
Department of Psychiatry and Medical Psychology, Maastricht University
Medical Center, Maastricht, Netherlands
Contact E-mail Address: z.mujagic@maastrichtuniversity.nl
INTRODUCTION: Irritable Bowel Syndrome (IBS) is a prevalent gastro-intest-
inal (GI) disorder with chronic and fluctuating symptoms, of which abdominal
pain is the most prominent. Standardized and well validated methods to assess
abdominal pain are lacking and the available methods, i.e. retrospective ques-
tionnaires, display limitations, such as recall bias and failure to detect triggers
and recognize cognitive and emotional aspects. A possible solution is the
United European Gastroenterology Journal 2(5S)
Experience Sampling Method (ESM); a digital tool, developed to measure real
time symptoms at multiple time points per day.
AIMS & METHODS: 1) To evaluate ESM as an assessment tool for GI symp-
toms and psychological complaints, with a focus on abdominal pain, in IBS
patients with and without comorbid panic disorder and 2) to compare the
ESM to retrospective paper questionnaires.
27. IBS patients (Rome III) were recruited. A subgroup of 17 patients was
diagnosed with comorbid panic disorder (DSM-IV-TR). For 7 days patients
carried a digital device (ESM), which randomly sent off beep signals 10 times/
day and patients filled in symptom scores on the device following every beep.
Additionally participants fulfilled a paper end-of-day GI symptom diary during
14 days and the Gastrointestinal Symptom Rating Scale, Hospital Anxiety and
Depression Scale and the Rand-36-item Health Survey at the end of the test
period. Somersd test (for ordinal data) was used to assess correlations between
ESM and paper questionnaire data. Mean and maximum ESM scores per day
and mean end-of-day diary scores were calculated and analyzed using two-way
ANOVA for repeated measurements.
RESULTS: For the total group of 27 IBS patients correlations between corre-
sponding items on ESM and end-of-day diary, i.e. abdominal pain, nausea,
belching, bloating and flatulence, were all highly significant (Somers d (t)
6.43 40.05, p50.001), and interestingly the weakest correlation was found
for abdominal pain (t 6.43). When comparing mean and maximum pain
scores of ESM data with the pain scores of end-of-day diary, scores filled in at
the end of the day were higher than the mean ESM scores, with a mean difference
of 0.4 point (significant on 6 of 7 days, p50.05) on a 5 point Likert scale. The
pain scores of the end-of-day diary correlate best with the maximum pain scores
on ESM. Furthermore, ESM items were significantly associated with 31 corre-
sponding items on the different GI and psychological symptom questionnaires (t
4.63 26.06, p50.001). Overall, the results for the group with and without
panic disorder were comparable.
CONCLUSION: IBS symptoms assessed real time by ESM significantly corre-
late to GI and comorbid psychological symptoms assessed by paper retrospective
questionnaires, in IBS patients with and without comorbid panic disorder.
However the weakest correlation was found for abdominal pain and our data
show that patients report the most intense pain of the day in an end-of-day diary,
rather than average pain over the day. This indicates over-reporting of pain by
IBS patients in retrospective questionnaires, and demonstrates an advantage of
ESM as a new digital symptom assessment tool.
Disclosure of Interest: Z. Mujagic: None declared, C. Leue: None declared, L.
Vork: None declared, R. Lousberg: None declared, M. Hesselink: None declared,
J. van Os: None declared, A. Masclee Consultancy for: Pentax medical,
Grunenthal GmbH, Ferring, J. Kruimel: None declared
OP395 SYMPTOM-BASED CRITERIA FOR THE DIAGNOSIS OF
IRRITABLE BOWEL SYNDROME PERFORM POORLY: A META-
ANALYSIS
R. Sood1,2,*, G.R. Law3, A.C. Ford 1,2
1
Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, 2Leeds
Institute of Biomedical and Clinical Sciences, 3Leeds Institute of Genetics, Health
and Therapeutics, University of Leeds, Leeds, United Kingdom
Contact E-mail Address: ruchitsood@gmail.com
INTRODUCTION: Irritable bowel syndrome (IBS) remains difficult to diag-
nose. Symptom-based criteria, the latest adaptation of these being the Rome
III criteria, are the current gold standard for diagnosing IBS. However, these
have not been well-validated, and recently attention has turned to novel
approaches to the diagnosis of IBS, including biomarkers and markers of psy-
chological affect. We performed a systematic review and meta-analysis to assess
the performance of various methods for diagnosing IBS.
AIMS & METHODS: A literature search was conducted using MEDLINE
(through to January 2014). Eligible studies had to assess the accuracy of accepted
symptom-based diagnostic criteria, biomarkers, psychological markers, or com-
binations thereof, in diagnosing IBS against an accepted reference standard. For
each study identified, we extracted the raw data from the paper, in order to
calculate the positive and negative likelihood ratios (LRs) of each of the diag-
nostic tests. Where a diagnostic method was reported by 41 study we pooled the
LRs from each study using meta-analytic techniques.
RESULTS: LRs with confidence intervals (CIs), of each of the diagnostic meth-
ods, are shown in table 1. Five studies validated the Manning criteria, two studies
the Rome I criteria, and one study the Rome II and Rome III criteria. Two
studies validated the same 10-biomarker algorithm in diagnosing IBS. One of
these studies also added 24 biomarkers to the original 10-biomarker panel, and
also combined this new 34-biomarker panel with measures of psychological
affect. This same study also used psychological markers alone. One study used
faecal volatile organic metabolites (VOMs), chemicals that are released in faeces.
Finally, four studies validated the Kruis statistical model.
United European Gastroenterology Journal 2(5S) A125
Table 1- Positive and Negative LRs of Diagnostic Methods for IBS OP397 THE ODDS OF GASTROESOPHAGEAL REFLUX SYMPTOMS
Table to abstract OP395 INCREASE BY 35% PER DECADE IN A 23 YEAR PROSPECTIVE,
LONGITUDINAL STUDY
Number of Number of Positive LRs Negative A. Andreasson1,2,*, M. Jones3, N. Talley4, A. Forsberg5, B. Wallner6,
Diagnostic Method studies participants (95% CI) LRs (95% CI) L. Kjellstrom1, P.M. Hellstrom7, L. Agreus1
1
Karolinska Institutet, Centre for Family Medicine, Huddinge, 2Stress Research
Manning 5 2428 3.04 (1.88, 4.90) 0.33 (0.18, 0.60)
Institute, Stockholm University, Stockholm, Sweden, 3Department of Psychology,
Rome I 2 2468 3.86 (3.00, 3.53) 0.14 (0.01, 1.52) Macquarie University, North Ryde, 4Faculty of Medicine, University of Newcastle,
Rome II 1 1848 3.19 (2.92, 3.48) 0.14 (0.10, 0.19) Newcastle, Australia, 5Molecular Medicine and Surgery, Karolinska Institutet,
Rome III 1 1848 3.35 (2.97, 3.79) 0.39 (0.34, 0.46) Stockholm, 6Umea University, Umea, 7Uppsala University, Uppsala, Sweden
10-biomarker panel 2 760 3.03 (1.48, 6.23) 0.52 (0.43, 0.64) Contact E-mail Address: anna.andreasson@ki.se
34-biomarker panel 1 244 2.28 (1.67, 3.11) 0.30 (0.21, 0.42)
INTRODUCTION: The assumption that the prevalence of gastroesophageal
Faecal VOMs 1 140 22.00 (8.27, 58.50) 0.21 (0.10, 0.42) reflux symptoms (GERS) increase with time needs to be confirmed in prospective
Psychological markers 1 760 2.95 (1.98, 4.40) 0.35 (0.26, 0.46) studies of the general population.
Biomarkers and 1 760 8.63 (2.89, 25.80) 0.18 (0.12, 0.25) AIMS & METHODS: By means of a validated questionnaire on gastrointestinal
psychological markers symptom (the Abdominal Symptom Questionnaire, ASQ) an adult population
Kruis statistical model 4 1171 7.14 (3.85, 13.23) 0.26 (0.17, 0.41) was surveyed 4 times over 23 years: 1988 (n1156, 21-79 years of age (yoa)
response rate of original number approached (rr) 90%), 1989 (n1097, 22-80
yoa, rr 87%), 1995 (n1139, 20-87 yoa, rr 82%) and 2011 (n1175, 20 yoa and
CONCLUSION: Available symptom-based diagnostic criteria for IBS perform above, rr 64%). Altogether 490 persons participated in all four surveys.
modestly, and with striking similarity. Serum biomarkers are disappointing, given The effect of time on GERS prevalence was calculated using random effects
their potentially expensive nature. Faecal VOMs appear promising but warrant logistic regression models using GERS as the dependent variable and gender,
replication in other studies. The superior performance of a combination of bio- age and time as independent variables. All participants in all surveys are included
markers and psychological markers, and the Kruis statistical model, over symp- in the analyses (1847 participants, 4466 observations).
tom-based diagnostic criteria perhaps suggests the future of IBS diagnostics lies in RESULTS: GERS increased significantly with time, the odds of reporting reflux
combining demographic data, gender, symptoms, biomarkers, and psychological increasing by 35% per decade (OR:1.34; 95%CI: 1.18-1.53, p5.001) independent
markers. However, this may come at the price of increasing complexity. of gender and age. This increase was driven by an increase in heartburn (OR:1.53;
Disclosure of Interest: None declared 95%CI: 1.35-1.73, p5.001) and in acid regurgitation (OR:1.30, 95%CI: 1.14-
1.47, p5.001).
In this 23 year prospective longitudinal study on an adult population, the odds of
OP396 PHENOTYPING PATIENTS WITH IRRITABLE BOWEL GERS has increased by 35% per decade. On an individual basis, there is a large
SYNDROME WITH DIARRHOEA (IBS-D): MECHANISTIC STUDY symptom turnover both within a year and over longer periods, reflecting the
LOOKING AT STOOL CALPROTECTIN AND GENE EXPRESSION IN natural history of GERS.
COLON BIOPSIES Table. Prevalence and turnover of GERS in participants completing all surveys
C. Lam1,*, M. Lingaya1, Y. Falcone1, A. Bennett2, R. Spiller1 (N490)
1
NIHR Nottingham Digestive Diseases Biomedical Research Unit, 2Frame
Laboratory, School of Life Sciences, University of Nottingham, Nottingham,
United Kingdom Loss from GERS Gain from
Contact E-mail Address: ching.lam@nottingham.ac.uk Prevalence GERS to non-GERS non-GERS to GERS

INTRODUCTION: Irritable bowel syndrome is a heterogeneous condition with Year N % Year N/N GERS % N/N non-GERS %
multiple factors leading to the symptoms of IBS such as stress, infection and diet.
Recent demonstration of immune activation in the gut has prompted trials of 5- 1988 86 17.7 (14.5-21.4) 1988-1989 31/86 36.1 36/404 8.9
aminosalicylates; however identifying the phenotype of who will respond remains 1989 91 18.6 (15.2-22.3) 1989-1995 29/91 31.9 36/399 9.0
elusive.
AIMS & METHODS: Our previous multicentre study1 showed Mesalazine (M) 1995 98 20.0 (16.5-23.8) 1995-2011 53/98 54.1 59/392 15.1
was not effective in unselected IBS-D patients. Here we report the value of a 2011 104 21.2 (17.7-25.1)
number of biomarkers collected in this same trial in an attempt to identify
responders. Stool samples and sigmoid biopsies were collected at baseline CONCLUSION: In this 23 year prospective longitudinal study on an adult
and 12 weeks later at the end of study from IBS-D patients and were randomised population, the odds of GERS has increased by 35% per decade. On an indivi-
into either M or placebo(P) to be taken for 12 weeks in Nottingham. Group 1:53 dual basis, there is a large symptom turnover both within a year and over longer
pairs of stool samples were obtained. Stool calprotectin (SCal) was analysed by periods, reflecting the natural history of GERS.
using a commercial Elisa kit. High level of SCal level is defined as 100 ug/ml. Disclosure of Interest: None declared
Group 2:43 pairs of sigmoid biopsies obtained. These samples were compared
with biopsies obtained from 21 healthy volunteers(HV). Gene expressions were
analysed by mRNA quantification via 2 step reverse transcription quantitative OP398 DISCREPANCIES BETWEEN UPPER GI SYMPTOMS
polymerase chain reaction technique. Relative expression levels for each mRNA DESCRIBED BY THOSE WHO HAVE THEM AND THEIR
were calculated using mean Ct values of 4 mRNA endogenous genes. IDENTIFICATION BY CONVENTIONAL MEDICAL TERMINOLOGY:
RESULTS: [Mean (SD)] Group 1: SCal levels did not improve with M[mean A SURVEY IN FOUR COUNTRIES
difference(md)-12.16 (82.69);p0.43] when compared to P[md0.10 (87.05); R. Heading1,*, E. Thomas2, P. Sandy3, G. Smith2, R. Fass4, P. Hungin1
p0.73]. Baseline SCal negatively correlated with anxiety score (Spearman r- 1
School of Medicine, Pharmacy and Health, Durham University, Durham,
0.28;p0.04). There was no correlation between baseline SCal with clinical symp- 2
Category Development Organisation, Reckitt Benckiser plc, Slough, United
toms such as abdominal pain severity, urgency, bloating, stool frequency or stool Kingdom, 3Winkle, Amsterdam, Netherlands, 4Gastroenterology, Case Western
consistency. When Scal were divided into 2 subgroups of high and low levels, the Reserve University, Cleveland, Ohio, United States
total hospital and anxiety (HAD) scores in the high SCal group [5.7(3.5)] were
significantly lower than the low SCal group [8.6 (4.4)];p0.03 however there were INTRODUCTION: Modern self-administered questionnaires assessing upper GI
no significant differences in abdominal pain severity, average stool frequency or symptoms are usually designed by reconciling the descriptive vocabulary used by
stool consistency. Group 2: Toll-like receptor 4(TLR-4) and myeloid differentia- symptomatic individuals with conventional medical terminology for symptoms
tion primary response 88(MYD88) mRNA were both elevated compared to HV. (e.g. heartburn, regurgitation, epigastric discomfort etc.). It is often assumed that
Quantity mRNA (mRNAq) for TLR-4 in HV vs IBS-D were 0.75(0.42) and the conventional medical vocabulary is able to identify the symptoms adequately.
1.96(0.86);p50.01. When treated with M, TLR-4 levels showed significant AIMS & METHODS: We aimed to develop a self-administered questionnaire for
reduction [md-0.29(0.68) compared to P group [md0.22(0.78)];p0.03. upper GI symptoms based on lay vocabulary without imposition of medical
There was no correlation between TLR-4 and SCal (Spearman r0.17; concepts or terminology for use in a large survey of symptom occurrence
p0.26). mRNAq for MYD88 was significantly higher in IBS-D vs HV being among sufferers in 4 countries.
1.12(0.42) vs 0.63(0.25); p50.01. Treatment with M did not alter MYD88 levels The questionnaire was designed by integrating symptom descriptions used by 38
[md0.03(0.37)] compared to placebo [md0.12(0.39)]; p0.43. symptomatic adults in Brazil, Russia, UK and USA. The resulting questionnaire,
CONCLUSION: A small cohort of IBS-D patients demonstrated patients with low in the appropriate language, was distributed on-line daily for 6 weeks to indivi-
SCal are more anxious and depressed that those with high SCal suggesting their duals experiencing upper GI symptoms in the 4 countries. Detailed information
symptoms may be centrally rather than driven by changes in the gastrointestinal was sought on up to 7 symptom episodes occurring on different days, identifying
tract. Elevated gene expression in TLR-4 and MYD88 could be a feature in a small the nature, severity, timing and duration of the predominant symptom on each
subgroup of IBS-D patients where symptoms are driven peripherally by mucosal/ occasion together with other symptoms experienced concurrently. They were also
microbiome interactions. Further larger studies are needed to confirm this. asked what term they would use to describe their symptoms to a friend or a
REFERENCES doctor.
1. Lam, et al. DDW 2014 A multi-centre, parallel group, randomised placebo RESULTS: The questionnaire development identified and described 9 symptoms
controlled trial of mesalazine for treatment of diarrhoea-predominant irritable using non-medical vocabulary. They occurred with a frequency of 24 61 % in
bowel syndrome (IBS-D). 2665 survey respondents who reported on 10,659 symptom episodes. One of the
Disclosure of Interest: C. Lam: None declared, M. Lingaya: None declared, Y. symptoms appeared to correspond with regurgitation while two distinct symp-
Falcone: None declared, A. Bennett: None declared, R. Spiller Financial support toms (experienced by 28% and 34% of subjects) possibly corresponded with
for research from: Grants from Lesaffre and Ironwoom, Consultancy for: heartburn. However, 58% of individuals who reported these two concurrently
Almirall, Astellas, Danone, Sanofi, Other: Free drug from Norgine on some occasions reported one being present without the other on other
A126
occasions. Five stomach or abdominal symptoms were recognised and distin-
guished and there was one chest symptom, reported by about 30% of subjects in
all 4 countries, for which a corresponding medical term was uncertain.
Statistically significant differences in occurrence and severity of some symptoms
were evident between countries, between genders and between age groups. Both
the predominant symptom and the pattern of concurrent symptoms often varied
from one symptom episode to another. Respondents use of the terms heartburn,
reflux, regurgitation, burning stomach and indigestion to describe their symp-
toms to a friend or doctor varied considerably between countries.
CONCLUSION: Discrepancies between the symptoms described by those who
suffer them and the way in which they can be described by conventional medical
terminology were evident in all four countries. These discrepancies deserve more
attention with a view to identifying the limitations of current upper GI symptom
enquiry and developing validated questionnaires, possibly derived solely from the
vocabulary of individuals suffering the symptoms, which will improve symptom
identification and assessment.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 14:0015:30
INNOVATIONS IN BILIARY STENTING HALL N_____________________
OP399 METALLIC VS. PLASTIC STENT IN THE PREOPERATIVE
TREATMENT FOR BILIARY OBSTRUCTION OF RESECTABLE
PERIAMPULLARY TUMOURS: A RANDOMIZED CONTROLLED
TRIAL
F. Gonzalez-Huix1, M.A. Alburquerque1,2,*, M. Figa1,3, S. Lopez Ben4,5,
M.T. Albiol5, J. Figueras4,5
1
Gastroenterology, Clnica Girona, 2Gastroenterology, Hospital de Palamos,
3
Gastroenterology, Hospital Universitario Dr. Josep Trueta, 4Surgery, Clnica
Girona, 5Surgery, Hospital Universitario Dr. Josep Trueta, Girona, Spain
Contact E-mail Address: fgonzhuix@gmail.com
INTRODUCTION: The fully covered self-expanding metal stents (SEMSc)
could be a cost-safe alternative instead of plastic stents (PS) for preoperative
endoscopic drainage of resectable periampullary tumours.
AIMS & METHODS: To compare the safety and costs of SEMSc vs. PS in the
preoperative endoscopic drainage for biliary obstruction due to periampullary
tumours potentially resectable with curative intent.
Method: Open label randomized controlled trial. Participants: Patients with
malignant biliary obstruction caused by resectable periampullary tumours.
Inclusion criteria: total bilirubin 415 mg/dl, unable to operate in 510 days,
to pass guidewire through biliary obstruction in ERCP. Intervention: We ran-
domly assigned patients to receive either a SEMSc (Wallflex) or a PS
(Flexima). Main outcome measures: Complications related to stent type
during the stent-surgery interval. Secondary outcomes measures: Number of
admissions and hospitalization days in preoperative period, re-intervention
requirement (additional ERCP and others), direct costs, surgical difficulties attri-
butable to stent, surgical and postsurgical complications.
RESULTS: We included 63 patients. Age: 68.038.5 y; 42 men. There were 35
pancreatic tumours, 11 cholangiocarcinomas and 17 ampullary carcinomas.
Were placed 35 SEMSc and 28 PS. 13 patients were finally ruled out to surgery.
Regarding intention-to-tread there were 3/35 (8.6%) preoperative complications
in SEMSc group and 10/28 (35.7%) in PS group (p0.012), while per protocol
there were 1/26 (3.8%) in SEMSc group and 9/24 (37.5%) in PS group (p0.004).
Stent-surgery interval (days): SEMSc group 37.5; PS group 37; p0.9.
Hospitalization days during the stent-surgery interval: SEMSc group: 0.21.0;
PS group: 2.74.7; p0.011. In SEMSc group were necessary additional inter-
ventions in 8.6% of patients and in PS group in 25%; p0.077. The average
direct costs were lesser in SEMSc group than PS group 1486129 vs.
2117643E; p0.34. It was done a resected surgery in 38 patients while in 12,
only a bypass procedure without differences between both groups. In SEMSc
group there were anatomical disorders in the hepatic hilum attributable to stent
in 42.3 % of patients and in 25% in PS group, although these disorders did not
difficult the surgery. There were not differences, neither in surgical and postsur-
gical complications (follow-up by 1 month post discharge) nor in hospitalization
days at ICU or in the number of deaths.
CONCLUSION: The SEMSc showed lower complication rate, lesser hospitali-
zation days and re-interventions during preoperative period without increase of
costs. We consider that SEMSc should be the first option for preoperative endo-
scopic drainage of resectable periampullary tumours.
Disclosure of Interest: None declared
OP400 THE COSTS OF PLASTIC STENT FAILURE IN MALIGNANT
JAUNDICE
D.R. Moffat1,*, F. Rose1, V. Pirjamali1, I. Gooding1
1
Department of Gastroenterology, Colchester Hospital, Colchester, United
Kingdom
Contact E-mail Address: danielmoffat@hotmail.com
INTRODUCTION: Metal biliary stents have better patency rates than plastic
stents, but cost substantially more. A current European guideline recommends
that plastic stents are used where expected survival from malignant disease with
biliary obstruction is less than 4 months1. This is a subjective judgement that is
difficult to apply in clinical practice. We retrospectively reviewed the perfor-
mance of biliary stents placed at endoscopic retrograde cholangiopancreatogra-
phy (ERCP) to determine the full healthcare costs of stent failure. We then
performed a cost comparison of the two stent types in patient subgroups.
AIMS & METHODS: We reviewed all ERCPs performed at Colchester General
Hospital from January 2008 to December 2010 and identified cases where a
United European Gastroenterology Journal 2(5S)
patient received a stent for malignant biliary obstruction for the first time. We
then collected data on (i) tumour size and presence of metastases on computed
tomography (CT) at diagnosis, (ii) subsequent ERCPs, (iii) subsequent hospital
admissions for biliary problems and (iv) survival. Using costings provided by the
hospital finance department, we assessed the total cost of failure of plastic stents.
Using costings provided by our supplier of metal stents we then performed a
comparison of the cost implications of metal and plastic stents for different
patient groups. This analysis was based on the prediction derived from meta-
analysis that the metal stent failure rate is 52% of the plastic stent failure rate2.
RESULTS: 111 patients received a 1st plastic stent, of which 11 later had surgery,
leaving 100 cases where plastic stents were used for palliation alone. All these
patients have now died. 82 had successful relief of jaundice but the success rate
for Klatskin tumours was only 5/11. In 77 cases no further biliary intervention
was required. The remaining 23 patients had 38 subsequent biliary problems,
requiring 27 admissions (totalling 403 days) and 33 further ERCPs. In the
table actual costs after plastic stenting per patient are compared with predicted
costs had a metal stent been used instead.
Median survival Total costs with Total costs
PATIENT SUBGROUP n (days) plastic stent with metal stent
KLATSKIN 11 21 1717.45 Not applicable
METASTATIC 37 62 689.16 857.92
TUMOUR 4 2CM 26 62 281.12 645.74
TUMOUR 5 2CM 8 238.5 1126.50 1085.34
TUMOUR NOT SEEN 15 258 2160.27 1622.90
OTHER 3 No CT performed
TOTAL 100 74.5 934.07 985.28
CONCLUSION: Metal stents should be used for patients with small tumours
(less than or equal to 2cm) with no metastases. Plastic stents remain the lower
cost option for larger tumours and metastatic disease.
REFERENCES
1. Dumonceau JM, Tringali A, Blero D, et al. Biliary stenting: indications, choice
of stents and results: European Society of Gastrointestinal Endoscopy (ESGE)
clinical guideline. Endoscopy 2012; 44: 277.
2. Moss AC, Morris E, Leyden J, et al. Do the benefits of metal stents justify the
costs? A systematic review and meta-analysis of trials comparing endoscopic
stents for malignant biliary obstruction. Eur J Gastroenterol Hepatol 2007; 19:
1119.
Disclosure of Interest: None declared
OP401 MULTIPLE PLASTIC STENTS OR FULLY COVERED SELF-
EXPANDABLE METAL STENTS FOR ENDOSCOPIC
MANAGEMENT OF REFRACTORY BILIARY LEAKS?
L.C. Meireles1, J. Canena1,2,*, M. Liberato2, I. Marques1, C. Romao1,
A.P. Coutinho1,2, B.C. Neves1
1
Department of Gastroenterology - H. Pulido Valente, CHLN, 2Center of
Gastroenterology, Cuf Infante Santo Hospital Faculty of Medical Sciences
Lisbon, Lisbon, Portugal
Contact E-mail Address: lilianeenailil@gmail.com
INTRODUCTION: Endoscopic management of postcholecystectomy biliary
leaks is widely accepted as the treatment of choice. However refractory biliary
leaks after combination of biliary sphincterotomy and placement of a large-bore
(10-French) plastic stent can occur and the optimal rescue endotherapy for this
situation is unclear.
AIMS & METHODS: We compared the clinical effectiveness of 2 types of
endotherapy: use of a Fully covered self-expandable metal stent (FCSEMS) or
placement of multiple plastic stents (MPS) for the treatment of postcholecystect-
omy refractory biliary leaks. This study prospectively evaluated 2 groups of 40
consecutive patients with refractory biliary leaks who underwent temporary pla-
cement of either multiple plastic stents (n20) or FCSEMSs (n20). Data were
collected to analyze the clinical outcome of endotherapy as well as technical
success, adverse events, need for reinterventions and prognostic factor for clinical
success.
RESULTS: Endotherapy was possible in all patients. At the end of endotherapy
closure of the leak was obtained in 13 patients (65%) submitted to placement of
MPS and in 20 patients (100%) submitted to the use of FCSEMS respectively
(P0.004). The Kaplan-Meier (log-rank) leak-free survival analyze showed a
statistically significant difference between the two patient populations
(2(1)8.30; P50.01) in favor of the FCSEMS group. A number of plastic
stents less than 3 (P0.015), a plastic stent diameter below 20 French
(P0.006) and a high-grade biliary leak (P0.004) proved to be significant pre-
dictors of treatment failure with MPS. The 7 patients in whom placement of MPS
failed were retreated with a FCSEMS with closure of the leak in all cases.
CONCLUSION: Temporary placement of a FCSEMS in postcholecystectomy
refractory biliary leaks is the treatment of choice and has a high success rate.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP402 MULTICENTRE COMPARATIVE EVALUATION OF
ENDOSCOPIC PLACEMENT OF EXPANDABLE METAL STENTS
FOR MALIGNANT DISTAL CBD OBSTRUCTION BY ERCP OR EUS-
GUIDED APPROACH IN PATIENTS WITH OR WITHOUT
DUODENAL STENOSIS
V. Dhir1,*, T. Itoi2, M.A. Khashab3, D.H. Park4, A. Teoh5, R. Attam6,
A. Messallam3, S. Varadarajulu7, A. Maydeo8
1
Endosonography, Baldota Institute of digestive endoscopy, Mumbai, India, 2Tokyo
Medical University, Tokyo, Japan, 3Johns Hopkins university school of medicine,
Baltimore, United States, 4Asan Medical Centre, Seoul, Korea, Republic Of,
5
Chinese University of Honk Kong, Hong Kong, Hong Kong, 6University of
Minnesota, Minneapolis, 7Florida Hospital, Orlando, United States, 8Baldota
Institute of digestive sciences, Mumbai, India
Contact E-mail Address: vinaydhir@gmail.com
INTRODUCTION: ERCP is the procedure of choice for relief of jaundice due to
distal malignant biliary obstruction. However ERCP may fail in up to 10%
patients. A single session EUS-guided biliary drainage (EUS-BD) can be per-
formed in patients with or without duodenal stensosis (DS). There is no study
comparing results of EUS-BD and ERCP for relief of distal malignant biliary
obstruction.
AIMS & METHODS: To compare the outcome of self-expandable metallic stent
(SEMS) placement for malignant distal biliary obstruction by ERCP or EUS-
BD. Patients with malignant distal CBD obstruction, who failed a previous
ERCP, formed the EUS-BD group (choledocho-duodenostomy (CDS) and ante-
grade (AG) procedures). Data for ERCP group was collected from consecutive
patients at one center (Mumbai).
RESULTS: There were 117 patients in the ERCP group and 98 patients in EUS-
BD (67 CDS, 31 AG). SEMS placement was successful in 113 patients in ERCP
and 93 patients in EUS-BD group (96.6% vs.94.8%, p0.734). The complication
rates in the ERCP and EUS-BD group were 5.1%, and 9.1% respectively
(p0.285). The ERCP group had 5 pancreatitis, compared to none in the
EUS-BD group (p0.065). The mean procedure time in ERCP and EUS-BD
group was not significantly different (30.10 and 35.95 minutes, p0.052).
There was no significant difference in the success rate, complications, and
mean procedure time between CDS and AG procedures. The success rate of
EUS-BD was significantly higher (p0.0001) in patients with type II DS.
CONCLUSION: In patients with malignant distal bile duct obstruction requiring
SEMS placement, the short-term outcome of EUS-BD is comparable to ERCP in
patients with normal duodenum, and those with type I DS. EUS-BD has sig-
nificantly superior success rate than ERCP in patients with type II DS.
Disclosure of Interest: None declared
OP403 QUALITY OF LIFE AFTER STENT PLACEMENT FOR
PALLIATION OF COMMON BILE DUCT OBSTRUCTION: A
RANDOMIZED CONTROLLED TRIAL COMPARING PLASTIC AND
METAL STENTS
D. Walter1,*, P.D. Siersema1, F.P. Vleggaar1 on behalf of on behalf of the
PLAMET study group
1
Departement of Gastroenterology and Hepatology, University Medical Center
Utrecht, Utrecht, Netherlands
Contact E-mail Address: d.walter@umcutrecht.nl
INTRODUCTION: Endoscopic stent placement is the procedure of choice for
palliation of common bile duct (CBD) obstruction. It is known that self-expand-
able metals stents (SEMS) are superior to plastic stents in terms of stent patency
and occurrence of stent dysfunction. However, it is unknown whether this also
translates in improved quality of life (QoL) in patients with SEMS.
AIMS & METHODS: Our aim was to compare QoL between patients treated
with a plastic stent or SEMS for the palliation of CBD obstruction. We per-
formed a randomized multicentre trial in 18 hospitals with 219 patients rando-
mized to plastic stent (n73) or SEMS (n146) placement. QoL was assessed
with two general questionnaires (EQ-5D-5L with visual analogue scale (VAS)
and QLQ-C30) and one disease specific questionnaire (PAN-26). Questionnaires
were filled out before treatment, 14 days and 1-6 months after treatment. We
compared QoL scores using linear mixed model analyses and included all patients
with baseline and at least one follow-up measurement. Quality-adjusted life
months (QALMs) were calculated using EQ-5D utilities.
RESULTS: Baseline questionnaires and at least one follow-up measurement were
available in 140/219 patients (64%), 71 patients (32%) declined participation and
in 8 patients (4%) only baseline questionnaires were available. In patients with
QoL data, significantly more patients had a SEMS (42% vs. 29%, p0.05), a
second stent placement (26% vs. 14%, p0.04) and metastatic disease (59% vs.
39%, p0.005). Baseline characteristics from the patients that QoL data were the
same for patients with a plastic stent or SEMS. The mean functional stent time
was significantly longer in the SEMS group (289 days, 95% CI 258-320) com-
pared to the plastic stent group (148 days, 95% CI 101-196, p50.005). Survival
was not different between the two stent groups with an overall mean survival of
158 days (95% CI 136-178). On the QLQ-C30, the interaction between follow-up
time and type of stent was significantly different on two of five functional scales
(physical functioning (p0.004) and emotional functioning (p0.01)) in favor of
patients with a SEMS. Strong trends in favor of SEMS were seen in global health
(p0.09), EQ-VAS (p0.08), role functioning (p0.096) and cognitive function-
ing scales (p0.07). EQ-VAS scores significantly decreased in time in both treat-
ment groups. On all other scales scores of the SEMS group remained stable and
decreased in the plastic stent group. On the PAN-26 a reduction of hepatic
symptoms was seen in both groups during the first month after stent placement
with no significant difference between the groups (p0.13). After 1 month, the
score for hepatic symptoms remained stable in the SEMS group, while in the
plastic stent group there was a trend towards an increase of symptoms (p0.09).
A127
Digestive symptoms significantly increased in both groups, with a significant
stronger increase in the plastic stent group (p0.003). Mean QALMs were 2.13
in patients with a plastic stent and 2.47 in patients with SEMS (p0.52).
CONCLUSION: In patients with malignant extrahepatic bile duct obstruction
SEMS placement results in better scores on both general- and disease specific
HRQoL scales over time compared to plastic stent placement. In addition, the
number of QALMs was higher in the SEMS group, although this difference was
not statistically significant.
Disclosure of Interest: D. Walter: None declared, P. Siersema Financial support
for research from: Boston Scientific, USA, Consultancy for: Boston Scientific,
USA, F. Vleggaar: None declared
OP404 IN VIVO ENDOSCOPIC BILIARY IN-STENT PHOTODYNAMIC
THERAPY USING POLYMERIC PHOTOSENSITIZER-EMBEDDED
MEMBRANE-COVERED METAL STENT IN A SWINE MODEL
S. Jeong1,*, D.H. Lee1, Y.W. Shin1
1
Internal Medicine, Inha University School of Medicine, Incheon, Korea, Republic
Of
Contact E-mail Address: inos@inha.ac.kr
INTRODUCTION: The photodynamic therapy (PDT) which has been used for
palliative treatment of cholangiocarcinoma, has some limitations and drawbacks
in clinical application.
We developed a polymeric photosensitizer-embedded membrane-covered metal
stent (PDT-stent), and performed in vitro release test and in vivo animal experi-
ment of photodynamic activities against xenografted tumor.
AIMS & METHODS: The aim of this study is to estimate the safety, efficacy and
photosensitizer stability of the switch on and off and repeated endobiliary in-
stent PDT using PDT-stent in swine model. Single session of endoscopic biliary
in-stent PDT was performed with various energy amount of laser (670 nm; 40, 70,
100, and 150 J/cm2) after the insertion of PDT-stent in the common bile duct
(CBD) of twelve mini pigs to determine proper energy level of laser for PDT.
Two days later, all the animals were euthanized and bile ducts were extracted for
the pathologic examination. And 3 or 5 sessions of endoscopic biliary in-stent
PDT with 70 J/cm2 of light energy, and cholangiogram were repeated at 2-week
intervals over a period of 4 weeks or 8 weeks after PDT-stent insertion in 6 swine
to assess the safety and photosensitizer stability of repeated PDT. Then the bile
ducts and the inserted stent of all the animals were obtained after two days for
pathologic analysis and quantification of fluorescence intensity (FI) for
Pheoporbide A (Pheo-A) remained from PDT-stent.
RESULTS: There was no evidence of bile duct perforation in all animals on
follow up cholangiograms after single or repeated biliary PDT. Repeated PDT
with fixed energy level, 70 J, caused only surface mucosal necrosis in all animals
and the degree of inflammation was constant irrespective of number of PDT
session. The FI of Pheo-A from PDT-stent was reduced to 50 and 60% of base-
line FI for 100 and 150 J/cm2 group, respectively after single session of PDT.
After 3 or 5 sessions of PDT at 2-week intervals over a period of 4 weeks or 8
weeks with 70 J/cm2, the FI of PDT-stents observed to be similar to that of the
PDT-stent before laser irradiation.
CONCLUSION: Endoscopic biliary PDT using the PDT-stent was safe, effec-
tive, and repeatable over a period of 8 weeks for the treatment of
cholangiocarcinoma.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 14:0015:30
EOSINOPHILIC OESOPHAGITIS AND OTHER IMMUNE MEDIATED UPPER GI DISEASES
HALL O_____________________
OP405 DEVELOPMENT OF A SYMPTOM-BASED ACTIVITY INDEX
FOR EOSINOPHILIC ESOPHAGITIS
A. Schoepfer1,*, A. Straumann2, R. Panczak3, C. Kuehni3, Y. Romero4,
J. Alexander4, I. Hirano5, N. Gonsalves5, G. Furuta 6, E. Dellon7, J. Leung8,
M. Collins9, C. Bussmann10, P. Netzer3, S. Gupta11, M. Chehade 12,
F. Moawad13, S. Aceves14, J. Wo15, M. Zwahlen3, E. Safroneeva3
1
University Hospital Lausanne / CHUV, Lausanne, 2University Hospital Basel,
Basel, 3University of Bern, Bern, Switzerland, 4Mayo Clinic Rochester, Rochester,
5
Northwestern University of Chicago, Chicago, 6University of Colorado, Aurora,
7
University of North Carolina, Chapel Hill, 8Tufts Medical Center, Boston,
9
Cincinnati Children Hospital, Cincinnati, United States, 10Viollier Pathology
Basel, Basel, Switzerland, 11Indiana University of Medicine, Indianapolis, 12Mount
Sinai Food Allergy Institute, New York, 13Walter Reed Army Hospital, Bethesda,
14
University of California, San Diego, 15Indiana University, Indianapolis, United
States
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: Instruments assessing disease activity in adult patients with
eosinophilic esophagitis (EoE) are urgently needed to provide endpoints for
clinical trials and for disease monitoring in observational studies. The interna-
tional Eosinophilic Esophagitis Activity Index (EEsAI) study group developed 3
instruments to assess clinical, endoscopic, and histologic activity of EoE. The
clinical activity was assessed by the means of patient-reported outcomes (PRO)
instrument.
AIMS & METHODS: We aimed to develop a PRO instrument and score based
on the items that best explain the variability in patient global assessment of EoE
severity (PatGA) (on a Likert scale from 0 to 10). To assess whether endoscopic
and histologic findings help to explain the variability in PatGA. The EEsAI PRO
instrument assesses, among others, dysphagia characteristics, including dyspha-
gia due to foods with 8 distinct consistencies, the time needed to eat a meal, and
behavioral adaptations to dysphagia, such as food modification and avoidance.
A128
Patient input for item generation was gained using a mixed methods approach,
involving psychologist-guided focus group interviews, individual patient cogni-
tive interviews, and patient questionnaires using open-ended questions. Physician
input by Delphi rounds was used to develop the hypothetical framework.
Patients were asked to recall symptoms and behavioral adaptations over the
previous 24 hour-, 7 day-, and 30 day-periods. Linear regression and analysis
of variance (ANOVA) was used to evaluate the extent to which variations in
patient-reported disease characteristics explain the variability in PatGA.
ANOVA was used to examine the extent to which variations in endoscopic,
histologic and laboratory parameters help to explain the variability in PatGA
over and above PRO items.
RESULTS: The PRO instrument was evaluated in 153 adult EoE patients
(72.5 % males, median age 38 years) recruited in Switzerland and in the
United States. A recall period of 7 days was best suited to measure EoE severity.
The following 7 PRO items explained 67 % of the total variability in PatGA:
frequency of dysphagia, duration of dysphagia, swallowing-associated pain, the
visual dysphagia questionnaire (VDQ, 1 item), food avoidance, modification
and slow eating. The VDQ assesses dysphagia in the context of consuming
foods of 8 different consistencies. The EEsAI PRO score ranges from 0 to 100.
Addition of endoscopic and histologic features into the model explained only an
additional 4 % of the PatGA.
CONCLUSION: Seven PRO items can be used to assess clinical EoE symptom
severity over a 7-day recall period. Endoscopic and histologic features contrib-
uted negligibly over and above PRO items. The validity of the current PRO score
is currently being tested in a second independent patient group.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP407 EFFECTS OF DIETARY TREATMENT OVER THE MAST CELL
POPULATIONS AND GENE EXPRESSION IN ESOPHAGEAL
MUCOSA OF ADULTS WITH EOSINOPHILIC ESOPHAGITIS
A. Arias1, A.J. Lucendo2,*, P. Mart nez-Fernandez3, A.M. Gonzalez Castro4,
M. Fortea4, J. Gonzalez-Cervera5, J.L. Yague-Compadre6, T. Mota-Huertas6,
M. Vicario4
1
Research Support Unit, Hospital General La Mancha Centro, Alcazar de San
Juan, 2Gastroenterology, Hospital General de Tomelloso, Tomelloso, 3Molecular
genetics laboratory, Hospital Universitario La Paz, Madrid, 4Laboratory of Neuro-
immuno-gastroenterology., Vall dHebron Institut de Recerca, Barcelona, 5Allergy,
Hospital General de Tomelloso, Tomelloso, 6Patholoy, Hospital General La
Mancha Centro, Alcazar de San Juan, Spain
Contact E-mail Address: alucendo@vodafone.es
INTRODUCTION: Mast cells (MC) are increased in the inflammatory infiltra-
tion which characterizes eosinophilic esophagitis (EoE). However, MC nature
and changes after dietary treatment have been not assessed.
AIMS & METHODS: To characterize MC population in the esophageal mucosa
of adult EoE patients by analysing MC-related gene expression and immunohis-
tochemistry, define its chemotactic factors, and evaluate changes induced after
dietary treatment. Esophageal mucosal samples from 10 consecutive adult EoE
patients obtained before and after 6 weeks of treatment with an empiric six-food
elimination diet (SFED) and from 10 control subjects were analyzed. qPCR and
immunohistochemistry were used to analyze the expression levels of MC-related
proteases (CPA3, CMA & TPSB2) and to define MC-types densities. Changes in
gene expression of chemoattractants for eosinophils (eotaxins) and MC (SCF &
TGF-) and their receptors (CCR3 & c-KIT) were assessed.
RESULTS: The mean density of esophageal MC was significantly increased in
OP406 A RANDOMIZED, DOUBLE-BLIND, DOUBLE-DUMMY, EoE regarding to controls, and decreased after diet (from 18.6 to 1.44 cells/hpf;
PLACEBO-CONTROLLED, EUROPEAN MULTICENTRE TRIAL OF p50.001). The 90% of MC observed in the inflammatory infiltrate in EoE
TWO NEW BUDESONIDE FORMULATIONS FOR TREATMENT OF patients were MCTC subtype, and only 10% was MCT subtype. Atopic back-
ACTIVE EOSINOPHILIC ESOPHAGITIS ground of patients did not associate with differences in MC counts or gene
P. Hruz1,*, S. Miehlke2, U. von Arnim3, A. Madisch4, M. Vieth5, C. Bussmann6, expression levels. Genes of most chemotactic factors for MC and its receptors
M. Bajbouj7, C. Fibbe8, H. Wittenburg9, H.D. Allescher10, M. Reinshagen11, were upregulated in EoE patients compared to controls (Table), and significantly
S. Schubert12, J. Tack13, M. Muller14, A. Eckardt14, P. Krummenerl15, J. Arts16, downregulated after a SFED; however, TGF- and c-KIT remained unchanged
K. Dilger17, R. Greinwald17, R. Mueller17, A. Straumann18 on behalf of the after diet. Statistically significant relationships (Spearman Rho) between gene
International, BUU-2 Study Group expression levels and epithelial MC counts were documented in EoE samples.
1
University Hospital Basel, Basel, Switzerland, 2Center for Digestive Diseases Peak MC significantly correlated with pick eosinophil count in baseline EoE
Eppendorf, Hamburg, 3Otto v. Guericke University, Magdeburg, 4Klinikum Siloah, samples (rho0.808) and with symptoms score (rho0.782). Table: Genes ana-
Hannover, 5Klinikum Bayreuth, Bayreuth, Germany, 6Pathologie Viollier AG, lized, fold changes in active EoE and p values compared to controls.
Basel, Switzerland, 7Klinikum rechts der Isar - TU Munchen, Munich,
8
Israelitisches Krankenhaus, Hamburg, 9University Hospital of Leipzig, Leipzig,
10
Klinikum Garmisch-Partenkirchen, Garmisch-Partenkirchen, 11Klinikum CCL11 8.5 0.008 SCF 5.6 0.003
Braunschweig, Braunschweig, 12Gastroenterologist in private practice, Berlin,
Germany, 13University Hospital Leuven, Leuven, Belgium, 14Deutsche Klinik fur
Diagnostik, Wiesbaden, 15Krankenhaus Martha-Maria Halle-Dolau, Halle
(Saale), Germany, 16AZ Sint-Lucas Brugge, Brugge, Belgium, 17Dr. Falk Pharma
GmbH, Freiburg, Germany, 18Swiss EoE Research Group, Olten, Switzerland
INTRODUCTION: Swallowed topical corticosteroids have been shown effective
in the treatment of Eosinophilic Esophagitis (EoE), but so far no approved
therapy with an esophageal-adjusted formulation including an optimal dosing
is available.
AIMS & METHODS: To evaluate the efficacy and safety of two different bude-
sonide formulations (effervescent tablet [BET] and viscous suspension [BVS]) and
two different doses for short-term treatment of EoE.
Adults with active EoE (n76) randomly received 14-days treatment with either
BET 2x1mg/d (BET1, n19) or BET 2x2mg/d (BET2, n19), or BVS 2x2mg/d
(BVS, n19) or placebo (n19) in a double-blind, double-dummy fashion, with a
2-week follow-up. Primary endpoint was histological remission (mean of 516
eos/mm2 hpf). Secondary endpoints included endoscopy score, dysphagia score,
and preference of drug formulation.
RESULTS: Histological remission occurred in 100%, 93.8%, and 93.3% of
budesonide (BET1, BET2, BVS, respectively) and in 0% of placebo recipients
(p50.0001). The improvement in total endoscopic intensity score was signifi-
cantly higher in the 3 budesonide groups compared with placebo. Dysphagia
improved in all groups at the end of treatment. The improvement persisted
during the 2-weeks follow-up only in those treated with BET1 and BET2, with
BET1 showing a significant difference to placebo (p0.0196). There was sus-
pected local fungal infection in 3 patients in each of the three budesonide
groups. However, in a post-hoc histopathology analysis hyphae were only
found in 2 patients in each of the budesonide groups. Neither serious adverse
events nor clinically relevant changes in plasma cortisol were observed. 80% of
patients preferred the effervescent tablet.
CONCLUSION: Budesonide administered as effervescent tablet or as viscous
suspension was highly effective and safe for short-term treatment of EoE. The
1mg BID dose was equally effective as the 2mg BID dose. The majority of
patients preferred the effervescent tablet formulation.
The first two authors contributed equally to the first authorship
Disclosure of Interest: P. Hruz: None declared, S. Miehlke Lecture fee(s) from: Dr
Falk Pharma GmbH, U. von Arnim: None declared, A. Madisch Lecture fee(s)
from: Falk Foundation, M. Vieth Lecture fee(s) from: Falk Foundation, C.
Bussmann: None declared, M. Bajbouj: None declared, C. Fibbe: None declared,
H. Wittenburg Lecture fee(s) from: Falk Foundation, H. Allescher: None
declared, M. Reinshagen Lecture fee(s) from: Falk Foundation, S. Schubert
Lecture fee(s) from: Abbvie, Falk Foundation, MSD, J. Tack: None declared,
M. Muller: None declared, A. Eckardt: None declared, P. Krummenerl: None
declared, J. Arts: None declared, K. Dilger Other: Employee of Dr Falk Pharma,
R. Greinwald Other: Employee of Dr Falk Pharma, R. Mueller Other: Employee
of Dr Falk Pharma, A. Straumann Consultancy for: Dr Falk Pharma
CCL24 12.2 0.001 TGF- - 0.740
CCL26 51.1 0.002 c-KIT 3.7 0.002
CCR3 3.7 0.039 CPA3 3.2 0.011
CMA 3.2 0.049 TPSB2 1.7 0.025
CONCLUSION: MCTC subtype was the predominant in the inflammatory infil-
trate of EoE patients. MC densities correlated with eosinophil counts and symp-
toms. Dietary treatment significantly reduced gene expression of MC-related
proteases and chemotactic factors.
Disclosure of Interest: None declared
OP408 EMPIRIC FOUR-FOOD ELIMINATION DIET FOLLOWED BY
RESCUE SIX-FOOD ELIMINATION DIET FOR ADULT
EOSINOPHILIC ESOPHAGITIS: A PROSPECTIVE MULTICENTER
STUDY
J. Molina- Infante1,*, A. Arias2, J. Barrio3, J. Rodriguez-Sanchez4, M. Sanchez-
Cazalilla5, A.J. Lucendo5
1
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, 2Research Support
Unit, Hospital General Mancha Centro, Alcazar de San Juan, 3Gastroenterology,
Hospital Rio Hortega, Valladolid, 4Gastroenterology, Hospital General
Universitario, Ciudad Real, 5Gastroenterology, Hospital General, Tomelloso, Spain
INTRODUCTION: Eosinophilic oesophagitis (EoE) is an esophageal disorder
predominantly triggered by food antigens. A six-food elimination diet (SFED)
achieves remission in over 70% of adult EoE patients. After individual food
reintroduction, just one or two food triggers for EoE can be identified in
65%485% of patients, so some dietary restrictions and endoscopies after food
challenge may be unnecessary.
AIMS & METHODS: We aimed to evaluate the efficacy of a four-food elimina-
tion diet (FFED) (dairy products, wheat, egg and legumes) for adult EoE
patients. Prospective multicenter study. All patients were re-evaluated after 6
weeks on a FFED. Response to FFED was defined by clinical and histological
(515 eos/HPF) remission. Responders underwent reintroduction of each indivi-
dual food over 6 weeks followed by endoscopy and esophageal biopsies.
Nonresponders were offered a rescue SFED.
RESULTS: 52 adult patients were included, of whom 12 patients (23%) had previous
failure to topical steroid therapy. 28/52 patients (54%) achieved clinicopathological
remission on FFED and 6/19 (31%) nonresponders to FFED were successfully
rescued with SFED. 22/28 responders to FFED (78%) finished the individual food
reintroduction challenge. Milk was identified as an EoE trigger in 11 patients (50%),
egg in 8 (36%), wheat in 7 (31%) and legumes in 4 (18%). All patients had just 1 or 2
food triggers, being milk the only causative food in 27% of patients.
CONCLUSION: A FFED achieved clinico-pathologic remission in 54% of adult
EoE patients. SFED was effective in almost a third of FFED nonresponders,
coming to a combined efficacy of both strategies of 72%.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
OP409 TRANSGLUTAMINASE EXPRESSION AND COELIAC
AUTOANTIBODY BINDING TO THE PANCREAS IN DIABETES
MELLITUS
I. R. Korponay-Szabo1,2,*, M. Oikarinen3, J.E. Laiho3, K. Laurila1, M. Maki1,
H. Hyoty3 on behalf of The nPOD Study Group
1
Tampere Center for Child Health Research, University of Tampere Medical
School, Tampere, Finland, 2Paediatrics, University of Debrecen, Debrecen,
Hungary, 3Virology, University of Tampere Medical School, Tampere, Finland
Contact E-mail Address: loilko@uta.fi
INTRODUCTION: Coeliac disease and type-1 diabetes (T1DM) are often co-
existing and share common genetic background. However, it is still a question
whether coeliac disease can directly induce damage of the pancreas leading to
beta cell loss and endocrine insufficiency. The aim of this study was to investigate
if pancreas tissue is an autoantigenic target for coeliac anti-transglutaminase
(TG2) antibodies in vivo.
AIMS & METHODS: Frozen pancreas and full thickness duodenum tissue spe-
cimens from cadaveric organ donors with T1DM (n22), diabetes antibody
positive subjects (n11) and non-diabetic controls (n21) were kindly provided
by the Network of Pancreatic Organ Donors with Diabetes (nPOD). None of
these subjects had a coeliac disease diagnosis during lifetime. The tissues were
investigated for transglutaminase and glucagon expression, in vivo- bound celiac
disease-related IgA antibodies, CD3 and gamma-delta T cell counts by immu-
nohistochemistry in a blinded fashion without knowledge of the clinical details.
RESULTS: Pancreas specimens expressed abundantly TG2 around the islets and
acinar structures corresponding to the reticulin network of the pancreas.
Furthermore, TG2 was also present in vessel walls of islet capillaries. IgA class
coeliac autoantibodies bound to TG2 were detected on the surface of TG2 in 5 of
the diabetic pancreas specimens and in the corresponding duodenum samples
within the mucosa and in the gut wall muscular layer endomysium. The presence
of villous atrophy consistent with untreated coeliac disease was confirmed from
H&E sections from the same subjects in 4 of these cases, all adults (one specimen
being inadequately orientated). All control pancreas samples were negative for
IgA deposition. One non-diabetic donor had slight endomysial positivity in the
gut without villous antrophy and had no IgA in the pancreas.
CONCLUSION: Pancreas tissues express the transglutaminase 2 autoantigen
important for coeliac disease pathology. Celiac antibodies bound to the pancreas
may initiate inflammation and tissue damage leading to diabetes. A fraction of
T1DM cases may be preventable by screening and treatment for coeliac disease at
an early age.
REFERENCES
Acknowledgments: Network of Pancreatic Organ Donors with Diabetes,
Juvenile Diabetes Research Foundation, TAMOP 4.2.2.A-11/1/KONV-2012-
0023, OTKA K101788.
Disclosure of Interest: None declared
OP410 TREATMENT WITH SOMATOSTATIN ANALOGUES OF
RECURRENT TYPE I GASTRIC CARCINOID IN PATIENTS WITH
AUTOIMMUNE CHRONIC ATROPHIC GASTRITIS
S. Massironi1, A. Zilli2,*, R.E. Rossi2, D. Conte2, I. Fanetti3, C. Ciafardini4,
M. Peracchi3
1
Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca Granda - Ospedale
Maggiore Policlinico, 2Gastroenterology and Endoscopy Unit, 3Department of
Medical, Surgical and Transplant Pathophysiology, University of Milan,
4
Fondazione IRCCS Ca Granda - Ospedale Maggiore Policlinico, Milan, Italy
Contact E-mail Address: alessandra.zilli86@gmail.com
INTRODUCTION: The treatment of type 1 gastric carcinoids (GC1) is still
debated, in view of their usual benign behaviour.
AIMS & METHODS: To evaluate the outcome of patients with recurrent GC1
treated with somatostatin analogues (SSA).
From January 2000 to September 2013, among 111 patients with chronic auto-
immune atrophic gastritis, 23 patients were diagnosed with GC1. After they had
the GC endoscopically removed, they underwent regular clinical and endoscopic
follow-up. Plasma chromogranin A (CgA) and gastrin levels were measured in all
patients. Patients showing recurrent GC1 were treated with SSA until gastrin fell
below 400 pg/mL and there was no endoscopic and histological evidence of GC1
anymore.
RESULTS: 12 patients (52%) showed GC1 recurrence and were treated with
SSA for a median time of 13 months. At baseline, median gastrin and CgA levels
were 719 pg/mL and 33 U/L, respectively and they decreased to 389 pg/mL
(p0.001) and 14 U/L (p0.005), respectively, after a six-month period of treat-
ment. In all but one patient, GC1 disappeared after a median treatment of 12
months. In one case it was necessary to extend the therapy for 32 months to get
the carcinoid disappearance. After SSA discontinuation, 4 patients (36%)
showed GC1 recurrence after a median of 19.5 months and they were successfully
retreated with a schedule of 12 months on treatment alternated to 6 months off
treatment.
CONCLUSION: This cohort study confirms that GC1 tend to recur. SSA,
administered in cycles of 12 months, represent an effective treatment.
REFERENCES
1. Solcia E, Fiocca R, Villani L, et al. Hyperplastic, dysplastic, and neoplastic
enterochromaffin-like-cell proliferations of the gastric mucosa. Classification and
histogenesis. Am J Surg Pathol 1995; 19(Suppl. 1): S1S7.
2. Campana D, Nori F, Pezzilli R, et al. Gastric endocrine tumors type I: treat-
ment with long-acting somatostatin analogs. Endocr Relat Cancer 2008; 15: 337-
342.
3. Grozinsky-Glasberg S, Kaltsas G, Gur C, et al. Long-acting somatostatin
analogues are an effective treatment for type 1 gastric carcinoid tumours. Eur
J Endocrinol 2008; 159: 475-482.
A129
4. Grozinsky-Glasberg S, Thomas D, Strosberg JR, et al. Metastatic type 1
gastric carcinoid: a real threat or just a myth? World J Gastroenterol 2013; 19:
8687-8695.
5. Fykse V, Sandvik AK, Qvigstad G, et al. Treatment of ECL cell carcinoids
with octreotide LAR. Scand J Gastroenterol 2004; 39: 621-628.
Disclosure of Interest: None declared
WEDNESDAY, OCTOBER 22, 2014 14:0015:30
VIRAL HEPATITIS, CYTOKINES AND LIVER REGENERATION LOUNGE
5_____________________
OP411 HBX DIRECTLY MEDIATES DEREGULATION OF SEVERAL
LNCRNAS IDENTIFIED BY CHIP-SEQ EXPERIMENT
F. Guerrieri1,2,* on behalf of, F. Guerrieri, S. Jeddari, L. Belloni, D. DAndrea,
A. Tramontano, M. Levrero
1
Dept Internal Medicine, 2Sapienza Life NanoScience Laboratory, SAPIENZA
UNIVERSITY OF ROME, rome, Italy
Contact E-mail Address: fraguerrieri@gmail.com
INTRODUCTION: HBx regulatory protein is required for HBV cccDNA tran-
scription/viral replication and contributes to HBV oncogenicity. HBx affects the
epigenetic control of HBV viral chromatin, by preventing HDACs recruitment
onto the cccDNA, as well as of cellular chromatin, by favouring the recruitment
of acetyl-transferase on activated target genes and of DNMT3a on repressed
genes. (Guerrieri et al. 2013). LncRNAs are broadly defined as endogenous
cellular RNAs molecules longer than 200 nt capable to regulate gene expression
at various levels, including chromatin modification, transcription and post-tran-
scriptional processing. DLEU2 encodes a putative lncRNA, with one exon
directly overlapping the first exon of the TRIM13 gene in the opposite orienta-
tion (Skoblov et al. 2006). Upregulation of specific DLEU2 splicing variants
correlates with HCC (Garding et al. 2013). TRIM13 induces autophagy and
increase ectopic levels of p53 (Tomar D et al, .2012).
AIMS & METHODS: Aim of this study was to indentify HBx role in the
lncRNA regulation.
High-throughput sequencing of anti-HBx ChIP-enriched DNA fragments
(ChIPSeq) was performed in HepG2 cells. Chromatin immunoprecipitated
from mock, wt and HBx-mt monomeric linear full length HBV DNA cells was
analysed by TaqMan real-time PCR using lncRNA specific primers. HBx target
lncRNAs levels were assessed both by PCR and real-time RT-PCR.
RESULTS: ChIPSeq analysis of HBx chromatin recruitment revealed a specific
binding to a large number of new and known target sequences. In particular HBx
binds to 39 long non coding RNAs. Focusing on DLEU2 lncRNA, we demon-
strated that HBx is able to deregulate its expression and the neighboring genes.
We show that HBx can bind DLEU2 promoter and modifies its epigenetic status.
Therefore, HBx occupancy results in a different DLEU2 splicing profile leading
to down-regulation of hsa-mir-15 and hsa-mir-16, as previously published, but
also to up-regulation of the antisense autophagic gene TRIM13. Selective degra-
dation of DLEU2 RNA resulted in a reduced H4 acetylation on TRIM13 pro-
moter and a 50% reduction of TRIM13 expression in HBV replicating HepG2
cells. These results directly link DLEU2 RNA species with TRIM13 transcrip-
tional regulation in the presence of HBx. In silico analysis indicates that DLEU2
RNA potentially binds HBx and using a RIP (RNA Immune Precipitation)
approach we confirmed HBx-DLEU2 interaction. Finally we found that
DLEU2 inactivation has a profound impact on pgRNA transcription, thus sug-
gesting a functional relevance of the DLEU2-HBx interaction of HBV
replication.
CONCLUSION: HBx is recruited to 39 lncRNA promoters. HBx binds to the
DLEU2 promoter region and affects its epigenetic status and expression by
inducing a different DLEU2 splicing profile. HBx also directly binds DLEU2
and affects HBV replication.
REFERENCES
Guerrieri F, Belloni L, Pediconi N, et al. Molecular mechanisms of HBV-asso-
ciated hepatocarcinogenesis. Semin Liver Dis 2013.
Tomar D, Singh R, Singh AK, et al. TRIM13 regulates ER stress induced
autophagy and clonogenic ability of the cells. Biochim Biophys Acta 2012.
Garding A, et al. Epigenetic upregulation of lncRNAs at 13q14.3 in leukemia is
linked to the In Cis downregulation of a gene cluster that targets NF-kB. PLoS
Genet 2013.
Disclosure of Interest: None declared
OP412 MAPPING OF ACCURATE LOCATION FOR COMBINATION OF
HEPATITIS B VIRUS X PROTEIN AND CYTOCHROME C OXIDASE
III
D. Li1,*, X. Wang1
1
Gastroenterology, digestion, Fuzhou, China
Contact E-mail Address: doctorlidan@163.com
INTRODUCTION: Human hepatitis B virus (HBV) infection has been strongly
associated with development of hepatocellular carcinoma(HCC). The mechan-
isms whereby HBV causes malignant transformation remain uncertain. Much of
the evidence available supports a pathogenetic role for the product of the HBV x
gene, the HBx. However, the molecular mechanisms underlying effects of HBx
protein on transcription, cellular proliferation and transformation are only par-
tially deEned. As HBx has no ability to bind dsDNA, proteinprotein interaction
seems to be crucial for HBx function. IdentiEcation of cellular HBx -interactive
proteins would provide insight into the mechanism of HBV cellular effects.
AIMS & METHODS: In previous study, we have screened a new HBx-interact-
ing protein, cytochrome C oxidase subunit III(COXIII). The aim of this study is
to map an accurate binding site in HBx protein with COXIII. Two fragments of
A130
HBx mutants (X1 aa1-72; X2 aa1-117) were amplified by polymerase chain
reaction (PCR) and inserted into pAS2-1 to reconstruct the mutant plasmids.
PCR and gene sequencing were used to confirm the mutants fragments expressed
in the plasmids. PCR showed the mutants fragments expressed in yeast cells and
western blot testified the fusion proteins were translated correctly in yeast cells.
United European Gastroenterology Journal 2(5S)
(VEHDMSO). Hemodynamic measurements were performed after 7 days of
treatment including mean arterial pressure (MAP), heart rate (HR), portal pres-
sure (PP) and superior mesenteric artery blood flow (SMABF). Genes involved in
inflammatory response, antibacterial response, and innate immunity were
assessed by RT-PCR RNA-array from ileum. Bacterial translocation was
Hybrid in solid medium and gal activity detection mapped the key domain for
combination of HBx and COXIII. Coimmunoprecipitation was performed to
confirmed specific interaction between HBx mutant proteins with COXIII.
RESULTS: Two mutant plasmids which contain HBx aa1-72 and aa1-117 were
successfully constructed respectively. PCR and gene sequencing confirmed the
two mutant fragments were inserted in the plasmids. PCR and Western blot
proved the mutant genes expressed the mutant proteins correctly in yeast cells.
assessed by mesenteric lymph node culture and LBP-ELISA.
RESULTS: In the PPVL group, both portal hypertension (PP: 10.53.2 vs.
8.82.4mmHg, p0.059) and splanchnic blood flow (SMABF: 0.1770.031 vs.
0.1100.003 mL/min/g; p0.024) were reduced by PX treatment. HR and MAP
were not affected by PX treatment in SO or PPVL animals. Positive lymph node
cultures were observed in 60% of PPVL-VEH mice but reduced to 30% in PPVL-
PX mice. LBP serum levels were non-significantly decreased in PPVL-PX vs.
Hybrid in solid medium and gal activity detection indicated the binding site of
HBx with COXIII is located between aa72 to aa117. The specific interaction
between HBxX2 protein and COXIII was verified by coimmunoprecipitation.
CONCLUSION: For the first time, it is reported aa72-117 of HBx are key
binding peptides for combination of HBx with COXIII.
REFERENCES
Hakami A, Ali A and Hakami A. Effects of hepatitis B virus mutations on its
replication and liver disease severity. Open Virol J 2013; 7: 12-18.
Wang XZ, Li D, Tao QM, et al. A novel hepatitis B virus X-interactive protein:
cytochrome C oxidase III. J Gastroenterol Hepatol 2006; 21: 711-715.
Pelicano H, Lu W, Zhou Y, et al. Mitochondrial dysfunction and reactive oxygen
species imbalance promote breast cancer cell motility through a CXCL14-
mediated mechanism. Cancer Res 2009; 69: 2375-2383.
McClain SL, Clippinger AJ, Lizzano R, et al. Hepatitis B virus replication is
associated with an HBx-dependent mitochondrion-regulated increase in cytosolic
calcium levels. J Virol 2007; 81: 12061-12065.
Kumar V, Jayasuryan N and Kumar R. A truncated mutant (residues 58-140) of
the hepatitis B virus X protein retains transactivation function. Proc Natl Acad
Sci U S A 1996; 93: 5647-5652.
Disclosure of Interest: None declared
OP413 HEPATITIS C NONSTRUCTURAL PROTEIN 3/4A DAMPENS
INFLAMMATION AND CONTRIBUTES TO SLOW FIBROSIS
PROGRESSION DURING CHRONIC LIVER INJURY IN MICE
R. Bansal1,*, L. Frelin2, E. Brenndorfer 2, J. Prakash1, M. Sallberg2
1
MIRA institute for Biomedical Technology and Technical Medicine, University of
Twente, Enschede, Netherlands, 2Laboratory Medicine, Division of Clinical
Microbiology, Karolinska Institute, Stockholm, Sweden
Contact E-mail Address: r.bansal@utwente.nl
INTRODUCTION: Hepatitis C virus (HCV) primarily infects hepatocytes and
the infected hepatocytes with ongoing inflammation appear to promote fibrogen-
esis. To date, the underlying mechanism of HCV-induced fibrogenesis remains
unclear. The aim is therefore to understand the role of HCV non-structural
protein (NS3/4A) in the disease progression.
AIMS & METHODS: We used HCV non-structural NS3/4A expressing trans-
genic mice (NS3/4A-Tg) to accomplish the aims of the study. Hepatic fibrosis
was induced in wild-type and NS3/4A-Tg mice either by single injection of
carbon tetrachloride (acute) or multiple injections for 4 or 8 weeks. Fibrotic
parameters (collagen and HSC markers), inflammatory response (macrophages)
and hepatocyte turnover (proliferation and apoptosis) were examined.
RESULTS: Hepatic expression of NS3/4A did not induce spontaneous liver
damage. During acute liver injury and intermediate fibrosis (4 weeks), NS3/
4A-Tg mice exhibited enhanced liver fibrogenesis. Surprisingly, reduced fibrosis
was observed in NS3/4A-Tg during chronic liver fibrosis (8 weeks). No difference
in inflammation and hepatocyte turnover was observed in 4 weeks fibrosis model,
while decreased inflammation was observed in NS3/4A-Tg during chronic liver
fibrosis. Interestingly, increase in M2 macrophages and increased hepatocyte
proliferation (and decreased apoptosis) was found in NS3/4A transgenics
during chronic liver fibrosis.
CONCLUSION: During early fibrogenesis, HCV induces liver damage. While
during chronic liver fibrosis, HCV (or HCV NS3/4A) dampens inflammation and
induces hepatocyte proliferation thereby contributing to slow fibrosis progres-
sion to promote its survival or persistence.
Disclosure of Interest: None declared
OP414 THE SYNTHETIC FXR AGONIST PX20606 ATTENUATES
BACTERIAL TRANSLOCATION, INTESTINAL INFLAMMATION,
AND REDUCES SPLANCHNIC BLOOD FLOW IN PORTAL
HYPERTENSIVE MICE
P. Schwabl1,*, M. Wagner1, L. Garnys1, F. Riedl1, T.L. Schubert1, B.A. Payer1,
D. Mitteregger2, C. Kremoser3, M. Trauner1, M. Peck-Radosavljevic1,
T. Reiberger1 on behalf of Hepatic Experimental Hemodynamic Laboratory of
Vienna
1
Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Dept. of
Laboratory Medicine, Div. of Clinical Microbiology, Medical University of Vienna,
Vienna, Austria, 3PheneX Pharmaceuticals AG, Ludwigshafen, Germany
Contact E-mail Address: philipp.schwabl@meduniwien.ac.at
INTRODUCTION: The farnesoid X receptor (FXR) is expressed in liver and
gut, and affects bile acid and lipid homeostasis. In addtion, FXR agonists have
been shown to be antifibrotic and enteroprotective.
AIMS & METHODS: The aim of our study was to assess the effects of the non-
steroidal FXR agonist PX20606 (PX) on hemodynamics, intestinal barrier and
bacterial translocation in a portal hypertensive mouse model. Male C56/Bl6 mice
underwent partial portal vein ligation (PPVL) or sham-operation (SO) and were
treated with FXR agonist PX20606 (PX,10mg/kg/day, gavage) or vehicle
PPVL-VEH mice (20.36.9 vs. 27.312.1mg/mL; p0.067). PPVL upregulated
proinflammatory gene expression, while PX treatment suppressed selective pro-
inflammatory genes (TLR2, TNF, IL-1, IL-6). However, genes involved in anti-
bacterial defense (iNOS) were not suppressed upon FXR activation.
CONCLUSION: The FXR ligand PX20606 reduced splanchnic blood flow and
portal pressure in PPVL mice. A reduction of bacterial translocation and a
modified intestinal expression of proinflammatory and immunoregulatory med-
iators indicate beneficial non-hepatic/non-hemodynamic mechanisms of FXR
agonism in portal hypertension.
Disclosure of Interest: None declared
OP415 LYMPHOCYTE SUBSETS AND CYTOKINES IN ASCITIC FLUID
OF DECOMPENSATED CIRRHOTIC PATIENTS WITH AND
WITHOUT SPONTANEOUS ASCITES INFECTION
Z.A. Sayed1,*, E.A. Alkareemy1, N.F. Ameen1, A.M. Sabry1
1
Internal Medicine Department, Gastroenterology Unit., Asssiut University
Hospital, Assiut. Egypt., Assiut, Egypt
Contact E-mail Address: zain4373@yahoo.com
INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a frequently
encountered and important complication of decompensated liver cirrhosis. The
immune system plays an important role in the development or eradication of this
infection. A number of compositional and functional alterations in immune
system cells have been demonstrated in cirrhotic patients; however, there is a
lack of knowledge about this issue in ascitic infections.
AIMS & METHODS: The aim of the present study was to evaluate lymphocyte
subsets and levels of some ascitic and lymphocytic intracytoplasmic cytokines in
decompensated cirrhotic patients with or without spontaneous bacterial perito-
nitis. This case-control study included 50 decompensated cirrhotic patients.
Patients with ascitic polymorphonuclear leukocyte count 250/mm3 and/or posi-
tive ascitic bacterial cultures were classified as the patients group (n25,
meanSD of age was 57.84  6.66 years). Patients with ascitic polymorpho-
nuclear leukocyte count 5250/mm3 and/or negative ascitic bacterial cultures
were classified as the controls group (n25, meanSD of age was 60.36 
6.51years). Comparison was made between the patients and controls groups
for the following parameters: ascites leukocyte counts and differentiations; ascitic
fluid protein; albumin levels and serum-ascites albumin gradients; flow cyto-
metric detection of ascitic lymphocyte subsets (CD3, CD4, CD8, CD4/CD8
ratio, CD19, CD45) and ascitic cytokine TNF-alpha.
RESULTS: Ascitic total protein and albumin levels were significantly decreased
in patients group. The CD4, CD19, CD45 and CD4/CD8 ratio were significantly
decreased in the patients group. Furthermore, ascites CD3, CD8 and TNF-
levels were significantly elevated in this group. The incidence of renal impair-
ment, gastrointestinal bleeding and hepatic encephalopathy was higher in
patients group and there was a significant correlation between TNF-alpha and
renal impairment in this group.
CONCLUSION: These results suggest that a cytotoxic, especially Th1, immune
response predominates in ascites infections. It also demonstrates that TNF-
might be involved in the pathogenesis of ascites infections.
REFERENCES
1. Bonnel AR, Bunchorntavakul C, Reddyel KR. Immune dysfunction and infec-
tions in patients with cirrhosis. Clin Gastroenterol Hepatol 2011; 9: 727738.
2. Blaise M, Pateron D, Trinchet JC, et al. Systemic antibiotic therapy prevents
bacterial infections in cirrhotic patients with gastrointestinal hemorrhage.
Hepatology 1994; 20: 34-33.
3. Borzio M, Salerno F, Piantoni L, et al. Bacterial infection in patients with
advanced cirrhosis: a multicentre prospective study. Dig Liver Dis 2001; 33: 41
48.
4. Caly W and Strauss E. A prospective study of bacterial infections in patients
with cirrhosis. J Hepatol 1993; 18: 353-358.
Disclosure of Interest: None declared
OP416 LGR5 LIVER ORGANOIDS AS A MODEL TO STUDY
POLYCYSTIC LIVER DISEASE
E.S. Wills1,2,*, R. te Morsche3, R. Roepman1,4, J. H. de Wilt5, M. Huch6,
H. Clevers7, J.P. Drenth2
1
Department of Human Genetics, 2Department of Medicine, Division of
Gastroenterology and Hepatology, 3Laboratory Gastroenterology & Hepatology,
4
Nijmegen Center for Molecular Life Sciences, 5Department of Surgery,
Radboudumc, Nijmegen, Netherlands, 6The Gurdon Institute, University of
Cambridge, Cambridge, United Kingdom, 7Hubrecht Institute for Developmental
Biology and Stem Cell Research, University Medical Center Utrecht, Utrecht,
Netherlands
Contact E-mail Address: edgar.wills@radboudumc.nl
INTRODUCTION: Liver stem cells are capable of expanding into LGR5
organoids constituted of cholangiocytes. Important features of polycystic liver
United European Gastroenterology Journal 2(5S)
disease (PLD) are increased cholangiocyte proliferation and fluid secretion,
which can be suppressed by somatostatin analogues such as lanreotide. PLD is
caused by mutations in genes such as PRKCSH, SEC63, LRP5 and PKD2. There
is no human in vitro model available that truly recapitulates polycystic liver
disease. We hypothesize that PLD cholangiocytes can form LGR5 liver orga-
noids with aforementioned features of cyst development.
AIMS & METHODS: We aim: 1.) To isolate cholangiocytes from human cyst
biliary epithelium and cyst fluid and expand these into LGR5 liver organoids.
2.) To characterize stem cell, cholangiocyte and PLD-associated gene expression
and polarization of liver organoids. 3.) To determine the effect of lanreotide on
liver organoids.
Cholangiocytes from patient cyst biliary epithelium and cyst fluid were isolated
and placed under conditions suitable for expansion of adult liver stem cells.
Following organoid development, LGR5, SOX9, KRT7, KRT19, PRKCSH,
SEC63, LRP5 and PKD2 expression were determined by quantitative real-time
A131
as PLD-associated genes PRKCSH, SEC63, LRP5 and PKD2. Lanreotide sig-
nificantly decreases expansion of liver organoids in comparison to control (197%
 46% versus 547%  28%; p: 0.038).
CONCLUSION: LGR5 liver organoids are an appropriate in vitro model to
study PLD. Organoids respond to lanreotide by decreased expansion. Our model
has potential to be used for large scale drug screening.
REFERENCES
1. Huch M, Dorrell C, Boj SF, et al. In vitro expansion of single Lgr5 liver stem
cells induced by Wnt-driven regeneration. Nature 2013; 494: 247-250.
2. Masyuk TV, Masyuk AI, Torres VE, et al. Octreotide inhibits hepatic cysto-
genesis in a rodent model of polycystic liver disease by reducing cholangiocyte
adenosine 3,5-cyclic monophosphate. Gastroenterology 2007; 132: 1104-1116.
Disclosure of Interest: E. Wills: None declared, R. te Morsche: None declared, R.
Roepman: None declared, J. de Wilt: None declared, M. Huch Other: MH is
inventor on several patent applications related to organoid culture, H. Clevers
polymerase chain reaction. Confocal microscopy staining for -catenin was per- Other: HC is inventor on several patent applications related to organoid culture,
formed to determine organoid polarization. In three independent experiments, J. Drenth Financial support for research from: MLDS, Axcan Pharma, BBMRI,
control (0.1 M acetic acid) or lanreotide (107M in 0.1M acetic acid) was added PIDON, IPSEN, Novartis and the Dutch Kidney Foundation.
twice a day, at 12-hour intervals for seven days. Organoid development was
followed by light microscopy and circumferential areas were quantified by
Image J software (NIH). Data were expressed by percentage change in circum-
ferential area (mean  SEM) on day 7 in comparison to day 1. Statistical analysis
was performed by Students t-test.
RESULTS: We successfully isolated cholangiocytes from cyst biliary epithelium
and cyst fluid that were expanded as liver organoids. Organoids form cysts with
monolayered walls, which display predominant basolateral membranous -cate-
nin staining. In addition, they express LGR5, SOX9, KRT7 and KRT19, as well
UEG Week 2014 Poster Presentations
MONDAY, OCTOBER 20, 2014 9:0017:00
POSTER PLUS VIDEO I POSTER EXHIBITION HALL XL_____________________
P0001 EUS GUIDED TRANSMURAL DRAINAGE OF WOPN;
COMPARISON BETWEEN A NEW FULLY COVERED LARGE BORE
WIDE FLARE METAL STENT (NAGI STENT) VS MULTIPLE
PLASTIC STENTS: A SINGLE CENTRE RETROSPECTIVE STUDY
N. Dubale1,*, A. Bapaye2, S.K. Davavala1, H. Gadhikar1, S. Dhadpahale1,
S. Date1, J. Bapaye3
1
Digestive Diseases and Endoscopy, 2Digestive Diseases and Endoscopy, Deenanath
Mangeshkar Hospital and Research Centre, Pune, 3Shreemati Kashibai Nawale
Medical College, Pune, India
Contact E-mail Address: amolbapaye@gmail.com
INTRODUCTION: WOPN is a frequent sequel of acute necrotizing pancreatitis.
The best approach for drainage of these collections is still controversial. We
present our retrospective data comparing the two endoscopic methods for drai-
nage of WOPN.
AIMS & METHODS: Outcomes of patients undergoing EUS guided transmural
drainage (EUTMD) using a newly designed fully covered large-bore wide-flare
metal stent (Nagi stent) (Gr I) were compared to the outcomes of patients who
underwent placement of multiple plastic stents (Gr II). The pre-op CECT con-
firmed suitability of endoscopic drainage based on location, wall thickness &
contents. Visual quantification of necrosis (450% solid debris) by EUS excluded
8 patients (3 in Gr I and 5 in Gr. II). The procedure in both groups is done by
standard technique by a single endoscopist. The difference between the two
groups was tract dilatation (6 mm in Gr I vs. 18 mm in Gr II). Placement of
NCT and subsequent necrosectomy was done whenever necessary. Follow-up
imaging was done at 72 hrs and thereafter at 2, 4, & 6 weeks. The outcomes
were compared in terms of clinical success, need for surgery, complications,
hospital stay and mortality.
RESULTS: N: 21(Gr. I), 61(Gr. II). The two groups were comparable in terms of
demographics, etiology of pancreatitis, cyst location, size and amount of debris.
Placement of NCT, need of necrosectomy and no of sessions required were also
not different between the two groups. Clinical success defined as resolution of
symptoms was seen in 100% of Gr. I patients vs. 73% in Gr. II (p 0.048). None
of the patients in Gr I required subsequent surgery vs 20/61 (32.7%) in Gr. II
(p 0.025). Complications: 15% in Gr. I vs 37% in Gr. II (p 0.016)
Mean hospital stay was 4 days (1-33) in Gr. I vs 8 (4-65) in Gr II (p 0.012).
Mortality was none in Gr. I vs. 6.5% (4/61) in Gr. II (p 0.22)
CONCLUSION: The Nagi stentTM is effective and safe for EUTMD of WOPN.
It permits rapid clinical resolution with 100% technical and clinical success rates.
It offers distinct advantage over plastic stents although further prospective stu-
dies are warranted.
Disclosure of Interest: None declared
P0002 ENDOSCOPIC ESOPHAGEAL RECONSTRUCTION FOR THE
TREATMENT OF A TOTAL AND EXTENSIVE DISRUPTION OF
THE ESOPHAGUS USING A RENDEZ-VOUS TECHNIQUE
J.-M. Gonzalez1,*, G. Vanbiervliet2, M. Barthet1
1
Gastroenterology, Aix-Marseille University, North Hospital, Marseille,
2
Gastroenterology, Nice Hospital, Nice, France
INTRODUCTION: Complete esophageal obstruction leads to definitive fasting.
The rendez-vous endoscopic approach had already been described for complex
stenoses as an alternative to surgery that has high morbid-mortality.
AIMS & METHODS: This is a case series report about six patients referred for
complete esophageal disruption classified in two groups: 1/ Long disruption (4
5cm), one after caustic ingestion and two due to an esophageal stripping during
SEMS removal. Two had an associated loss of the SES; 2/ Short disruption (5
5cm), consecutive to radiation therapy for a neck neoplasia. They had been
fasting for 3 to 18 months. All the procedures were performed according the
anterograde retrograde approach, under anesthesia and with CO2 insufflation
and X-rays guidance.
RESULTS: There were 3 men and women between 25 and 71 years old. All the
reconstructions have been successful in one to three endoscopic sessions, using
the non hydrophilic tip of a guide wire passed through a straight catheter in 5
cases and a EUS needle in only one case. In 2 cases, a neo-SES had to be created,
by transillumination (n 1) or head and neck surgery (n 1). In order to guide
the reconstruction, SEMS was used in one case, NGT in one case, and both were
used in one patient. The first dilation was performed with a CRE balloon
(12-15mm). All the patients could eat mixed after 2 POD. There was no intra-
operative or post-operative complication. Then, the patients underwent 3 to 18
dilations sessions during 1.5 to 15 months; two are still undergoing dilations and
all eat normally.
CONCLUSION: Endoscopic rendez-vous for esophageal reconstruction is safe
and effective in case of esophageal disruption even with loss of SES, avoiding
surgery.
Disclosure of Interest: None declared
United European Gastroenterology Journal
2(5S) A132A605
! Author(s) 2014
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DOI: 10.1177/2050640614548980
ueg.sagepub.com
P0003 ENDOSCOPIC SUBMUCOSAL DISSECTION OF EARLY
GASTRIC CANCERS USING THE CLUTCH CUTTER
K. Akahoshi1,*, Y. Motomura1, M. Kubokawa1, J. Gibo1, N. Kinoshita1,
S. Osada1, Y. Shimokawa1, K. Tokumaru1, Y. Otsuka1, T. Hosokawa1,
N. Tomoeda1, R. Utsunomiya1, T. Miyazaki1, K. Miyamoto1, M. Oya1
1
Gastroenterology, ASO IIZUKA HOSPITAL, Iizuka, Japan
Contact E-mail Address: kakahoshi2@aol.com
INTRODUCTION: To reduce the risk of complications related to ESD using
conventional knives, we developed the Clutch Cutter (CC), which can grasp and
incise the targeted tissue using electrosurgical current.
AIMS & METHODS: From June 2007 to March 2014, 325 consecutive patients
(228 men, 97 women; mean age 74 years, range 35-95) with a diagnosis of intra-
mucosal or superficial submucosal gastric cancer without lymph node involve-
ment, that had been confirmed by preliminary endoscopy, EUS, and endoscopic
biopsies, were enrolled into this prospective study. The CC was used for all steps
of ESD (marking, circumferential marginal incision, submucosal dissection, and
hemostatic treatment). The therapeutic efficacy and safety were assessed.
RESULTS: The mean size of the early gastric cancers and resected specimens was
17.3 mm and 46.7 mm, respectively. The mean operating time was 97.2 minutes.
The rate of en-bloc resection was 99.7% (324/325), and en-bloc resection with
tumor-free lateral/basal margins (R0 resection) was 95.1% (309/325), respec-
tively. The R0 resection rates according to tumor size and location were 97.4%
(229/235) in less than 20 mm, 88.9% (80/90) in larger than 20 mm; 96.9%
(127/131) in lower portion, 91.9% (91/99) in middle portion, and 94.7% (91/
95) in upper portion. The mean operating time according to tumor size and
location was 93.4 min in less than 20 mm, 140 min in larger than 20 mm; 73.9
min in lower portion, 108.8 min in middle portion, and 117.2 min in upper
portion. Perforation during ESD occurred in one case (0.3%), which was man-
aged with conservative medical treatment after endoscopic closure of the perfora-
tion. Post ESD bleeding occurred in 11 cases (3.4%), which were successfully
treated by endoscopic hemostatic treatment.
CONCLUSION: ESD using CC is a safe and technically efficient method for
resecting early gastric cancers.
REFERENCES
1) Akahoshi K, Akahane H, Murata A, et al. Endoscopic submucosal dissection
using a novel grasping type scissors forceps. Endoscopy 2007; 39: 1103-1105.
2) Akahoshi, K, Akahane H, Motomura Y, et al. A new approach: endoscopic
submucosal dissection using the clutch cutter for early stage digestive tract
tumors. Digestion 2012: 85: 80-84.
Disclosure of Interest: K. Akahoshi Other: Kazuya Akahoshi and FUJIFILM
have applied for the patent in Japan, Europe, and USA for the Clutch Cutter
described in this article. China has already granted the patent., Y. Motomura:
None declared, M. Kubokawa: None declared, J. Gibo: None declared, N.
Kinoshita: None declared, S. Osada: None declared, Y. Shimokawa: None
declared, K. Tokumaru: None declared, Y. Otsuka: None declared, T.
Hosokawa: None declared, N. Tomoeda: None declared, R. Utsunomiya:
None declared, T. Miyazaki: None declared, K. Miyamoto: None declared, M.
Oya: None declared
P0004 ENDOSCOPIC MYOTOMY FOR ACHALASIA USING A
COMBINATION OF NESTIS WATER JET SYSTEM AND HOOK
KNIFE: EVALUATION OF THE SAFETY AND THE EFFECTIVENESS
M. Pioche1,2,*, S. Roman3, M. Ciocirlan4, F. Mion3, T. Ponchon5
1
Gastroenterology and endoscopy, Hopital Edouard Herriot, 2Inserm U1032,
3
Functional disorders unit, Hopital Edouard Herriot, Lyon, France,
4
Gastroenterology and endoscopy unit, Institut Carol Davila, Bucharest, Romania,
5
Gastroenterology and endoscopy unit, Hopital Edouard Herriot, Lyon, France
Contact E-mail Address: mathieupioche@free.fr
INTRODUCTION: The peroral endoscopic myotomy (POEM) is a promising
method for the treatment of the esophageal achalasia. But the precise technique
can be refined. We developed a combined technique of water jet system for
tunnelling and hook knife section for myotomy and we evaluated its results in
a prospective study.
AIMS & METHODS: The patients presented with an achalasia without any
prior instrumental treatment. The submucosal tunnel was created 12 cm over
the cardia and 3 cm below, and then the endoscopic myotomy was performed
using the Olympus Hook Knife by a single operator with CO2 insufflation,
beginning 8 cms over the cardia and finishing 2 cms below. The clinical evalua-
tion was realized before and then after the procedure at 1, 3, 6 and 12 months
(score of Eckardt, score of quality of life GIQLI). A high-resolution manometry
was realized before POEM and 3 months later to classify the achalasia (classifi-
cation of Chicago) and to measure basal pressure and pressure of relaxation
integrated (PRI) of the lower esophageal sphincter. Then an esophageal
pHmetry of 24 hours was performed at 3 months to diagnose GERD. The
United European Gastroenterology Journal 2(5S)
data are expressed in median (extremes) and compared before and later myoto-
mie by paired t-test.
RESULTS: 21 patients (13 men, average age 61 years) were included. 18 proce-
dures were complete, 1 was not realized because of a large esophageal diverticu-
lum, 2 were interrupted (1 sub-mucosal fibrosis preventing the realization of the
tunnel and 1 mucosal injury of the tunnel in the cardia). 2 other mucosal injuries
occurred but did not prevent to continue the procedure after mucosal closure by
clips. Dual Knife (n 7) or the water jet Nestis Enki 2 (n 11) were used for
the tunnel. No mucosal injuries were observed with the water-jet system. Hook
Knife was used for all myotomies. The average time of procedure was 94.2 min
with a clear learning curve (135-35 min). A pneumoperitoneum was exsufflated
with a needle during the procedure in 13 cases without any visible perforation.
CT scan at day 1 showed a pneumomediastinum (n 14/18), a pneumoperito-
neum (n 14/18) and/or a peumothorax (n 3/18). No sepsis was observed.
Feeding was always possible with liquids at day 1. All patients noted a clinical
improvement. At 3 months, the basal pressure of the SIO was decreased for all
patients (8 mmHg (0-15) against 23 mmHg (7-48) initially, p50.01) as well as the
PRI (8 mmHg (0-16) against 23 mmHg (9-28), p50.01). pH metry showed a
pathological GERD (esophageal pH 4 during more than 5% of time in 3 cases.
Inclusion 1 month 3 months 6 months 1 year
n 21 17 14 10 3 with extensive atrophy and/or intestinal metaplasia. A total of 43 patients (mean
Eckardt 6 (3-11) 1 (0-3)* 1 (0-3)* 0 (1-4)* 0 (0-0)*
GIQLI 82 (50-114) 115 (66-135)* 115 (82-140)* 131 (94-143)* 140 (130-142)
CONCLUSION: Water-jet injection allows rapid and safe tunneling of the sub-
mucosa and myotomy with hook knife is very precise. Safety and effectiveness of
mytomy is reinforced using these technical refinements.
Disclosure of Interest: None declared
P0005 COMPUTER-AIDED DECISION SUPPORT SYSTEM IN HIGH-
MAGNIFICATION AND NARROW-BAND IMAGING ENDOSCOPY
FOR DIFFERENTIATION OF GASTRIC LESIONS
R. Kuvaev1,*, S. Kashin1, H. Edelsbrunner2, M. Machin3, O. Dunaeva3,
E. Nikonov4, V. Kapranov5, A. Rusakov6
1
Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, Russian Federation,
2
Institute of Science and Technology Austria (IST Austria), Klosterneuburg,
Austria, 3Delone Laboratory of Discrete and Computational Geometry, P. G.
Demidov Yaroslavl State University, Yaroslavl, 4Administration, Polyclinic 1 of
the Business Administration for the President of Russian Federation, Moscow,
5
Internet Center, 6Administration, P. G. Demidov Yaroslavl State University,
Yaroslavl, Russian Federation
Contact E-mail Address: kuvaev_roman@mail.ru
INTRODUCTION: High-magnification endoscopy with narrow-band imaging
(HME-NBI) has been used for diagnosis of gastric pathology because of its high
accuracy. Nevertheless, the application of these advanced techniques in clinical
practice is difficult due to the presence of various histological changes of gastric
mucosa with different modifications of microvascular and microsurface patterns.
Newly developed computer-aided decision support systems are designed to detect
and/or classify abnormalities and thus assist a medical expert in improving the
accuracy of medical diagnosis. However, there is lack of data for computer-aided
devices for classification of gastric lesions with HME-NBI.
AIMS & METHODS: The aim of this study was to evaluate the effectiveness of
computer-aided classifier of endoscopic magnification images of gastric lesions.
We analyzed our database contains 78 endoscopy NBI magnification images of
gastric lesions (Olympus Exera GIF Q160Z, Lucera GIF Q260Z). All images
were classified into three classes: oval (13 images), tubular (31 images), and
destroyed with vessel network (34 images). Initially we divided images of every
class into two sets training set and test set. Then we selected uniformly dis-
tributed random points with fixed density (one random point for every 300
pixels) at every picture, which were analyzed by extracting topological features
for building the classifier. Training set images were used for classifier training
with Adaboost algorithm and testing set images of each group were utilized for
testing with previously trained classifier. We repeated the procedure described
above for the estimation of classifier quality.
RESULTS: From 78 database images there were 50 images (66.6%) with the
success rate of correct classification exceeding 80%. In 14 images (17.9%) all
points (100%) were recognized correctly. The mean percentage of points with the
correct classification was 79%.
CONCLUSION: Topological features were successfully used for description of
endoscopic magnification images. The combination of topological features ana-
lyzed with Adaboost algorithm allowed for creating and effective training of
computer-aided classifier of endoscopic magnification images of gastric lesions.
Disclosure of Interest: None declared
A133
P0006 NOVEL NARROW-BAND IMAGING SYSTEM WITH DUAL
FOCUS MAGNIFICATION IN ENDOSCOPIC MAPPING OF THE
GASTRIC MUCOSA IN PATIENTS WITH PRECANCEROUS
CONDITIONS AND LESIONS OF THE STOMACH
R. Kuvaev1,*, S. Kashin1, E. Nikonov2, A. Nadezhin3
1
Endoscopy, Yaroslavl Regional Cancer Hospital, Yaroslavl, 2Administration,
Polyclinic 1 of the Business Administration for the President of the Russian
Federation., Moscow, 3Pathology, Yaroslavl Regional Cancer Hospital, Yaroslavl,
Russian Federation
Contact E-mail Address: kuvaev_roman@mail.ru
INTRODUCTION: Endoscopic mapping of the entire stomach with advanced
techniques has been recommended as an important step of surveillance of pre-
malignant gastric conditions/lesions [1]. Although current imaging technologies,
such as narrow-band imaging (NBI) and high-magnification endoscopy, allow
enhanced visualization of gastric mucosa, their application is still limited due to
low contrast and brightness of endoscopic view and complexity of usage. Newly
developed NBI system with dual focus (DF) magnification might be a promising
tool to overcome this challenge.
AIMS & METHODS: The aim of this study was to evaluate diagnostic accuracy
of new NBI-DF system in detection, characterization of gastric lesions in patients
age 51.3 years, SD 12.1) were initially examined by conventional white light
endoscopy (WLE) followed by NBI overview. Afterwards chromoendoscopy
(CE) with indigocarmine was performed as the gold standard for detection
of lesions. Any suspicious areas detected by NBI or CE were subsequently further
assessed with NBI with DF (Olympus Exera III GIF H190) and characterized
accordingly. Biopsies were taken from all lesions for histological assessment.
RESULTS: From 93 detected gastric lesions there were 75 non-neoplastic
(chronic gastritis, intestinal metaplasia), 3 low-grade dysplasia, and 15 high-
grade dysplasia/early gastric cancer. All lesions (100%) detected by CE were
found with NBI observation. Endoscopic histology prediction was successful in
88 cases (94.6%) Endoscopic misdiagnosis was found in 5 cases (5.4%): over-
estimation in 3 cases, underestimation in 2 cases; sensitivity, specificity, positive
predictive value and negative predictive value were 80%, 97.4%, 85.7% and
96.2% respectively for early gastric cancer/high-grade dysplasia.
CONCLUSION: Observation of gastric mucosa with a novel NBI system was at
least as effective as CE with indigocarmine in detection of suspicious gastric
lesions in patients with precancerous conditions and lesions of the stomach.
Dual focus magnification provides sufficient assessment of microvascular and
microsurface patterns in order to differentiate gastric lesions. Further rando-
mized controlled studies are needed to be performed for clarifying the role of
novel endoscopic system in diagnosis of gastric pathology.
REFERENCES
1. Dinis-Ribeiro M, Areia M, de Vries AC, et al. Management of precancerous
conditions and lesions in the stomach (MAPS): guideline from the European
Society of Gastrointestinal Endoscopy (ESGE), European Helicobacter Study
Group (EHSG), European Society of Pathology (ESP), and the Sociedade
Portuguesa de Endoscopia Digestiva (SPED). Endoscopy 2012; 44: 74-94.
Disclosure of Interest: None declared
P0007 DEVELOPMENT OF A PROTOTYPE OF VIDEO
SYNCHRONISATION FOR RELOCALISATION OF BIOPSY SITES
DURING ENDOSCOPIC EVALUATION OF BARRETTS
OESOPHAGUS: PRELIMINARY EXPERIMENTAL AND CLINICAL
STUDY
S. Adrien1,*, V. Anant1, H. Jerome1, N. Stephane2, S. Luc2, D. Michel1
1
CHU Strasbourg, 2IRCAD, Strasbourg, France
Contact E-mail Address: adrien.sportes@free.fr
INTRODUCTION: The prevalence of Barretts oesophagus (BE) is 5 to 6% in
the general population, with a progression from dysplasia to adenocarcinoma 0.6
to 0.7 patient-years. Hence, endoscopic surveillance is justified to detect early
lesions accessible to endoscopic treatment. However, the relocalisation of lesions
detected by biopsies may be difficult during follow-up endoscopies. The purpose
of this study was to evaluate the prototype of a magnetic probe for accurate
location of the position of the endoscope, allowing the relocalisation of this
position in a subsequent endoscopy. We report the results of a feasibility study
in pigs and the use of this device in two patients with BE.
AIMS & METHODS: The system consists of an electromagnetic (EM) field
transmitter and an EM probe constituting the electromagnetic tracking system
(EMS) (NDI, Aurora). The EM probe is inserted through the operating channel
of a double channel gastroscope. The EM field generator is positioned on the
patients chest wall. The system also includes new software developed at IHU/
IRCAD, which performs simultaneous recording of the video from the endo-
scope alongwith its corresponding position, as measured by the EMS. During a
second endoscopy, this software allows automatic synchronisation of the
recorded video to provide relocalisation of the endoscope in front of previous
biopsy sites in the oesophagus.
The system was tested in 5 anesthetised pigs. During the first endoscopy, ten
markings were performed by argon plasma electrocoagulation (ERBE Tubingen,
Germany) in the distal oesophagus. The position of each marking was recorded
by the system. A second operator to then performed a blind endoscopy on the
same pigs and was asked to follow the system implicitly as a guide to relocate the
markings.
In 2 patients with BE, the system was then tested to facilitate relocalisation of the
biopsy sites.
RESULTS: Ten markings were made in the distal oeosphagus of 5. After with-
drawal of the endoscope the second operator found 48 of the 50 markings (96%)
A134
using the guidance provided by the system. The positioning of the endoscope
provided by the EMS system was within a 2mm range from the initial position-
ning. In the evaluation of BE patients, the system relocalised the biospy sites
within a range of 3mm.
CONCLUSION: This preliminary study shows the feasibility of the EMS pro-
totype to relocalise the endoscope in the oesophagus within an acceptable range.
The clinical usefulness of this system should be evaluated further during the
follow-up of patients with BE.
Disclosure of Interest: None declared
P0008 THE UTILITY OF ROUTINE CHROMOENDOSCOPY FOR
DETECTION OF DYSPLASTIC LESIONS DURING SURVEILLANCE
COLONOSCOPY IN PATIENTS WITH COLONIC INFLAMMATORY
BOWEL DISEASE. DOES RESEARCH TRANSLATE TO CLINICAL
PRACTICE?
U. Javaid1, R. Thethi1, P. Luthra1, N. Mohammed2,*, J. Hamlin1,
B. Rembacken1, V. Subramanian2
1
Gastroenterology, St James University Hospital, Leeds Teaching Hospital NHS
Trust, 2Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences,
University of Leeds, Leeds, United Kingdom
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: Dysplasia in colonic inflammatory bowel disease (IBD) is
often multifocal and flat. Chromoendoscopy (CE) has been shown in prospective
studies to improve dysplasia detection rates by improving the ability to detect
subtle mucosal changes. (1) The utility of CE in dysplasia detection in patients
with IBD during routine clinical practice has not been reported so far. We aimed
to compare the yield of dysplastic lesions detected by CE with standard white
light endoscopy (WLE).
AIMS & METHODS: Retrospective cohort study of patients with long standing
(47 years) colonic IBD undergoing surveillance colonoscopy at Leeds Teaching
Hospital NHS Trust between January 2012 to December 2013. Details of diag-
nosis, duration of disease and outcomes of the colonoscopy were collected from
the endoscopy database, electronic patient records and patient notes.
RESULTS: There were 120 colonoscopies in the CE group and 220 colonosco-
pies in the WLE group. The groups were well matched for all demographic
variables. 27 dysplastic lesions were detected in 20 patients in the CE group
and 9 dysplastic lesions were detected in 6 patients in the WLE group. All the
lesions were detected on targeted biopsy and harboured low grade dysplasia. The
adjusted prevalence ratio (on a per patient basis) for detecting any dysplastic
lesion was 4.6 (95% CI 1.6-13.7) in favour of CE.
CONCLUSION: CE colonoscopy improves detection of dysplastic lesions
during surveillance colonoscopy of patients with colonic IBD even in routine
clinical practice, confirming data from prospective trials. CE should be the stan-
dard of care for all IBD surveillance procedures as advocated by both BSG and
ECCO guidelines.
REFERENCES
(1) Subramanian V, Mannath J, Ragunath K, et al. Meta-analysis: the diagnostic
yield of chromoendoscopy for detecting dysplasia in patients with colonic inflam-
matory bowel disease. Aliment Pharmacol Ther 2011; 33: 304-312.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
LIVER & BILIARY I POSTER EXHIBITION HALL XL_____________________
P0009 INVOLVEMENT OF B-CELLS IN HEPATIC INFLAMMATION
DURING NONALCOHOLIC STEATO-HEPATITIS (NASH)
A. Jindal1,*, S. Sutti1, I. Locatelli1, M. Vacchiano1, C. Bozzola1, E. Albano1 on
behalf of Laboratory of General Pathology, Prof. Albano, Novara, Italy
1
Department of Medical Sciences, University of Eastern Piedmont, Novara, Italy
Contact E-mail Address: aastha.jindal@med.unipmn.it
INTRODUCTION: Growing evidence indicates that adaptive immunity contri-
butes to the process leading to chronic hepatic inflammation in NASH. However,
the mechanisms involved are still incompletely characterized. Recently, B-lym-
phocytes have emerged as players in orchestrating adipose tissue inflammation in
obesity contributing to the development of insulin resistance.
AIMS & METHODS: We investigated the possible role of B-cell responses in the
pathogenesis of NASH. NASH was induced by feeding four weeks C57BL/6 mice
with a methionine-choline deficient (MCD) diet.
RESULTS: In mice receiving the MCD diet the development of steatohepatitis
was associated with an increased hepatic infiltration by B220 (CD20) positive B-
lymphocytes and by the detection of circulating IgG targeting oxidative stress-
derived antigens such as malonildialdehyde- (MDA) and 4-hydroxynonenal-pro-
tein adducts. Moreover, immunohistochemistry showed the presence of IgG
deposits within the hepatic inflammatory infiltrates that co-localized with
MDA-derived antigens, indicating the formation of immunocomplexes. To sub-
stantiate the role of oxidative stress in triggering B-cell responses in NASH, mice
were immunized with MDA-adducted bovine serum albumin (MDA-BSA)
before feeding the MCD diet. In MCD-fed, but not in control mice, MDA-
BSA immunization promoted liver B-cell expansion and enhanced transaminase
release, lobular inflammation and the hepatic production of the pro-inflamma-
tory cytokines TNF-, IFN-, IL-12. Among immunized MCD-fed mice there
were also positive correlations between the individual expression of the B-cell
marker B220 and those of macrophage M1 activation markers IL-12p40 and
iNOS (r 0.87 and 0.71 respectively; p50.02).
This effect was likely mediated by B-cell interaction with CD4 T-cells as in the
same animals B220 expression also positively correlated with that of IFN-
(r 0.76; p50.03) and of the co-stimulatory molecule CD40 (r 0.72;
United European Gastroenterology Journal 2(5S)
p50.05). Furthermore, depleting CD4 T-cells in MCD-fed immunized mice
by using an anti-CD4 monoclonal IgG did not affected B220 expression, but
significantly lowered the hepatic mRNAs IFN-, iNOS and IL-12p40 and ame-
liorated lobular inflammation and focal necrosis.
CONCLUSION: These results indicate that B-cell responses triggered by oxida-
tive stress can contribute to inflammation in NASH by stimulating T-cellular
responses.
Disclosure of Interest: None declared
P0010 GENERATION OF A VECTOR CONTAINING AN SHRNA FOR
THE RECEPTOR CB1 AS AN ANTIFIBROGENIC STRATEGY IN
LIVER DISEASE
A. D az Rivera1,*, V. Chagoya de Sanchez 2, G. Velasco Loyden 2, L. Garc a
Benavides 3, J. Armendariz Borunda 1, A. Sandoval Rodr guez1
1
Molecular Biology and Gene Therapy Institute, Guadalajara, 2Cellular Physiology
Institute, Mexico, D. F, 3Institute of Experimental and Clinical Therapeutics,
Guadalajara, Mexico
Contact E-mail Address: adrianadiaz.riv@gmail.com
INTRODUCTION: Blockade of cannabinoid type I receptor (CB1) by pharma-
cological antagonist has demonstrated antifibrogenic effects in models of cirrho-
sis. Gene therapy with a shRNA molecule for CB1 wthinin an adenovirus has the
advantage of hepatic tropism, which will reduce side effects and increase the
transduction efficiency.
AIMS & METHODS: Design a shRNA that efficiently inhibit the expression of
CB1, evaluate its antifibrogenic effect in an experimental model of liver cirrhosis
and generate an adenoviral vector coding for the shRNA-CB1.
shRNA sequences were designed to blockade mRNA of CB1 at positions 877,
1232, 1501 (pshCB1-A, B, D). The effectiveness of the shRNA was evaluated by
inhibition of the mRNA-CB1 after transfection of the plasmids in primary cul-
ture rHSC. To determine the optimum dose for transfection in primary cultures,
lipofectamine 2000 and Fugene HD were tested using a GFP expressing plas-
mid (pITR-GFP). Later, we evaluated shRNA mediated-CB1 inhibition in cir-
rhotic rats intoxicated with CCl4. The plasmids were administrated by
hydrodynamic injection in a volume of 4 mL. Then, in animals transfected
with the most potent shRNA-CB1, mRNA levels of fibrogenic molecules
(TGF-1, Col 1 and -SMA) and percentage of fibrotic liver tissue was mea-
sured. Finally, Ad5 backbone coding for shRNACB1-1232 or shRNA-Irrelevant
was generated by homologous recombination between pshRNA and the pAd /
BLOCK-iT TM DEST.
RESULTS: In vitro shRNA designed to block position 877 and 1232 signifi-
cantly inhibited mRNA (p4 0.05) CB1 gene expression in 77% and 91%, respec-
tively using Fugene HD. The sequence of shRNA-Irrelevant did not affect
mRNA expression of CB1. Hydrodynamics-based transfection of shRNA-CB1
via iliac vein in the rat allows efficient and repeatable delivery to the liver. A
volume of 4 mL carrying 3 mg/kg was administered in 5-7 seconds. In CCl4
model shCB1-1232 showed major decrease in CB1 mRNA and protein
(p50.05), and in consequence fibrogenic molecules TGF-1, Col I, -SMA
also reduced (60%, 47% and 77% (p50.05); respectively). Fibrosis diminished
49% (p50.05) compared to untreated controls. Thus pshRNACB1-1232 was
selected for production of adenovector. Homologous recombination between
attL and attR regions between pshRNA-1232-CB1 and pAd / BLOCK-iT TM
DEST allowed the generation of Ad-shRNA1232-CB1 backbone.
CONCLUSION: shCB1-1232 demonstrates CB1 gene and protein silencing
in vitro and in vivo, decreasing mRNA levels of key fibrogenic molecules and
fibrosis, showing potential to be used as therapeutic strategy for liver fibrosis.
Recombinant adenovirus expressing this shRNA will have the advantage of high
titers production conserving efficient liver transduction, which will facilitate its
therapeutic application in experimental models of liver cirrhosis or even clinical
scenarios.
Disclosure of Interest: None declared
P0011 CORRELATION BETWEEN INDIRECT SERUM MARKERS AND
MORPHOMETRIC VALUES OF FIBROTIC TISSUE IN PBC
C. Stasi1,*, L. Leoncini1, M.R. Biagini1, S. Madiai1, F. Marra1, G. Laffi1,
S. Milani2
1
Department of Experimental and Clinical Medicine, 2Department of Biomedical,
Experimental and Clinical sciences, University of Florence, Florence, Italy
INTRODUCTION: The accuracy of non-invasive methods for the quantification
of liver fibrosis in patients with PBC is still debated. Moreover, the Ludwigs
PBC stages do not represent a measurement of quantitative fibrosis.
AIMS & METHODS: We determined the histomorphometrical measurement of
fibrotic tissue and analyzed the accuracy of a number of indirect markers of liver
fibrosis for the detection of different histological stages of PBC and the associa-
tion between indirect serum markers and morphometric values (MV) of fibrotic
tissue.
Methods: Sections of liver tissue were stained with hematoxylin/eosin and
Sirius red. Only samples with a 4 25 mm length and including at least 11
complete portal tracts were considered adequate for the study.
Histomorphometrical measurement of fibrotic tissue was performed on sirius
red stained sections of liver biopsies. Area percentage measures of fibrotic
tissue were ranked into 4 groups reflecting Ludwigs staging and compared
with values of the following serum markers of liver fibrosis: APRI, LOK,
FORNS, FIB-4. The percentage of fibrosis was calculated with ImageJ. All
results were expressed as mean  standard deviation. The numerical comparison
of continuous data was performed using the Wilcoxon signed ranks test applied
to two-samples. Linear regression analysis between two variables was performed
by using Pearson correlation. Statistical significance was set at a value of p50.05.
United European Gastroenterology Journal 2(5S)
RESULTS: We enrolled 50 patients with PBC (mean age, 5712.30 years; 43 F
and 7 M; 8 AMA negative, 42 AMA positive). There were 19 (38%) patients in
Ludwigs PBC stage I, 14 (28%) in stage II, 12 (24%) in stage III and 5 (10%) in
stage IV. The morphometric values (Table 1) of fibrotic tissue were significantly
different in the various Ludwigs stages of PBC (p50.05). Only LOK score was
statistically different between stage II and III (p 0.02). No other significant
differences were found in the various Ludwigs stages of PBC for APRI,
FORNS, FIB-4 and LOK scores (Table 1). A statistically significant correlation
was found between MV and Forns (R2 0.3643, p 0.0004), MV and FIB-4
(R2 0.3945, p 0.0002), MV and LOK (R2 0.3367, p 0.0010), MV and
APRI (R2 0.1476, p 0.0361).
Table 1.
Ludwigs Morphometric
stages values FORNS FIB-4 LOK
Stage I 0.74%  0.65 3.61  1.62 0.24  0.26 0.20  0.16
Stage II 3.87%  1.5 4.55  1.8 0.35  0.39 0.22  0.18
Stage III 6.15%  1.68 5.52  2.06 0.35  0.16 0.38  0.19
Stage IV 14.06%  8.45 8.05  1.76 1.00  0.76 0.69  0.34
CONCLUSION: Histomorphometric values of fibrotic tissue increase progres-
sively in Ludwigs stages of PBC, where non-invasive markers do not, and cor-
relate positively with indirect serum markers of liver fibrosis.
Disclosure of Interest: None declared
P0012 THE NGF RECEPTOR P75NTR LEADS TO
HYPERTROPHY DURING THE DEVELOPMENT OF LIVER
CIRRHOSIS AND MALIGNANT LIVER TUMORS
D. Hartmann1,*, S. Werscher1, R. Go1, S. Teller1, M. Schlitter2, K. Becker2,
H. Friess1, G.O. Ceyhan1
1
Department of Surgery, 2Institute of Pathology, Technische Universitat Munchen,
Munich, Germany
Contact E-mail Address: daniel.hartmann@tum.de
INTRODUCTION: The autonomic nervous system is the involuntary part of the
peripheral nervous system and regulates the intestinal motor activity, smooth
muscles and exocrine glands. Autonomic nerves that innervate the liver reach
the organ via the hepatic hilum and run together with the portal vein, the hepatic
artery and the bile duct. In the full clinical picture of liver cirrhosis, no parench-
ymal innervation can be detected. In addition, malignant liver tumors, such as
hepatocellular carcinoma (HCC) and cholangiocellular carcinoma (CCC), are
not innervated.
AIMS & METHODS: The aim of this work is the characterization of a possible
hepatic neuroplasticity, including responsible neurotrophic factors. In the present
work, a collective consisting of 103 patients (22 patients with normal liver tissue,
23 patients with liver cirrhosis, 45 patients with HCC and 13 patients with CCC)
was examined for variations in nerve number and nerve size. In addition, growth
factors, such as Growth-Associated Protein (GAP-43) and Nerve Growth Factor
(NGF), as well as their receptors TrkA and p75NTR were investigated by immu-
nohistochemistry and qRT-PCR in terms of their involvement in a possible
hepatic neuroplasticity.
RESULTS: The multiple comparison of median nerve sizes of the examined
entities showed a clearly significant difference. The largest nerves were discovered
in HCC samples. However, no difference in neural density was detected.
Furthermore, significant differences were observed for the high affinity NGF-
receptor TrkA and the low affinity NGF-receptor p75NTR with regards to
immunoreactivity and relative expression. The highest p75NTR expression was
found in normal liver tissue and both, relative expression as well as immuno-
reactivity, decrease with increasing nerve size.
CONCLUSION: The results of the present study suggest that the observed
neural changes in the liver are related to active neural remodeling processes.
The NGF receptor p75NTR seems to take on a key role in this context. Since
p75NTR binds all neurotrophins with low affinity, further research is warranted
concerning its involvement in the plasticity of hepatic nerves.
Disclosure of Interest: None declared
P0013 HIGH CONCENTRATION OF FIBROTIC AND INFLAMMATORY
MARKERS AMONG PATIENTS WITH SCHISTOSOMAL LIVER
DISEASES
E. Sinkala1,2, P. Kelly3,4, E. Sinkala1,2,*
1
Internal Medicine, University of Zambia, 2Internal Medicine, TROPGAN,
Lusaka, Zambia, 3Internal Medicine, Barts and London, Blizzard Institute,
London, United Kingdom, 4Internal Medicine, University Teaching Hospital,
Lusaka, Zambia, Lusaka, Zambia
Contact E-mail Address: sinkalaeddie@yahoo.com
INTRODUCTION: Worldwide the commonest cause of portal hypertension is
cirrhosis, but in tropics it is schistosomiasis. Some parts of Zambia are hyper-
endemic with prevalence of 77%. Hepatocellular function is preserved in hepa-
tosplenic schistosomiasis hence prognosis is better than cirrhosis. Liver biopsy
can confirm fibrosis but it is invasive.
AIMS & METHODS: This is an ongoing case control study involving 70 cases
and 20 controls. All cases had varices and were negative for HIV, hepatitis B and
C viruses. Hyaluran was used as a marker of liver fibrosis while TNF receptor 1,
sCD14, IL1 beta, IL 6 and CRP were inflammatory markers.
A135
We set out to investigate fibrotic and inflammatory makers in hepatosplenic
schistosomiasis patients at the University Teaching Hospital, Lusaka, Zambia.
RESULTS: Eighty patients were evaluated and serology for schistosomiasis was
positive in 74 (93%) and negative in 6 (7%). Hyaluran levels compared with
controls were higher, p50.001 (median 111.6ng/ml, IQR 39.1, 240.3).
Inflammatory markers were elevated: TNF receptor 1 concentrations compared
with controls were higher, p 50.001 (median 3150.1pg/ml (IQR 1703.2, 10460.0),
sCD14 values were higher than in controls p50.001, median 2365.0ng/ml
(IQR1744.9, 3128.6). IL 1 beta values were higher than in controls p 0.013,
median 4.3pg/ml (IQR 0.8, 13.2) and so were IL 6 values p 0.001 (median
15.26pg/ml, IQR 10.15, 38.13). Spearmans rank correlation of hyaluran and
TNF receptor 1 was positive (r 0.44, p 0.002) and so was hyaluran and IL6
(r 0.251, p 0.045).
CONCLUSION: Schistosomiasis is a leading cause of portal hypertension in
APRI Zambia and induces a liver fibrotic marker which could be used to assess disease
severity. It seems hepatosplenic schistosomiasis also induces high levels of TNF
0.61  0.76 receptor 1, sCD14, IL1 beta and IL6. These elevated markers could be due to
0.49  0.35 bacterial translocation which needs to be confirmed by markers of bacterial
0.67  0.44 translocation such as LPS.
1.24  0.79 Disclosure of Interest: None declared
P0014 LIVER FIBROSIS PREVENTION AFTER INTRAMUSCULAR
ADMINISTRATION OF MATRIX METALLOPROTEINASE-8
ADENOVIRAL VECTOR IN A MODEL OF HEPATIC FIBROSIS
J. Garcia-Banuelos1,*, E. Eden Oceguera-Contreras1, D. Gordillo-Bastidas1,
A. Sandoval-Rodr guez1, B. Bastidas-Ram rez2, J. Gonzalez-Cuevas1, J. Macias-
Barragan1, B. Belinda Gomez-Meda1, J. Armendariz-Borunda1 on behalf of
INNOVARE, Guadalajara, Jalisco, Mexico
NEURAL 1
Instituto de Biologa Molecular y Terapia Genica, Centro Universitario de
Ciencias de la Salud, 2Instituto de Enfermedades Cronico Degenerativas, Centro
Universitario de Ciencias de la Salud, Universidad de Guadalajara, Guadalajara,
Mexico
INTRODUCTION: MMP-8 degrades preferentially collagen type I (collagen of
higher proportion of hepatic fibrosis). We delivered MMP-8 gene in to the
muscle, using an Adenovirus vector, protein is released systemically and is acti-
vated in the liver.
AIMS & METHODS: Our aim was to evaluate profibrogenic gene expression
pattern and liver fibrosis prevention.
We used four groups of rats (n 15): control; thioacetamide (TAA), induced-
fibrosis; TAAAdGFP; TAAAdMMP8. At the beginning of the fifth week of
TAA intoxication, administration of vectors in soleum muscle was accomplished.
Sub-groups of rats (n 5) at the end of first, second and third week after vector
administration were sacrificed. Percentage of fibrosis, liver function, gene expres-
sion of MMP8, proinflammatory genes (IL1-beta, TNF-alpha), profibrogenic
genes (collagen 1(I), CTGF and TGF-beta) and antifibrogenic genes (MMP1
and MMP9), were determined.
RESULTS: After 3 weeks of treatment: In the liver and serum, amount of MMP8
protein was sustained, fibrosis decreased up to 48%, proinflammatory genes
expression was modified only at the end of the third week, profibrogenic gene
expression decreased (Col 1(I) 4 times, TGF-beta 3 times and CTGF 2 times),
antifibrogenic genes expression increased (MMP9 2.8 times and MMP1 10
times). According to Knodell score, a clearly diminution of inflammatory cells
infiltration in comparison with counterpart animals treated with AdGFP, could
be appreciated.
CONCLUSION: A single dose of AdMMP8 in muscle is enough in order to
obtain a stable liver MMP8 protein expression and activity during 21 days.
Degradation of collagen in the liver modifies pro and anti-fibrogenic gene expres-
sion allowing a restoration of hepatic architecture.
Disclosure of Interest: None declared
P0015 WHOLE-PROTEIN MASS SPECTROMETRY TO IDENTIFY
CONGENITAL DISEASE OF GLYCOSYLATION IN END-STAGE
LIVER DISEASE
J.C. Jansen1,*, M.van Scherpenzeel2, D.J. Lefeber2, J.P. Drenth1
1
Gastroenterology and Hepatology, 2Laboratory of Genetic, Endocrine and
Metabolic Disease, Radboud University Medical Center, Nijmegen, Netherlands
Contact E-mail Address: Jos. Jansen@radboudumc.nl
INTRODUCTION: Congenital disorders of glycosylation (CDG) are a hetero-
geneous group of autosomal recessive metabolic diseases with a wide spectrum of
clinical symptoms. Depending on localization of the defective protein, two types
are distinguished (CDG-I; endoplasmatic reticulum and CDG-II; Golgi appara-
tus). Liver involvement is frequent in both groups and can even be predominant
for some CDG-II variants. Abnormal glycosylation is seen in liver cirrhosis,
probably resulting from affected liver synthesis. We hypothesized that mass
spectrometry (MS) differentiates between secondary and bonafide genetic
causes in end-stage liver disease.
AIMS & METHODS: To determine the effect of a diminished liver function on
glycosylation we analyzed anonymous serum samples drawn from end-stage liver
disease patients prior to their liver transplantation. As a first step we used trans-
ferrin isoelectric focusing (tIEF) to detect abnormal glycosylation. Selected sam-
ples were further analyzed with transferrin whole-protein MS to obtain a
comprehensive readout of the glycosylation profile.
We also obtained serum from 100 patients with a presumed CDG. Patients with a
predominant liver phenotype were selected for further analysis using exome
sequencing for identification of the pathogenic mutation.
RESULTS: We collected 1065 serum samples and found an abnormal tIEF
pattern in 30%. All abnormalities were mild and resembled a CDG-II pattern.
A136
MS of abnormal tIEF samples had increased fucosylation of transferrin and loss
of one sialic acid.
We identified 18 patients with a phenotype resembling Wilson disease with liver
fibrosis, elevated transaminases, low ceruloplasmin and liver copper accumula-
tion. DNA is currently prioritized for exome sequencing. MS comparison of the
Wilson disease-like patients and liver transplant patients showed that desializa-
tion is more abundant in Wilson disease-like patients and transferrin fucosylation
is seen more often in liver transplant patients.
CONCLUSION: Whole protein MS enables differentiation between abnormal
glycosylation secondary to liver failure and bonafide CDG. This can aid in the
detection of CDG as a cause for liver pathology.
Disclosure of Interest: None declared
P0016 MICRORNA EXPRESSION PROFILE IN SIMPLE STEATOSIS
AND NON-ALCOHOLIC STEATOHEPATITIS
K. Okamoto1,*, T. Okamoto1, T. Onoyama1, K. Miyoshi1, M. Kishina1, J. Kato1,
S. Tokunaga1, T. Sugihara1, Y. Hara2, M. Koda1, K. Hino2, Y. Murawaki1
1
2nd. Dept. of Internal Medicine, Tottori Univ. School of Medicine, Yonago,
2
Department of Hepatology and Pancreatology, Kawasaki Medical School,
Kurashiki, Japan
Contact E-mail Address: okamotka@grape.med.tottori-u.ac.jp
INTRODUCTION: Simple steatosis (SS) and non-alcoholic steatohepatitis
(NASH) are regarded as histological subtypes of non-alcoholic fatty liver disease
(NAFLD). The distinctive pathological difference between SS and NASH is that
NASH induces chronic liver inflammation and fibrogenesis, which can lead to
liver cirrhosis. The difference in pathogenesis between SS and NASH is still not
clear. MicroRNAs (miRNAs) are endogenous, non-coding short RNAs that
regulate gene expression by repressing translation or degrading target mRNAs.
Accumulating evidence indicates that miRNAs play important roles in various
life functions including inflammation, metabolism, and fibrosis.
AIMS & METHODS: The purpose of this study was to examine the relationship
of miRNA expression profiles with SS and NASH in animal models and humans.
DD Shionogi (DS), Fatty Liver Shionogi (FLS), and FLS ob/ob mice were
subjected as the normal control, SS model, and NASH model, respectively.
Microarray analysis was used to assess 375 miRNA expression profiles in
mouse liver tissue. Normalized miRNA expression ratios over 2log2 between
FLS and FLS ob/ob were identified as candidates. Real time PCR was used to
check the reproducibility of the microarrays predicting miRNAs from 4 mice in
each group. The putative miRNA target genes were predicted using the web-
driven software DIANA microT-CDS. DAVID 6.7 was used to perform gene
ontology annotation and KEGG pathway enrichment analysis. The putative
miRNA expression profiles in human serum were also examined in every 10
patients with asymptomatic gallbladder stones, SS, and NASH.
RESULTS: In microarray analysis, 18 miRNAs were identified as candidates.
Among the 18 miRNAs, 6 showed good expression ratio reproducibility in real
time PCR and were confirmed to express commonly between mice and humans.
The expression levels of miR-200a and miR-200b increased in the order of
normal control, SS, and NASH. miR-1 was downregulated in NASH. miR-
376c, miR-409, and miR-411 showed potent high expression in SS, over 30-
fold of DS. KEGG pathway analysis indicated that the strongly expressed
miRNAs in SS (miR-376c, miR-409, and miR-411) had multiple targets in the
TGF- signaling pathway including TGFR, smad 2, 3, and 4. The analysis
suggests that miR-376c, miR-409, and miR-411 may protect liver fibrosis
through silencing the TGF- signaling pathway. In human serum, hierarchical
clustering analysis of the putative miRNA expression also showed clearly differ-
ent expression profiles between SS and NASH.
CONCLUSION: The expression profiles of 6 miRNAs were different between SS
and NASH models. Some potential target genes of the putative miRNAs were
found to be involved in the TGF- signaling pathway. Furthermore, the putative
miRNA expression profiles in human serum were also clearly different between
SS and NASH patients. These miRNAs have high potential as biomarkers to
distinguish the fate of NAFLD patients and contribute to further research in the
pathogenesis and treatment of NASH.
Disclosure of Interest: None declared
P0017 PROTECTIVE EFFECTS OF MELATONIN ON
THIOACETAMIDE-INDUCED LIVER FIBROSIS IN RATS
K. Celinski1,*, G. Czechowska 1, A. Korolczuk2, G. Wojcicka3, J. Dudka4,
A. Bojarska-Junak5, A. Ma dro1, H. Cicho_z-Lach1
1
Gastroenterology, 2Department of Clinical Pathomorphology, 3Department of
Clinical Pathophysiology, 4Medical Biology, 5Clinical Immunology, MEDICAL
UNIVERSITY OF LUBLIN, Lublin, Poland
Contact E-mail Address: celinski.krzysztof@gmail.com
INTRODUCTION: The aim of the present study was to determine the effect of
melatonin on liver fibrosis induced with long-term administration of thioaceta-
mide (TAA) in an animal model. The antifibrotic effects of melatonin were
assessed by determining activity indirect markers of fibrosis, i.e. aspartate ami-
notransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase
(AP), and direct markers represented by proinflammatory cytokines such as
interleukin 6 (IL-6), interleukin beta 1 (IL-beta1), tumour necrosis factor alpha
(TNF-alpha, transforming growth factor beta 1 (TGF-beta1) and platelet-
derived growth factor (PDGF- AB). Moreover, parameters of oxidative stress
were determined, i.e. concentrations of oxidised glutathione (GSSG) and reduced
glutathione (GSH), activity of paraoxonase 1 (PON-1), an enzyme of antioxida-
tive properties. Inflammatory changes and extent of fibrosis were evaluated
histologically.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: Experiments were carried out in Wistar rats. Animals
were divided into 4 groups, 8 individuals each: group I- controls receiving drink-
ing water ad libitum for 12 weeks, group II TAA, 300 mg/L ad libitum for 12
weeks, group III- melatonin, 10 mg/kg b.w. administered intraperitoneally (IP)
daily for 4 weeks, group IV TAA, 300 mg/L ad libitum for 12 weeks followed
by melatonin, 10 mg/kg/b.w. administered IP daily for 4 weeks.
RESULTS: Results of serum determinations demonstrated significantly lower
activity of AST, ALT and AP in the group receiving TAA followed by melatonin
(IV) compared to the group receiving only TAA (II). Immunoenzymatic findings
regarding the effect of melatonin on concentration of proinflammatory cytokines
(Il-6, Il-beta1, TNF-alpha, TGF-beta 1, PDGF-AB) confirmed these data.
CONCLUSION: Biochemical examinations in liver homogenates revealed statis-
tically significant improvement of oxidative stress parameters (concentration of
GSH increases and concentration of GSSG decreases) in animals with TAA-
induced liver damage receiving melatonin (IV). Moreover, the activity of PON-
1 toward phenyl acetate and paraoxon was found to be increased in liver homo-
genates and serum in the group receiving TAA followed by melatonin (IV)
compared to the TAA group (II). Microscopic evaluation disclosed inhibitory
effects of melatonin on inflammatory changes and extent of liver fibrosis.
Disclosure of Interest: None declared
P0018 ROLE OF GAMMA-KETOALDEHYDES AS NOVEL MEDIATORS
OF EXPERIMENTAL FIBROGENESIS AND STELLATE CELLS
ACTIVATION
L. Longato1,*, K. Rombouts1, D. Dhar1, S. Davies2, J. Roberts2, T. V. Luong1,
M. Pinzani1, K. Moore1
1
UCL Institute for Liver & Digestive Health, University College London, London,
United Kingdom, 2Pharmacology, Vanderbilt University, Nashville, United States
Contact E-mail Address: l.longato@ucl.ac.uk
INTRODUCTION: Reactive lipid aldehydes formed during lipid oxidation such
as 4-hydroxynonenal (4-HNE), are key activators of hepatic stellate cells (HSCs)
to a pro-fibrogenic phenotype. -Ketoaldehydes (-KAs) are highly reactive lipid
aldehydes formed during oxidation of arachidonic acid or as a by-product of the
cyclo-oxygenase pathway. -Ketoaldehydes are 100x more reactive than HNE,
and form protein adducts and cross-links. Increased circulating concentrations of
proteins cross-linked to -ketoaldehydes are present in patients with alcoholic
liver disease.
AIMS & METHODS: The aim of this study was to investigate whether one
specific -ketoaldehyde, namely levuglandin E2 (LGE2), can induce activation
of HSCs. Cultured activated, serum-starved primary mouse and human HSCs
were exposed to various concentrations (0.5 pM-5 mM) of levuglandin E2 (LGE2)
for up to 48 hours. Endpoints measured included proliferation (BrdU incorpora-
tion), cytotoxicity (lactate dehydrogenase (LDH) release and tetrazolium (MTS)
reduction), RNA expression (qRT-PCR), protein expression (Western Blot), and
collagen secretion in conditioned medium (SirCol assay).
RESULTS: HSCs exposed to LGE2 exhibited profound cytotoxicity at 5 M
concentration, as indicated by LDH leakage and reduced MTS. This was
mediated by an induction of apoptosis, indicated by an increase in PARP clea-
vage, occurring as early as 8 hours after LGE2 exposure. However, at lower, non-
cytotoxic doses (ranging from 50 pM-500 nM, with a maximum effect observed
at 0.5 nM), LGE2 promoted HSC activation as indicated by increased expression
of -smooth muscle actin and vimentin, as well as increased proliferation and
collagen secretion. In addition, LGE2 exposure promoted sustained activation of
signalling pathways, as indicated by the increased phosphorylation of the kinases
ERK1/2 and JNK, as well as an increase in mRNA levels of chemokines such as
IL-8 and MCP-1. We are currently investigating the potential protective action of
administration of a -ketoaldehyde scavenger in an animal model of hepatic
fibrosis.
CONCLUSION: -Ketoaldehydes represent a newly identified class of activators
of HSCs in vitro, which are biologically active at concentrations as low as 50 pM.
Disclosure of Interest: None declared
P0019 NONINVASIVE SERUM FIBROSIS MARKERS IN COMPARISON
WITH GRADING AND STAGING IN CHRONIC HEPATITIS
M. Abdollahi1,*, A. Pouri2, M. Somi2
1
Young Researchers and Elite Club, Tabriz Branch, Islamic Azad University,
2
Liver and Gastrointestinal Diseases Research Center, Tabriz University of
Medical Sciences, Tabriz, Iran, Islamic Republic Of
Contact E-mail Address: Dr. M. R. Abdollahi@gmail.com
INTRODUCTION: Chronic hepatitis is defined as a necroinflammatory disease
of the liver continuing for at least six months. The aim of this study was to
evaluate the role of noninvasive fibrosis markers by assessing the association
among grading and staging and these diagnostic parameters in patients with
chronic hepatitis.
AIMS & METHODS: We retrospectively studied 221 patients with chronic
hepatitis between 2011 and 2013. Routine biochemical indices and serum fibrosis
indexes such as aspartate aminotransferase (AST)/alanine aminotransferase
(ALT) ratio (AAR), AST to platelet ratio index (APRI) and Fibrosis 4 score
(FIB-4) were determined, and the histological grade and stage of the liver biopsy
specimens were scored according to the Ishak scoring system. Receiver operating
characteristic curve (ROC) analysis was conducted to compare diagnostic
accuracies of these markers for prediction of significant fibrosis.
RESULTS: We identified 221 liver biopsies from chronic hepatitis patients with
contemporaneous laboratory values for imputing AAR, APRI and FIB-4. From
all, 135 males (61.1%) and 86 females (38.9%), with the mean age of 39.614.4
were studied. FIB-4, APRI and AAR were correlated significantly with the stage
of fibrosis, with a higher correlation coefficient than other markers in the patients
United European Gastroenterology Journal 2(5S)
with Hepatitis B (r 0.46), C (r 0.58) and autoimmune hepatitis (r 0.28). on the MCD diet these cells prevalently expressed markers of inflammatory
FIB-4 (AUROC 0.84) and APRI (AUROC 0.78) was superior to AAR at
distinguishing severe fibrosis from mild-to-moderate fibrosis and gave the highest
diagnostic accuracy.
CONCLUSION: Application of these markers was good at distinguishing sig-
nificant fibrosis and decreased the need for staging liver biopsy specimens among
patients with chronic hepatitis.
Disclosure of Interest: None declared
P0020 REVEALING THE MOLECULAR MECHANISM OF RAT LIVER
RESPONSE TO LONG-TERM OMEPRAZOLE TREATMENT WITH
BIOINFORMATICS APPROACH
S. Vakal1, E.A. Virag2, K. Dvorshchenko1, L. Ostapchenko1,*
1
ESC "Institute of Biology", Taras Shevchenko National University of Kyiv, Kyiv,
Ukraine, 2University of Pecs, Pecs, Hungary
Contact E-mail Address: sergii.vakal@univ.kiev.ua
INTRODUCTION: Omeprazole is a widely prescribed acid-suppressing drug
available for clinical use for 25 years. Despite well-studied adverse effects of
short-term omeprazole treatment, underlying mechanisms of some hepatotoxic
effects of long-term injection of high omeprazole doses (e.g. development of
oxidative stress and histopathologic changes [1]) are not understood.
Transcriptome analysis is a powerful tool for elucidation of possible mechanisms
of cellular response to different conditions on molecular level. Bioinformatics
approach is suitable for processing of large datasets, prediction of possible
regulatory circuits and generation of hypotheses on involved molecular mechan-
isms [2].
AIMS & METHODS: The purpose of the research was to find out possible
molecular mechanisms of rat liver cells response to long-term injection of
omeprazole.
GSE8858 dataset and GPL2454 platform description were downloaded from
NCBI Genome Expression Omnibus database. Gene expression data from
livers of rats treated with 30 mg/kg and 415 mg/kg for 1 and 25 days were
compared in order to reveal differentially expressed genes (DEGs). DEGs were
determined with GEO2R tool on the basis of t-criterion and adjusted p value.
Gene ontology (GO), pathway enrichment analyses and building of protein-pro-
tein interactions (PPI) network were performed with STRING 9.1. Prediction of
miRNAs and cis-elements for DEGs was carried out with WebGestalt toolkit.
Clusters were identified by K-means analysis in ClusterONE. All networks were
visualized using Cytoscape.
RESULTS: In total 79 DEGs (21 up- and 58 down-regulated) and 87 DEGs (41
up- and 46 down-regulated) were identified in samples of rat livers treated with
30 and 415 mg/kg during 25 days, respectively. At the same time 22 genes with
similar pattern of expression (9 up- and 13 down-regulated) were found for both
types of dosage. Among them are Arntl, Cdk1a, Chka, Gpam, Litaf, Slc2a5, Usp2
etc. Enrichment in such GO terms was revealed: cell cycle, mitosis, nuclear divi-
sion, lipid metabolism. Only genes involved in lipid metabolism were up-
regulated, while others were suppressed. Genes involved in PPAR signalling
pathway were found to be differentially regulated upon 25-day treatment with
omeprazole. Most of DEGs (51 genes) were of cytoplasmic proteins (house-
keeping genes). PPI networks were constructed for 98 proteins and 102 interac-
tions revealed. The optimal amount of clusters was equal to 3. MiRNA-9, 17-5p,
20A, 20B, 106A, 106B, 200B, 200C, 429, 506 and 519D were found to be involved
in regulation of revealed DEGs. 24 probable cis-elements were predicted for
promotors of identified DEGs.
CONCLUSION: Thus, long-term treatment of rats with omeprazole is asso-
ciated with changes in expression of housekeeping genes: down-regulation of
genes involved in cell-cycle process and cellular division, up-regulation of genes
involved in lipid metabolism, and changes in expression of PPAR signalling
pathway genes.
REFERENCES
1. Dvorshchenko KO, Bernyk OO, Dranytsyna AS, et al. Influence of oxidative
stress on the level of genes expression Tgfb1 and Hgf in rat liver upon long-term
gastric hypochlorhydria and administration of multiprobiotic Symbiter. Ukr
Biokhim Zh 2014; 85: 114-123.
2. Shen B, Zhou S, He Y, et al. Revealing the underlying mechanism of ischemia
reperfusion injury using bioinformatics approach. Kidney Blood Press Res 2013;
38: 99-108.
Disclosure of Interest: None declared
P0021 MORPHOLOGICAL AND FUNCTIONAL CHANGES OF LIVER
MACROPHAGES DURING THE PROGRESSION OF
NONALCOHOLIC STEATOHEPATITIS (NASH)
S. Bruzzi1,*, S. Sutti1, A. Jindal1, I. Locatelli1, M. Vacchiano1, C. Bozzola1,
E. Albano1
1
Health Sciences, University of Eastern Piedmont "A. Avogadro", Novara, Italy
Contact E-mail Address: stefania.bruzzi@med.unipmn.it
INTRODUCTION: Recent reports indicate that both human and experimental
NASH is characterized by an increase in hepatic monocyte infiltration and that
macrophages have an important role in regulating the disease evolution.
However, little is known about the functional changes occurring in liver macro-
phages during the progression of NASH.
AIMS & METHODS: NASH was induced in C57BL/6 mice by feeding a methio-
nine-choline deficient (MCD) diet up to 8 weeks.
RESULTS: Mice receiving the MCD diet showed a progressive worsening of
parenchymal damage and lobular inflammation, while liver fibrosis was evident
only after 8 weeks of treatment. Hepatic F4/80-positive macrophages increased in
parallel with the disease progression. In the early phases of NASH after 4 weeks
A137
monocytes such as Ly6C and CD11b, but the prevalence of Ly6C/CD11b
cells decreased by extending the treatment up to 8 weeks. This paralleled with
a lowering in the monocyte chemokines CCL1/CCL2 and their receptors CCR8/
CCR2. We observed that the expression of the macrophage M1 activation mar-
kers iNOS and IL-12 also peaked at 4 weeks and declined thereafter. No appreci-
able changes were instead observed in the levels of M2 polarization markers
arginase-1 and MGL-1. Histology revealed that the macrophages accumulating
in advanced NASH (8 weeks MCD) were enlarged, vacuolized and formed small
aggregates. Immunofluorencesce showed that these cells contained lipid vesicles
positive for the apoptotic cell marker Annexin V suggesting that they have pha-
gocytosed apoptotic bodies derived from dying fat-laden hepatocytes. At flow
cytometry, enlarged macrophages were characterized by a weak Ly6C/CD11b
expression and by a low IL-12 production. On the other hand, these cells showed
an enhanced expression of the anti-inflammatory mediators IL-10 and annexin
A1. The production of the pro-fibrogenic cytokine TGF- was increased in the
macrophages obtained from NASH livers, irrespective of the cell phenotype.
CONCLUSION: Altogether, these data indicate that during the progression of
NASH liver macrophages down-modulate their pro-inflammatory phenotype in
parallel with the phagocytosis of apoptotic hepatocytes and acquired anti-inflam-
matory properties.
This work has been supported by a grant from the Fondazione Cariplo (Milan).
Disclosure of Interest: None declared
P0022 MICRORNA-27B DEVELOP THE FATTY LIVER FORMATION
AND INSULIN RESISTANCE AT THE SAME ONSET
T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, Y. Eguchi2, K. Wada3,
A. Nakajima1
1
gastroenterology and hepatology, Yokohama city university, yokohama, 2internal
medicine, saga university, saga, 3 Pharmacology, Osaka University Graduate
School of Dentistry, Oosaka, Japan
Contact E-mail Address: takaomi-kesso@hotmail.co.jp
INTRODUCTION: Nonalcoholic fatty liver disease (NAFL) morbidity rate in
Asia Pacific region is close to 1224%, while in Western countries is about 20
30%1). And nonalcoholic fatty liver disease (NAFLD) can progress to nonalco-
holic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma. In spite of
its high prevalence, up till now there is no proven effective treatment for
NAFLD3). Along with the obesity epidemic, the worldwide prevalence of
NAFLD is increasing rapidly and is generally assumed to be a consequence of
obesity-induced insulin resistance 2). On the other hand, not all obese individuals
are insulin resistant, nor are all insulin-resistant individuals obese 4). MicroRNAs
(miRs) are a class of small non-coding RNAs that function to control gene
expression by inducing the degradation or inhibiting the translation of mRNA
through an association with its 3-untranslated region (3UTR). Although miRs
play a key role in the pathogenesis of nonalcoholic fatty liver disease (NAFLD)
and diabetes mellitus (DM), detailed mechanisms of this pathogenesis remain
unclear.
AIMS & METHODS: We found that miR-27b increased in liver biopsy speci-
mens of NAFLD patients with DM using microarray analysis, as compared with
controls. The aim of this study was to investigate whether overexpression of miR-
27b in liver could cause fatty liver formation and insulin resistance, and to
examine the mechanism of NAFLD and DM onset in a murine model.
Five-week-old male C57BL/6J mice were randomized into 2 groups (n 16
mice): basal diet (BD)-fed control mimic (BD-Con, n 4), BD-fed miR-27b-
mimic (BD-miR-27b, n 4). In this study, miR-27b mimic is injected intrave-
nously at 7mg/kg. We comfirmed the target genes of miR-27b using quantitative
RT-PCR analysis. Insulin serum concentrations were measured by a local labora-
tory for clinical examinations. As an alternative method for assessing insulin
resistance (IR), the homeostasis model assessment of IR (HOMA-IR) was calcu-
lated using the following formula: fasting insulin (mU/mL) plasma glucose (mg/
dL) / 405.
RESULTS: BD-miR-27b significantly showed steatosis using oil red o staining
and increased hepatic tryglyceride content, as compared with BD-Con. In the
analysis of fat accumulation-related gene expression, hepatic Peroxisome prolif-
erator-activated receptor  (PPAR) and Microsomal triglyceride transfer pro-
tein (MTTP) are significantly decreased. At the same time, BD-miR-27b showed
hyperinsulinemia and insulin resistance. In the analysis of insulin resistance-
related gene expression, hepatic Insulin receptor substrate 1 (IRS-1) is signifi-
cantly decreased.
CONCLUSION: miR-27b controls multiple gene levels that are involved in fat
accumulation and insulin resistance, resulting in the NAFL and DM pathology.
These results propose a therapeutic approach for NAFL and DM by targeting
miR-27b.
REFERENCES
1) Farrell GC, Chitturi S, Lau GK, et al. Guidelines for the assessment and
management of non-alcoholic fatty liver disease in the AsiaPacific region: execu-
tive summary. J Gastroenterol Hepatol 2007; 22: 775777.
2) Clark JM, Brancati FL and Diehl AM. Nonalcoholic fatty liver disease.
Gastroenterology 2002; 122: 16491657.
4) Ferrannini E, Natali A, Bell P, et al. Insulin resistance and hypersecretion in
obesity: European Group for the Study of Insulin Resistance (EGIR). J Clin
Invest 1997; 100: 11661173.
Disclosure of Interest: None declared
A138
P0023 EFFICACY OF ABSORBABLE EMBOLIZATION MATERIALS
FOR PORTAL VEIN EMBOLIZATION TO INDUCE LIVER
REGENERATION IN A RABBIT MODEL
F. Huisman1,*, K.P. van Lienden2, J. Verheij3, T.M. van Gulik1
1
Surgery, 2Radiology, 3Pathology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: f.huisman@amc.nl
INTRODUCTION: Unilateral portal vein embolization (PVE) is used to increase
future remnant liver volume in patients requiring extended resections. Reversible
PVE is of interest when generating sufficient hypertrophy while preserving the
embolized liver lobe. The concept of reversible PVE requires an absorbable
embolization material.
AIMS & METHODS: The aim of this study is to modulate lysis time of a fibrin-
glue based embolization material while using different concentrations of
Aprotinin. Aprotinin inhibits fibrinolysis and thereby delays absorption of FG.
PVE of the cranial liver lobe was performed in twenty-four rabbits, divided into 5
groups:
 Fibrin glue with Aprotinin (FG1000 KIU (Kallikrein Inactivotor Unit), n 4)
 Fibrin glue with Aprotinin (FG700KIU, n 5)
 Fibrin glue with Aprotinin (FG500KIU, n 5)
 Fibrin glue with Aprotinin (FG300KIU, n 5)
 Fibrin glue without Aprotinin (FG-Aprot, n 5)
The rabbits were sacrificed after 7, 14 and 49 days, respectively. CT volumetry of
non-embolized lobe (NELVol), liver damage parameters, liver-to-body weight
ratio of NEL were evaluated.
RESULTS: Data were compared with a previous series using a permanent embo-
lization material, i.e. polyvinyl alcohol coils (PVAc), showing complete and
permanent occlusion of the embolized portal vein branch in all rabbits after 7
days.
FG-Aprot was completely absorbed in 7 days and did not give any hypertrophy
response of the NEL. At sacrifice on day 7, the embolized portal vein in all 4 of
the FG1000KIU Aprotinin group was still occluded and showed a hypertrophy
response comparable to the PVAc group. The group of FG 700KIU Aprotinin
survived 14 days and in two of the five rabbits, the embolized portal vein was
recanalized at sacrifice. The hypertrophy response in these rabbits was not dif-
ferent from the PVAc group. The rabbits with FG 500KIU and 300KIU
Aprotinin were sacrificed at day 49. In the group with FG 500KIU Aprotinin,
4 out of 5 showed recanalization of the cranial portal branches. In the group with
FG 300KIU Aprotinin, 3 out of 5 rabbits showed recanalization. Both groups
showed hypertrophy response rates not different compared to the PVAc group.
CONCLUSION: Fibrin glue with the concentrations 300KIU and 500KIU
Aprotinin resulted in 70% reversible embolization with a hypertrophy response
comparable to the PVAc group.
Disclosure of Interest: None declared
P0024 TRANSPLANTATION OF HUMAN AMNION-DERIVED
MESENCHYMAL STEM CELLS AMELIORATES CARBON
TETRACHLORIDE-INDUCED LIVER FIBROSIS IN RATS
K. Kubo1,*, S. Ohnishi1, N. Sakamoto1
1
Gastroenterology and Hepatology, Hokkaido University, Sapporo, Japan
Contact E-mail Address: sonishi@pop.med.hokudai.ac.jp
INTRODUCTION: Liver fibrosis is a progressed stage of chronic hepatic disease
caused by a variety of factors, such as viral infections, alcohol, drugs and che-
mical toxicity. The only effective available treatment for end stage liver fibrosis is
transplantation; however, due to the lack of donors, complications and trans-
plant rejection, alternative treatment is needed. Mesenchymal stem cells (MSCs)
have been reported to be a valuable cell source in cell therapy. Recently, bone
marrow- or adipose tissue-derived MSCs have been reported to be effective in the
treatment of liver fibrosis. In addition, several studies have shown that MSCs can
be easily isolated from human amnion, and a large amount of cells can be
obtained. Therefore, we examined the effects of transplantation of human
amnion-derived MSCs (hAMSCs) in rats with liver fibrosis.
AIMS & METHODS: All pregnant women gave written informed consent, and
amnion was obtained at Cesarean delivery. hAMSCs were isolated by collage-
nase treatment, and expanded with culture medium containing fetal bovine
serum. Liver fibrosis was induced in 6-week-old male Sprague-Dawley rats by
intraperitoneal injection of 2 ml/kg of 50% carbon tetrachloride (CCl4) twice a
week for 7 weeks. At 3 weeks, hAMSCs (1106 cells) were transplanted intrave-
nously. Rats were sacrificed at 7 weeks, and histological analyses and quantita-
tive RT-PCR were performed.
RESULTS: Transplantation of hAMSCs significantly reduced the fibrotic area
and deposition of type I collagen. In addition, hAMSC transplantation signifi-
cantly decreased the number of -SMA-positive hepatic stellite cells and and
CD68-positive Kupffer cells in the liver of hAMSC-treated rats. mRNA expres-
sion of -SMA was significantly decreased in the liver of hAMSC-treated rats,
and mRNA expression of type I collagen, TGF- and IL-1 tended to be
decreased by hAMSC transplantation.
CONCLUSION: Transplantation of hAMSCs provided significant improvement
in a rat model of liver fibrosis, possibly through inhibition of inflammatory
reaction. hAMSC would be considered as a new cell source for the treatment
of liver fibrosis.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0025 VITAMIN D: HYPOTHESIS OF TROPHIC EFFECT ON LIVER
CELLS IN AN ANIMAL MODEL OF NAFLD
V. Lembo1,*, G. Mazzone1, G. DArgenio1, M. DArmiento2, F. Morisco1,
N. Caporaso1
1
Department of Clinical Medicine and Surgery, 2Department of Advanced
Biomedical Science, University of Naples Federico II, Naples, Italy
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD), the most
common liver disease in Western countries, is pathogenetically related to a seden-
tary lifestyle as well as to poor quality diet characterized by an excessive energy
intake including high fatty foods and high amounts of fructose, the so-called
Western Diet (WD). The hallmark of NAFLD is hepatic accumulation of trigly-
cerides. Vitamin D in addition to the effects on lipid metabolism, plays other
biological functions, among which a trophic effect on human cultured cells.
AIMS & METHODS: To evaluate, in a rat model of NAFLD induced by
Western Diet, the relationship between body weight, liver weight and grade of
steatosis; and if these parameters are modified by vitamin D supplementation.
Methods: Eighteen male Wistar rats were divided into 3 groups, each of 6 rats.
The 3 groups were fed respectively with Standard Diet (SD); Western Diet (WD);
WDVitD: WD supplemented with 23 IU/day/rat of vitamin D3. The experiment
was conducted for 6 months. Weekly, the rats, body weight was recorded. At
sacrifice, livers were excised and weighed and samples were stored at -80 C. Liver
histology was examined by haematoxylin/eosin and Oil Red-O staining. Steatosis
was numerically scored following semi-quantitative pathological standard.
RESULTS: During the experiment the increase of body weight was similar in the
three groups. In the two groups fed with WD liver weight was significantly higher
than SD group (p50.01). A positive correlation between body weight and liver
weight was observed in WD groups (p50.0001). The liver/body weight ratio was
significantly higher in WD and WDVitD groups than SD: 2.90.05, 2.80.07
and 2.00.04, respectively; p50.001). Steatosis was present in 61% and 21% of
hepatocytes in WD group and WDVitD group, respectively, and absent in SD
group. No correlation was found between the grade of steatosis and liver or body
weight nor between the grade of steatosis and liver/body weight ratio. Although
vitamin D supplementation reduced the degree of steatosis, liver/body weight
ratio in WDVitD group was similar to WD group.
CONCLUSION: In a rat model of NAFLD induced by WD the presence and
extent of steatosis are independent from body weight. Interestingly and unex-
pectedly, in WD groups the supplementation with vitamin D reduces liver stea-
tosis but not liver weight: this sustains the hypothesis of a trophic effect of
vitamin D on liver cells.
Disclosure of Interest: None declared
P0026 VITAMIN D PREVENTS STEATOSIS AND DIABETES IN A RAT
MODEL OF NAFL
G. Mazzone1,*, V. Lembo1, G. DArgenio1, M. Guarino1, M. DArmiento2,
F. Morisco1, N. Caporaso1
1
Department of Clinical Medicine and Surgery, 2Department of Advanced
Biomedical Science, University of Naples Federico II, Napoli, Italy
Contact E-mail Address: giovanna.mazzone@gmail.com
INTRODUCTION: The last decade has seen nonalcoholic fatty liver disease
(NAFLD) rise to become the most common cause of chronic liver disease in
Western countries. It is known that insulin resistance and type 2 diabetes mellitus
(T2DM) have an important role in the pathogenesis of obesity and NAFLD. A
growing body of evidence points to a linked and potentially causative relation-
ship between serum 25-hidrossivitamin D3 [25-(OH)D] levels and NAFLD.
AIMS & METHODS: Aim of this study was to evaluate whether daily vitamin
D3 supplementation is able to modulate the liver effects and glucose homeostasis
of a westernized diet, high in fat and fructose, in an animal model of NAFL
without vitamin D deficiency. Methods: Eighteen male Wistar rats were divided
into 3 groups, each of 6 rats. Group 1: Standard Diet (SD); Group 2: Western
Diet (WD) containing 13 IU/day/rat of vitamin D3; Group 3: WD containing 23
IU/day/rat of vitamin D3 (WDVitD). The experiment was conducted for 6
months. Liver histology was examined by haematoxylin/eosin and Oil Red-O
staining. Insulin resistance was determined according to the Homeostasis
Model of Assessment (HOMA-IR) method. Grade of liver steatosis was evalu-
ated according to Brunt EM et al.
RESULTS: In SD group, livers were normal and no hepatocytes contained fat; in
WD group the percentage of hepatocytes with steatotic vacuoles was 61%, while
in WDVitD group only 27% of hepatocytes contained fat. In WD group
HOMA-IR was significantly higher than in SD (41.98.9 vs 6.171.3, p50.01)
and it was reduced by vitamin D supplementation in WDVitD group (41.98.9
vs 19.45.2, p50.05). Interestingly SD and WDVitD rats were not diabetic
(98.78.0 and 103.26.1, respectively) while all rats in WD group were diabetic
(1399.6) with glycemic values significantly higher than SD (p50.01) and
WDVitD (p50.05).
CONCLUSION: These results suggest that a daily supplementation of vitamin
D3 is able to improve insulin sensitivity and to prevent the development of
diabetes and hepatic steatosis in WD rats.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0027 INVOLVEMENT OF SPHINGOMYELIN METABOLISM IN THE
DEVELOPMENT OF NAFLD AND INSULIN RESISTANCE
S. Ohnishi1,2,*, S. Mitsutake3, H. Hanamatsu3, K. Yuyama3, S. Sakai3,
H. Takeda4, Y. Igarashi3, S. Hashino2, N. Sakamoto1
1
Gastroenterology and Hepatology, 2Health Care Center, 3Frontier Research
Center for Post-genome Science and Technology, 4Pathophysiology and
Therapeutics, Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo,
Japan
Contact E-mail Address: sonishi@pop.med.hokudai.ac.jp
INTRODUCTION: Sphingomyelin (SM) is a major component in lipid micro-
domains, and SM is synthesized from ceramide by the action of SM synthase
(SMS). We have recently reported that mice deficient for SMS2 are resistant to
high fat diet-induced obesity, fatty liver and insulin resistance (J Biol Chem
2011:286;28544). In this study, we examined the relationship between SM and
ceramide molecular species and the development of NAFLD and insulin resis-
tance in human.
AIMS & METHODS: Non-alcoholic students of our university with body mass
index (BMI)  35 kg/m2 at the regular physical checkup in 2013 were enrolled,
and volunteer students with BMI of 20-22 kg/m2 were set as a control group.
Serum levels of SM and ceramide containing saturated (C14:0, C16:0, C18:0,
C20:0, C22:0 and C24:0) and unsaturated (C16:1, C18:1, C20:1, C22:1 and
C24:1) fatty acids were measured using LC/MS/MS. Serum levels of liver
enzymes, lipids and insulin resistance were measured by blood examination.
Abdominal ultrasound was performed to confirm the existence of fatty liver,
and body composition including percent body fat (PBF) was measured by bioim-
pedance analysis.
RESULTS: The levels of total SM and ceramide were not altered in obese group
(19-28 y.o., n 12), compared with control group (18-27 y.o., n 11). The con-
centrations of SM C18:0 and C24:0 in the obesity group were significantly higher
than in the control group. Moreover, in the obese group, SM C20:0 and C22:0
tended to be higher than in the control group. In the analysis of total 23 cases, the
serum levels of SM containing saturated fatty acids positively correlated with
PBF, ALT, ChE, LDL-C, TG and HOMA-R. However, SM species containing
unsaturated acyl chain and almost all ceramide species did not correlate with
those items.
CONCLUSION: The present study demonstrated that the serum levels of SM
species containing saturated fatty acids (C18:0, C20:0, C22:0 and C24:0) are
correlated with liver function and insulin resistance, suggesting that distinct
SM species are involved in the development of NAFLD and insulin resistance.
Disclosure of Interest: None declared
P0028 GOOD CORRELATION BETWEEN PLASMA CYTOKERATIN-18
AND CONTROLLED ATTENUATION PARAMETER (CAP) IN
HEALTHY POPULATION
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
metabolismo, FML, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA, Lisbon,
Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: Liver steatosis measurement by controlled attenuation para-
meter (CAP) is a non-invasive method for diagnosing steatosis, based on tran-
sient elastography. Plasma caspase-generated cytokeratin-18 fragments (CK-18)
have been proposed as a non-invasive alternative for the diagnosis of NAFLD,
especially NASH.
AIMS & METHODS: Aims: compare CK-18 serum levels in apparently healthy
individuals with and without steatosis. Methods: Recruitment from a prospective
epidemiological study of the general Portuguese adult population. Steatosis eval-
uated using CAP and ultrasound. Performance of CK-18 for diagnosing steatosis
compared with US and CAP was assessed using AUROC.
RESULTS: 146 individuals studied (60% male), mean age and BMIs (body mass
index) were 52.617.1 years and 28.24.9 kg/m2, respectively; 25% had a
normal BMI, 46% were overweight and 29% were obese. Prevalence of steatosis
on ultrasound was 52.1%.
The mean (SD), median (minimum-maximum), and 5th and 95th percentile
values of CK-18 values were 73.4 (67.7), 57.6 (25-508), 25 and 220.1 U/L, respec-
tively. Median CK-18 were elevated in patients with vs. without hepatic steatosis
by ultrasound: 33.4 [IQR: 25151] vs. 73.7 [IQR: 25508] U/L, p 50.0001.
CK-18 significantly correlated with steatosis ( 0.40), ALT ( 0.40), CAP
( 0.38), triglyceride ( 0.32), waist circumference ( 0.30), HDL ( -
0.28), AST ( 0.27), LDL ( 0.26), total cholesterol ( 0.21) and the
number of metabolic syndrome criteria ( 0.29), but not with LSM or BMI.
The CK-18 AUROC to predict steatosis using ultrasound and CAP (cut-offs of
243 dB/m) were 0.78 (95% CI 0.710.86) and 0.74 (95% CI 0.650.82),
respectively.
CONCLUSION: In the absence of steatosis, CK-18 serum levels were below 151,
with a very large range. It showed a good discriminating capacity for diagnosing
steatosis.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
A139
P0029 PREVALENCE OF HEPATIC STEATOSIS IN THE GENERAL
PORTUGUESE POPULATION: USING FATTY LIVER INDEX (FLI)
AND ULTRASOUND
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, A. Carvalho3, H. Cortez-
Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutricao e
Metabolismo, FML, IMM, Lisbon, 3Internal Medicine, CHUC, Coimbra, 4INSA,
Lisbon, Portugal
INTRODUCTION: The fatty liver index (FLI) derived from an Italian popula-
tion includes serum triglycerides, serum gamma-glutamyltransferase, body mass
index (BMI) and waist circumference. It has been used as a noninvasive measure
of hepatic steatosis (HS), but has not been widely validated and not examined in
the Portuguese population.
AIMS & METHODS: Estimate the prevalence of HS in the Portuguese adult
population by fatty liver index (FLI) and correlate with the ultrasound findings;
validate FLI for prediction of fatty liver in the Portuguese population.
Methods: Recruitment from a prospective epidemiological study of the general
Portuguese adult population. Steatosis evaluated using ultrasound (US) and FLI.
Performance of FLI for diagnosing steatosis compared with US was assessed
using AUROC.
RESULTS: We studied 950 subjects, 50.5% men. The mean age, waist circum-
ference and BMIs were 50.518.4 years, 94.412.7 cm and 26.94.7 kg/m2,
respectively; 43% were overweight and 22% were obese. The median of FLI
was 38.1. Ultrasound was performed in 411 subjects, showing fatty liver in 35%.
Using the FLI, 27.6% of subjects had HS (FLI 4 60), 41.8% had no HS (FLI 5
30) and 30.6% were not classifiable (FLI 30-60). However, these cut-offs pro-
posed by Bedogni appears to be inappropriate as 11.5% of subjects with FLI
530 exhibited HS on ultrasound and 13.4% of subjects with FLI 4 60 showed
no steatosis. For the FLI, the area under the ROC curve was 0.88 for the
diagnosis of HS.
There was a significant correlation (p 5 0.01) between the FLI and the following
variables: weight ( 0.80), waist circumference ( 0.74), presence of steatosis
( 0.65), triglycerides ( 0.58), BMI ( 0.51), ALT ( 0.43), GGT
( 0.39), HDL ( -0.36), age ( 0.33), female sex ( -0.33), insulin
( 0.29), AST ( 0.28), LDL ( 0.24) and total cholesterol ( 0.22). No
correlation was found with physical activity.
CONCLUSION: FLI could accurately identify hepatic steatosis in the general
Portuguese population. The calculation of FLI may be useful to suggest the
possibility of the presence of steatosis and indicate the need for an abdominal
ultrasound.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0030 NORMAL CONTROLLED ATTENUATION PARAMETER (CAP)
VALUES: A POPULATION-BASED STUDY OF HEALTHY SUBJECTS
S. Carvalhana1,2, J. Leitao3, C. Alves4, M. Bourbon4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de Nutricao e
Metabolismo, FML, IMM, Lisbon, 3Internal Medicina, CHUC, Coimbra, 4INSA,
Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: Liver steatosis measurement by controlled attenuation para-
meter (CAP) is a non-invasive method for diagnosing steatosis, based on tran-
sient elastography. The normal range of controlled CAP values needs to be
explored in clinical and anthropometrically diverse healthy subjects. A recent
study has shown an association of CAP with BMI and the number of metabolic
syndrome criteria.
AIMS & METHODS: Aim: define the normal range of CAP values in healthy
subjects and evaluate the associated factors.
Methods: Recruitment from a prospective epidemiological study of the general
Portuguese adult population. CAP was performed using Fibroscan in 134 healthy
subjects, without fatty liver on ultrasonography or positivity serology for
HBsAg, anti-HBc and anti-HCV, and normal aminotransferase levels.
RESULTS: From 134 consecutive individuals studied (66 males), 4 were
excluded due to failure/unreliable liver stiffness measurements (LSM). The
mean age and BMIs (body mass index) were 46.918.0 years and 24.93.5 kg/
m2, respectively; 50% had a normal BMI, 43% were overweight and 7% were
obese. The mean (SD), median (minimum-maximum), and 5th and 95th percen-
tile values of CAP values were 202.29 (48.4), 205.5 (100.0-297.0), 108.2 and 276.3
dB/m, respectively. Men had a higher mean CAP value than women (meanSD:
213.147.1 dB/m versus 191.847.8 dB/m, respectively; p 0.012).
CAP significantly correlated with gender ( 0.22), age ( 0.22), waist circum-
ference ( 0.33), BMI ( 0.22), alcohol consumption ( 0.25), systolic blood
pressure ( 0.27), ALT ( 0.27), fasting glucose ( 0.24) and the number of
metabolic syndrome criteria.
After allowance for potential confounders, CAP was not independently asso-
ciated with BMI or other risk factors for nonalcoholic fatty liver disease.
CONCLUSION: CAP values vary between 108.2 and 276.3 dB/m in healthy
subjects and is not associated with BMI or the number of metabolic syndrome
criteria.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
A140
P0031 EFFECT OF LANREOTIDE ON POLYCYSTIC LIVER AND
KIDNEY GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT
POLYCYSTIC KIDNEY DISEASE: AN OBSERVATIONAL TRIAL
T.J. G. Gevers1,*, J.C. Hol1, R. Monshouwer2, H.M. Dekker3, J.F. Wetzels4,
J.P. Drenth1
1
Gastroenterology and Hepatology, 2Radiation Oncology, 3Radiology,
4
Nephrology, RadboudUMC, Nijmegen, Netherlands
Contact E-mail Address: tom.gevers@radboudumc.nl
INTRODUCTION: Several trials have demonstrated that somatostatin analo-
gues decrease liver volume in mixed populations of patients with autosomal
dominant polycystic kidney disease (ADPKD) and isolated polycystic liver dis-
ease. Chronic renal dysfunction in ADPKD may affect treatment efficacy of
lanreotide and possibly enhances risk for adverse events.
AIMS & METHODS: The aim of this open-label clinical trial (RESOLVE trial)
was to assess efficacy of 6 months lanreotide treatment 120 mg subcutaneously
every 4 weeks in ADPKD patients with symptomatic polycystic liver disease. We
excluded patients with an estimated glomerular filtration rate (eGFR) 5 30 ml/
min/1.73m2. Primary outcome was change in liver volume, secondary outcomes
were changes in kidney volume, eGFR, symptom relief and health-related quality
of life (Euro-Qol5D). We used the Wilcoxon signed-rank test or paired two-sided
t-test to analyze within-group differences.
RESULTS: We included 43 ADPKD patients with polycystic liver disease (84%
female, median age 50 years, mean eGFR 63 ml/min/1.73m2). Median liver
volume decreased from 4,859 ml to 4.595 ml (-3.1%;p50.001), and median
kidney volume decreased from 1.023 ml to 1.012 ml (-1.7%;p 0.006). eGFR
declined 3.5% after the first injection and remained stable up to study end.
Lanreotide significantly relieved postprandial fullness, shortness of breath and
abdominal distension, but had no effect on any of the EuroQol-5D dimensions.
Three participants had a suspected episode of hepatic or renal cyst infection
during the study.
CONCLUSION: Lanreotide reduced polycystic liver and kidney volumes and
decreases symptoms in ADPKD patients. Moreover, eGFR decreased acutely
after starting lanreotide, but stabilized thereafter.
Disclosure of Interest: None declared
P0032 THE EFFECTS OF POLY-UNSATURATED FATTY ACIDS
(PUFAS) IN A RODENT NUTRITIONAL MODEL OF NON-
ALCOHOLIC STEATOHEPATITIS (NASH)
V. Smid1,2,*, K. Dvorak1, B. Stankova2, A. Zak1, L. Vitek1,2, R. Bruha1
1
4th Department of Internal Medicine, General University Hospital and 1st Faculty
of Medicine, 2Institute of Medical Biochemistry and Laboratory Diagnostics,
General University Hospital and 1st Faculty of Medicine, Charles University in
Prague, Prague, Czech Republic
INTRODUCTION: NAFLD and subsequent NASH are probably the most
common chronic liver diseases in western countries and have a high risk of
development of liver cirrhosis associated with high morbidity and mortality.
AIMS & METHODS: The aim of the study was to determine effects of admin-
istration of PUFAs in the MCD dietary model of NASH and to assess the
potential anti-inflammatory role of PUFAs in the pathogenesis of NASH.
For 6 weeks were male mice fed either with MCD or with chow. There were 4
groups of animals. Both experimental and control groups received from the
beginning either PUFAs or saline. Detailed liver histology, serum biochemistry,
total lipid and fatty acids compound, adiponectin and leptin levels were deter-
mined. Expressions of mRNA of key pro- and anti-inflammatory cytokines were
measured.
RESULTS: Feeding with MCD resulted in histopathological changes of
NAFLD/NASH and these changes were ameliorated in PUFAs-group (MP).
Administration of PUFAs led to significant decreases of total animal and liver
weight in MP. PUFAs also decreased cholesterol levels (P50.001), ALT
(P50.01) and AST levels (P50.01). MP developed significantly less pro-inflam-
matory cytokine profile, had lower leptin (P50.01) and higher adiponectin levels
(P50.01) than controls. Administration of PUFA led also to lower serum con-
centrations of saturated and monounsaturated FA and to higher serum concen-
trations of polyunsaturated FA in MP. Total lipid content of liver was
significantly lower in MP.
CONCLUSION: We conclude that PUFAs may play a causal role in the patho-
physiology of NASH. In summary, PUFAs have favorable effects on histopatho-
logical changes, serum markers of liver damage, fatty acid compound and show
anti-inflammatory properties. We expect that PUFAs may represent a promising
way in prevention and treatment of this increasingly common disorder.
Disclosure of Interest: None declared
P0033 DYSBIOSIS SIGNATURE OF FECAL MICROBIOTA IN HUMANS
WITH NON-ALCOHOLIC FATTY LIVER DISEASE
W. Jiang1, N. Wu2, X. Wang1, Y. Zhang1, Y. Chi2, Y. Hu1, X. Qiu1, J. Li1,
Y. Liu1,*
1
Department of Gastroenterology, 2Institute of Clinical Molecular Biology &
Central Laboratory, Peking University Peoples Hospital, Beijing, China
Contact E-mail Address: liuyulan@pkuph.edu.cn, wuna1030@163.com
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is characterized
by a broad spectrum of hepatic pathology that is closely linked to obesity and
ranges from simple steatosis (SS), to non-alcoholic steatohepatitis (NASH) and
even cirrhosis. NAFLD is recently believed to be under the influence of the gut
microbiota, which may have toxic effects on the human host after intestinal
absorption and delivery to the liver via the portal vein.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We explored the composition of gut bacterial commu-
nities of NAFLD and healthy subjects using 16S ribosomal RNA Illumina next-
generation sequencing.
RESULTS: Partial least-squares discriminant analysis (PLS-DA) indicated that
most of the microbiota samples were clustered by disease status. Differences were
abundant at phylum, family, and genus levels between NAFLD and healthy
subjects. Lentisphaerae at phylum level was significant higher in NAFLD micro-
biota. Among those taxa with greater than 0.1% average representation in all
samples, five genera including Alistipes and Prevotella were the genus types
exhibiting significant higher level in healthy microbiota, while genera
Escherichia, Anaerobacter, Lactobacillus and Streptococcus were increased in
NAFLD microbiota. In addition, lymphocyte profiles (CD4T cell and
CD8T cell) and proinflammatory cytokines (TNF-, IL-6 and IFN-) in gut
biopsies of patients and healthy controls was analyzed to monitor the inflamma-
tion caused by dysbiosis microbiota. The levels of CD4 T cells and CD8 T cells
were lower in NAFLD patients compared with healthy subjects, and the proin-
flammation cytokine TNF-, IL-6 and IFN- showed high level in NAFLD
patients. What was more, irregular arrangements of microvilli and widening of
the tight junction were observed in gut mucosa of the NAFLD patients by
transmission electron microscope.
CONCLUSION: The increased abundance of dysregulated bacteria in NAFLD
microbiota, decreased numbers of CD4T cells and CD8T cells, and increased
levels of TNF-, IL-6 and IFN- in gut mucosa of NAFLD patients suggest a
role for gut microbiota in the gut inflammation and the dysregulated gut immu-
nity, which promote pathogenesis of NAFLD. We postulate that the distinct
composition of the gut microbiome among NAFLD and healthy controls
could offer a target for intervention or a marker for disease.
REFERENCES
1 Moschen AR, Kaser S and Tilg H. Non-alcoholic steatohepatitis: a microbiota-
driven disease. Trends Endocrinol Metab 2013; 24: 537-545.
2 Mouzaki M, et al. Intestinal microbiota in patients with nonalcoholic fatty liver
disease. Hepatology 2013; 58: 120-127.
Disclosure of Interest: None declared
P0034 ASCITIC FLUID LACTOFERRIN FOR DIAGNOSIS OF
SPONTANEOUS BACTERIAL PERITONITIS
A.A. Ghweil1,*
1
TROPICAL MEDICINE AND GASTROENTEROLOGY, QenaFACULTY
OF MEDICINE EGYPT, Qena, Egypt
Contact E-mail Address: alimena1@yahoo.com
INTRODUCTION: The diagnosis of spontaneous bacterial peritonitis (SBP) is
based on a manual count of ascitic fluid polymorphonuclear cells (PMNs). This
procedure is operator-dependent and lysis of PMNs during transport to the
laboratory may lead to false-negative results. Furthermore, ascitic fluid culture
is insensitive and leads to delays in diagnosis. The aim of this study was to assess
the utility of ascitic fluid lactoferrin (AFLAC) for the diagnosis of SBP and to
identify a cut-off level that can be used for future development of a rapid bedside
test.
AIMS & METHODS: Sixty ascites samples from cirrhotic patients were exam-
ined for PMN count, bedside culture, and lactoferrin concentration. AFLAC
concentrations were determined using a polyclonal antibody-based enzyme-
linked immunosorbent assay. An ascitic fluid PMN count of 250 cells/mL or
greater with or without a positive culture was used for diagnosis of SBP.
RESULTS: Fifteen (25%) samples fulfilled diagnostic criteria for SBP. Samples
with SBP had a significantly higher lactoferrin concentration (median, 3200 ng/
mL; compared with non-SBP samples (median, 39 ng/mL P 5 .001). The sensi-
tivity and specificity of the assay for diagnosis of SBP were 95.5% and 97%,
respectively. The area under the receiver operating characteristic curve was 0.98.
Conclusions: AFLAC can serve as a sensitive and specific test for diagnosis
CONCLUSION: AFLAC can serve as a sensitive and specific test for diagnosis
of SBP. Qualitative bedside assays for the measurement of AFLAC can be devel-
oped easily and may serve as a rapid and reliable screening tool for SBP in
patients with cirrhosis.
Disclosure of Interest: None declared
P0035 MODULAR COMPUTER-AIDED DIAGNOSIS AND PREDICTION
SYSTEM FOR EARLY HEPATOCELLULAR CARCINOMA IN
CIRRHOTIC PATIENTS
C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, L. Streba1, D.
I. Gheonea1, I. Rogoveanu1
1
Gastroenterology, UMF CRAIOVA, Craiova, Romania
Contact E-mail Address: costinstreba@gmail.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most complex
treatable malignancies as its management is dependent on the stage of the under-
lying condition liver cirrhosis. An early diagnosis assures best curative chances,
as liver resection or transplantation have good survival rates in the general
population. Computer aided diagnostic and prognosis (CADP) models are cur-
rently being developed for a number of malignancies to help clinicians manage
cases based on individual needs of the patients rather than general statistics.
AIMS & METHODS: Our aim was to develop a CADP based on our previous
work involving artificial neural networks (ANN) [1] for successfully diagnosing
early HCC cases and better prognosticate their evolution, based on a set of
criteria in accordance with current guidelines.
Ethical clearance was obtained from the local board and 107 consecutive patients
with previously diagnosed liver cirrhosis signed informed consents for entering
the study, between January 2009 and February 2010. Clinical and demographic
parameters (age, sex, body mass index, waist circumference, type of viral
United European Gastroenterology Journal 2(5S)
infection, alcohol consumption, smoking, clinical ascites, jaundice), laboratory
data (AST, ALT, GGT, alkaline phosphate, bilirubin, triglycerides, thrombocyte
count, prothrombin time, alpha fetoprotein), ultrasound data (portal vein throm-
bosis, size and number of possible tumors), elastography data (strain ratio, com-
plexity, kurtosis, skewness, contrast, entropy, inverse difference moment, angular
second moment, correlation) and stiffness value (FibroScan) were collected and
imputed in the CADP. For patients with clear liver tumors contrast-enhanced
ultrasound was performed and time-intensity curve parameters were calculated
and fed to the ANN system: peak enhancement, time to peak, rise time, fall time,
mean transit time, area under the curve. We have followed the 4-year incidence of
HCC patients in tumor-free cases and assessed the evolution when any forma-
tion, either regeneration nodule or early HCC was found.
RESULTS: We found liver tumors in 21 patients; 12 were regeneration nodules
[median number of tumors per patient: 2 (min: 1, max: 5), median size 1.1 cm
(min: 0.4, max: 1.6)] and 9 were early HCC [median number of tumors per
patient: 1 (min: 1, max: 2), median size 1.8 cm (min: 0.7, max: 2.4)]. The
CADP system correctly diagnosed HCC in all 9 cases and in 8/12 regeneration
nodules based on clinical, laboratory and imaging data. A total of 28 patients
also developed HCC in the four-year follow-up period; the system correctly
predicted high possibility for HCC occurrence in 26 of these patients (92.85%),
while giving high estimates for HCC in another 16 patients that remained cancer-
free until now.
CONCLUSION: We could successfully predict the rate of malignancy in cirrho-
tic patients by using a novel CADP system. We believe that such tools may
become worthy aids to clinical management of patients with various types of
digestive pathologies.
REFERENCES
1. Streba CT, et al. Using contrast-enhanced ultrasonography time-intensity
curves as classifiers in neural network diagnosis of focal liver lesions. World J
Gastroenterol 2012; 18: 44274434.
Disclosure of Interest: None declared
P0036 POSTOPERATIVE RESOURCE UTILIZATION AND SURVIVAL
AMONG LIVER TRANSPLANT RECIPIENTS WITH A MELD
SCORE GREATER THAN OR EQUAL TO 40: A RETROSPECTIVE
COHORT STUDY
F.S. Cardoso1,2,*, C. Karvellas2, N. Kneteman3, G. Meeberg3, P. Fidalgo2,4,
B. Sean2
1
Gastroenterology, Hospital Professor Doutor Fernando Fonseca, Amadora,
Portugal, 2Intensive Care, 3Transplantation, University of Alberta, Edmonton,
Canada, 4Nephrology, Hospital Professor Doutor Fernando Fonseca, Amadora,
Portugal
Contact E-mail Address: desousac@ualberta.ca
INTRODUCTION: Cirrhotic patients with Model for End-stage Liver Disease
(MELD) score 40 have high risk of death without liver transplant (LT). This
study aimed to evaluate these patients outcomes after transplant.
AIMS & METHODS: The retrospective cohort included 519 adult cirrhotic
patients who underwent LT at one Canadian center between 2002 and 2012.
Primary exposure was severity of end-stage liver disease measured by MELD
score at transplant (40 vs. 540). Primary outcome was duration of first inten-
sive care unit (ICU) stay after LT. Secondary outcomes were duration of first
hospital stay after LT, rate of ICU readmission, re-transplant rate, and survival
rates.
RESULTS: On the day of LT, 5% (28/519) of patients had a MELD score 40.
These patients had longer first ICU stay after LT (14 vs. 2 days; p 50.001).
MELD score 40 at transplant was independently associated with first ICU stay
after transplant 10 days (OR, 3.21). These patients had longer first hospital stay
after LT (45 vs. 18 days; p 50.001); however, there was no significant difference
in the rate of ICU readmission (18% vs. 22%; p 0.58) or re-transplant rate (4%
vs. 4%; p 1.00). Cumulative survival at 1 month, 3 months, 1 year, 3 years, and
5 years was 98%, 96%, 90%, 79%, and 72%, respectively. There was no sig-
nificant difference in cumulative survival stratified by MELD score 40 vs. 540
at transplant (p 0.59).
CONCLUSION: Cirrhotic patients with MELD score 40 at transplant utilize
greater postoperative health resources; however, derive similar long-term survival
benefit with LT.
REFERENCES
Shawcross DL, Austin MJ, Abeles RD, et al. The impact of organ dysfunction in
cirrhosis: survival at a cost? J Hepatol 2012; 56: 1054-1062.
Alexopoulos S, Matsuoka L, Cho Y, et al. Outcomes after liver transplantation
in patients achieving a model for end-stage liver disease score of 40 or higher.
Transplantation 2013; 95: 507-512.
Oberkofler CE, Dutkowski P, Stocker R, et al. Model of end stage liver disease
(MELD) score greater than 23 predicts length of stay in the ICU but not mor-
tality in liver transplant recipients. Crit Care 2010; 14: R117.
Disclosure of Interest: None declared
P0038 DISTINGUISHING NASH CIRRHOSIS FROM NON-CIRRHOTICS
BY URINE VOLATILE ORGANIC COMPOUND ANALYSIS - A PILOT
STUDY
J. Covington1, E. Daulton1, E. Westenbrink1, M. McFarland2,*, C. Bailey2,
N. OConnell2, C. Nwokolo2, K. Bardhan3, R. Arasaradnam4
1
Engineering, University of Warwick, 2Gastroenterology, UHCW NHS Trust,
Coventry, 3Gastroenterology, Rotherham NHS Trust, Rotherham, 4CSRI,
University of Warwick, Coventry, United Kingdom
Contact E-mail Address: r.arasaradnam@warwick.ac.uk
A141
INTRODUCTION: There is a quest for biomarker discovery in liver disease
especially to detect cirrhosis at an early stage. Current methods are invasive,
more often requiring a liver biopsy to confirm the diagnosis. For patients with
Non-alcohol related Steatohepatitis (NASH), the use of fibroscan whilst gener-
ally helpful, is unable to confirm the presence of fibrosis particularly in the
presence of fat within the liver which is inevitable in most cases with NASH.
The gut microbiome is altered in several gastrointestinal disorders, resulting in
altered gut fermentation patterns, which we (and others) have been able to
recognise by analysis of volatile organic compounds (VOC) in urine, breath
and faeces1. The altered structure of the small intestinal mucosa and increased
gut permeability (noted in liver disease), we hypothesised, would also change the
microbiome, hence recognisable by its unique fermentome pattern, making
NASH distinguishable from controls.
AIMS & METHODS: To determine if NASH results in an altered VOC pattern
in the urine, detectable by ion mobility spectrometry (FAIMS), and distinguish-
able from cirrhotics vs non-cirrhotics.
33 patients were recruited; 8 with NASH cirrhosis; (confirmed histologically), 8
with non-cirrhotic NASH; 5 with NAFLD (non-alcohol fatty liver disease) and
12 controls (normal synthetic liver function). Urine was collected and 10 ml
aliquots were stored frozen in universal containers. For assay, the containers
were first heated to 40  0.1oC. The headspace (the air above the sample) was
then pumped from the containers and analysed by Field Asymmetric Ion
Mobility Spectrometry (FAIMS). Linear discriminant analysis (LDA) was used
for initial statistical evaluation, with a re-classification using a leave one out
for calculating sensitivity and specificity.
RESULTS: LDA showed that FAIMS is able to distinguish the VOC pattern in
these different groups of liver disease. The control group was significantly dif-
ferent to all of the other groups with a sensitivity of 100%. Of the disease groups,
NASH and NASH with cirrhosis had sensitivity of 83% and 77% respectively
with specificity of 80%. NAFLD however had sensitivity of 50% but specificity
of 80%.
CONCLUSION: This pilot study suggests the IMS (FAIMS technology) offers
a novel non-invasive approach to separate not only NASH from controls but
also those with established cirrhosis using urine. It offers the potential for early
non-invasive tracking of NASH and its complications.
REFERENCES
1. Arasaradnam RP, Covington JA, Harmston C, et al. Next generation diag-
nostic modalities in gastroenterology gas phase volatile compound biomarker
detection. Aliment Pharmacol Ther 2014; 39: 780-789.
Disclosure of Interest: None declared
P0039 ELASTOGRAPHY PLUS PLATELET COUNT RATHER THAN
ENDOSCOPY TO SCREEN FOR LARGE OESOPHAGEAL VARICES
N. Ding1,*
1
Gastroenterology, St Vincents Hospital, Melbourne, Australia
Contact E-mail Address: dingnik@gmail.com
INTRODUCTION: Endoscopic screening for gastro-oesophageal varices (GOV)
is currently recommended for all cirrhotic patients. Noninvasive methods for
liver fibrosis assessment are identifying increasing numbers of patients with cir-
rhosis-range liver stiffness measurements (LSM), increasing the number of
referrals for screening endoscopy. The identification of simple non-invasive mar-
kers for the presence/absence of large gastroesophageal varices (GOV) would be
clinically useful. We evaluated the performance of liver stiffness measurement
(LSM)  platelet count to identify the presence of large GOV in patients with
Child Pugh (CP) A cirrhosis.
AIMS & METHODS: Data were collected retrospectively. The presence of cir-
rhosis was defined by LSM 4 13.6 kPa using elastography. We performed a
database search for patients with LSM 4 13.6 kPa who underwent screening
gastroscopy (2010 2013). Only patients with compensated liver disease were
included. Large GOV were defined by diameter 4 5mm or the presence of high
risk stigmata. We assessed the accuracy of LSM, platelet count (Pl) or the com-
bination of these factors to identify patients with large GOV. A training set of 71
patients was used, and results were validated using a second cohort of 201
patients from two independent centres.
RESULTS: The combination of LSM and Pl was more accurate for identifying
CSPH than either marker alone (training cohort AUROC: 0.87 [0.77-0.94] vs.
0.78 [0.66 0.87] and 0.77 [0.66-0.86] for LSM or Pl alone). The optimal risk
score was 0.11 (Sens 0.88, Spec 0.77, PPV 0.33, NPV 0.98,
accuracy 78%). Results in the validation cohort confirmed the discriminatory
power of this model (AUROC: 0.76 [0.68-0.83]). We then tested clinically rele-
vant cut-offs to improve the negative predictive value (NPV) for large GOV. The
NPV for the combination of LSM 5 25 kPa and Pl  100 and was 100% in both
the training cohort and validation cohort. 82 (42%) of patients overall met this
criteria.
CONCLUSION: The combination of LSM 5 25 kPa and Pl  100 can be used
to identify patients with compensated cirrhosis who do not have large GOV.
These patients do not benefit from endoscopic screening, but could be followed
with annual LSM and full blood count.
REFERENCES
1. Grace ND. Diagnosis and treatment of gastrointestinal bleeding secondary to
portal hypertension. American College of Gastroenterology Practice Parameters
Committee. Am J Gastroenterol 1997.
2. de Franchis R. Revising consensus in portal hypertension: report of the
Baveno V consensus workshop on methodology of diagnosis and therapy in
portal hypertension. J Hepatol 2010; 53: 762768.
3. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet
count identify portal hypertension in patients with compensated cirrhosis.
Gastroenterology 2013; 144, 102111.e1.
A142
4. Stefanescu H, Grigorescu M, Lupsor M, et al. Spleen stiffness measurement
using Fibroscan for the noninvasive assessment of esophageal varices in liver
cirrhosis patients. J Gastroenterol Hepatol 2011; 26: 164170.
Disclosure of Interest: None declared
P0040 PATIENTS EXPERIENCING REPEATED EPISODES OF HEPATIC
ENCEPHALOPATHY HAVE INCREASING RISK OF SUBSEQUENT
EPISODES. A POST HOC ANALYSIS OF RIFAXIMIN-A OPEN
LABEL STUDY DATA
C.A. Bannister1, P. Conway2,*, A. Radwan2, K. Nanuwa2, C.L. Morgan1,
E. Berni3, C.J. Currie1
1
Cochrane Institute of Primary Care & Public Health, Cardiff University, Cardiff,
2
Norgine, Uxbridge, 3Global Epidemiology, Pharmatelligence, Cardiff, United
Kingdom
Contact E-mail Address: PConway@norgine.com
INTRODUCTION: Hepatic encephalopathy (HE) is a chronic complication of
cirrhosis. In recurrent, overt, episodic HE, which is the most common subcate-
gory, its seriousness is due to the chronic debilitating effects of the recurrent
episodes.
AIMS & METHODS: The aim of this study was to characterise the impact of the
number of prior HE episodes on the risk of future HE episodes. A post-hoc
analysis was carried out using data from 322 patients with a history of HE
from a phase 3, open-label study evaluating the long-term safety and tolerability
of rifaximin- 550mg BID. All eligible patients had a Conn score of 02 at
enrolment, and had either successfully participated in a previous HE study
with rifaximin- (RFHE3001), or they were new patients enrolled with 1 ver-
ifiable episode of HE within the preceding 12 months.
RESULTS: 319 of 322 patients (647 observations) aged 18 years had all the
information required for analysis. Median duration of follow-up was 17 months
(IQR 8.925.4). Stratifying patient observations by number of prior HE episodes
and using the Kaplan Meier method the probability of being event free at year
one was 0.644 (95% CI; 0.543-0.763), 0.615 (0.541-0.700), 0.396 (0.303-0.518) and
0.302 (0.246-0.371) and the probability at year two was 0.579 (0.469-0.713), 0.539
(0.455-0.638), 0.292 (0.1999-0.428) and 0.218 (0.163-0.290) for one, two, three 70% males). The majority (78%) had compensated cirrhosis. 45 patients (90%)
and four or more prior HE episodes, respectively. Plotting the Kaplan Meier
curves of time to next HE episode, stratified by the number of prior HE episodes,
a clear association between decreased time to next HE episode and increased
number of prior episodes was seen. Using log-rank tests, there was no significant
difference between the survival curves of one prior and two prior HE episodes
(2 0 on 1 degree of freedom (d.f.), p 0.899), however there were significant
differences between survival curves of one prior or two prior episodes and greater
numbers of prior episodes (2 72 on 3 d.f., p50.001).
CONCLUSION: This study supports the current understanding of the natural
history of end-stage encephalopathy; as the number of prior HE episodes
increased, the risk of subsequent HE episodes increased.
Disclosure of Interest: C. Bannister Consultancy for: Norgine, P. Conway Other:
Employee of Norgine, A. Radwan Other: Employee of Norgine, K. Nanuwa
Other: Employee of Norgine, C. Morgan Consultancy for: Norgine, E. Berni
Consultancy for: Norgine, C. Currie Consultancy for: Norgine
P0041 NEW QUALITY CRITERIA FOR TRANSIENT ELASTROGRAPHY
CAN INCREASE THE PROPORTION OF VALID MEASUREMENTS
WITH HIGH ACCURACY FOR DETECTION OF LIVER CIRRHOSIS
AND PORTAL HYPERTENSION
P. Schwabl1,*, S. Bota1, P. Salzl1, M. Mandorfer1, B.A. Payer1, A. Ferlitsch1,
J. Stift2, F. Wrba2, M. Trauner1, M. Peck-Radosavljevic1, T. Reiberger1 on
behalf of Vienna Hepatic Hemodynamic Lab
1
Dept. of Internal Medicine III, Div. of Gastroenterology & Hepatology, 2Clinical
Institute of Pathology, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: philipp.schwabl@meduniwien.ac.at
INTRODUCTION: Transient elastography (TE) is a non-invasive, easily repea-
table tool to assess liver fibrosis and portal hypertension (HVPG). Recently, new
quality criteria for TE measurements have been proposed (Boursier et al.
Hepatology 2013): very reliable: IQR/M 50.1; reliable: IQR 0.10.3, or IQR/
M 40.3 if TE 57.1 kPa; poor reliable: IQR/M 40.3 if TE 47.1 kPa.
AIMS & METHODS: We evaluated the diagnostic power and accuracy of TE
measurements according to these new quality criteria (accurate very reliable
reliable) for non-invasive assessment of liver fibrosis (liver biopsy) and portal
hypertension. Therefore we retrospectively identified patients undergoing TE,
HVPG measurement and liver biopsy within 3 months at our tertiary care center.
RESULTS: Among 278 patients (48.713.1 years, 74.7% male, 75.7% viral
etiology, 57% F3/F4), traditional TE quality criteria identified 71.6% reliable
measurements, while new criteria yielded in 83.2% accurate LS measurements
(23.1% very reliable, 60.1% reliable). Reliable TE values according to traditional
or new criteria were all significantly and similarly strong correlated with fibrosis
stage (R 0.648 vs. R 0.636) and HVPG (R 0.836 vs. R 0.846). The accu-
racy for diagnosing liver cirrhosis (F4, cut-off: 14.5 kPa) was 76.5% and 75.0%
for traditional and new TE criteria, respectively. The positive (PPV) and negative
(NPV) values for new criteria at the 14.5 kPa cut-off were 83% and 70%. For
predicting HVPG 10mmHg (cut-off: 16.1 kPa), the accuracies were 88.9% and
89.8% using traditional or new criteria, respectively. Both criteria resulted in
AUCs for diagnosis of HVPG 10mmHg of over 0.95 with a PPV and NPV
of 76% and 97%, respectively.
CONCLUSION: Applying new quality criteria for TE measurements signifi-
cantly increases the number of valid TE measurements without affecting accu-
racy of TE for diagnosis of liver cirrhosis and portal hypertension.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0042 EVALUATION OF A NOVEL, PORTABLE, PROBE-BASED
TRANSNASAL ENDOSCOPE: SUPERIOR PATIENT PREFERENCE
AND ACCEPTABLE DIAGNOSTIC ACCURACY FOR
OESOPHAGEAL VARICES COMPARED TO CONVENTIONAL
ENDOSCOPY
S.S. Sami1,*, E. Wilkes1, M. James1, R. Mansilla-Vivar2, J. Fernandez-Sordo1,
J. White1, A. Khanna1, M. Coletta1, S. Samuel1, G. Aithal1, K. Ragunath1,
I. N. Guha1
1
Digestive Diseases NIHR Biomedical Research Unit, University of Nottingham,
UK, Nottingham, United Kingdom, 2Department of Gastroenterology, Pontifical
Catholic University of Chile, Santiago, Chile
INTRODUCTION: Conventional oesophagogastroduodenoscopy (C-OGD)
remains the gold standard test to screen for oesophageal varices (OV) in patients
with liver cirrhosis. However, it has many limitations in terms of costs, accessi-
bility and tolerability. Hence, there is a need for less invasive and simple techni-
ques to replace C-OGD in this setting.
AIMS & METHODS: We aimed to compare the accuracy and acceptability of a
portable, disposable, office-based, unsedated transnasal video endoscope (EG
ScanTM II) with C-OGD for the detection of OV.
This was a prospective diagnostic study. Consecutive adult patients with con-
firmed liver cirrhosis, scheduled for screening or surveillance of OV, were invited
to participate in this study. We excluded patients with recurrent epistaxis (more
than once a week); nasal obstruction; disease of the nasal cavity; history of
variceal bleeding or band ligation therapy in the past 12 weeks. All subjects
underwent two procedures on the same day (EG Scan followed by C-OGD),
performed by two different operators blinded to the findings of the other test.
Patients completed validated tolerability (10-point visual analogue scale (VAS))
and adverse events questionnaires on day 0 and day 14.
The primary outcome measure was diagnostic accuracy of EG scan (performed
by one operator) against C-OGD (reference standard). In addition, interobserver
agreement of the EG scan was calculated using the kappa (k) statistic, by nine
blinded endoscopists, evaluating video recordings of 47 EG Scan procedures.
RESULTS: 50 patients were recruited to the study (mean age 59 years /-11,
completed both procedures (3 failed EG Scan (6%) and 2 failed C-OGD (4%),
p 0.882). OV prevalence was 48.9%.
Sensitivity, specificity and area under the receiver operating characteristic curve
(AUROC) of the EG Scan for the diagnosis of any varices were 0.82 (95%
confidence interval (CI) 0.60-0.95), 0.78 (95%CI 0.56-0.93), and 0.80 (95%CI
0.68-0.92), respectively. Corresponding values for the diagnosis of medium/large
varices were 0.92 (95%CI 0.62-1.0), 0.97 (95%CI 0.84-1.0), and 0.94 (95%CI
0.86-1.0), respectively. Interobserver agreement was modest for the diagnosis
of any size OV (K 0.45, 95%CI 0.40-0.49) and medium/large OV (K 0.47,
95%CI 0.42-0.52).
Patients reported better experience (mean VAS/-standard deviation (SD)) and
higher preference (percentage) with EG Scan compared to C-OGD at day 0
(7.8/-2.2 vs. 6.8/-3.0, p 0.058; 76.5% vs. 23.5%, p50.001, respectively)
and day 14 (7.0/-2.3 vs. 5.5/-3.2, p 0.0013; 77.8% vs. 22.2%, p50.001,
respectively). There was no association between procedure preference and seda-
tion use for C-OGD (day 0: odds ratio (OR) 0.16, 95%CI 0.02-1.49, p 0.106;
day 14: OR 0.24, 95%CI 0.02-2.56, p 0.238). 4 patients (8.5%) experienced
minor self-limiting epistaxis. No serious adverse events occurred.
CONCLUSION: EG Scan was accurate for the diagnosis of any varices and
clinically significant OV. Interobserver agreement was modest. More impor-
tantly, patients experience and preference remained significantly higher for EG
Scan 14 days after procedures independent of sedation use.
Disclosure of Interest: S. Sami Financial support for research from: Intromedic
Ltd, Seoul, South Korea, E. Wilkes: None declared, M. James: None declared,
R. Mansilla-Vivar: None declared, J. Fernandez-Sordo: None declared, J.
White: None declared, A. Khanna: None declared, M. Coletta: None declared,
S. Samuel: None declared, G. Aithal: None declared, K. Ragunath Financial
support for research from: Intromedic Ltd, Seoul, South Korea and Olympus
Keymed UK., I. N. Guha: None declared
P0043 NONINVASIVE PREDICTIVE MODEL FOR DETECTION OF
HIGH-RISK ESOPHAGEAL VARICES IN B-VIRAL LIVER
CIRRHOSIS: THE PH RISK SCORE AND VARICES RISK SCORE
S.H. Shin1,*, B.K. Kim1
1
Department of Internal Medicine, Institue of Gastroenterology, Yonsei University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: earth-peace@yuhs.ac
INTRODUCTION: Periodic endoscopic screening for esophageal varices (EVs)
and prophylactic treatment for high-risk EVs ((HEVs); (1) medium/large EVs
and (2) small EVs with red sign or decompensated cirrhosis) are currently recom-
mended for all cirrhotic patients. Recently, two new liver stiffness measurement
(LSM)-based statistical equation models (PH risk score and Varices risk score)
were introduced as a noninvasive, simple, accurate models for identifying pre-
sence of EVs and clinically significant portal hypertension [1].
AIMS & METHODS: We aimed to validate predictive value of the two models for
detection of HEVs comparing with LSM alone or LSM-spleen diameter to platelet
ratio score (LSPS) [2]. We tried to suggest a cutoff of the two models, as well.
Between November 2004 and October 2011, we recruited 675 B-viral cirrhosis
patients. All underwent laboratory workups, endoscopy, LSM, and ultrasono-
graphy. LSM was measured by transient elastography; endoscopy was used as
the standard for detection of EVs. PH risk score, Varices risk score and LSPS
were calculated in all cases as follows: PH risk score -5.953 0.188 x LSM
1.583 x sex (1: male; 0: female) 26.705 x spleen diameter/platelet count ratio,
United European Gastroenterology Journal 2(5S)
Varices risk score -4.364 0.538 x spleen diameter 0.049 x platelet count of carvedilol versus non-specific betablockers (NSBB) on mortality on patients
0.044 x LSM 0.001 x (LSM x platelet count).
RESULTS: Among all the patients, 239 (35.4%) patients had EVs and 172
(25.5%) had HEVs. The area under the receiver-operating characteristic curve
(AUROC) of PH risk score was 0.951 (95% CI 0.934-0.968) and LSPS was 0.950
(95% CI 0.931-0.970), showing superiority of diagnostic accuracy over other
factors: Varices risk score (0.907, 95% CI 0.876-0.939, p50.001), LSM alone
(0.873, 95% CI 0.842-0.904, p50.001). At PH risk score 5 4.0, 94.6% negative
predictive value (NPV) was provided (481 patients), whereas 94.3% positive
predictive value (PPV) was achieved (70 patients) at PH risk score 4 10.0. In
the same way, at Varices risk score 5 -2.5, 95.6% NPV was provided (413
patients), whereas 91.7% PPV was achieved (72 patients) at Varices risk score
4 1.3. Overall, the likelihood of HEVs was correctly diagnosed in 551 patients
(81.6%) and 485 patients (71.9%), respectively.
CONCLUSION: The PH risk score is a reliable, noninvasive predictive model
for detection of HEVs. Furthermore, the LSPS is considered as more simply
applicable model having similar predictive value. Patients with PH risk score
5 4.0 may avoid endoscopy safely, whereas those with 4 10.0 should be con-
sidered for appropriate prophylactic treatments.
REFERENCES
1. Berzigotti A, Seijo S, Arena U, et al. Elastography, spleen size, and platelet
count identify portal hypertension in patients with compensated cirrhosis.
Gastroenterology 2013; 144: 102-111.e101.
2. Kim BK, Han KH, Park JY, et al. A liver stiffness measurement-based, non-
invasive prediction model for high-risk esophageal varices in B-viral liver cirrho-
sis. Am J Gastroenterol 2010; 105(6): 1382-1390.
Disclosure of Interest: None declared
P0044 PLALA SCORE PREDICT CIRRHOSIS PATIENT IN
NONALCOHOLIC FATTY LIVER DISEASE
T. Kessoku1,*, Y. Honda1, Y. Ogawa1, K. Imajo1, M. Yoneda1, A. Nakajima1 on
behalf of JSG-NAFLD
1
gastroenterology and hepatology, Yokohama city university, yokohama, Japan
Contact E-mail Address: takaomo-kesso@hotmail.co.jp
INTRODUCTION: Nonalcoholic fatty liver disease (NAFLD) is an important
cause of chronic and progressive liver injury in many countries1). NAFLD
includes a wide spectrum of liver diseases that range from simple steatosis,
which is generally a nonprogressive condition, to nonalcoholic steatohepatitis
(NASH), which can progress to liver cirrhosis and hepatocellular carcinoma
(HCC), despite the absence of significant alcohol consumption. If NAFLD
patients have liver cirrhosis, they need to be kept under surveillance for early
detection of hepatocellular carcinoma and gastroesophageal varices. Liver biopsy
is the gold standard for diagnosis and staging of fibrosis in patients with
NAFLD2). However, ad the number of NAFLD patients has reached 80100
million in the United States and about 10 million NAFLD patients are estimated
in Japan, it is virtually impossible to enforce in all patients.
AIMS & METHODS: To develop a mass screening system for general physi-
cians, which can be used for predicting liver cirrhosis in NAFLD patients, using
routine laboratory parameters.
A total of 1048 patients with liver-biopsy-confirmed NAFLD were enrolled from
nine hepatology centers in Japan (stage 0, 216; stage 1, 334; stage 2, 270; stage 3,
190; stage 4, 38). Statistical analysis was conducted using SPSS version 12.0.
Continuous variables were expressed as mean  SD.
RESULTS: Platelet counts, serum albumin levels, and aspartate aminotransfer-
ase/alanine aminotransferase (AST/ALT) ratio were selected as independent vari-
ables associated with cirrhosis in NAFLD patients by multiple logistic regression
analysis. The optimal cutoff value of platelet count, serum albumin, and AST/
ALT ratio was set at 515.3 104/l (sensitivity; 81.6% specificity; 88.6%), 54.0
g/dl (sensitivity; 84.2% specificity; 84.6%), and 40.9 (sensitivity; 78.9%, speci-
ficity; 82.0%), respectively, by the receiver operating characteristic curve. These
three variables were combined in an unweighted sum (platelet count 1 point,
serum albumin 1 point, AST/ALT ratio 1 point) to form an easily calculated
composite score for predicting cirrhosis in NAFLD patients, called the PLALA
(platelet, albumin, AST/ALT ratio) score. The diagnosis of PLALA 2 had
sufficient accuracy for detecting liver cirrhosis in NAFLD patients (86.8% sen-
sitivity, 90.8% specificity, 99.4% negative predictive value, 26.1% positive pre-
dictive value).
CONCLUSION: The PLALA score may be an ideal scoring system for detecting
cirrhosis in NAFLD patients with sufficient accuracy and simplicity to be con-
sidered for clinical use.
REFERENCES
1) Angulo P. Nonalcoholic fatty liver disease. N Engl J Med 2002; 346: 1221-
1231.
2) Angulo P, Keach JC, Batts KP, et al. Independent predictors of liver fibrosis in
patients with nonalcoholic steatohepatitis. Hepatology 1999; 30: 1356-1362.
Disclosure of Interest: None declared
P0045 CARVEDILOL VERSUS NON-SPECIFIC BETABLOCKERS AND
MORTALITY IN ALCOHOLIC CIRRHOSIS. A NATIONWIDE
RETROSPECTIVE STUDY
U.C. Bang1,*, T. Benfield2, L. Hyldstrup3, J.-E. B. Jensen3, F. Bendtsen1
1
Gastrounit, 2Infectious Diseases, 3Endocrinology, Hvidovre Hospital, Hvidovre,
Denmark
Contact E-mail Address: ulrichbangbang@gmail.com
INTRODUCTION: Carvedilol may have a greater effect on portal and systemic
hypertension than propranolol although reports are conflicting 1, 2. The impact
A143
with cirrhosis remains to be evaluated.
AIMS & METHODS: We wanted to compare the impact on mortality of carve-
dilol versus NSBB in patients with cirrhosis. We identified patients with alcoholic
cirrhosis from the Danish National Patient Register during the period 1995
through 2010. We used the anatomical therapeutic chemical (ATC) classification
to identify the user of NSBB (C07AA) or carvedilol (C07AG02). We defined risk
time as the time from the first prescription of either carvedilol or NSBB until
death or end of follow-up (December 31, 2010). We adjusted for gender, age,
heart disease, variceal bleeding, socioeconomic status, Charlson score, and use of
diuretics. We used univariate and multivariate Cox proportional hazard models
to assess the HR. Persons with missing data were excluded from the analyses
(0.03%). All analyses were done using SAS 9.3 (SAS Institute Inc., Cary, NC,
USA).
RESULTS: We identified 83 and 2.060 patients, who were treated with carvedilol
and NSBB, respectively. Three patients had received both carvedilol and NSBB
and were excluded. Patients from the carvedilol group were mainly classified with
uncomplicated cirrhosis without a history of laparocentesis (96%). Hence, we
only included patients with uncomplicated cirrhosis in our mortality analysis (80
versus 1.857 patients). Significantly fewer patients in the carvedilol group died
during follow-up compared with the NSBB group (20.5% vs. 46.5%, Chi-square
p50.0001). We found the un-adjusted HR for carvedilol vs. NSBB to be 0.45
(95% CI 0.3-0.7) and the HR adjusted for covariates was 0.46 (95% CI 0.3-0.7).
The prevalences of variceal bleeding (11% vs. 40%) or heart disease (70% vs.
14%) prior to cohort entry were un-evenly distributed between users of carvedilol
and NSBB. We did a sub-analysis where we matched patients on the presence of
heart disease and variceal prior to cohort entry. In this sub-analysis we compared
80 patients using carvedilol with 240 patients (1:3 ratio) using NSBB and found
an adjusted HR of 0.38 (95% CI 0.2-0.7).
CONCLUSION: The use of carvedilol compared with NSBB in patients with
cirrhosis was associated with lower mortality in this retrospective study.
REFERENCES
1. Hobolth L, Bendtsen F, Hansen EF, et al. Effects of carvedilol and propra-
nolol on circulatory regulation and oxygenation in cirrhosis: a randomised study.
Dig Liver Dis 2014; 46: 251-256.
2. Banares R, Moitinho E, Matilla A, et al. Randomized comparison of long-
term carvedilol and propranolol administration in the treatment of portal hyper-
tension in cirrhosis. Hepatology 2002; 36: 1367-1373.
Disclosure of Interest: None declared
P0046 RESULTS OF THE UK MULTI-REGIONAL AUDIT OF BLOOD
COMPONENT USE IN CIRRHOSIS
V. Jairath1,*, M. Desborough2, B. Hockley2, M. Sekhar3, S. Stanworth2,
A. Burroughs3
1
Nuffield Department of Medicine, University of Oxford, 2NHS Blood and
Transplant, Oxford, 3Royal Free Hospital, London, United Kingdom
INTRODUCTION: Cirrhosis is a complex acquired disorder of coagulation with
a recent paradigm shift in understanding to consider cirrhosis as a pro-thrombo-
tic disorder. It is a frequent indication for transfusion of blood components, both
for prophylaxis and for treatment of bleeding, although indications and patterns
of blood use are poorly characterised.
AIMS & METHODS: All NHS trusts with representation on the British Society
of Gastroenterology membership list were invited to take part in a national audit.
Data were collected prospectively on consecutive admissions with a confirmed
diagnosis of liver cirrhosis over a 4 week period, with follow up to discharge/
death/day 28. Specific information was requested on use of blood components,
including indication, type of component and laboratory indices prior to transfu-
sion. Standards were defined against guidelines on the use of red blood cells
(RBCs), fresh frozen plasma (FFP), platelets and cryoprecipitate.
RESULTS: Data on 1313 consecutive patients with cirrhosis (mean age 58 years,
65% male) were collected from 85 hospitals. The predominant aetiology was
alcohol (70%; 921/1313); 74% of admissions were for features of decompensa-
tion; and 21% (275/1313) cases had a positive septic screen. 30% (391/1313) of all
admissions were transfused a blood component; in 61% (238/391) this was for
treatment of bleeding and in 39% (153/391) for prophylaxis. In patients trans-
fused for bleeding (81%, 192/238 for gastrointestinal bleeding), 92% (220/238)
received RBCs, 32% (77/238) FFP, 14% (34/238) platelets and 4% (10/238)
cryoprecipitate; in patients with bleeding who received RBCs, the Hb threshold
was 48g/dL prior to RBC transfusion in 31% (69/220) cases. For prophylaxis
the majority (61%, 94/153) received transfusion in the absence of a planned
procedure. In patients transfused for prophylaxis prior to a procedure (59/
153): 19% (3/16) received FFP at an INR 1.5 for high risk procedures and
33% (6/18) received FFP at an INR2 for low risk procedures; 36% (9/25)
received platelet transfusion at a platelet count450 prior to a procedure. The
most frequent procedures resulting in prophylactic transfusion were paracentesis
(18/59), surgery (15/59) and endoscopy (10/59). In-hospital venous thromboem-
bolism was documented in 2% (29/1313) cases. Case fatality during follow up
was 10% overall (128/1313) with decompensated cirrhosis (41%; 52/128) as the
most frequent cause of death.
CONCLUSION: Patients with cirrhosis are frequently transfused during hospi-
talisation. This audit highlights areas where greater scrutiny of blood component
use is required, particularly in the group transfused for prophylaxis of bleeding.
Further work is needed to improve patterns of blood use in cirrhosis to ensure
patients are not exposed to unnecessary transfusion and its attendant harms.
Disclosure of Interest: None declared
A144
P0047 SVR12 OF 99% ACHIEVED WITH A RIBAVIRIN-FREE REGIMEN
OF ABT-450/R/OMBITASVIR AND DASABUVIR IN HCV GENOTYPE
1B-INFECTED PATIENTS
A. Maieron1,*, M. Puoti2, J. V. Enejosa3, P. Andreone4, Z. Ben Ari5,
G. Norkrans6, M. Romero-Gomez7, W. Xie3, D.E. Cohen3, T. Podsadecki3
1
Elisabeth Hospital, Linz, Austria, 2A. O. Ospedale Niguarda Ca Granda, Milan,
Italy, 3AbbVie Inc., North Chicago, United States, 4University of Bologna,
Bologna, Italy, 5The Chaim Sheba Medical Center, Tel Hashomer, Israel,
6
Sahlgrenska University Hospital, Goteborg, Sweden, 7Hospital Universitario
Nuestra Senora De Valme, Seville, Spain
INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor (identified
by AbbVie and Enanta) dosed with ritonavir (r). Ombitasvir (formerly ABT-267)
is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is a non-nucleoside
NS5B RNA polymerase inhibitor. We report the sustained virologic response
12 weeks post-treatment (SVR12) achieved in HCV genotype 1b-infected patients
after treatment with these 3 direct-acting antivirals (3D regimen) with or without
ribavirin (RBV).
AIMS & METHODS: Five hundred ninety-nine treatment-na ve and prior
pegIFN/RBV-experienced HCV genotype 1b-infected patients without cirrhosis
were enrolled and received study drugs in the PEARL-II and PEARL-III rando-
mized phase 3 studies. Patients were randomized 1:1 to co-formulated ABT-450/
r/ombitasvir (150 mg/100 mg/25 mg once daily) and dasabuvir (250 mg twice
daily) with or without weight-based RBV (1000 1200 mg daily).
RESULTS: The combined SVR12 rate from PEARL-II and PEARL-III was
99.3% in 301 patients who received 3D regimen without RBV vs. 98.7% in 298
patients who received 3D RBV. Two patients (0.7%) receiving 3D without RBV
did not achieve SVR12, both due to missing week 12 post-treatment follow-up.
Four 3D RBV patients did not achieve SVR12: 1 (0.3%) due to virologic break-
through, 1 (0.3%) due to missing SVR12 data, and 2 (0.7%) due to study drug
discontinuation for adverse events. SVR12 rates did not differ between 3D and 3D
RBV by baseline factors including IL28B genotype, sex, age, race, ethnicity,
BMI, fibrosis stage, and HCV RNA viral load. No patients receiving 3D and 0.7%
of patients receiving 3D RBV discontinued due to adverse events.
SVR12 by baseline factors, n/N (%) 3D 3D RBV
Overall 299/301 (99.3) 294/298 (98.7)
Treatment-na ve 208/210 (99.0) 209/210 (99.5)
PegIFN/RBV Treatment-experienced 91/91 (100) 85/88 (96.6)
IL28B non-CC genotype 249/250 (99.6) 240/244 (98.4)
Female 160/160 (100) 147/149 (98.7)
Age 65 34/34 (100) 29/29 (100)
Black race 16/16 (100) 13/13 (100)
BMI  30 kg/m2 62/64 (96.9) 44/45 (97.8)
Fibrosis stage, F3 31/33 (93.9) 33/34 (97.1)
CONCLUSION: Irrespective of previous pegIFN/RBV treatment response and
other baseline factors, HCV genotype 1b-infected patients achieved high SVR
rates after 12 weeks of 3D without RBV. Overall, only 1 (3D RBV) of 599
(0.2%) patients experienced virologic breakthrough and none experienced
relapse. Both regimens were well tolerated. ABT-450/r/ombitasvir and dasabuvir
without RBV achieves optimal treatment efficacy in HCV genotype 1b-infected
patients without cirrhosis.
Disclosure of Interest: A. Maieron Financial support for research from: Roche,
MSD, Consultancy for: MSD, Janssen Therapeutics, AbbVie, Boehringer
Ingelheim, Gilead Sciences, BMS, Rottapharm-Madaus, M. Puoti: None
declared, J. Enejosa Shareholder of: AbbVie, Other: AbbVie, P. Andreone
Financial support for research from: Roche, Merck, Gilead, Consultancy for:
Roche, Merck, Janssen Cilag, AbbVie, Boehringer Ingelheim, Gilead, MSD,
BMS, Z. Ben Ari Consultancy for: MSD, Janssen, AbbVie, Boehringer
Ingelheim, BMS, GSK, G. Norkrans: None declared, M. Romero-Gomez
Lecture fee(s) from: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz,
BMS, Boehringer Ingelheim, GSK, Consultancy for: AbbVie, Roche, Gilead
Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK, W. Xie
Shareholder of: AbbVie, Other: AbbVie, D. Cohen Shareholder of: AbbVie,
Other: AbbVie, T. Podsadecki Shareholder of: AbbVie, Other: AbbVie
P0048 ADHERENCE TO PRESCRIBED DOSES OF ABT-450/R/
OMBITASVIR, DASABUVIR, AND RIBAVIRIN IN THE PHASE 3
PEARL-II, PEARL-III, AND PEARL-IV TRIALS
D. Bernstein1, R. Marinho2,*, D. Cohen3, F. Bredeek4, F. Schneider5,
G. Norkrans6, M. Curescu7, M. Bennett8, M. Maevskaya9, J. Fessel10, W. Xie3,
Y. Luo3, J. Enejosa3
1
Hofstra North Shore- LIJ School of Medicine, Manhasset, United States, 2Centro
Hospitalar Lisboa Norte, Medical School of Lisbon, Lisbon, Portugal, 3AbbVie
Inc., North Chicago, 4Metropolis Medical Group, San Francisco, United States,
5
Markusovszky Hospital, Szombathely, Hungary, 6Sahlgrenska University
Hospital, Goteborg, Sweden, 7Life Search SRL, Timisoara, Romania, 8Medical
Associates Research Group, San Diego, United States, 9First Moscow State
Medical Universita n.a. I. M. Sechenov, Moscow, Russian Federation, 10Kaiser
Permanente, San Francisco, United States
INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor identified by
AbbVie and Enanta, dosed with ritonavir(r); ombitasvir(ABT-267) is an NS5A
United European Gastroenterology Journal 2(5S)
inhibitor; dasabuvir(ABT-333) is an NS5B RNA polymerase inhibitor. The
phase 3 PEARL trials examined the efficacy and safety of all-oral, interferon-
free, 12-week regimens of ABT-450/r/ombitasvirdasabuvir(3D) with or without
ribavirin(RBV) in HCV genotype(GT) 1a- and 1b-infected patients(pts). We
report pt adherence to the regimens in these trials.
AIMS & METHODS: Pts were randomized to co-formulated ABT-450/r/ombi-
tasvir(150mg/100mg/25mg QD)dasabuvir(250mg BID) with either weight-
based RBV or placebo (PBO)/no RBV. Adherence was calculated by pill
counts as the percentage of capsules/tablets taken relative to the total capsules/
tablets expected to be taken.
RESULTS: In each trial, mean pt adherence to every study drug was
498.5%(Table). Adherence was comparable in those who received 3D with
RBV, 3D with PBO, or 3D alone. SVR12 rates were 96.6-100% in treatment-
experienced and treatment-na ve HCV GT1b-infected pts receiving 3D/-RBV.
SVR12 rates were 97.0% and 90.2%, respectively, in treatment-na ve GT1a-
infected pts receiving 3DRBV or 3DPBO. Only 1 GT1b-infected pt had
virologic failure. Pts with virologic failure had adherence rates comparable to
the overall rates, but the majority was GT1a-infected and did not receive RBV.
Five pts had adherence rates580% for one or more study drugs, none of whom
had virologic failure. Among 401 pts receiving 3D with RBV and 509 pts receiv-
ing 3D without RBV, 2(0.5%) and 2(0.4%), respectively, discontinued study drug
due to adverse events.
PEARL-II PEARL-III PEARL-IV
Treatment-experienced* Treatment-na ve Treatment-na ve
GT1b GT1b GT1a
3DRBV 3D 3DRBV 3DPBO 3DRBV 3DPBO
Adherence, Mean % (SD)
ABT-450/r/ ombitasvir 99.7 (2.3) 100.0 (2.6) 99.8 (1.2) 100.0 (1.1) 99.7 (1.9) 99.7 (3.3)
n 87 n 92 n 205 n 205 n 98 n 190
dasabuvir 99.0(3.2) 99.2 (1.6) 99.8 (1.2) 99.9 (1.1) 99.2 (2.0) 99.1 (3.6)
n 90 n 94 n 205 n 205 n 98 n 190
RBV 99.1 (6.5) NA 99.6 (2.1) 99.6 (2.6) 98.6 (3.2) 98.7 (3.6)
n 87 n 205 n 203 n 90 n 181
SVR12, % (n/N) 96.6 100 99.5 99.0 97.0 90.2
(85/88) (91/91) (209/210) (207/209) (97/100) (185/205)
Adherence data for each capsule/tablet not available for all pts.
In PEARL-II, 7 randomized patients were excluded from the intent-to-treat
efficacy population because they received non-coformulated ABT-450/r/ombitas-
vir (N 6) or could not be genotyped (N 1).
CONCLUSION: Participants in these phase 3 trials had excellent adherence
(498.5%) to doses of ABT-450/r/ombitasvir, dasabuvir, and RBV. Low adher-
ence rates, while infrequent, were not associated with virologic failure.
Disclosure of Interest: D. Bernstein Financial support for research from: AbbVie,
BMS, Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie,
Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen,
Vertex, Merck, R. Marinho Lecture fee(s) from: AbbVie, Gilead, BMS, Roche,
Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche, Merck, Janssen,
D. Cohen Shareholder of: AbbVie, Other: AbbVie, F. Bredeek Financial support
for research from: AbbVie, BMS, Gilead, Janssen, Merck, Sumagen, ViiV,
Lecture fee(s) from: Merck, ViiV, Consultancy for: Merck, ViiV, F. Schneider:
None declared, G. Norkrans: None declared, M. Curescu: None declared, M.
Bennett Shareholder of: AbbVie, M. Maevskaya: None declared, J. Fessel: None
declared, W. Xie Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder
of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie, Other: AbbVie
P0049 ASSOCIATION BETWEEN TLR-3 GENE POLYMORPHISM
RS3775291 AND PROGRESSION OF HEPATITIS C VIRUS
INFECTION
F.-Z. Fakhir1,2,*, M. LKHIDER1
1
Faculte des Sciences, Chouaib Doukkali University, El Jadida, 2Viral Hepatitis
Laboratory, Institut Pasteur du Maroc, Casablanca, Morocco
Contact E-mail Address: fatimazohra.fakhir@gmail.com
INTRODUCTION: Hepatitis C virus (HCV) is a major global health problem
with about 210 million people infected worldwide, and constitutes the most
important cause of chronic liver disease. HCV is an enveloped positive-strand
RNA virus belonging to the genus Hepacivirus of the family Flaviviridae. During
the viral replication cycle, double-stranded RNA (dsRNA), produced as an inter-
mediate, is sensed by several pattern recognition receptors (PRRs) of the innate
immune system including Toll-like receptors (TLR). TLRs constitute a family of
receptors playing a key role in innate and adaptive immune response, among
them TLR3,-7 and -8, which are expressed on endosomal membrane, and have
been suggested to play an important role in antiviral immune responses based on
their recognition of dsRNA and single-stranded RNA (ssRNA). Single nucleo-
tide polymorphisms (SNPs) may shift balance between pro- and anti-inflamma-
tory cytokines, contributing to successful resistance to infection or leading to
chronic inflammation and cancer. The aim of this study was to investigate the
association between the TLR-3, -7 and -8 polymorphism and the outcome of
HCV infection.
AIMS & METHODS: 517 patients were enrolled in the study and genotyped for
the TLR3, -7 and -8 SNPs. Logistic regression was used to assess the association
between the polymorphisms and the outcome of the infection.
RESULTS: A significant association between TLR-3 SNP at rs3775291 and risk
of advanced liver disease was identified. The rs3775291-A/A genotype was more
common in subjects with advanced liver disease than subjects with mild chronic
United European Gastroenterology Journal 2(5S)
hepatitis C (OR 3.81; 95% CI, 2.16-6.72; p 0.000004) and this difference was
higher with healthy controls (OR 5.34; 95% CI, 2.70-10.58; p 0.000002).
CONCLUSION: Our findings indicate that a TLR-3 SNP rs3775291 is asso-
ciated with progression of HCV infection to cirrhosis and hepatocellular
carcinoma.
Disclosure of Interest: None declared
P0050 LOW INCIDENCE OF HYPERBILIRUBINAEMIA EVENTS WITH
ABT-450/R/OMBITASVIR AND DASABUVIR WITH OR WITHOUT
RIBAVIRIN IN HCV GENOTYPE-1 INFECTED PATIENTS
M. Romero-Gomez1,*, R.T. Marinho2, R. Planas Vila3, D. Bernstein4,
F. Rodriguez-Perez5, T. Hassanein6, K.R. Reddy7, N. Tsai8, S. Lovell9, J.
V. Enejosa9, Y. Luo9, D.E. Cohen9, M. Pedrosa9, M.G. Colombo10
1
Hospital Universitario Nuestra Senora De Valme, Seville, Spain, 2Centro
Hospitalar Lisboa Norte, Medical School of Lisbon, Lisboa, Portugal, 3Hospital
Germans TrasiPujol, CIBERehd, Badalona, Spain, 4Hofstra North Shore-LIJ
School of Medicine, Manhasset, United States, 5Gastroenterology and Hepatic
Wellness Center, Santruce, Puerto Rico, 6Southern California Liver Centers and
Southern California Research Center, Coronado, 7University of Pennsylvania,
Philadelphia, 8The Queens Medical Center Liver Center, Honolulu, 9AbbVie
Inc., North Chicago, United States, 10University of Milan, Milan, Italy
INTRODUCTION: Ribavirin (RBV) is known to cause haemolytic anaemia that
can lead to hyperbilirubinaemia. In addition, the NS3/NS4A protease inhibitor
ABT-450 can increase unconjugated bilirubin levels due to transporter inhibition.
We report the rate of hyperbilirubinaemia in HCV genotype 1-infected patients
treated with ABT-450/r/ombitasvir (formerly ABT-267) and dasabuvir (formerly
ABT-333) (3D regimen) with or without RBV.
AIMS & METHODS: Data from 910 patients randomized in 3 phase 3 trials
(PEARL-II, PEARL-III, and PEARL-IV), which examined the contribution of
RBV to the safety and efficacy of the 3D regimen, were used to evaluate the
incidence and severity of clinical events related to bilirubin (hyperbilirubinaemia,
jaundice) during 12 weeks of treatment. Total, direct, and indirect bilirubin were
assessed at baseline and every 1-2 weeks per protocol.
RESULTS: Total bilirubin elevations of 43X ULN occurred in 23/401 (5.7%)
3DRBV patients and in 2/509 (0.4%) patients receiving the RBV-free 3D regi-
men. The majority of patients in each group (490%) had normal total bilirubin
levels at the end of treatment. Mean total bilirubin levels were significantly higher
at each treatment visit in the RBV-containing treatment groups. Mean total
bilirubin peaked at week 1 in both treatment groups (predominantly indirect),
and declined to baseline by week 2 in the RBV-free group. Events of hyperbilir-
ubinaemia and jaundice were mostly mild, occurred within the first 2 weeks of
treatment and did not result in study drug discontinuation. One patient under-
went RBV dose modification and one interrupted study drug due to hyperbilir-
ubinaemia; both patients achieved sustained virologic response 12 weeks post-
treatment. Two patients receiving 3DRBV experienced ALT 3X ULN and
total bilirubin 2X ULN, however, the timing and predominance of indirect
bilirubin were not consistent with drug induced liver injury. No serious adverse
events related to hyperbilirubinaemia were reported.
Bilirubin-related events, n (%) 3DRBV (N 401) 3D (N 509)
Any bilirubin-related event 21 (5.2) 4 (0.8)
Hyperbilirubinaemia 13 (3.2) 3 (0.6)
Jaundice 11 (2.7) 1 (0.2)
Total bilirubin 43X ULN 23 (5.7) 2 (0.4)
CONCLUSION: Low rates of hyperbilirubinaemia were observed with both 3D
regiments but was less frequent in the RBV-free 3D regimens, suggesting that
increases in bilirubin associated with ABT-450-containing regimens are enhanced
by RBV-induced haemolysis. Bilrubin-related adverse events were infrequent
with both regimens and did not affect treatment response.
Disclosure of Interest: M. Romero-Gomez Lecture fee(s) from: AbbVie, Roche,
Gilead Sciences, MSD, Janssen, Merz, BMS, Boehringer Ingelheim, GSK,
Consultancy for: AbbVie, Roche, Gilead Sciences, MSD, Janssen, Merz, BMS,
Boehringer Ingelheim, GSK, R. T. Marinho Lecture fee(s) from: AbbVie, Gilead,
BMS, Roche, Merck, Janssen, Consultancy for: AbbVie, Gilead, BMS, Roche,
Merck, Janssen, R. Planas Vila Financial support for research from: Roche,
MSD, BMS, Gilead, Janssen, Lecture fee(s) from: Roche, MSD, BMS, Gilead,
Janssen, Boehringer Ingelheim, Consultancy for: Roche, MSD, BMS, Gilead,
Janssen, D. Bernstein Financial support for research from: AbbVie, BMS,
Gilead, Janssen, Vertex, Merck, Genentech, Lecture fee(s) from: AbbVie,
Gilead, Janssen, Vertex, Merck, Consultancy for: AbbVie, Gilead, Janssen,
Vertex, Merck, F. Rodriguez-Perez Lecture fee(s) from: BMS, Merck,
Consultancy for: AbbVie, Gilead, Janssen, Merck, T. Hassanein Financial sup-
port for research from: AbbVie, Boehringer-Ingelheim, BMS, Eisai, Gilead,
Janssen, Idenix, Ikaria, Mochida, Takeda, Mochida, Roche, Ocera, Sundise,
Salix, Taigen, Takeda, Vertex, Lecture fee(s) from: BMS, Genentech, Gilead,
Salix, Consultancy for: AbbVie, BMS, K. R. Reddy Financial support for
research from: AbbVie, BMS, Gilead, Vertex, Janssen, Merck, Genentech-
Roche, Genfit, Consultancy for: AbbVie, BMS, Gilead, Vertex, Janssen,
Merck, Genentech-Roche, Idenix, N. Tsai Financial support for research from:
AbbVie, Janssen, Genentech-Roche, Vertex, BMS, Lecture fee(s) from: Gilead,
Genentech-Roche, BMS, Vertex, Merck, Janssen, Consultancy for: AbbVie,
Gilead, Janssen, S. Lovell Shareholder of: AbbVie, Other: AbbVie, J. Enejosa
Shareholder of: AbbVie, Other: AbbVie, Y. Luo Shareholder of: AbbVie, Other:
AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, M. Pedrosa
A145
Shareholder of: AbbVie, Other: AbbVie, M. Colombo Financial support for
research from: Merck, Roche, BMS, Gilead, Lecture fee(s) from: Tibotec,
Roche, Novartis, Bayer, BMS, Gilead Sciences, Vertex, Consultancy for:
AbbVie, Merck, Roche, Novartis, Bayer, BMS, Gilead Sciences, Tibotec,
Vertex, Janssen Cilag, Achillion, Lundbeck, Abbott, Boehringer Ingelheim,
GSK, GenSpera
P0051 SUSTAINED VIROLOGIC RESPONSE 12 WEEKS
POST-TREATMENT WITH ABT-450/RITONAVIR/OMBITASVIR AND
DASABUVIR WITH RIBAVIRIN (SAPPHIRE I AND II) IS
INDEPENDENT OF PATIENT SUBGROUPS
M.R. Brunetto1,*, M. Makara2, H. Hinrichsen3, J. Hanson4, M. Bennett5,
E. Lawitz6, J. Xiong7, E. Coakley7, T. Baykal7, G. Neff7
1
Liver Unit, University Hospital of Pisa, Pisa, Italy, 2Saint Laszlo Hospital,
Budapest, Hungary, 3Gastroenterologisch-Hepatologisches Zentrum, Kiel,
Germany, 4Charlotte Gastroenterology & Hepatology, PLLC, Charlotte, 5San
Diego Digestive Diseases, San Diego, 6Texas Liver Institute, University of Texas
Health Science Center, San Antonio, 7AbbVie, North Chicago, United States
Contact E-mail Address: brunetto@med-club.com, laurinda.cooker@abbvie.com
INTRODUCTION: ABT-450 is a potent hepatitis C virus (HCV) protease inhi-
bitor (dosed with ritonavir 100mg, ABT-450/r) identified by AbbVie and Enanta;
ombitasvir (ABT-267) is an NS5A inhibitor and dasabuvir (ABT-333) is a non-
nucleoside polymerase inhibitor. In phase 3 trials of this 3 direct-acting antiviral
(3D) regimen with ribavirin (RBV) in non-cirrhotic HCV genotype 1-infected
patients, 96.3% of treatment-na ve patients (SAPPHIRE-I trial) and 96.2% of
pegINF/RBV-experienced patients (SAPPHIRE-II trial) achieved SVR12 (HCV
RNA 525 IU/mL at post-treatment week 12).
AIMS & METHODS: Patients in the SAPPHIRE-I and -II trials were rando-
mized to receive the 3D regimen of co-formulated ABT-450/r/ombitasvir
(150mg/100mg/25mg QD) and dasabuvir (250mg BID) with weight-based RBV
(1000 or 1200 mg daily divided BID), or placebo, for 12 weeks. Data from the
two trials were pooled, and SVR12 rates were calculated overall and according to
race, ethnicity, and region.
RESULTS: 770 patients assigned to the 3DRBV regimen received 1 dose of
study drug. The overall SVR12 rate in the combined studies was 96.2%; high
SVR rates were achieved regardless of race, ethnicity, or region (Table).
Tolerability was similar across populations. Most adverse events were mild or
moderate; the 3 most common adverse events were headache (34.3%), fatigue
(34.2%) and nausea (22.3%). Few patients discontinued due to adverse events (6/
770, 0.8%).
3DRBV
% with SVR12 (n/N)
Overall SAPPHIRE-I and SAPPHIRE-II 96.2 (741/770)
Race Black 96.0 (48/50)
Non-black 96.3 (693/720)
Ethnicity Hispanic/Latino 93.9 (46/49)
Non-Hispanic/Latino 96.4 (695/721)
Region Australia/New Zealand 95.5 (42/44)
Europe 95.8 (346/361)
North America 96.7 (353/365)
CONCLUSION: High pooled SVR12 rates were achieved in non-cirrhotic HCV
GT1 treatment-na ve and pegINF/RBV-experienced patients in the SAPPHIRE-
I and SAPPHIRE-II trials, regardless of the baseline demographics assessed in
this analysis.
Disclosure of Interest: M. Brunetto Lecture fee(s) from: AbbVie, BMS, Gilead,
Janssen, MSD, Roche, Novartis, M. Makara: None declared, H. Hinrichsen
Lecture fee(s) from: AbbVie, Gilead, Janssen, BMS, MSD, Roche, J. Hanson:
None declared, M. Bennett Shareholder of: AbbVIe, E. Lawitz Financial support
for research from: AbbVie, Achillion Pharmaceuticals, Anadys Pharmaceuticals,
Biolex Therapeutics, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead
Sciences, GlaxoSmithKline, GlobeImmune, Idenix Pharmaceuticals, Idera
Pharmaceuticals, Inhibitex Pharmaceuticals, Intercept Pharmaceuticals,
Janssen, Medarex, Medtronic, Merck & Co., Novartis, Pharmasset, Presidio,
Roche, Schering-Plough, Santaris Pharmaceuticals, Scynexis Pharmaceuticals,
Vertex Pharmaceuticals, ViroChem Pharma, ZymoGenetics, Lecture fee(s)
from: Gilead, Kadmon, Merck, Vertex, Consultancy for: AbbVie, Achillion
Pharmaceuticals, Anadys Pharmaceuticals, Biolex Therapeutics, BioCryst,
Biotica; Enanta; GlobeImmune, Idenix Pharmaceuticals, Inhibitex
Pharmaceuticals, Janssen, Merck & Co., Novartis, Pharmasset, Santaris
Pharmaceuticals, Tibotec, Theravance, Vertex Pharmaceuticals, J. Xiong
Shareholder of: AbbVIe, Other: AbbVie, E. Coakley Shareholder of: AbbVIe,
Other: AbbVIe, T. Baykal Shareholder of: AbbVIe, Other: AbbVIe, G. Neff
Shareholder of: AbbVIe, Other: AbbVIe
A146
P0052 SAFETY OF ABT-450/R/OMBITASVIR DASABUVIR WITH OR
WITHOUT RIBAVIRIN IN HCV GENOTYPE 1-INFECTED PATIENTS:
RESULTS FROM PEARL II, PEARL III, AND PEARL IV
R. Aspinall1,*, J. Lalezari2, Y. Luo3, R. Pruitt4, V. Luketic5, G. Gaeta6,
I. Olszok7, W. King8, S. Gurel9, Y. Hu3, J. Enejosa3, D. Cohen3, N. Shulman3
1
Queen Alexandra Hospital, Portsmouth, United Kingdom, 2Quest Clinical
Research, San Francisco, 3AbbVie Inc., North Chicago, 4Nashville Gastrointestinal
Specialists, Inc./Nashville Medical Research Institute, Nashville, 5Virginia
Commonwealth University, Richmond, United States, 6A. O. U. Seconda
Universita` degli Studi di Napoli, Naples, Italy, 7Szpital Rejonowy, Oddzial
Obeserwacyjno-Zakazny, Raciborz, Poland, 8Trial Management Associates; LLC,
Wilmington, United States, 9Uludag University, Bursa, Turkey
INTRODUCTION: ABT-450 is an HCV NS3/4A protease inhibitor dosed with
ritonavir (r) 100mg, identified by AbbVie and Enanta. Ombitasvir (formerly
ABT-267) is an NS5A inhibitor, and dasabuvir (formerly ABT-333) is an
NS5B RNA polymerase inhibitor. The phase 3 trials PEARL II, PEARL III,
and PEARL IV examined the efficacy and safety of 12 week regimens of ABT-
450/r/ombitasvir dasabuvir (3D) with or without ribavirin (RBV) in non-cir-
rhotic patients with HCV genotype (GT) 1a and 1b infection. Safety outcomes in
patients receiving RBV-containing and RBV-free regimens in these trials are
reported.
AIMS & METHODS: GT1b-infected treatment-experienced patients (PEARL
II), GT1b-infected treatment-naive patients (PEARL III), and GT1a-infected
treatment-naive patients (PEARL IV) were randomized to co-formulated ABT-
450/r/ombitasvir (150mg/100mg/25mg QD) dasabuvir (250mg BID) with
weight-based RBV or placebo/no RBV. Adverse event (AE) assessment and
clinical laboratory testing occurred at study visits during treatment and follow-
up and included all randomized patients who received at least one dose of study
drug.
RESULTS: In PEARL II, PEARL III, and PEARL IV, respectively, 186, 419,
and 305 patients were randomized and received at least one dose of study drug.
In total across the 3 trials, 401 patients received 3DRBVand 509 received 3D.
Treatment-emergent AEs and laboratory values of note are in the Table. In both
the 3DRBV and 3D groups, the majority of AEs were mild. AEs occurring in
420% of patients in both the 3DRBV and 3D groups were fatigue (29.9% and
26.5%) and headache (24.4% and 25.3%). 8.5% of patients receiving 3DRBV
had an AE leading to RBV dose modification; all of these patients achieved
SVR12. The rate of discontinuation due to AEs was 0.5% or less among patients
treated with 3DRBV or 3D.
3DRBV 3D
N 401 N 509
Any AE, n (%) 332 (82.8) 383 (75.2)
Any AE leading to study drug discon- 2 (0.5) 2 (0.4)
tinuation, n (%)
Any serious AE, n (%) 9 (2.2) 7 (1.4)
Any AE leading to RBV/placebo dose 34 (8.5) 1* (0.2)
modification, n (%)
RBV/placebo dose modification due to 25 (6.2) 0 additional marker to predict the rapid progression to liver failure in patients with
decrease in hemoglobin, n (%)
Hemoglobin (g/dL), n (%) 209 (52.1)/ 34 (6.7)/0/0
23 (5.7)/2 (0.5)
Total bilirubin 43X ULN, n (%) 23 (5.7) 2 (0.4)
ALT 45X ULN, n (%) 3 (0.7) 1 (0.2)
CONCLUSION: In the PEARL II, PEARL III, and PEARL IV trials, ABT-450/
r/ombitasvir dasabuvir was well tolerated either with or without RBV.
Comparable low rates of discontinuation were observed in patients receiving
the RBV-containing and RBV-free regimens. Clinically significant hemoglobin
reductions and bilirubin elevations were infrequent and not treatment-limiting.
Disclosure of Interest: R. Aspinall: None declared, J. Lalezari: None declared, Y.
Luo Shareholder of: AbbVie, Other: AbbVie, R. Pruitt: None declared, V.
Luketic: None declared, G. Gaeta Consultancy for: Merck, Roche, BMS,
Gilead, BI, AbbVie, I. Olszok: None declared, W. King: None declared, S.
Gurel Lecture fee(s) from: Roche, MSD, BMS, Johnson and Johnson,
Consultancy for: Roche, MSD, BMS, Johnson and Johnson, Y. Hu
Shareholder of: AbbVie, Other: AbbVie, J. Enejosa Shareholder of: AbbVie,
Other: AbbVie, D. Cohen Shareholder of: AbbVie, Other: AbbVie, N.
Shulman Shareholder of: AbbVie, Other: AbbVie
P0053 ALBENDAZOLE CAN ENHANCE THE RESOLUTION OF
EOSINOPHILIC LIVER ABSCESS ASSOCIATED WITH
TOXOCARIASIS
E.-Y. Jang1,*, M.S. Choi1, W. Sohn1, G.-Y. Gwak1, K.C. Koh1, S.W. Paik1, Y.-
H. Paik1, B.C. Yoo1
1
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea, Republic Of
Contact E-mail Address: hand1@dreamwiz.com
INTRODUCTION: Visceral larva migrans, which is caused by Toxocara canis
and Toxocara cati, has emerged as a significant cause of eosinophilic liver abscess
(ELA). It is sometimes difficult to differentiate ELA associated with toxocariasis
(ELA-T) from metastasis or primary liver malignancy. However, the role of
United European Gastroenterology Journal 2(5S)
albendazole treatment remains uncertain in this condition. We aimed to evaluate
whether albendazole can enhance the radiologic resolution of ELA-T.
AIMS & METHODS: We retrospectively reviewed the medical records of the
patients diagnosed with ELA-T at our institution between January 2008 and
December 2011. ELA-T was diagnosed based on the imaging findings on com-
puted tomography or magnetic resonance imaging and the presence of positive
serum IgG antibody for Toxocara canis. Among a total of 163 patients, 32
patients received albendazole (albendazole group) and 131 did not (control
group). Baseline characteristics and fate of liver nodules were compared between
the two groups.
RESULTS: Baseline characteristics (age, sex, number and maximal size of
lesions, eosinophil count) were similar between the two groups. Median duration
for achieving radiologic resolution in the albendazole group was significantly
shorter than in control group (207 days [range 186-228] vs. 302 days [range
224-380], p 0.023). Cox regression analysis of the cumulative rates of radiologic
resolution showed that hazard ratio for albendazole treatment was 1.99 (95%
confidence interval: 1.22-3.23).
CONCLUSION: Radiologic resolution of ELA-T can be accelerated with alben-
dazole treatment. Hence, inconvenience associated with long-term follow-up and
unnecessary worries among the patients can be eliminated with albendazole
treatment.
Disclosure of Interest: None declared
P0054 ABERRANT EXPRESSION OF KERATIN 7 IN HEPATOCYTES AS
A PREDICTIVE MARKER OF RAPID PROGRESSION TO HEPATIC
FAILURE IN ASYMPTOMATIC PRIMARY BILIARY CIRRHOSIS
H. Seki1,*, F. Ikeda1, S. Nanba1, K. Yamamoto1
1
Department of Gastroenterology and Hepatology, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, okayama, Japan
Contact E-mail Address: jhare25@yahoo.co.jp
INTRODUCTION: Routine testing for antimitochondrial antibodies has
increased the identification of patients with asymptomatic primary biliary cirrho-
sis (PBC). A predictive marker of the rapid progression to hepatic failure is
desired for patients with asymptomatic PBC.
AIMS & METHODS: We performed a systematic cohort analysis of 101 patients
diagnosed as having asymptomatic PBC and the rapid progression to liver fail-
ure, by focusing on cholestasis. Cholestasis was assessed by aberrant keratin
(CK) 7 expressions in the patients hepatocytes.
RESULTS: Intralobular expressions of CK-7 were found in nine of the 101
patients (9%). The grades of CK-7 expression was significantly associated with
the levels of alanine aminotransferase, alkaline phosphatase, and total bilirubin
(p 0.0060, 0.020, and 0.0015, respectively), but not with bile duct loss or cho-
lestasis in orcein staining. The stepwise logistic regression analysis revealed that
high grades of CK-7 expression in hepatocytes had positive correlations with
high levels of total bilirubin (p 0.0020). During the follow-up period, eight
patients developed jaundice, and the mean period until the development of jaun-
dice was 5.2 years. The proportional hazards models for the risk of developing
jaundice identified only high grades of aberrant CK-7 expression in hepatocytes
as significant risk factor (hazards ratio 8.7, p 0.019).
CONCLUSION: Aberrant CK-7 expression in hepatocytes can be used as an
asymptomatic PBC at the time of diagnosis.
Disclosure of Interest: None declared
P0055 THE VALUE OF 2D SHEAR WAVE ELASTOGRAPHY (2D-SWE)
IN THE EVALUATION OF ESOPHAGEAL VARICES IN PATIENTS
WITH LIVER CIRRHOSIS
O. Gradinaru Tascau1, A.S. Popescu1,*, I. Sporea1, R. Sirli1, M. Popescu1,
S. Bota1, M. Danila1, R. Sirli1, I. Ratiu1, on behalf of Flavia Mot;iu, Athena
Plaian
1
Department of Gastroenterology and Hepatology Timisoara, Emergency County
Hospital of Timisoara, Timisoara, Romania
Contact E-mail Address: bluonmyown@yahoo.com
INTRODUCTION: 2D-SWE is a new elastographic technique for the evaluation
of chronic liver disease.
AIMS & METHODS: To evaluate the feasibility of 2D-SWE in cirrhotic patients
with esophageal varices and the performance of 2D-SWE for predicting the
presence of esophageal varices.
The study group included 71 subjects diagnosed with cirrhosis by clinical, biolo-
gical, ultrasound and/or endoscopic criteria. All subjects underwent 2D-SWE
with an AixplorerTM ultrasound system (SuperSonic Imagine S. A., Aix-en-
Provence, France). In each patient we aimed to perform three liver stiffness
measurements, with the patient in supine position and then a mean value was
calculated and expressed in kiloPascals (kPa).
RESULTS: The study included 71 subjects, 65.2% men and 34.8% women with a
median age of 60.5 years (ranging between 22-82 years). The etiology of liver
cirrhosis was: HCV-22.2%, HBV- 12.5%, HCV and HBV-2.7%, ethanol-13.8%
and other etiologies-47.2%. Esophageal varices were present in 39.4% of cases
and significant esophageal varices (grade II and III) in 22.5% of cases. 2D-SWE
had similar feasibility in patients with and without esophageal varices: 85.7% vs.
88.3%, (p 0.90). The mean 2D-SWE values (kPa) were not statistically different
in patients with and without esophageal varices: 3013.5 vs. 24.812.7, (p 0.1).
The mean 2D-SWE values (kPa) were also not statistically different in patients
with significant esophageal varices (grade II and III) vs. those without or grade I
esophageal varices: 32.413.4 vs. 25.314 kPa, (p 0.1).
United European Gastroenterology Journal 2(5S)
CONCLUSION: 2D-SWE is a feasible method in patients with cirrhosis and
esophageal varices but seems unable to predict the presence of esophageal
varices. Further studies, in a larger number of patients, are still needed.
Disclosure of Interest: None declared
P0056 IMPLEMENTING A VIRTUAL PALPATION MODEL
COMBINING SPIRAL CT AND ELASTOGRAPHY DATA INTO
MEDICAL TRAINING A PILOT STUDY
C.T. Streba1,*, I.A. Gheonea2, L. Sandulescu1, S. Adrian1, D. I. Gheonea1
1
Gastroenterology, 2Radiology, UMF CRAIOVA, Craiova, Romania
Contact E-mail Address: costinstreba@gmail.com
INTRODUCTION: There are inherent problems in providing training to novices
in any safety critical task. In particular, teaching medical clinicians to perform
procedures poses challenges and possible risk to patients. A palpation procedure
involves the examination of a patient through direct contact. That means that
palpation is traditionally restricted to organs in direct contact with the outer
layers of the body.
AIMS & METHODS: Our aim was to implement a previously described virtual
reality model for palpation of liver tumors based on combined spiral CT and
real-time elastography (RT-E) data in a haptic simulator used by medical stu-
dents in a pilot study. After clearing all ethical concerns with the local committees
and obtaining written consent, we acquired spiral CT and full RT-E imaging data
stored in DICOM format from 15 patients with primary liver cancers scheduled
for surgery. By using previously described methods [1] we created a three-dimen-
sional model of the liver and the tumor using the CT data and integrated elas-
ticity information by superimposing the RT-E data on the stiffness of each
tumor. We thus obtained 15 distinct virtual models containing segmented
color-map data superimposed on a high-fidelity representation of the tumors.
These computerized models were later integrated in a virtual reality system which
projected a three-dimensional image of the tumor to the operator and allowed
physical interaction through haptic devices attached to the students body. We
tested the system on a pilot group of 60 medical students in the fifth year of
training. Students were presented with the experimental design and were asked to
perform a series of tasks involving spatial manipulation and virtual palpation of
the virtual model. They were also presented with data on the real tumor (size,
shape, location). After completion, a standardized questionnaire was given to
each student and results were quantified using descriptive statistics and inter-
group analysis.
RESULTS: All students considered the model to be accurate in both size and
shape with the actual image of the tumor (60/60, 100%). The general impression
was that it increased knowledge on tumoral pathology of the liver and students
agreed that it provided useful insights otherwise unobtainable through standard
teaching techniques. The main issue with the physical haptic system were related
with the optical system for virtual reality, which the students found hard to wear
and interact. The tactile feedback device was however well accepted by the test
group.
CONCLUSION: We successfully tested a haptic medical simulator in a pilot
study involving medical students with already acquired clinical knowledge. The
general consensus was that the haptic simulator is useful for increasing knowl-
edge on liver tumors and provide additional data otherwise unobtainable
through traditional methods.
REFERENCES
1. Streba CT, Gheonea IA, Sandulescu LD, et al. Virtual Palpation Model
combining spiral CT and elastography data: a Proof-of-Concept study.
Gastroenterology 2013; 144: S992-S993.
Disclosure of Interest: None declared
P0057 COMPARISON OF THE ACCURACY OF SHEAR WAVE
ELASTOGRAPHY AND ACOUSTIC RADIATION FORCE IMPULSE
IN DETERMINING LIVER FIBROSIS AMONG PATIENTS WITH
CHRONIC LIVER DISEASE
J.-A. V. Bisnar1,*, J. Gopez-Cervantes1, J. Bocobo1, I.H. Cua1
1 1
Institute of Digestive and Liver Disease, St. Lukes Medical Center, Quezon City,
Philippines
Contact E-mail Address: joannebisnar@gmail.com
INTRODUCTION: The prognosis of chronic liver diseases (CLD) depends on
the extent of liver fibrosis. Liver fibrosis is the excessive accumulation of extra-
cellular matrix proteins including collagen that occurs in most types of chronic
liver diseases.
AIMS & METHODS: The study aims to compare the accuracy of Shear Wave
Elastography (SWE) and Acoustic Radiation Force Impulse (ARFI) in determin-
ing liver fibrosis among patients with chronic liver disease.
Cross-sectional study conducted between March-July 2012. SWE, ARFI and
ultrasound-guided liver biopsy were performed on 120 patients. Liver fibrosis
using Knodells histologic activity index and AUROC were determined for F0-F1
vs. F2-F4, F0-F2 vs. F3-F4, and F0-F3 vs. F4. SPSS 16.0, OpenEpi 2.3.1, and
Stata 11.0 software were utilized in the statistical analysis.
RESULTS: AUROCs were 0.858 (ARFI) and 0.893 (SWE), 0.944 (ARFI) and
0.95 (SWE), and 0.919 (ARFI) and 0.965 (SWE), between F0-F1 vs. F2-F4, F0-
F2 vs. F3-F4, and F0-F3 vs. F4, respectively. ARFI has a sensitivity and speci-
ficity of 87.5% (64-96.5) and 84.6% (76.5-90.3), 95.8% (79.8-99.3) and 78.1%
(68.9-85.2), 91.3% (79.7 96.6) and 43.2% (32.6-54.6) for F4 vs. F0-F3, F3-F4
vs. F0-F2, and F2-F4 vs. F0-F1. SWE has a sensitivity and specificity of 100%
(80.6-100) and 83.7% (75.4-89.5), 95.8% (79.7-99.3) and 85.4% (77-91.1), and
78.3% (64.4-87.7) and 86.5% (76.9-92.5).
CONCLUSION: SWE is more accurate in assessing liver cirrhosis. Both sensi-
tivity and specificity of ARFI and SWE increased with the severity of liver
A147
fibrosis. SWE is more sensitive between F4 vs. F0-F3 and more specific between
F3-F4 vs. F0-F2 and F2-F4 vs. F0-F1. ARFI is more specific between F4 vs. F0-
F3 and more sensitive between F2-F4 vs. F0-F1. Differences in estimates between
SWE and ARFI were statistically significant between F0-F1 and F2-F4. Thus,
both SWE and ARFI can be used as non-invasive tools in detecting liver fibrosis.
REFERENCES
[1] Bataller R. Liver fibrosis. J Clin Invest 2005; 115: 209-218.
[2] Rockey DC. Liver biopsy. AASLD Position Paper. Hepatology 2009: 1017-
1044.
[3] Pol S. Non-invasive staging of liver fibrosis with shearwave elastography
imaging. Aixplorer Multiwave White Paper; pp. 1-12.
[4] Rahn SB. Liver biopsy interpretation in chronic hepatitis. J Insur Med 2001;
33: 110-113.
[5] Ferraioli G. Accuracy of real-time shearwave elastography for assessing liver
fibrosis in chronic hepatitis C: a pilot study. Hepatology 2012; 1-9.
[6] Poynard T. Prospective analysis of discordant results between biochemical
markers and biopsy in patients with chronic hepatitis C. Clin Chem 2004; 50:
1344-1355.
Disclosure of Interest: None declared
P0058 NON-INVASIVE ASSESSMENT OF PORTAL HYPERTENSION
USING ELASTOGRAPHY OF SPLEEN
K. Dvorak1,*, V. Smid1, R. Sroubkova1, A. Novotny1, J. Mengerova1, J. Petrtyl1,
R. Bruha1
1
4TH DEPARTMENT OF MEDICINE, GENERAL UNIVERSITY
HOSPITAL AND 1ST MEDICAL FACULTY CHARLES UNIVERSITY IN
PRAGUE, Prague 2, Czech Republic
Contact E-mail Address: k2dvorak@gmail.com
INTRODUCTION: The degree of portal hypertension is one of crucial prognos-
tic factors in patients with liver cirrhosis. Standard method used for the assess-
ment is measurement of hepatic venous pressure gradient (HVPG) during liver
vein catheterisation. Being an invasive procedure this approach is not common,
has complications and moreover it does not enable monitoring of changes in the
long term. Recently non-invasive approaches have been increasingly employed in
evaluation of liver fibrosis; one such method is elastography.
AIMS & METHODS: The aim of our study was to evaluate the possibility of
assessment of portal hypertension with elastography of the spleen in patients with
various etiology of liver cirrhosis. Elastography of liver and spleen was assessed
using ARFI (Acoustic Radiation Force Impulse) measurement with ultrasound
system Siemens Acuson S2000 and then HVPG was measured in all patients. A
total of 20 patients was examined (13 men, 7 women), average age 5910.9, with
different etiology of liver cirrhosis (10 ethylic, 4 viral hepatitis, 6 other).
Diagnosis of cirrhosis was confirmed by liver biopsy or with presence of portal
hypertension. There was a control group of 20 healthy individuals without signs
of liver disease.
RESULTS: Clinically significant portal hypertension was diagnosed in 15 from
20 examined patients. The HVPG values were (mmHg; median, IQ range) 15 (3-
26), ARFI of liver (m/s; median, IQ range) 2.96 (1.31-3.54), ARFI of spleen 3.13
(1.99-3.74). The value of ARFI of spleen significantly correlated with the degree
of portal hypertension (p 0.038), the ARFI of liver did not (p 0.251).
CONCLUSION: Spleen elastography which is simple, reproducible and easy to
repeat, could enable assessing portal hypertension in cirrhotic patients
noninvasively.
Supported by IGA MZCR NT 12290/4, SVV 260032-2014
Disclosure of Interest: None declared
P0059 OUR PRELIMINARY EXPERIENCE WITH ELASTOPQ SHEAR
WAVE ELASTOGRAPHY TECHNIQUE AND DOPPLER INDICES IN
THE NON-INVASIVE ASSESSEMENT OF LIVER FIBROSIS
M. Garcovich1,*, M.A. Zocco1, L. Riccardi1, M.E. Ainora1, E.B. Annicchiarico1,
D. Roccarina1, G. Caracciolo1, A. Grieco1, G.L. Rapaccini1, M. Siciliano1,
M. Pompili1, A. Gasbarrini1
Internal Medicine, Catholic University of Sacred Heart, Rome, Italy
INTRODUCTION: Real-time shear wave elastography (RTE) is a novel non-
invasive technique that assesses liver fibrosis by measuring liver stiffness (in kPa).
The purpose of this study was to determine the efficacy and the feasibility for the
assessment of hepatic fibrosis as compared with the histological grade in patients
undergoing liver biopsy (LB).
AIMS & METHODS: Consecutive patients scheduled for LB were studied by
using the iU22 Philips ultrasound system with ElastPQ technique. In addition,
Doppler indices at various sites, hepatic vein and portal venous blood velocity
and flows were evaluated. The correlations between these quantitative para-
meters and the Metavir score were analyzed using Spearman correlation and
ROC curve analyses were performed to calculate AUC for F42, F43, and
F 4.
RESULTS: We enrolled 60 patients (39/21 males/females) who underwent LB for
viral or non-viral chronic hepatitis (HCV 58%; NASH 30%). Liver stiffness
measurements performed on the right lobe were reliable in almost all cases, while
15% of left lobe measurements were not obtainable/unreliable. Median kPa
values were 4.43(range 2.984.82) and 3.92(2.51-6.73) for F0-F1, 7.65(4.28-
12.9) and 8.21(5.43-12.3) for F2-F3, 15.12(9.9-29.16) and 18.54(9.31-31.34) for
F4 in the right and left lobe, respectively. AUCs calculated for the right lobe were
0.90(0.840.92;95%CI) for F42, 0.84(0.730.88;95%CI) for F43 and
0.92(0.900.96;95%CI) for F 4. Adding Doppler indices to liver stiffness
increased no further the diagnostic accuracy of RTE.
A148
CONCLUSION: RTE with ElastPQ appears to be a useful tool for non-invasive
evaluation of fibrosis in patients with viral and non-viral chronic hepatitis,
although these findings need to be confirmed in larger studies.
Disclosure of Interest: None declared
P0060 LIVER FIBROSIS ASSESSED BY TRANSIENT ELASTOGRAPHY
IN LONG-TERM METHOTREXATE-TREATED PATIENTS
R. Shah1,*, M. Petrova1, S. Redhead1, P. Berry1, A. ALA1,2
1
DEPARTMENT OF GASTROENTEROLOGY AND HEPATOLOGY,
FRIMLEY PARK NHS FOUNDATION TRUST, FRIMLEY,
2
GASTROENTEROLOGY, FACULTY OF HEALTH SCIENCES AND
HEALTH CARE MANAGEMENT AND STATERGY, UNIVERSITY OF
SURREY, GUILDFORD, United Kingdom
Contact E-mail Address: rahulhshah@hotmail.com
INTRODUCTION: Methotrexate (MTX) is among most commonly used immu-
nosupressive agents but requires careful monitoring due to risks of hepatotoxi-
city. The amino-terminal of type III pro-collagen peptide (serum P3NP) is used
as a surrogate of collagen turnover. Its measurement has been proposed as a
marker for ongoing hepatic fibrogenesis. Liver stiffness measurement (LSM) is a
simple non-invasive method for assessment of liver fibrosis (LF). Currently, only
liver biopsy for assessment of liver fibrosis in long-term (424weeks) MTX-trea-
ted patients is used. Our aim was to evaluate the presence of liver fibrosis by
transient elastography (TE) in patients treated with MTX in a long-term clinical
practice.
AIMS & METHODS: We consecutively enrolled 34 patients with rheumatoid
arthritis or psoriasis taking MTX between 2011 and 2012. We only included
patients with normal liver function and no history of underlying chronic liver
disease. All patients had P3NP measurements close to TE. Liver stiffness was
evaluated by TE (single operator). Cut-off of LSM to predict liver fibrosis was
7.1 KPa.
RESULTS: The study population consists of 34 patients (12 males, 35%) at
mean age of 65.2 years (range 34-77, SD 11.04). Seven patients (20%) had psor-
iasis, 23 (68%) had RA and the remaining were with SLE. Mean MTX cumula-
tive dose was 5320 (SD 3682) mg, and mean treatment duration was 427 weeks
(range 104-670). Mean hepatic stiffness was 7.4 KPa (SD 4.46) and mean level of
P3NP was 6.7 mcg/l (SD 2.25). In six patients abdominal ultrasound was sug-
gestive of fatty liver disease and they were excluded from further analysis. The
remaining 28 patients had mean LSM of 7.4 KPa (SD 4.74), which correlated
significantly with serum P3NP (Pearson r 0.46, p50.02). Ten patients had
LSM 4 7.2 KPa, suggestive of significant fibrosis. Patients age, steroids, treat-
ment duration or cumulative doses of MTX were not associated with LF.
CONCLUSION: In our series, 33% of long-term MTX treated patients devel-
oped liver fibrosis, as assessed by LSM. Transient elastography may be poten-
tially useful in evaluation and follow-up of liver fibrosis in long-term MTX-
treated patients. Further work is required to evaluate the diagnostic yield of
TE as a predictor of liver fibrosis in these patients.
REFERENCES
Laharie D, Seneschal J, Schaeverbeke T, et al. Assesment of liver fibrosis with
transient elastography and fibrotest in patients on methotrexate in chronic
inflammatory conditions.
Disclosure of Interest: None declared
P0061 XL VS. M PROBE FOR LIVER FIBROSIS ASSESSMENT BY
TRANSIENT ELASTOGRAPHY
O. Gradinaru Tascau1, R. Sirli1,*, I. Sporea1, A. Deleanu1, A. Popescu1,
M. Danila1 on behalf of Laura Culcea, Milana Szilaski, Cristian Ivascu-Siegfried
1
Department of Gastroenterology and Hepatology Timisoara, Emergency County
Hospital of Timisoara, Timisoara, Romania
Contact E-mail Address: roxanasirli@gmail.com
INTRODUCTION: Liver stiffness measurement (LSM) using Transient
Elastography (TE) for liver fibrosis assessment is difficult to perform in obese
and overweight patients by standard M probe, thus the XL probe was developed.
AIMS & METHODS: The aim of our paper was to compare the LS values
obtained by the XL probe vs. M probe in daily clinical practice.
Our study included 88 difficult to evaluate patients (mean BMI 29.63.4 kg/m2)
with chronic hepatopathies, in which paired measurements were made with the M
(3.5MHz) and XL (2.5 MHz) probes in the same session. In each patient 10 valid
LSM were acquired with each probe, a median was calculated, expressed in
kiloPascals (kPa). Unreliable TE measurements were considered: fewer than 10
valid shots; with a success rate (SR)560% and/or interquartile range interval
(IQR)30%. We used published cut-offs for M probe (7.6kPa) to divide p with
no significant fibrosis (F52 Metavir) from those with significant fibrosis (F2),
and those with no cirrhosis (F54) vs. cirrhosis (F4) (15kPa)*.
RESULTS: XL LS values strongly and significantly correlated with those
obtained by M probe (Spearman r 0.782, p50.0001), but were significantly
lower [median 6.3 kPa (range 3.152.3) vs. 7.2 kPa (range 3.757.3), Wilcoxon
paired t test p50.001)]. XL LS values were also lower in the F52 group (47
patients): median 5.1 kPa (range 3.112.7) vs. 5.9 kPa (range 3.77.4), Wilcoxon
paired t test p 0.0006); in the F2-F3 group (23 patients): median 7.3 kPa (range
5.116.3) vs.10.5 kPa (range 7.714.1), Wilcoxon paired t test p 0.0154); and in
the cirrhotic group (18 patients): median 18.2 kPa (range 13.352.3) vs. 21.3 kPa
(range 15.957.3), Wilcoxon paired t test p50.0001.
CONCLUSION: LSM by XL probe are significantly correlated, but lower, than
those obtained by M probe in patients with no significant fibrosis (F52), in
patients with moderate and severe fibrosis (F2,F3) and in patients with cirrhosis
(F4).
United European Gastroenterology Journal 2(5S)
REFERENCES
Tsochatzis EA, Gurusamy KS, Ntaoula S, et al. Elastography for the diagnosis
of severity of fibrosis in chronic liver disease: a meta-analysis of diagnostic accu-
racy. J Hepatol 2011; 54: 650-659.
Disclosure of Interest: None declared
P0062 THE USEFULNESS OF SPLEEN STIFFNESS EVALUATED BY
2D-REAL TIME SHEAR WAVE ELASTOGRAPHY (2D-SWE) FOR
PREDICTING THE PRESENCE OF LIVER CIRRHOSIS
S. Bota1,*, R. Paternostro1, A. Etschmaier1, R. Schwarzer1, M. Mandorfer1,
M. Ferlitsch1, C. Kienbacher1, T. Reiberger1, M. Trauner1, M. Peck-
Radosavljevic1, A. Ferlitsch1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: bota_simona1982@yahoo.com
INTRODUCTION: Recently, spleen stiffness (SS) assessed by various elasto-
graphic methods was evaluated for predicting liver fibrosis. Recently (Leung-
Radiology, 2013) good results were published for predicting liver cirrhosis byus-
ing SS by 2D-SWE.
AIMS & METHODS: Our aim was to validate this cut-off in an independent
cohort, considering liver stiffness (LS) by Transient Elastography (TE) as the
reference method.
We analyzed 89 patients with chronic liver disease. In each of the patients, in the
same session LS was evaluated by TE (FibroScan, Echosens, Paris, France) and
SS by 2D-SWE (Aixplorer, SuperSonic Imagine S. A., Aix-en-Provence, France).
TE reliability criteria defined as: median of 10 valid LS measurements with a
SR60% and IQR530%. 2D-SWE results were recorded as median value of 3
valid SS measurements. For predicting the presence if liver cirrhosis, we used the
LS cut-off proposed in the most recently published meta-analysis (Tsochatzis-J
Hepatol 2011): 14.5 kPa. For SS the following cut-off was analyzed (Leung-
Radiology2013): 22 kPa.
RESULTS: Reliable LS measurements by TE were obtained in 71 (79.7%)
patients and valid SS measurements by 2D-SWE in 63/71 (88.7%) patients,
who were included in the final analysis. According to the pre-specified cut-off
values for LS and SS, the performance of SS assessed by 2D-SWE for predicting
the presence of liver cirrhosis was: 58.3% sensitivity, 82.3% specificity, 43.7%
positive predictive value (PPV), 89.3% negative predictive value (NPV) and
77.7% accuracy.
CONCLUSION: In our patient cohort, SS by 2D-SWE was a good method for
excluding liver cirrhosis, with a very good NPV (89.3%), but less useful for
predicting cirrhosis, with a rather poor PPV(only 43.7%).
Disclosure of Interest: None declared
P0063 COMPARISON BETWEEN 2D-REAL TIME SHEAR WAVE-
ELASTOGRAPHY (2D-SWE) AND SIMPLE SEROLOGICAL SCORES
FOR LIVER FIBROSIS ASSESSMENT FOR CLINICAL ROUTINE,
CONSIDERING TRANSIENT ELASTOGRAPHY (TE) AS REFERENCE
METHOD
S. Bota1,*, R. Paternostro1, A. Etschmaier1, R. Schwarzer1, P. Salzl1,
M. Mandorfer1, T. Purevsambuu1, M. Ferlitsch1, C. Kienbacher1, T. Reiberger1,
M. Trauner1, M. Peck-Radosavljevic1, A. Ferlitsch1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
INTRODUCTION: 2D-Shear Wave elastography (2D-SWE) is a new method
for non-invasive assessment of liver fibrosis.
AIMS & METHODS: Our aim was to assess the performance of 2D-SWE and
simple serological scores for liver fibrosis assessment, considering TE as reference
method.
Our study included 127 consecutive patients with chronic liver disease undergoing
both TE (FibroScan, Echosens, Paris, France) and 2D-SWE (Aixplorer,
SuperSonic Imagine S. A., Aix-en-Provence, France). Biochemical parameters
were recorded to calculate the noninvasive fibrosis scores. TE reliability criteria
defined as: median of 10 valid LS measurements with a SR60% and IQR530%.
2D-SWE results were recorded as median value of 3 valid LS measurements. TE
cut-offs to stage liver fibrosis were used according to a recent meta-analysis
(Tsochatzis-J Hepatol 2011): F1: 6kPa, F2: 7.2kPa, F3: 9.6kPa and F4: 14.5kPa.
RESULTS: Reliable LS measurements by TE and 2D-SWE were obtained in
74.8% and 98.4% of patients (p50.0001), respectively. The following noninva-
sive fibrosis scores were correlated in univariate analysis with fibrosis estimated
by TE: 2D-SWE (r 0.699; p50.0001), Forns (r 0.534; p50.0001), Kings
(r 0.512; p50.0001), APRI (r 0.373, p 0.001) Fibrosis Index score
(r 0.363; p 0.0008) and Lok score (r 0.316, p 0.006), while FIB-4
(r 0.195; p 0.09) was not correlated. In multivariate analysis only LS by
SWE was significantly correlated with fibrosis estimated by means of TE
(p50.0001).
The best LS cut-off by 2D-SWE for predicting different stages of liver fibrosis,
considering TE as the reference method, are presented in the table.
Table to abstract P0063
SWE Se Sp PPV NPV Accuracy
Fibrosis Cut-off (kPa) AUC (%) (%) (%) (%) (%)
F2 4 8.03 0.832 77.1 76.1 77.1 76.1 76.5
F3 4 9.2 0.919 88.2 85 76.9 92.7 86.1
F4 4 13.1 0.915 76.2 94.5 80 93.2 90.4
United European Gastroenterology Journal 2(5S)
CONCLUSION: 2D-SWE results in a higher rate of successful liver stiffness
measurements than TE and is superior to simple serological scores for non-inva-
sive liver fibrosis assessment.
Disclosure of Interest: None declared
P0064 THE CONTROLLED ATTENUATION PARAMETER (CAP)
EVALUATED WITH TRANSIENT ELASTOGRAPHY ACCURATELY
ESTIMATES THE SEVERITY OF STEATOSIS INDEPENDENT OF
FIBROSIS AND DISEASE ETIOLOGY IN PATIENTS WITH
CHRONIC LIVER DISEASE
Y. Yilmaz1,2,*, A. Yesil3, F. Gerin4, R. Ergelen5, H. Akin2, C.A. Celikel4,
N. Imeryuz2
1
Institute of Gastroenterology, 2Department of Gastroenterology, Marmara
University, School of Medicine, 3Department of Gasdtroenterology, Haydarpasa
Numune Education and Research Hospital, 4Department of Pathology,
5
Department of Radiology, Marmara University, School of Medicine, Istanbul,
Turkey
Contact E-mail Address: dryusufyilmaz@gmail.com
INTRODUCTION: Currently only liver biopsy can accurately establish the diag-
nosis and severity of hepatic steatosis. Few studies to date have addressed the
feasibility of the Controlled Attenuation Parameter (CAP) measured by transient
elastography for measuring hepatic fat content. However, the effects of hepatic
fibrosis and disease etiology on the accuracy of CAP values for grading the
severity of liver steatosis are still unclear.
AIMS & METHODS: The aims of this study were (1) to determine whether CAP
values can discriminate grades of steatosis in a sample of consecutive patients
with a spectrum of liver disease etiology and steatosis severity, and (2) to evaluate
the effect of hepatic fibrosis and disease etiology on the quantification of steatosis
by CAP measurements. The study involved 50 sequential patients (64% males;
mean age, 47.4 years; range, 19-70 years) who had undergone a percutaneous
liver biopsy and CAP measurements. The causes of liver disease were nonalco-
holic fatty liver disease (n 20), chronic viral hepatitis (n 23), autoimmune
hepatitis (n 3), and others (n 4). A pathologist scored the specimens in a
four-graded scale as follows: 55% steatosis S0, 5-33% S1, 33-66% S2,
and 466% S3. All liver biopsy specimens were at least 20 mm long and/or
contained more than 11 complete portal tracts.
RESULTS: The pathology results showed that 16 (32%) patients had S0, 12
(24%) had S1, 9 (18%) had S2, and 13 (26%) had S3. Overall a close relationship
was observed between the CAP values and histology steatosis scores (r 0.709, P
5 0.001). There was a stepwise increase in CAP with increasing stages of hepatic
steatosis: S0, 222 dB/m; S1, 250 dB/m; S2, 270 dB/m; and S3, 318 dB/m.
Regression analysis, that included a number of potential confounders, was per-
formed to determine the influence of hepatic fibrosis and disease etiology on the
relationship between CAP values and the histological assessment of steatosis.
However, neither liver fibrosis (p 0.58) nor disease etiology (p 0.96) were
found to have an interaction between CAP and the stage of steatosis.
CONCLUSION: Liver fibrosis or disease etiology does not impact on the accu-
racy of CAP for the assessment of steatosis. The results of this study strengthen
the role of CAP measured by transient elastography as a non-invasive alternative
to liver biopsy for the evaluation of liver fat content in subjects with liver disease.
Given its accuracy and lack of confounding by fibrosis and disease etiology, CAP
assessment is an attractive method to evaluate the presence and severity of stea-
tosis in clinical practice and may also be a useful tool to monitor change in
steatosis in subjects undergoing an intervention.
Disclosure of Interest: None declared
P0065 FOCAL LIVER LESIONS CLASSIFICATION BY ARTIFICIAL
NEURAL NETWORKS AND SUPPORT VECTOR MACHINES
EMPLOYING DYNAMIC IMAGING DATA
C.T. Streba1,*, C.C. Vere1, L. Sandulescu1, A. Saftoiu1, D. I. Gheonea1,
L. Streba1, I. Rogoveanu1
1
Gastroenterology, UMF CRAIOVA, Craiova, Romania
Contact E-mail Address: costinstreba@gmail.com
INTRODUCTION: Early diagnostic of liver malignancies is essential for therapy
efficiency; differentiating hepatocellular carcinoma (HCC) from intrahepatic
cholangyocarcinoma, liver metastases or benign lesions is therefore essential
even in early phases. Successful classification of liver lesions by computerized
methods is currently possible and artificial neural networks emerged as optimal
tools for independent diagnostic.
AIMS & METHODS: Our aim was to test the validity of two separate decision
making systems an artificial neural network (ANN) and a support vector
machine (SVM) in classifying focal liver lesions (FLLs) by using dynamic ima-
ging data.
Expanding on our previous work involving ANN use in interpreting imaging
data for HCC [1], we now proposed a comparative approach between two dif-
ferent machine learning systems, one based on ANNs and contrast-enhanced
ultrasound (CEUS) quantitative data and one employing a SVM and spiral
computed tomography (CT). After obtaining ethical clearance and signing indi-
vidual consent forms, we prospectively included 191 patients who underwent
both spiral CT and CEUS as part of their clinical work-up at the University
County Hospital of Craiova between January 2009 September 2013. Final
diagnosis was based on post-treatment evaluation, follow-up and pathology,
when available. Imaging data from CEUS was obtained through time-intensity
curve (TIC) analysis and the main parameters (time to peak, rise time, fall time,
mean transit time, area under the curve) were fed to an ANN. Spiral CT data was
obtained through manually segmenting the tumor and a tumor-free parenchyma
portion in distinctive images and obtaining Gray Level Co-occurrence Matrix
A149
GLCM parameters (entropy, correlation and contrast) by using the free ImageJ
software and a dedicated plug-in. These parameters were then fed to a SVM.
RESULTS: We included 54 cases of HCC, 9 intrahepatic cholangiocarcinomas,
71 liver metastases (41 hypervascular), 38 liver hemangiomas and 19 focal fatty
changes. The SVM classified lesions into malignant or benign, obtaining 141
correct classifications (malignant: 113/134, benign: 28/57). Overall, the ANN in
correlation with TIC-derived parameters proved to be a superior combination to
SVM and GLCM.
CONCLUSION: ANNs are superior to SVMs when employed in medical classi-
fication problems. Established quantitative parameters improve the diagnostic
accuracy. The differences shown here were not given by the quality of the two
investigations, showing rather the adequacy of the chosen parameters and the
diagnostic yields of the computer methods employed.
REFERENCES
1. Streba CT, et al. Computer aided differentiation model for automatic classi-
fication of focal liver lesions based on contrast enhanced ultrasound (CEUS)
time-intensity curve (TIC) analysis. J Hepatol 56(Suppl. 2): S296.
Disclosure of Interest: None declared
P0066 LONG-TERM OUTCOMES AFTER TREATMENT OF SINGLE
SMALL HEPATOCELLULAR CARCINOMA IN ELDERLY
PATIENTS WITH WELL-PRESERVED LIVER FUNCTION AND
GOOD PERFORMANCE STATUS
G. Lee1, M.S. Choi1,*, D.H. Sinn1, G.-Y. Gwak1, Y.H. Paik1, J.H. Lee1,
K.C. Koh1, S.W. Paik1, B.C. Yoo1
1
Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of
Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: iamann81@gmail.com
INTRODUCTION: Aging of general population and advances in diagnostic
imaging have led to more frequent detection of small hepatocellular carcinoma
(HCC) in elderly adults. However, long-term outcome and its predictive factors
after treatment of small HCC in these patients have not been established.
AIMS & METHODS: Between 2006 and 2009, 897 patients who had Eastern
Cooperative Oncology Group (ECOG) score 0-1 and Child-Pugh class A liver
function were diagnosed with single small HCC (size3 cm) at Samsung Medical
Center. They were divided into elderly group (age65 years, n 186) and young
group (age565 years, n 711). We compared baseline characteristics, initial
treatment modality, and treatment outcomes between the two groups.
RESULTS: At baseline, male patients were less common, and HCV infections
and alcoholic liver disease were more common in elderly group. Elderly group
underwent surgical resections less frequently but TACE more frequently com-
pared to young group (21.5% vs. 38.8% for surgery and 26.9% vs. 12.9% for
TACE, p50.001). One-, 3-, and 5-year overall survival (OS) rates (OSR) of
elderly group were lower than those of young group (96.7%, 81.4%, and
60.5% vs. 97.3%, 87.9%, and 82.4%, respectively, p50.001).
One-, 3-, and 5-year OS rates were after surgery, RFA, and TACE were 94.9%,
89.7%, and 86.6% vs. 97.9%, 79.6%, and 56.7% vs. 96.0%, 80.0%, and 50.6%,
respectively in elderly group (p 0.014); 98.2%, 91.8%, and 89.5% vs. 98.2%,
87.6%, and 80.3% vs. 92.3%, 79.0% and 70.5%, respectively in young group
(p50.001). Although OS rates after surgery and TACE were comparable
between the two groups, elderly group showed lower 1-, 3-, and 5-year OS
rates than young group after RFA. In addition, 1-, 3-, and 5-year recurrence-
free survival (RFS) rates of elderly subgroup were lower than those of young
group (63.2%, 30.5%, and 23.0% vs. 75.7%, 48.0%, and 36.6%, respectively,
p50.001).
One-, 3-, and 5-year RFS rates after surgery, RFA, and TACE were 74.4%,
61.5%, and 52.5% vs. 70.2%, 23.5% and 13.8% vs. 40.8%, 18.4%, and
16.3%, respectively in elderly group (p50.001); 81.4%, 63.5%, and 51.5% vs.
75.1%, 41.4%, and 29.9% vs. 59.2%, 23.6%, and 11.7%, respectively in young
group (p50.001). RFS rates after surgery and TACE were comparable between
the two groups, whereas elderly group showed lower 1-, 3-, and 5-year RFS rates
than young group after RFA. Multivariate analysis showed that sex and initial
treatment modality were the significant predictive factor for OS and RFS.
CONCLUSION: Although long-term outcomes after treatment of single small
HCC in elderly group were lower than those in young group, adoption of cura-
tive treatment modality was an independent predictive factor for the better out-
comes irrespective of age. Therefore, in elderly patients with well-preserved liver
function and good performance status, curative treatment including surgery
should be more positively considered for single small HCC.
REFERENCES
Arii S, et al. Results of surgical and nonsurgical treatment for small-sized hepa-
tocellular carcinomas. The Liver Cancer Study Group of Japan. Hepatology
2000; 32: 1224-1229.
Mirici-Cappa F, et al. Treatments for hepatocellular carcinoma in elderly
patients are as effective as in younger patients. Gut. Mar 2010; 59: 387-396.
Disclosure of Interest: None declared
P0067 EFFICACY OF SORAFENIB ACCORDING TO THE NUMBER OF
PRIOR TACE PROCEDURES IN HCC PATIENTS
R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1,
G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1 on behalf
of ITA.LiCA Group
1
Gastroenterology, Pisa University Hospital, Pisa, Italy
Contact E-mail Address: r.sacco@ao-pisa.toscana.it
INTRODUCTION: It has been recently suggested that sorafenib should be
initiated as early as possible in patients with hepatocellular carcinoma (HCC)
who failed transarterial chemoembolization (TACE); however, the correlation
A150
between the efficacy of sorafenib and the number of prior TACE procedures has
not been documented. We analyze here the correlation between the efficacy of
sorafenib and the number of prior TACE procedures in HCC patients included in
the Nation-wide Italian database ITA. LI. CA.
AIMS & METHODS: The ITA. LI. CA. database contains data of 5136 HCC
patients treated at 18 Italian Centers. All patients treated with sorafenib were
included in this analysis. The following endpoints were considered: overall sur-
vival (OS), time to progression (TTP) and disease control rate (DCR). These
endpoints were compared in patients with no TACE, one and 2 prior TACE
procedures.
RESULTS: In total, 321 patients had received sorafenib (271 males; age 6511
years; 225 in BCLC-C stage). Of these, 201 received no TACE (187 were in
BCLC-C stage), 60 one TACE and 60 2 TACE procedures. Median OS was
significantly longer in patients who received one single TACE procedure, with
respect to those with no or 2 TACE procedure(s) (19 months with one TACE
versus 11 months with no TACE and 12 months for 2 TACE; p50.05). No
differences among groups were observed in TTP (one TACE: 4 months; no
TACE: 4 months; 2 TACE: 5 months; p not significant), but patients with
only one TACE prior to sorafenib treatment had an improved DCR (one TACE:
34%; no TACE: 24%; 2 TACE: 28%; p50.05).
CONCLUSION: Although with all the limitations of any observational study,
this analysis, conducted in a large field-practice database, suggests that HCC
patients who start sorafenib after one single TACE procedure present improved
OS and DC with respect to those who received TACE 2 TACE procedures.
Disclosure of Interest: None declared
P0068 CORRELATION BETWEEN LDH LEVELS AND RESPONSE TO
SORAFENIB IN HCC PATIENTS
R. Sacco1,*, A. Romano1, V. Mismas1, M. Bertini1, M. Bertoni1, G. Federici1,
G. Parisi1, A. Scaramuzzino1, S. Metrangolo1, E. Tumino1, G. Bresci1 on behalf
of ITA.LiCA Group
1
Gastroenterology, Pisa University Hospital, Pisa, Italy
Contact E-mail Address: r.sacco@ao-pisa.toscana.it
INTRODUCTION: Lactate dehydrogenase (LDH) is a predictor of clinical out-
come in hepatocellular carcinoma (HCC) patients. However, the predictive role
of LDH on the clinical outcomes of sorafenib treatment has been poorly docu-
mented. The correlation between LDH levels and clinical outcomes in HCC
patients treated with sorafenib included in the Nation-wide Italian database
ITA. LI. CA is investigated here.
AIMS & METHODS: The ITA. LI. CA. database contains data of 5136 HCC
patients treated at 18 Italian Centers. All patients treated with sorafenib treat-
ment and with available LDH values were considered. A ROC analysis was
performed to find a suitable threshold for baseline LDH levels. Overall
Survival (OS) and time to progression (TTP) were compared in patients with
LDH above and below the identified threshold. Study endpoints were also eval-
uated according to different patterns of LDH levels during treatment.
RESULTS: Baseline LDH levels were available for 97 patients (85 males, 61 in
BCLC-C stage); data on LDH levels during sorafenib were reported for 10
patients. Mean baseline LDH concentration was 324141 U/L. The most accu-
rate cut-off value for LDH concentration was 297 U/L. Both study endpoints
were equal in patients with LDH values 297 U/L (n 47) and in those with
lower LDH concentrations (n 52) (OS: 12.0 months in each population; TTP:
4.0 months in each group). During treatment, LDH values decreased in three
patients (mean difference -219 U/L). Patients with decreased LDH concentra-
tions have a prolonged OS versus those with unmodified/increased values
(p 0.0083; all patients with decreasing LDH are alive, median OS for patients
with increasing LDH was 8.0 months). Median TTP was 19.0 months in patients
with decreasing LDH and 3.0 months in those with increasing values (p 0.008).
CONCLUSION: The clinical benefits of sorafenib do not seem influenced by
baseline LDH. However, a decreased LDH concentration during sorafenib might
be associated with improved clinical outcomes.
Disclosure of Interest: None declared
Table to abstract P0071
Table 1. HCC incidence in different groups, according to AFP levels at baseline and EOT (P0071 table)
Group A: n50 (3.8%) Group B: n81 (6.1%) Group C: n1167 (88%)
AFP410/ AFP410 AFP410 /AFP510 AFP510 /AFP510
Cohort (ng/ml,baseline/EOT) (ng/ml, baseline/EOT) (ng/ml,baseline/EOT)
All 24% 9.8% 1.8%
SVR 30.7% p0.77 7.1% p0.83 0.5%
Non-SVR 21.6% 11.3% 4.7%
United European Gastroenterology Journal 2(5S)
P0070 SAFETY AND EFFICACY OF SORAFENIB IN ELDERLY
PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA
S. Nakashita1,*, T. Otsuka1, Y. Eguchi2, S. Kawazoe3, K. Yanagita4, K. Ario5,
K. Kitahara6, S. Iwane7, H. Kato8, T. Mizuta1 on behalf of the Saga Liver
Cancer Study Group
1
Internal Medicine, 2Liver Disease Control and Assistance Task Force, Saga
University Hospital, 3Hepato-Biliary and Pancreatology, Saga-Ken Medical
Centre Koseikan, Saga, 4Internal Medicine, Saiseikai Karatsu Hospital, Karatsu,
5
Internal Medicine, NHO Ureshino Medical Center, Ureshino, 6Surgery, Saga
University Hospital, Saga, 7Internal Medicine, Karatsu Red Cross Hospital,
Karatsu, 8Internal Medicine, NHO Saga Hospital, Saga, Japan
INTRODUCTION: The average age of patients with hepatitis and hepatocellular
carcinoma (HCC) in Japan is increasing. Sorafenib is approved for the treatment
of advanced HCC; however, its safety and efficacy for elderly patients is not
established by published studies. Therefore, we aimed to evaluate the safety
and efficacy of sorafenib for elderly patients (80 years of age) included in the
Saga Liver Cancer Study Group.
AIMS & METHODS: We conducted a retrospective study between July 2008
and August 2013 that included 134 patients with advanced HCC who received
sorafenib in Saga, Japan until disease progression or treatment intolerance. We
divided the patients into two groups comprising 36 patients 80 years of age or
greater (80 group) and 98 patients less than 80 years of age (580 group). We
compared antitumour effect [objective response rate (ORR), disease control rate
(DCR), time to tumour progression (TTP)], overall survival (OS), and adverse
events (AEs) of the two groups.
RESULTS: Baseline characteristics were not significantly different between the
two groups. The median ORRs were 6.9% and 8.3%, and the median DCRs
were 37.9% and 46.4% in the 80 and 580 groups, respectively. These values
were not significantly different between the two groups (p 0.81, p 0.43). The
median TTPs were 2.9 months for both groups, and the median OSs were 14.7
and 9.2 months for the 80 and 580 groups, respectively, which were not sig-
nificantly different. The frequencies of AEs were 97.2% and 96.6% in the 80
and 580 groups. The frequencies of grade 3 AEs between the 80 and 580
groups were significantly different (69.4% and 49.0% respectively, p 0.036).
CONCLUSION: Sorafenib treatment is equally effective for elderly and non
elderly patients with advanced HCC. However, the high frequency of AEs in
elderly patients is problematic and requires close attention.
Disclosure of Interest: None declared
P0071 HEPATOCELLULAR CARCINOMA INCIDENCE IN CHRONIC
HEPATITIS C PATIENTS ACCORDING TO SUSTAINED
VIROLOGIC RESPONSE (SVR) AND FLUCTUATION OF ALFA
FETO-PROTEIN LEVELS DURING ANTIVIRAL TREATMENT
T. Purevsambuu1,*, S. Bota1, H. Florian1, H. Hofer1, P. Ferenci1, W. Sieghart1,
M. Peck-Radosavljevic1
1
Gastroenterology and Hepatology, Internal Medicine III, Medical University of
Vienna, Vienna, Austria
Contact E-mail Address: tuulaigirl@yahoo.com
INTRODUCTION: Chronic hepatitis C (CHC) is an important risk factor for
progression of liver disease to advanced fibrosis and hepatocellular carcinoma
(HCC) and the published studies showed that the kinetics of alfa feto-protein
(AFP) levels in cirrhotic patients are more valuable than single AFP values for
predicting the HCC.
AIMS & METHODS: Our aim was to assess the HCC incidence in relation to
antiviral treatment response and fluctuation of AFP levels during antiviral treatment
in a large number of patients from a single institution. We retrospectively collected
data of HCV patients, who were diagnosed and treated between 1989-2011. We
analyzed the HCC incidence according to AFP fluctuation (baseline vs. end of
treatment-EOT) in the entire Cohort of patients and in SVR and non-SVR patients.
RESULTS: We identified 2627 patients diagnosed with chronic hepatitis C. We
excluded 975 patients because they did not receive antiviral therapy, 5 because
they were diagnosed simultaneously with HCV/HCC and 321 patients due to lack
Group D: n28 (2.1%)
AFP510/AFP410
(ng/ml,baseline/EOT) P value
17.8% A vs. B: p0.004
Avs.C:p50.0001
A vs. D: p0.72
B vs.C: p50.0001
B vs. D: p0.42
C vs.D: p50.0001
p50.0001 12.5% p0.93 A vs. B: p0.12
A vs.C: p50.0001
A vs. D: p0.67
B vs. C: p0.003
B vs. D: p0.81
C vs. D: p0.04
20% A vs. B: p0.30
A vs.C: p0.0002
A vs. D: p0.84
B vs. C: p0.10
B vs. D: p0.56
C vs. D: p0.01
United European Gastroenterology Journal 2(5S)
of AFP values at baseline and EOT. We included in the final analysis 1326
patients. The median follow-up time was 10 years (0.2-25 years). The overall
HCC incidence was 3.5% and the median time between HCV and HCC diagnosis
was 7 years (0.5-15 years). According to baseline fibrosis stage, HCC incidence
was: 0.9% in F(0-2) patients, 1.8% in F3 and 10.1% in F4 patients.
The HCC incidence was significantly higher in non-SVR as compared with SVR
patients: 7.4% vs. 1.2%, p50.0001.
AFP values 4 10 ng/ml at baseline, EOT and the increase of AFP values during
the antiviral treatment are associated with high HCC incidence in both SVR and
non-SVR patients (Table 1). The decrease of AFP values during the antiviral
treatment is associated with reduced HCC incidence, comparative to the cases
with high AFP at baseline and EOT. AFP levels 5 10 ng/ml in both baseline and
EOT are protective against HCC development exclusively in the SVR group.
CONCLUSION: The fluctuation of AFP levels during antiviral treatment plays
an important role on HCC development. The patients with AFP 4 10 ng/ml at
both baseline and EOT had the highest risk to HCC, however they achieved
SVR. Hence, an intensified HCC surveillance should be performed in these
patients.
Disclosure of Interest: None declared
P0072 INFLUENCE OF HBV REACTIVATION ON THE RECURRENCE
OF HEPATITIS B-RELATED HEPATOCELLULAR CARCINOMA
AFTER CURATIVE RESECTION IN PATIENTS WITH LOW VIRAL
LOAD
W. Sohn1,*, Y.-H. Paik1, J.Y. Cho1, G.-Y. Gwak1, M.S. Choi1, J.H. Lee1,
K.C. Koh1, S.W. Paik1, B.C. Yoo1
1
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul,
Korea, Republic Of
Contact E-mail Address: hand1@dreamwiz.com
INTRODUCTION: It is unclear whether the reactivation of hepatitis B virus
(HBV) influences the prognosis of hepatocellular carcinoma (HCC) after resec-
tion in patients with chronic hepatitis B. The aim of this study was to identify the
effect of HBV reactivation on the recurrence of hepatitis B-related HCC after
curative resection in patients with low viral load (HBV DNA 52.000 IU/mL).
AIMS & METHODS: We retrospectively analyzed a total of 130 patients who
underwent curative resection for HBV-related early-stage HCC (single nodule;
55 cm / two or three nodules; 53 cm) with preoperative HBV DNA level
52.000 IU/mL and serial check-up on HBV DNA. The predictive factors includ-
ing HBV reactivation for the recurrence of HBV-related HCC after curative
resection were investigated. HBV reactivation was deEned as the reemergence
or an increase of more than 10-fold in serum HBV DNA as compared with the
level before resection.
RESULTS: Fifty-three patients (41%) had HBV reactivation after resection
among 130 patients. HBV reactivation was observed in 22 of 53 patients with
undetectable baseline HBV DNA and in 31 of 77 patients with detectable HBV
DNA. Cumulative recurrence rates after resection at 1, 2, and 3 years were
17.0%, 23.3%, and 31.4%, respectively. The multivariable analysis demonstrated
that the risk factors for the recurrence were the presence of microvascular inva-
sion (hazard ratio (HR) 2.62, p 0.003), multi-nodularity (HR 4.61, p 0.005),
HBV reactivation after resection (HR 2.03, p 0.032), and HBeAg positivity
(HR 2.06, p 0.044).
CONCLUSION: HBV reactivation after curative resection was associated with
the recurrence of HBV-related HCC in patients with low viral load. This study
suggests that aggressive viral suppression by anti-viral therapy can help to reduce
the recurrence of HCC after resection in chronic hepatitis B with low viral load.
Disclosure of Interest: None declared
P0073 A STUDY OF PLASMA PROLIDASE ACTIVITY IN CASES WITH
AND WITHOUT HEPATOCELLULAR CARCINOMA IN THE
SETTING OF UNDERLYING CIRRHOSIS
_
S. Uygun Ilikhan 1
, M. Bilici1, H. Sahin1, I. I. Oz2, M. Can3, M.C. Buyukuysal4,
Y. Ustundag5,*
1
Internal Medicine, 2Radiology, 3Biochemistry, 4Biostatistics, 5Gastroenterology,
Bulent Ecevit University Medical Faculty, Zonguldak, Turkey
Contact E-mail Address: yucelustundag@yahoo.com.tr
INTRODUCTION: Cancer cell prolidase enzyme activity has been reported to
be important for tumor invasiveness and metastasis. As far as we know, plasma
prolidase activity (PPA) has not been studied in patients with hepatocellular
carcinoma (hcc).
AIMS & METHODS: We aim to assess the correlation between the PPA and
AFP levels in patients with hepatocellular carcinoma. A total of 51 patients with
cytopathological diagnosis of HCC in the setting of cirrhosis, 31 patients with
cirrhosis without HCC and 33 cases as healthy volunteers were enrolled in this
study. There were no significant differences with respect to gender and age of the
study cohort with the healthy group. The patients with HCC were divided into
groups according to tumor size, number and presence of vascular invasion.
Barcelona-Clinic Liver Cancer (BCLC) criteria was used for staging of patients
with hcc. PPA was measured spectrophotometrically. AFP level was measured
with immunoassay method.
RESULTS: PPA was significantly higher in cases with HCC than cases with
cirrhosis without HCC and, healthy controls (1182 U/L versus 932 U/l and
880 U/l, respectively). Patients with cirrhosis had PPA similar to those of healthy
controls (p40.05). PPAs differed significantly in the group of tumor diameters
less than 3 cm (n:13), compared to the group of tumor diameters between 3-5 cm
(n:9) and more than 5 cm (n: 29) ((p 0.003) According to the tumor number, a
significant difference has been seen in the group which has more than two tumors
compared to the group which has one (p 0.001) and two tumors (p 0.027).
A151
PPA also differed in patients with regard to BCLC staging classification
(p 0.003). However, prolidase levels showed no statistically significant differ-
ence with presence of macrovascular invasion in patients with HCC (p 0.898).
There was a significant positive correlation between PPA and serum AFP values
(r 0.731; p50.001)
CONCLUSION: To our knowledge, this is the first study reporting increased PPA
in patients with HCC, and it was found to be significantly associated with size,
number and BCLC stage of the tumor. This was not seen in patients with cirrhosis
without HCC. Furthermore, PPA significantly associated with serum AFP levels.
However, further studies should be done to clarify clinical significance and patho-
physiological role of augmented prolidase activity in cases with HCC.
REFERENCES
Myara I, Myara A, Mangeot M, et al. Plasma prolidase activity: a possible index
of collagen catabolism in chronic liver disease. Clin Chem 1984; 30: 211215.
Peng SY, Chen WJ, Lai PL, et al. High alpha-fetoprotein level correlates with
high stage, early recurrence and poor prognosis of hepatocellular carcinoma:
significance of hepatitis virus infection, age, p53 and beta-catenin mutations.
Int J Cancer 2004; 112: 44-50.
Lu XY, Xi T, Lau WY, et al. Pathobiological features of small hepatocellular
carcinoma: correlation between tumor size and biological behavior. J Cancer Res
Clin Oncol 2011; 137: 567-575.
Disclosure of Interest: None declared
P0074 VALUE OF ESOPHAGOGASTRODUODENOSCOPY IN
PATIENTS REFERRED FOR CHOLECYSTECTOMY: A
SYSTEMATIC REVIEW AND META-ANALYSIS
M. Lamberts1,2,*, C. Ozdemir3, W. Kievit3, G. Westert4, C.van Laarhoven1,
J. Drenth2
1
Surgery, 2Gastroenterology and Hepatology, 3Health Evidence, 4Scientific
Institute for Quality of Healthcare (IQ healthcare), Radboud University Medical
Center, Nijmegen, Netherlands
Contact E-mail Address: Mark. Lamberts@Radboudumc.nl
INTRODUCTION: Up to 33 percent of patients with symptomatic cholelithiasis
report persisting abdominal pain after cholecystectomy, suggesting alternative
causes for these symptoms. Esophagogastroduodenoscopy (EGD) may serve as
a tool to identify additional symptomatic abdominal disorders beforehand, in
order to avoid unnecessary gallbladder surgery. There is controversy whether
routine EGD prior to cholecystectomy is appropriate.
AIMS & METHODS: We performed a systematic review and meta-analysis to
assess the value of EGD prior to cholecystectomy. A systematic literature search
was conducted in Pubmed, Embase, Web of Science, ClinicalTrials.gov, and the
Cochrane library. All studies were included that reported the proportion of
patients who were referred for cholecystectomy, but in whom surgery could be
avoided after treatment of abnormalities detected with EGD. Pooled estimates
were calculated using a random effects model.
RESULTS: Twelve eligible studies were included with a total of 6.317 patients
with cholelithiasis receiving EGD. The pooled estimate of abnormalities detected
with EGD was 36.3% (95% CI, 28.0-45.0). Treatment of these findings avoided
cholecystectomy in 11.0% (95% CI, 3.9-21.1) of patients. In a total of 3.8%
(95% CI, 1.4-7.6) of patients referred for cholecystectomy who underwent
prior EGD, gallbladder surgery was avoided.
CONCLUSION: Our study indicated that the value of prior EGD in preventing
gallbladder surgery is limited. EGD should only be considered selectively in
patients with cholelithiasis referred for cholecystectomy.
Disclosure of Interest: None declared
P0075 REFERENCE RANGES OF SERUM BILE ACID IN CHILDREN
AND ADOLESCENTS
E. Zohrer1,*, B. Stering1, G. Fauler2, H. Scharnagl2, J. Jahnel1, A. Hauer 1,
T. Stojakovic 2
1
Department of Paediatrics and Adolescent Medicine, 2Clinical Institute of Medical
and Chemical Laboratory Diagnostics, Medical University Graz, Graz, Austria
Contact E-mail Address: evelyn_zoehrer@gmx.at
INTRODUCTION: Serum total bile acid (tBA) concentrations are prognostic
and predictive markers for hepatic disorders. Due to the lack of data on normal
value ranges of tBA in children and adolescents we aimed to determine such
ranges as well as the composition of BA in this age group.
AIMS & METHODS: tBA concentration was measured in 194 healthy children
and adolescents (0 - 19 years). Unconjugated and taurine or glycin conjugated
BA were measured by using high performance liquid chromatography tandem
mass spectrometry (HPLC MS/MS). Patients were classified in five groups
according to their age: 0-5 months (n 17), 6-24 months (n 13), 3-5 years
(n 22), 6-11 years (n 44), and 411 years (n 98), respectively.
RESULTS: tBA values found in children were significantly higher compared to
reference ranges in adults (0.28 6.50 mmol/l). Serum tBA increased constantly
after delivery (0-5 months: 3.85 6.32 mmol/l) and reached a peak at the age of 6-
24 months (6.61 9.43 mmol/l). Henceforward tBA decreased continuously (3-5
years: 4.27 6.43 mmol/l, 6-11 years: 3.61 5.14 mmol/l and 411 years: 3.10
4.12 mmol/l). In neonates levels of taurine conjugated BA were elevated; however,
after 6 months glycine conjugated clearly predominated.
CONCLUSION: This study shows that serum tBA levels vary substantially in
the first years of life indicating age-dependent reference ranges for tBA and the
BA profile; the causes of the variations need further clarification.
REFERENCES
Barbara L, Lazzari R, Roda A, et al. Serum bile acids in newborns and children.
Pediatr Res 1980; 14: 1222-1225.
Chiang JY. Bile acids: regulation of synthesis. J Lipid Res 2009; 50: 1955-1966.
A152
Hofmann AF. The continuing importance of bile acids in liver and intestinal
disease. Arch Intern Med 1999; 159: 2647-2658.
Niijima S. Studies on the conjugating activity of bile acids in children. Pediatr
Res 1985; 19: 302-307.
Polkowska G, Polkowski W, Kudlicka A, et al. Range of serum bile acid con-
centrations in neonates, infants, older children, and in adults. Med Sci Monit
2001; 7(Suppl 1): 268-270.
Disclosure of Interest: None declared
P0076 EUS-GUIDED DRAINAGE WITH A LUMEN APPOSING METAL
STENT IS FEASIBLE FOR THE TREATMENT FOR ACUTE
CHOLECYSTITIS IN HIGH RISK PATIENTS
D. Walter1,*, A.Y. Teoh2, T. Itoi3, M. Perez-Miranda4, A. Larghi5, A. Sanchez-
Yague6, P.D. Siersema1, F.P. Vleggaar1
1
Dept. of Gastroenterology and Hepatology, University Medical Center Utrecht,
Utrecht, Netherlands, 2Dept. of Surgery, Prince of Wales Hospital, Chinese
University of Hong Kong, Hong Kong, China, 3Dept. of Gastroenterology and
Hepatology, Tokyo Medical University, Tokyo, Japan, 4Dept. of Gastroenterology,
Unit of Gastrointestinal Endoscopy, University Hospital Rio Hortega, Valladolid,
Spain, 5Dept. of Gastroenterology, Digestive Endoscopy Unit, Catholic University,
Rome, Italy, 6Dept. of Digestive Disease, Endoscopy Unit, Agencia Sanitaria Costa
del Sol, Marbella, Spain
Contact E-mail Address: d.walter@umcutrecht.nl
INTRODUCTION: Percutaneous gallbladder drainage is the treatment of choice
in high-risk surgical patients with acute cholecystitis. However, it is associated
with discomfort and risk of inadvertent drain removal which may lead to bile
leakage and recurrent cholecystitis. Recently, EUS-guided drainage has been
introduced as an alternative treatment option.
AIMS & METHODS: Our aim was to determine the feasibility and safety of
EUS-guided gallbladder drainage with a lumen apposing metal stent (AXIOS) in
patients with acute cholecystitis at high risk for surgery. We performed a pro-
spective, multicenter study. Stent removal was scheduled after 3 months and
patients were followed until 9 months after removal. Study endpoints included
safety, recurrent symptomatic cholecystitis, clinical and technical success.
RESULTS: Between June 2012 and Feb 2014, 30 patients were included (11 men
(37%), mean age 857 years). Median time between onset of symptoms and stent
placement was 2 days (range 1-28 days). The majority of patients (87%) pre-
sented with calculous cholecystitis. In 11 patients (37%) a transgastric approach
and in 19 patients (63%) a transduodenal approach was used. Stent placement
was technically successful in all patients (100%), but in 4 patients (13%) a second
stent was placed due to problems with stent deployment. Clinical success was
achieved in all but one patient (97%) after a median of 3 days (IQR 3-5 days). In
one patient with ongoing fever for 14 days, endoscopic irrigation was successfully
performed through the stent to drain large amounts of pus from the gallbladder.
Stent removal was successfully performed in 12 patients (40%) after a median of
91 days (range 15-133), of which one was evaluated as being difficult due to tissue
overgrowth (125 days). In 18 patients (60%) no stent removal was performed,
including 2 patients (2%) with significant tissue overgrowth (105 and 150 days), 5
patients (17%) with follow-up 53 months, 5 unrelated deaths 53 months
(17%), 4 patients (13%) with a poor clinical condition, 1 patient (3%) with a
polypoid lesion in the gallbladder and 1 patient (3%) with lingering stones.
Causes of death included urosepsis (n 1), pneumonia (n 1), myocardial
infarction (n 1) and progression of pancreatic adenocarcinoma (n 2). Major
complications were reported in 4 patients (13%). One patient presented with
melena due to mucosal gangrene of the gallbladder for which endoscopic irriga-
tion of the gallbladder was performed. One patient developed fever due to food
contents in the gallbladder for which stent removal was performed. This patient
also developed acute biliary pancreatitis 21 days later. Two patients developed
symptoms of cholestasis due to common bile duct stones for which ERCP was
performed. During a mean follow-up of 212 days (95% CI 149-274) none of the
patients developed recurrent cholecystitis.
CONCLUSION: EUS-guided gallbladder drainage with a lumen apposing stent
was found to be feasible in high-risk surgical patients with a high clinical success
rate. Difficulties with stent deployment was seen in approximately 15% of
patients. The overall number of major complications was low, but tissue over-
growth may complicate stent removal.
Disclosure of Interest: D. Walter: None declared, A. Teoh: None declared, T. Itoi
Consultancy for: Xlumena Inc. (Mountain View, CA, USA), M. Perez-Miranda:
None declared, A. Larghi: None declared, A. Sanchez-Yague: None declared, P.
Siersema: None declared, F. Vleggaar: None declared
P0077 THE EFFECT OF PERIAMPULLARY DIVERTICULUM ON THE
CLINICAL PRESENTATION OF CHOLEDOCHOLITHIASIS AND
OUTCOME AFTER ERCP
F. Benjaminov1,*, A. Stein1, V. Bieber1, T. Naftali1, F.M. Konikoff1
1
Gastroenterology and Hepatology, Meir medical center, Kfar Saba, Israel
Contact E-mail Address: fabianabenjaminov@gmail.com
INTRODUCTION: Periampullary diverticulum (PAD) is an incidental finding in
up to 20% of ERCPs. Its incidence increases with age. PAD is associated with
CBD stones and is considered a risk factor for obstructive jaundice, cholangitis
and pancreatitis even in the nascence of CBD stones. However, the impact of
PAD on the presentation and consequences in patients with CBD stones is
unclear.
AIMS & METHODS: The aim of our study was to investigate the effect of PAD
on the clinical presentation and course of patients with
suspectedcholedocholithiasis.
United European Gastroenterology Journal 2(5S)
All ERCPs performed in our unit from 1/2010 to 7/2013 were reviewed. Studies
performed for documented or suspected choledocholithiasis were included in the
study. Patients were divided into two groups. Group I- patients without PAD
and group II- with PAD. The following data were recorded: Age, gender, comor-
bidities, indication for ERCP, previous imaging studies, liver function tests, pre-
sence of gallbladder, prior sphincterotomy, CBD diameter,ERCP success and
complications, as well as the presence, size and type of PAD.
RESULTS: Three hundred and two patients met the inclusion criteria. Mean age
was 66.4  20.5y (range 19-98), 173 (57.3%) women. Altogether, 86 patients
(28.4%) had PAD. Ninety-nine percent of ERCPs were successful. Two hundred
and fifty-three patients (83.8%) had CBD stones on ERCP. Significant compli-
cations (pancreatitis, perforation, death) were recorded in 14 patients (6.5,3,
respectively) (4.6%). Patients with PAD were older (73.416.2y Vs
63.621.4y) and predominantly male (53.5% Vs 38.4%), p50.01. Patients
with PAD presented more often with cholangitis compared to those without
PAD (58.1% Vs 34.6%, p5 0.001). There were no differences between the two
groups regarding imaging findings, laboratory tests, presence of gallbladder,
comorbidities, procedural success, prior ERCP, inadvertent pancreatic duct can-
nulation, presence of CBD stones, number and size of CBD stones, procedure
related complications and their severity, or number of ERCPs for stone
clearance.
CONCLUSION: PAD is a risk factor for infectious complications ofcholedocho-
lithiasis. However, the presence of PAD does not predispose patients to misin-
terpretation of imaging studies, procedural difficulty, failure or complications of
ERCP.
REFERENCES
1) Zoepf T, Zoepf DS, Arnold JC, et al. The relationship between juxstapapillary
duodenal diverticula and disorders of the biliopancreatic system: analysis of 350
patients. Gastrointest Endoscopy 2011: 54; 56-61.
2) Wu SD, Su Y, Fan Y, et al. Relationship between intraduodenal periamoul-
lary diverticulum and biliary disease in 178 patients undergoing ERCP.
Hepatobiliary Pancreat Dis Int 2077: 6; 299-302.
3) Egawa N, Anjiki H, Takuma K, et al. juxstapapillary duodenal diverticula and
pancreaticobiliary disease. Dig Surg 2010: 27; 105-109.
4) San-Roman AL, Moreira VF, Garcia M, et al. Dirrect compression by duo-
denal diverticulum causing biliary obstruction. Endoscopy 1994: 26; 334.
5) Castilho Netto JM and Speranzini MB. Ampullary duodenal diverticulum and
cholangitis. Sao Pablo Med J 2003; 121: 173-175.
Disclosure of Interest: None declared
P0078 MULTICENTER TRIAL FOR EFFICACY OF MAGNESIUM
TRIHYDRATE OF UDCA AND CDCA (CNU)FOR GALLSTONE
DISSOLUTION
H.S. Lee1,*, C.D. Kim1, S.O. Lee2, T.N. Kim3, J. Lee4, J. Ryu5, E.T. Park6,
I.S. Lee7, D.H. Lee8, S.H. Dong9, J.H. Kim10 on behalf of Korean Gallstone
Study Group
1
Division of Gastroenterology, Dept. of Internal Medicine, Korea University
College of Medicine,Dept. of Gastroenterology, Seoul, 2Division of
Gastroenterology, Dept. of Internal Medicine, Cheonbuk University, Cheonjoo,
3
Division of Gastroenterology, Dept. of Internal Medicine, Youngnam University,
Deagu, 4Division of Gastroenterology, Dept. of Internal Medicine, Hanllym
University, 5Division of Gastroenterology, Dept. of Internal Medicine, Seoul
National University, Seoul, 6Division of Gastroenterology, Dept. of Internal
Medicine, Gosin University, Busan, 7Division of Gastroenterology, Dept. of
Internal Medicine, Catholic University, Seoul, 8Division of Gastroenterology, Dept.
of Internal Medicine, Inha University, Inchon, 9Division of Gastroenterology, Dept.
of Internal Medicine, Kyunghee University, Seoul, 10Division of Gastroenterology,
Dept. of Internal Medicine, Ajou University, Suwon, Korea, Republic Of
Contact E-mail Address: hslee60@korea.ac.kr
INTRODUCTION: The gallstone is still a most prevalent medical issues in the
pancreatobiliary system. Laparoscopic cholecystectomy is a treatment of choice;
however, oral litholysis with bile acids has been an attractive alternative thera-
peutic option for asymptomatic or mild symptomatic subgroups.
Ursodeoxycholic acid (UDCA) and chenodeoxycholic acid (CDCA) or both
had been investigated for their effectiveness on stone dissolution. Recently, the
prevalence of gallstones has increased due to the wide availability of sonographic
examination and dietary habit modification. We conducted a prospective, multi-
center, phase IV clinical study to evaluate the efficacy of magnesium trihydrate of
UDCA and CDCA for gallstone dissolution at present.
AIMS & METHODS: The objects of this study are to evaluate the effects of
CNU on GB stone dissolution and to assess the improvement of stone asso-
ciated symptoms and to find out predictive factors for gallstone dissolution.
In total 10 medical centers in Korea participated in the investigation from Jan
2011 to June 2013. Inclusion criteria were; GB stone (diameter 515mm) in
sonography, GB EF  50% in DICIDA biliary scan, radiolucent on Plain X-
ray and asymptomatic or mild symptomatic patients. Exclusion criteria were: age
under 18 years, complicated GB stones, patients with severe co-morbidity, abnor-
mal LFT (ALT 42x N). The treatment consisted of 1 tablet (114mg of UDCA
and 114mg of CDCA) at morning and 2 tables at bedtime. Patients were followed
up at 1Mo, 3Mo and 6Mo for LFT, symptom score and ultrasonography (6Mo)
RESULTS: Total 236 cases were enrolled and 196 cases (Male 87, Female 109,
mean age 54.812.8)) were finished the study and were analyzed. Complete
dissolution was achieved in 13.3% after 6 months administration of CNU.
Partial dissolution (defined as reduction in volume more than 25%) was
32.1%. Overall response rate was 45.4%. Stone size and BMI are factors for
predicting gallstone dissolution. Gallbladder ejection fraction is not a predictive
factor for dissolution. CNU treatment showed significant symptomatic improve-
ments regardless of stone dissolution.
United European Gastroenterology Journal 2(5S)
CONCLUSION: Magnesium trihydrate of UDCA and CDCA (CNU) is a well
tolerated and effective agent for gallstone dissolution. However, a substantial
portion of gallstones are still ineffectively treated with CNU. This group may
have pigment stones rather than cholesterol stones. Further study is needed to
evaluate effect of longer Tx duration and recurrent rate after cessation of Tx.
Development of methods for predicting chemical composition of gallstones is
warrant for selecting good candidates for medical dissolution Tx.
Disclosure of Interest: None declared
P0079 SIZE OF RECURRENT SYMPTOMATIC COMMON BILE DUCT
STONES AND FACTORS RELATED TO RECURRENCE
J.H. Chang1,*, M. Park1, C.W. Kim1, S.W. Han1
1
Internal Medicine, The Catholic University of Korea, Bucheon, Korea,
Republic Of
INTRODUCTION: Common bile duct (CBD) stones can be treated successfully
by endoscopic stone extraction. Unfortunately, 4% to 24% of patients have
recurrent CBD stones after the initial extraction of CBD stones. Some patients
even have multiple recurrences. Unfortunately, little information is available on
the size and recurrence interval of recurrent symptomatic CBD stones or on ways
to prevent recurrence.
AIMS & METHODS: Between January 2007 and December 2011, 481 consecu-
tive patients undergoing endoscopic extraction of CBD stones at a single institute
were enrolled. We selected 34 patients with recurrent symptomatic CBD stones
and 63 patients who were followed up more than five years without recurrence.
We evaluated the role of endoscopic papillary large-balloon dilation (EPLBD) (
10 mm) in preventing the recurrence of CBD stones while identifying risk factors
related to recurrence. Furthermore, the characteristics of symptomatic recurrent
CBD stones and the interval of recurrence were investigated in patients with the
first, second, and third recurrences of CBD stones.
RESULTS: The sizes of the CBD stones increased during the recurrences: 10.1 
5.2 mm, 13.5  7.3 mm, and 16.8  7.8 mm at the initial presentation, the first
recurrence, and the second recurrence, respectively (P 0.016). Among CBD
stone recurrences, 50% occurred within 2.3 years, and 80% occurred within
5.3 years. The recurrence group had a smaller proportion of patients under 50
years of age, larger CBD diameters, fewer histories of more than 10 mm EPLBD,
and more type I periampullary diverticula, compared with the non-recurrence
group (P 5 0.05). Multivariate analysis revealed that EPLBD more than 10 mm
and smaller CBD diameter were independently related to less recurrence of CBD
stones (P 0.001 and 0.012, respectively).
Table. Multivariate analysis of the factors related to the recurrence of common
bile duct stones
Factors OR (95% CI) P value
Endoscopic papillary large- 0.161 (0.055 0.473) 0.001
balloon dilation ( 10 mm)
CBD diameter 1.126 (1.027 1.235) 0.012
Type I periampullary 3.322 (0.608 18.17) 0.166
diverticulum
Age (5 50) 0.314 (0.073 1.360) 0.122
CONCLUSION: The sizes of CBD stones increased during recurrences. EPLBD
more than 10 mm and smaller CBD diameter were related to less recurrence of
CBD stones.
Disclosure of Interest: None declared
P0080 A COMPARATIVE STUDY BETWEEN PTGBD AND ETGD AS A
BRIDGE TO SURGERY IN PATIENTS WITH ACUTE
CHOLECYSTITIS AND A SUSPICION OF CBD STONE
J.H. Kim1,*, M.J. Yang1, B.M. Yoo1
1
Gastroenterology, Ajou Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: To compare the technical feasibility, clinical and surgical
outcomes between a single-step approach of endoscopic removal of CBD
stones with endoscopic transpapillary gallbladder drainage (ETGD group) and
a two-step approach of endoscopic removal of CBD stones and percutaneous
transhepatic gallbladder drainage (PTGBD group) as a bridge treatment before
cholecystectomy, in patients with acute cholecystitis and a high suspicion of
common bile duct (CBD) stones.
AIMS & METHODS: From March 2006 to May 2013, a total of 79 patients
were enrolled in this study retrospectively. The PTGBD group (n 39) was
compared with the ETGD group (n 40, ENGBD: 22, ERGBD: 18) in terms
of technical and clinical success rates, adverse events, and surgical outcomes of
surgery time and rate of conversion to open surgery in the non-inferiority
analysis.
RESULTS: PTGBD and ETGD groups had similar outcomes in terms of tech-
nical success rate (97.4% 38/39 vs 92.5% 37/40; 95% 1-sided confidence interval
(CI) lower limit, -14.6%; p 0.028 for noninferior margin of 15%) and clinical
success rate (94.7% 36/38 vs 91.9% 34/37; 95% 1-sided CI lower limit, -12.9%;
p 0.045 for noninferior margin of 15%). The two groups did not differ signifi-
cantly in the rates of adverse events (5.1% 2/39 vs 7.5% 3/40; p 1.000), surgery
time (59.3 vs 55.7 min; p 0.361), rates of conversion to open cholecystectomy
(5.2% 2/38 vs 0% 0/37; p 0.135). There was no significant differences in the
technical, clinical, and surgical outcomes between ENGBD and ERGBD groups
respectively.
A153
CONCLUSION: In patients with acute cholecystitis and a high suspicion of
CBD stones, the single-step approach through ERCP and simultaneous ETGD
could be an effective alternative treatment modality to the two-step approach
through PTGBD followed by ERCP.
Disclosure of Interest: None declared
P0081 VISCERAL ABDOMINAL FAT MEASURED BY CT SCAN IS
ASSOCIATED WITH AN INCREASED RISK OF SYMPTOMATIC
GALLSTONE DISEASE
K. Sekine1,*, N. Nagata1, K. Watanabe1, S. Mikami1, Y. Nozaki1, T. Sakurai1,
C. Yokoi1, Y. Kojima1, M. Kobayakawa1, J. Akiyama1, M. Yanase1
1
National Center for Global Health and Medicine, Tokyo, Japan
Contact E-mail Address: hawaiiantuberider@gmail.com
INTRODUCTION: Previous studies have shown that obesity measured as BMI
is a causal risk of gallstone disease. Visceral fat promotes systemic inflammation
by secreting adipokines and inflammatory cytokines.
AIMS & METHODS: This study aims to investigate whether visceral fat mea-
sured by computed tomography (CT) is a risk factor for symptomatic gallstone
disease (cholangitis or cholecystitis). A total of 582 participants (451 without
gallstone and 131 symptomatic gallstone disease) who underwent CT and
abdominal ultrasonography were analyzed. The associations between body
mass index (BMI), visceral adipose tissue (VAT) area, subcutaneous adipose
tissue (SAT) area, and symptomatic gallstone disease were estimated using
odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, sex,
dyslipidemia, and diabetes mellitus.
RESULTS: In multivariate analysis, symptomatic gallstone disease was signifi-
cantly associated with VAT area and SAT area (P for trend 50.001, and 0.045,
respectively), but not BMI (P for trend 0.40). When the obesity indices were
considered simultaneously, symptomatic gallstone disease remained significantly
associated with VAT area for both categorical data and trend (P for trend 0.003),
but not BMI (P for trend 0.536). The adjusted ORs for the highest quartile of the
VAT area in gallstone disease were 3.2, compared with the lowest quartile.
CONCLUSION: Abdominal visceral tissue measured by CT, rather than BMI, is
a better predictor for risk of symptomatic gallstone disease.
Disclosure of Interest: None declared
P0082 POSITIVE PREDICTIVE VALUE OF ENDOSCOPIC
ULTRASOUND (EUS) FOR THE DETECTION OF INTRALUMINAL
FILLING DEFECTS IN THE COMMON BILE DUCT (CBD) IN A
LARGE NON-ACADEMIC TEACHING HOSPITAL
L.Van Driel1,*, R. Quispel1, B. Veldt1, M. Bruno2
1
Reinier de graaf hospital, Delft, 2Erasmus medical centre, Rotterdam, Netherlands
Contact E-mail Address: L.vandriel@rdgg.nl
INTRODUCTION: In small academic studies, endoscopic ultrasound has been
shown a reliable and safe method to assess the presence of common bile duct
stones.
AIMS & METHODS: The aim of this study was to calculate the positive pre-
dictive value (PPV) for the presence of CBD stones with EUS. For this we
retrospectively included all patients in whom CBD stones were detected with
EUS and who subsequently underwent endoscopic retrograde cholangiography
(ERC). This study was performed in a large non-academic teaching hospital in
The Netherlands between November 2006 and January 2011. PPV was calculated
by dividing the number of true positives by the total number.
RESULTS: EUS detected CBD stones in 99 patients who subsequently under-
went ERC. The median time-interval between EUS and ERC was 5 days (inter-
quartile range 1-15 days). The PPV for the total group was only 56% (57/99).
However, the PPV depended on the time-interval between EUS and ERC, being:
80% (8/10) within 24 hours, 63% (32/51) within 1-6 days, and 47% (18/38) after
one week. Moreover, the PPV differed substantially depending on the type and
number of intraluminal filling defects in the CBD, namely sludge (10/21, PPV
48%), or one stone (29/51, PPV 58%), or more than one stone (18/24, PPV 75%),
or more than one stone with acoustic shadow (8/10, PPV 80%).
CONCLUSION: EUS performed in a large non-academic teaching hospital has
a lower PPV for detection of CBD stones than overall reported in literature. This
seems to be explained at least in part by the large variation in time-intervals
between EUS and ERC indicating that ERCP should promptly follow a positive
EUS and may be delayed a few days after the onset of symptoms to allow for
spontaneous stone passage. Sludge in the CBD as finding on EUS has the lowest
PPV when compared with stones with or without an acoustic shadow.
Disclosure of Interest: None declared
P0083 WHICH IS A BETTER PROCEDURE: SINGLE SESSION VERSUS
MULTIPLE SESSIONS OF ERCP FOR COMMON BILE DUCT
STONES WITH OR WITHOUT ACUTE CHOLANGITIS?
R. Maeshima1,*, M. Asano1, H. Kobashi1, H. Himei1, S. Inoo1, M. Omori1,
S. Ando1, E. Yoshimura1, M. Shigetoshi1, J. Toshimori1, M. Inoue1,
M. Yokoyama1
1
Gastroenterology and hepatology, Japanese Red Cross Okayama Hospital,
Okayama city, Japan
INTRODUCTION: Tokyo guidelines (TG13) for management of acute cholan-
gitis (AC) and acute cholecystitis were revised and published in 2013. TG13
recommend the elective, early or urgent biliary drainage using endoscopic retro-
grade cholangiopancreatography (ERCP), followed by treatment of etiology
such as common bile duct (CBD) stones after the resolution of AC. However,
A154
the usefulness of completion of endoscopic clearance of CBD stones with biliary
drainage in a single session, remains unclear.
AIMS & METHODS: The aim of this study is to clarify which of these, a single
session or multiple sessions of ERCP, is better for the patients with CBD stones
with and without AC. This is a retrospective study. Between August 2012 and
March 2014, a total of 411 ERCPs were performed in 252 patients with biliary
and pancreatic diseases in our hospital. The patients with CBD stones with or
without AC treated with ERCP-related procedure were eligible for the study. The
patients with recurrent disease were excluded. Finally 116 consecutive patients
(56 males and 60 females) were included in the study. They were divided into two
groups; Group A for the patients in a single session of ERCP, and Group B for
those in multiple sessions of ERCP. Groups A and B were compared with each
other for the clinical outcomes, namely total duration of hospitalization (DH)
and frequency of adverse events. The grade of AC, Grade I (mild), Grade II
(moderate) and Grade III (severe), were also taken into account. Wilcoxon/
Kruskal-Wallis test and Kaplan-Meier analysis were used as statistics. This
study was approved by the local committee of ethics.
RESULTS: Group A and Group B was consisted of 84 and 32 patients, respec-
tively. Mean age was 72.4 in Group A and 78.8 in Group B. The sphincterotomy
and the maneuver using retrieval basket or balloon were performed more fre-
quently in Group A (p50.001). In total, 74 patients were complicated with AC;
grade I in 44, grade II in 17 and grade III in 13, and 42 patients were without AC.
In Group A, grade I in 35, grade II in 10 and Grade III in 5, and without AC in
34 patients, respectively. In Group B, grade I in 9, grade II in 7 and grade III in 8,
and without AC in 8 patients, respectively. The mean DH was 12.7 days in total.
It was significantly shorter in Group A (9.9 days), as compared with Group B
(20.1 days) (p50.001). In total, DH was incrementally longer according to the
degree of AC grade (p50.0001); it was significantly longer (32.0 days) in grade
III, as compared with Grade I (11.3 days), grade II (15.6 days) and without AC
(7.0 days). In the patients with AC grade III, DH was significantly shorter in
Group A (18.0 days) as compared with Group B (40.75 days) (p 0.0437). Also
in the patients without AC, DH was significantly shorter in Group A (6.4 days)
as compared with Group B (9.9 days) (p 0.033). As for adverse events, post
ERCP pancreatitis was occurred in 4 patients in Group A and in 1 patient in
Group B, and there was no significant difference between both groups (p 0.69).
CONCLUSION: A single session of ERCP for completion of clearance of CBD
stones with biliary drainage is superior to multiple sessions of ERCP, especially
for the patients complicated with AC grade III and those without AC.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
PANCREAS I POSTER EXHIBITION HALL XL_____________________
P0084 THE ROLE OF PROINFLAMMATORY CYTOKINES AND
ADHESION MOLECULES IN VASCULAR DISORDERS AND
ORGAN DYSFUNCTION IN ACUTE PANCREATITIS PATIENTS
I. Osmilovska1,*, S. Chooklin1, O. Usach1
1
Regional Clinical Hospital, Lviv, Ukraine
Contact E-mail Address: docihor@ukr.net: chooklin_serge@hotmail.com
INTRODUCTION: The main component in the pathogenesis of acute pancrea-
titis is the transition from local to the system inflammation that causes the
severity of disease. Changes of microcirculation and endothelial dysfunction
are an important step from mild to severe disease.
AIMS & METHODS: The study involved 53 acute pancreatitis patients (28 -
severe, 25 - mild). We measured interleukin-6, interleukin-18, ICAM-1 and E-
selectin in the blood plasma. Flow in the visceral arteries was assessed with the
help of the Doppler sonography.
RESULTS: A significant increase of both pro-inflammatory cytokines and adhe-
sion molecules was determined only in severe acute pancreatitis. We determined
that the level of IL-6 significantly correlated with the appearance of liver dys-
function. There was a significant correlation between the concentration of IL-18,
ICAM-1, E-selectin and the appearance of multiple organ dysfunction syndrome.
There was a significant direct correlation concentrations of IL-6 with peak sys-
tolic velocity in the superior mesenteric artery (R 0.502941, p 0.047063), with
an index of resistance in common hepatic (R 0.532845, p 0.033574), splenic
(R 0.511125, p 0.043028) and superior mesenteric (R 0.563200,
p 0.023107) arteries. The level of IL-18 was significantly correlated with peak
systolic velocity in the common hepatic artery (R 0.589102, p 0.016342),
splenic artery (R 0.547865, p 0.028022) and superior mesenteric artery
(R 0.504783, p 0.046131), as well as the resistance index in the common
hepatic artery (R 0.524375, p 0.037051) and superior mesenteric artery
(R 0.573230, p 0.020271). The level of ICAM-1 was significantly correlated
with changes in blood flow in the visceral vessels, in particular, peak systolic
velocity in the common hepatic artery (R 0.802061, p 0.000186), splenic
(R 0.764581, p 0.000,562) and the superior mesenteric artery (R 0.768212,
p 0.000509), as well as the resistance index (R 0.527422, p 0.035770;
R 0.608824, p 0.012315; R 0.736152, p 0.001148, respectively) in them.
The level of soluble E-selectin may also affect splanchnic flow in patients with
acute pancreatitis, defined as a significant direct correlation between the concen-
tration dependence of E-selectin and peak systolic velocity of blood flow in the
common hepatic (R 0.838249, p 0.000095) and splenic (R 0.689902,
p 0.004424) arteries and resistance index in the common hepatic
(R 0.710321, p 0.003002) and superior mesenteric (R 0.759862,
p 0.001012) arteries.
CONCLUSION: It was determined that the levels of proinflammatory cytokines
and adhesion molecules increase in the blood of acute pancreatitis patients. Their
level correlates with the organ dysfunction and disturbances in splanchnic blood
flow.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0085 TIMING OF INTERVENTION IN INFECTED NECROTIZING
PANCREATITIS: AN INTERNATIONAL MULTIDISCIPLINARY
SURVEY AND CASE VIGNETTE STUDY
J.van Grinsven1,2,*, S.van Brunschot3, O. Bakker3, T. Bollen4, M. Boermeester5,
M. Bruno6, K. Dejong7, M. Dijkgraaf8, C.van Eijck9, P. Fockens1,
H.van Goor10, H. Gooszen11, K. Horvath12, K.van Lienden13, H.van Santvoort3,
M. Besselink5 on behalf of Dutch Pancreatitis Study Group
1
Gastroenterology and Hepatology, Academic Medical Center, Amsterdam,
2
Research and Development, St. Antonius Hospital, Nieuwegein, 3Surgery,
University Medical Center Utrecht, Utrecht, 4Radiology, St. Antonius Hospital,
Nieuwegein, 5Surgery, Academic Medical Center, Amsterdam, 6Gastroenterology
and Hepatology, Erasmus Medical Center, Rotterdam, 7Surgery, Maastricht
University Medical Center, Maastricht, 8Clinical Research Unit, Academic
Medical Center, Amsterdam, 9Surgery, Erasmus Medical Center, Rotterdam,
10
Surgery, 11OR/Evidence Based Surgery, Radboud University Medical Center,
Nijmegen, Netherlands, 12Surgery, University of Washington Medical Center,
Seattle, United States, 13Radiology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: j.vangrinsven@pancreatitis.nl
INTRODUCTION: It is unclear whether there is consensus regarding the timing
of intervention in patients with infected necrotizing pancreatitis (INP).
AIMS & METHODS: We evaluated the current expert opinion regarding timing
of intervention in INP. An anonymous digital survey was sent to 118 expert
pancreatologists (surgeons, gastroenterologists, radiologists) from all continents.
The survey consisted of 18 questions and 10 clinical cases including CECT images
of varying disease stages. Diagnostic and therapeutic options included fine needle
aspiration (FNA), antibiotics, (percutaneous or endoscopic) catheter drainage
and necrosectomy.
RESULTS: Response rate was 74% (N 87). The step-up approach, initial
catheter drainage if needed followed by necrosectomy, was accepted by most
experts (87%). Consensus was lacking regarding the use of FNA to diagnose
INP: 0% used FNA routinely, 40% only in case of clinical suspicion, 45% rarely
and 15% never. After definitively diagnosing INP, 55% would postpone an
intervention and await the effect of antibiotics, whereas 45% would immediately
perform an intervention. Walled-off necrosis was not considered a technical
prerequisite for percutaneous catheter drainage by 88% of experts whereas
66% considered it essential for endoscopic transluminal drainage. More experts
would intervene in case of proven INP (gas in the (peri)pancreatic necrotic col-
lection on CECT) vs. clinical signs of INP: i.e. day 7: 34% vs 2%, day 14: 57% vs
25%, day 30: 89% vs 72%.
CONCLUSION: Although the step-up approach is well accepted as routine
management strategy of INP, consensus regarding the timing of initiating this
approach is lacking. Proof of infection and disease duration influence the timing
of intervention. This study highlights the need for a randomized trial on timing of
intervention in INP.
Disclosure of Interest: None declared
P0086 PREDICTION OF POST-ERCP PANCREATITIS BY 4-HOUR
POST-ERCP SERUM AMYLASE AND LIPASE LEVEL
J.H. Kim1,*, M.J. Yang1
1
Gastroenterology, Ajou Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: Acute pancreatitis is the most common and serious compli-
cation of endoscopic retrograde cholangiopancreatography (ERCP). Early pre-
diction of possible post-ERCP pancreatitis (PEP) could allow for an earlier safe
discharge of a patient on the same day after ERCP.
AIMS & METHODS: The aim of this study was to investigate a predictive cut-
off value of 4-hour post-ERCP serum amylase and lipase levels for the PEP. In
patients who underwent ERCP procedures and had tests for serum amylase and
lipase levels of 4-hour post-ERCP and the next morning at Ajou Medical Center
from January 2012 to August 2013, patient demographics, the procedure reasons,
performance of pancreatograms, serum amylase and lipase levels were retrospec-
tively evaluated.
RESULTS: PEP occurred in 16 (3.1%) after 516 ERCP procedures. Its severity
was mild in 4 (25%), moderate in 9 (56.3%), and severe in 3 (18.8%). The mean
4-hour amylase level was significantly higher in patients with PEP, compared
with those without PEP (965 U/L vs. 158 U/L, p 0.001). There were no statis-
tically significant differences in age, gender, and the procedure reasons between
both groups. The sensitivity, specificity and negative predictive value (NPV) of a
4-hour post-ERCP amylase level with a cut-off value of 2.5 times of its normal
upper limit (290 U/L) was 75.0%, 88.0% and 99.1%, respectively. The sensitivity,
specificity and negative predictive value (NPV) of a 4-hour post-ERCP lipase
level with a cut-off value of 8 times of its normal upper limit (480 U/L) was
75.0%, 91.3% and 99.1%, respectively. The patient group undergoing pancrea-
togram revealed high incidence of post-ERCP pancreatitis, but no significant
difference in the 4-hour post-ERCP serum amylase and lipase level, compared
to its counterpart group.
CONCLUSION: The 4-hour post-ERCP serum amylase level and lipase level
with cut-off value of 2.5 times and 8 times of their normal upper limit have so far
proven to be useful predictive values for an earlier safe discharge of a patient on
the same day after ERCP.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0088 PREDICTING SUCCESS OF CATHETER DRAINAGE IN
INFECTED NECROTIZING PANCREATITIS
R.A. Hollemans1,*, T.L. Bollen2, S.van Bruschot3, U. Ahmed Ali4, O.J. Bakker4,
H.van Goor5, M.A. Boermeester6, H.G. Gooszen7, M.G. H. Besselink6, H.C.
van Santvoort4 on behalf of Dutch Pancreatitis Study Group
1
Surgery / Research and Development, University Medical Center Utrecht / St
Antonius Hospital Nieuwegein, Utrecht / Nieuwegein, 2Radiology, St Antonius
Hospital, Nieuwegein, 3Gastroenterology and Hepatology, Academic Medical
Center, Amsterdam, 4Surgery, University Medical Center Utrecht, Utrecht,
5
Surgery, Radboud University Medical Center, Nijmegen, 6Surgery, Academic
Medical Center, Amsterdam, 7Operating Rooms / Evidence Based Surgery,
Radboud University Medical Center, Nijmegen, Netherlands
Contact E-mail Address: H.vanSantvoort@umcutrecht.nl
INTRODUCTION: Catheter drainage as the first treatment step of infected
necrotizing pancreatitis is successful in at least 30% of patients. It is currently
not possible to predict which patients will also need necrosectomy. We evaluated
predictive factors for success of catheter drainage in infected necrotizing
pancreatitis.
AIMS & METHODS: We performed a post-hoc analysis of 130 prospectively
included patients who underwent primary catheter drainage for (suspected)
infected necrotizing pancreatitis. Using logistic regression we evaluated the asso-
ciation between success of catheter drainage (i.e. survival without necrosectomy)
and 22 factors regarding demographics, disease severity (e.g. CRP, APACHE-II
score and organ failure), morphologic characteristics on CT (e.g. percentage and
distribution of necrosis and CTSI) and drainage criteria (e.g. timing of drainage
and type of drain).
RESULTS: Drainage was performed percutaneously in 113 patients and endos-
copically in 17 patients. Infection was confirmed in 116 patients (89%). Catheter
drainage was successful in 45 patients (35%). In multivariable regression, the
following variables were associated with success of drainage: female gender
(odds ratio[OR] 4.84; 95%4 confidence interval[CI] 1.89-12.4; p 0.001),
absence of multi-organ failure (OR 6.19; 95%4CI 1.50-25.53; p 0.012), per-
centage of pancreatic necrosis (530%/30-50%/450%: OR 2.29; 95%4CI 1.21-
4.36; p 0.011), primarily left-sided pancreatic necrosis (OR 13.35; 95%4CI 1-
174; p 0.048) and homogeneity of the collection (OR 5.23; 95%4CI 1.60-
17.05; p 0.006). A prognostic nomogram including these factors yielded prob-
ability of success ranging from 99% (all factors present) to 1% (none of the
factors present).
CONCLUSION: Female gender, absence of multi-organ failure, low percentage
of necrosis, left-sided pancreatic necrosis and a homogeneity of the collection are
independent predictors for success of catheter drainage in infected necrotizing
pancreatitis. The constructed nomogram can easily predict success in clinical
practice.
Disclosure of Interest: None declared
P0089 FUNGAL INFECTION IN PATIENTS WITH WALLED-OFF
PANCREATIC NECROSIS IS ASSOCIATED WITH A POOR
PROGNOSIS
S. Roug1,2,*, M. Werge1, S. Novovic1, P.N. Schmidt 1, E. Feldager1,
B. Sndergaard1, J.D. Knudsen3
1
Department of Gastroenterology and Gastrointestinal Surgery Copenhagen
University Hospital, Hvidovre, 2Department of Medical Gastroenterology, Kge
Hospital, 3Department of Clinical Microbiology Copenhagen University Hospital,
Hvidovre, Denmark
Contact E-mail Address: stineroug@dadlnet.dk
INTRODUCTION: Patients with necrotizing pancreatitis and infected necrosis
have a worse prognosis than patients with sterile necroses. While there is clear
evidence that bacterial infection in pancreatic necrosis increases mortality and
morbidity, studies on the influence of fungal infections have been conflicting.
AIMS & METHODS: To evaluate the impact of fungal infections in patients
with walled-off pancreatic necrosis (WON) treated by endoscopic, transmural
drainage and necrosectomy (ETDN). In addition, to evaluate the effect of anti-
fungal treatment.
We retrospectively retrieved medical charts of 123 patients who underwent
ETDN for WON in our department between November 2005 and December
2013.
RESULTS: Fifty-seven out of the 123 patients (46%) had fungus in their necro-
sis. The median time from the symptom debut to the first fungal finding was 61
days (range 8-195). In 20 patients (35%) the first fungal finding was at the index
endoscopy, in 24 patients (42%) it was at the second endoscopy, and in 9 patients
(16%) at the third endoscopy. The prevailing fungal finding at both the index and
secondary endoscopy was Candida albicans (55% and 56%, respectively).
Ten of the 57 patients (18%) with fungal infection died during admission, and 18
(32%) developed organ failure. The mortality in patients infected with bacterial
infection, only, was 6.5% (p 0.046). Concomitant fungemia was found in 6
patients. Three patients with concomitant fungemia died, as opposed to seven
with fungi in the necrosis, only (50% vs. 14%, respectively p 0.027).
Thirty-nine of the 57 patients (70%) were treated with antifungals. There was no
significant difference in mortality or occurrence of organ failure between this
group and the group that was not treated with antifungals.
Culturing from the necrosis was repeated in 35 out of 57 patients (61%), of which
17 patients were positive for fungus. The same fungal species on both the first
and the second culture was found in 15 out of the 17 patients (88%) despite
adequate antifungal treatment based on the susceptibility pattern.
CONCLUSION: Fungal infection in WON, especially with concomitant funge-
mia, is associated with a poor prognosis. Whether the outcome may be explained
by the fungal infection per se or it is merely a consequence of a prolonged disease
A155
course is, however, at present unknown. Only about one-third of all cases with
fungal infection in necrosis were found at the index endoscopy, which is why
continuous culturing should be mandatory throughout the disease course
Disclosure of Interest: None declared
P0090 EFFECT OF INTRAVENOUS FLUID RESUSCITATION ON
INFLAMMATORY MARKERS OF ACUTE PANCREATITIS AND ITS
CLINICAL OUTCOME
Y.R. Reddy1,*, S. Talukder2, T.D. Yadav2, P.K. Siddappa1,1, R. Kochhar1
1
Gastroenterology, 2General surgery, Postgraduate Institute of Medical Education
and Research (PGIMER), Chandigarh, India
Contact E-mail Address: dr_kochhar@hotmail.com
INTRODUCTION: Early in the course of acute pancreatitis (AP) management
revolves primarily around supportive care and fluid resuscitation remains the
cornerstone. Inflammatory cytokines play a crucial role in extravascular fluid
sequestration. Recent evidence shows the superiority of Ringer lactacte (RL) over
normal saline (NS) as the fluid of resuscitation patients with AP.
AIMS & METHODS: To study the effect of two different types of resuscitation
fluids viz. normal saline (NS) and Ringers lactate (RL) on inflammatory markers
IL-6 and IL-10 and on the clinical course and outcome of patients with acute
pancreatitis (AP).
Consecutive adult patients with AP who presented within 5 days of onset of
symptoms between July 2012 and June 2013 were randomized to receive NS or
RL. The patients were classified as having mild, moderate or severe AP and
managed in a high dependency unit as per a uniform protocol. Intravenous
fluid was infused initially as 20ml/kg bolus till a base line CVP of 8 cm of
water and a urine output of 4 0.5ml/kg/hr. was established. Further fluids
were infused to maintain urine output as mentioned above. Serum samples
were obtained at admission days 0, 3 and 7. IL-6 and IL-10 were estimated on
the cryo-preserved serum samples using a Diaclone ELISA kit. Patients were
monitored for the development of organ failure, sepsis, local complications,
duration of hospital stay and final outcome till 28 days of admission. Data
was recorded using Microsoft excel and analyzed using SPSS software v17.0.
RESULTS: 50 patients of AP with a mean age of 45.8216.46 years (56% males)
were included. NS and RL groups included 25 patients each who were well
matched for age and sex. There was no significant difference in the severity of
AP between the 2 groups (p 0.77). IL-6 levels on day 0, day 3 and day 7 were
significantly elevated in patients with severe AP (SAP) compared to those with-
out severe disease [183.6643.92, 178.2036.28, 143.8547.21 pg/ml vs
145.9060.93, 119.9958.86, 86.4438.50 pg/ml (p50.05)] and remained persis-
tently elevated at the end of first week in SAP group. No such correlation was
seen with IL-10 level (p40.05). The cumulative fluid infused over first 7 days of
admission was not statistically significant between the 2 groups (13.564.93 liters
vs. 13.994.58 liters, p40.05). There was no statistically significant difference in
the serum IL-6 levels noted between the NS and RL groups but among patients
with severe disease (n 29), those who received RL had significantly lower serum
IL-6 levels at the end of first week than those in RL group; p 0.043. Patients
receiving NS had significantly longer duration of hospitalisation (2212.45 days
versus 147.17 days; (p 0.015), higher incidence of infective complication
(p 0.037) and a higher need for intervention (p 0.050). Patients receiving
RL were found to show a greater magnitude of reduction in their organ failure
score on day 3 and 7 in comparison to those receiving NS (p 0.012 and 0.001).
CONCLUSION: There was no significant reduction in cytokine levels among
patients resuscitated with RL or NS. However, patients receiving RL had an
early organ failure resolution, fewer infections and shorter hospital stay,
making RL the preferred fluid for resuscitation.
Disclosure of Interest: None declared
P0091 A C-REL/NFTAC2/COX-2 PATHWAY CONFERS TRAIL
RESISTANCE IN PANCREATIC CANCER
C. Geismann1, F. Grohmann1, R. Hasler2, S. Zeissig1, H. Schafer1,
P. Rosenstiel2, S. Schreiber1, A. Arlt1,*
1
1st Deparment of Medicine, Universityhospital Schleswig-Holstein, Campus Kiel,
2
IKMB, CAU Kiel, Kiel, Germany
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) represents one
of the deadliest malignancies with an overall life expectancy of six months despite
current therapies. NF-kB signalling has been shown to be critical for this pro-
found cell-autonomous resistance against chemotherapeutic drugs and death-
receptor induced apoptosis, but little is known about the role of the c-Rel subunit
in solid cancer and PDAC apoptosis control.
AIMS & METHODS: In the present study, by analysis of genome-wide patterns
of NF-kB dependent gene expression we investigated the role of c-Rel in apop-
tosis resistance of PDAC.
RESULTS: TRAIL resistant Panc1 and Patu8988 cells exhibited a strong
TRAIL inducible NF-kB activity, whereas TRAIL sensitive MiaPaca2 cells dis-
played only a small increase in NF-kB binding activity. Transfection with siRNA
against c-Rel sensitized the TRAIL resistant cells in a comparable fashion to
siRNA targeting the p65/RelA subunit. Gel shift analysis revealed that c-Rel is
part of the TRAIL inducible NF-kB complex in PDAC. Array analysis identified
NFATc2 as a c-Rel target gene amongst the 12 strongest TRAIL inducible genes
in apoptosis resistant Panc1 cells. By database search and chromatin immuno-
precipitation we were able to funcionally characterize one regulatory element for
c-Rel in the NFATc2 promoter. In line, siRNA targeting c-Rel strongly reduced
TRAIL induced NFATc2 activity in TRAIL resistant PDAC cells. Furthermore,
siRNA targeting NFATc2 sensitized these PDAC cells against TRAIL induced
apoptosis. Finally, TRAIL induced expression of COX-2 was diminished
A156
through siRNA targeting c-Rel or NFATc2 and pharmacological inhibition of
COX-2 with celecoxib enhanced TRAIL apoptosis.
CONCLUSION: In conclusion, we were able to delineate a novel c-Rel, NFATc2
and COX-2 dependent anti-apoptotic signalling pathway in PDAC with broad
clinical implications for pharmaceutical intervention strategies.
Disclosure of Interest: None declared
P0092 THE MICROARRAY TISSUE ANALYSIS OF GENES INVOLVED
IN PANCREATIC ADENOCARCINOMA
A. Seicean1,*, O. Balacescu1, I. Berindan1, R. Stan-Iuga1, R. Redis1,
L. Balacescu1, R. Seicean1
1
UNIVERSITY OF MEDICINE AND PHARMACY IULIU HATIEGAN,
CLUJ-NAPOCA, Romania
Contact E-mail Address: andradaseicean@gmail.com
INTRODUCTION: The pathogenesis of pancreatic ductal adenocarcinoma
involves the multi-stage development of molecular aberrations affecting signaling
pathways that regulate cancer growth and progression. Tissue microarray ana-
lysis of pancreatic tumors allows simultaneous assessment of genetic disorders,
which can lead to identification of biomarkers of poor prognosis.
AIMS & METHODS: To characterize the gene expression of pancreatic adeno-
carcinoma compared to normal tissue from the same patient. We investigated
sixteen samples of T3 pancreatic adenocarcinoma obtained intraoperatively and
compared them to normal pancreatic tissue from the same patients. RNA was
extracted and assessed qualitatively and quantitatively, followed by amplification
of cDNA using reverse transcriptase, cRNA synthesis, and hybridization of
microarray slides. For each sample 1000 ng of total RNA was available. The
overexpressed and underexpressed genes were classified by their known function
in the cell. We selected genes over- or underexpressed three times compared to
normal adjacent tissue some described previously in pancreatic pathology, and
used RT-PCR for validation.
RESULTS: On microarray tissue analysis 41 genes were overexpressed and 402
were underexpressed in the pancreatic adenocarcinoma samples. There were
selected genes involved in transcription process as ZNF 428, MIXL1, SEPT 1,
genes involved in intracellular signaling as FLJ21865, AGRP and genes involved
in transmembranar and intracellular transport as CCDC88, UTP14A,VPS11,
LLRC21,CHRM3, Marveld3. Validation by qRT-PCR confirmed the involve-
ment of AGRP and MIXL1 gene in pancreatic adenocarcinoma tissue.
CONCLUSION: Microarray tissue analysis of pancreatic adenocarcinoma
showed more underexpressed than overexpressed genes. After validation, the
overexpressed gene AGRP was shown to be one possible factor responsible for
anorexia and perineural invasion. The possible role in pancreatic cancer of
MIXL1, known to play a role in cellular proliferation and differentiation,
should be further clarified.
Disclosure of Interest: None declared
P0093 CCK-B RECEPTOR GENE VARIANT IS NOT ASSOCIATED WITH
INCREASED RISK, NOR WITH DECREASED SURVIVAL IN
PANCREATIC ADENOCARCINOMA
A. Balazs1,*, B.C. Nemeth2, E. Hegyi1,3, I. Hritz4, F. Izbeki5, J. Gervain5,
A. Szepes6, G. Gyimesi6, Z. Dubravcsik6, D. Kelemen7, A. Csiszko8,
Z. Szentkereszty9, B. Bod10, R. Szmola11, J. Sumegi12, J. Novak13, G. Farkas14,
L. Czako1, T. Takacs1, Z. Rakonczay1, A. Pap11, M. Sahin-Toth15, P. Hegyi1 on
behalf of Hungarian Pancreatic Study Group
1
First Department of Medicine, University of Szeged, Szeged, Hungary,
2
Department of Molecular and Cell Biology, Boston University, Boston, United
States, 32nd Department of Pediatrics, University Childrens Hospital, Comenius
University Medical School, Bratislava, Slovakia, 4First Deoartment of Medicine,
University of Szeged, Szeged, 5Fejer Megyei Szent Gyorgy Hospital,
Szekesfehervar, 6Bacs-Kiskun County Municipality Hospital, Kecskemet,
7
Department of Surgery, University of Pecs, Pecs, 8Department of Surgery,
University of Debrecen, 9Department of Surgery, University of Debrecen,
Debrecen, 10Dr. Bugyi Istvan Hospital, Szentes, 11National Institute of Oncology,
Budapest, 12B-A-Z County Hopspital, Miskolc, 13Pandy Kalman County Hopsital,
Gyula, 14Department of Surgery, University of Szeged, Szeged, Hungary,
15
Department of Molecular and Cell Biology, Boston University, Boston, United
States
Contact E-mail Address: anitabalazs@outlook.com
INTRODUCTION: Cholecystokinin-B (CCK-B) receptor is often over-
expressed in pancreatic ductal adenocarcionoma (PDAC); stimulation of the
receptor promotes tumor growth. An intronic mutation (c.81137C4A) in the
CCKBR gene causes retention of intron-4, resulting in a new spliceform, which
was previously shown to correlate with higher PDAC risk and a more aggressive
phenotype.
AIMS & METHODS: Our aim was to test the effect of the c.81137C4A
mutation on PDAC risk and prognosis in a Hungarian population. 122 subjects
with PDAC (cases) and 106 subjects with no pancreatic disease (controls) were
recruited from the Hungarian National Pancreas Registry. Genomic DNA was
isolated from peripheral blood. Intron-4 of the CCKBR gene, including exon-
intron boundaries, was amplified and sequenced.
RESULTS: We found the c.81137C4A intronic mutation in 35 heterozygous
and 5 homozygous cases and in 32 heterozygous and 3 homozygous controls
(allele frequency 18.4% and 17.9% respectively). One case subject carried a p.
R319Q and one control subject a p. R319W missense mutation. Survival analysis
showed no significant difference in median survival between wild type cases and
carriers for the mutation (8.7 months and 6.9 months respectively)
CONCLUSION: In our cohort, the c.81137C4A intronic mutation was not
associated with increased risk for PDAC. Also, the mutation was not associated
United European Gastroenterology Journal 2(5S)
with shorter survival, indicating that this genetic variant is not a clinically rele-
vant prognostic factor. Supported by TAMOP and OTKA.
Disclosure of Interest: None declared
P0094 HYPOXIA AND NEUROINFLAMMATION LEAD TO AN
INTERLEUKIN-6-INDUCED SCHWANN CELL ACTIVATION IN
PANCREATIC CANCER
E. Tieftrunk1,*, I.E. Demir1, S. Schorn1, M.U. Kurkowski2, E. Costello3,
H. Algul2, H. Friess1, G.O. Ceyhan1
1
Department of Surgery, 2Department of Internal Medicine II, Klinikum rechts der
Isar, Munchen, Germany, 3Liverpool NIHR Pancreas Biomedical Research Unit,
Liverpool, United Kingdom
Contact E-mail Address: elke.tieftrunk@tum.de
INTRODUCTION: Pancreatic cancer (PCa) is characterized by prominent intra-
pancreatic neuropathy and neuropathic pain. Up to now, the impact of glia cells
on the development of the pancreatic neuropathy has not yet been investigated.
AIMS & METHODS: We studied whether there is an activation of peripheral
glia cells (Schwann cells, SC) in PCa and what signalling pathways might be
responsible for intrapancreatic glial activation. SC were cultured under hypoxia,
in pancreatic cancer cell (PCC) supernatants or co-coltured with PCC and T-
lymphocytes and investigated via immunoblotting, MTT viability assay,
Multiplex-Luminex-ELISA and cell area measurement. Nerves in PCa and
normal pancreas (NP) were analysed for their immunoreactivity for glial fibril-
lary acidic protein (GFAP), hypoxia inducible factor 1 alpha (HIF-1) and
carboanhydrase IX (CA-IX). The SC distribution and frequency in conditional
PCa knock-out mice was assessed after in-vivo blockade of the IL-6 signalling
pathway.
RESULTS: Hypoxia leads to upregulation of the intermediate filaments GFAP,
Nestin and Vimentin and pro-inflammatory cytokines in SC. The nerves in PCa
were immunoreactive for HIF-1 and CA-IX, and the extent of neuro-immunor-
eactivity for HIF-1 and CA-IX correlated to the intraneural GFAP amount.
PCC supernatants led to upregulation of GFAP and Nestin in SC, cellular
hypertrophy (stellation) and higher proliferation rate. The serverity of pancreatic
neuritis correlated with the intraneural GFAP amount. The blockade of IL-6, but
not of IL-1 in PCC supernatants abolished the upregulation of GFAP and
Nestin. GFAP/SOX10 double positive SC were found around pancreatic intrae-
pithelial neoplasia (PanIN) of Ptf1a-Cre;KrasG12D, but not around PanINs of
Ptf1a-Cre;KrasG12D;IL6-/- mice. The blockade of IL-6 transsignalling in Ptf1a-
Cre;KrasG12D;sgp130tg mice had no influence on the SC distribution around
PanINs.
CONCLUSION: SC in PCa show typical features of reative gliosis, which is
induced via the classical IL-6 signalling.
Disclosure of Interest: None declared
P0095 DIAGNOSTIC EFFICIENCY OF CELL-BLOCK WITH
IMMUNOSTAINING, SMEAR CYTOLOGY, LIQUID-BASED
CYTOLOGY IN EUS-FNA ON PANCREATIC LESIONS: AN
INSTITUTIONS EXPERIENCE
H. Jiang1,*, S.-Y. QIN1, L. TAO1, W. LUO1, S.-B. SU1, X.-P. LU1, R.-E. LEI1
1
The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Contact E-mail Address: lihuan@erbechina.com
INTRODUCTION: The diagnostic efEciency of endoscopic ultrasound-guided
fine needle aspiration (EUS-FNA) cytology varies largely depending on the pro-
cessing methods of specimens.
AIMS & METHODS: The present study aimed to evaluate the diagnostic effi-
ciency of cell block (CB) with methods of immunostaining, smear cytology (SC)
and liquid-based cytology (LBC) without on-site cytopathologist in patients with
pancreatic lesions. 72 patients with pancreatic lesions were prospectively enrolled
in this study. After EUS-FNA, specimens were determined by SC, LBC and CB
with immunostaining, respectively. Diagnostic efEciency of SC was compared
with that of LBC and CB. The final diagnosis was conErmed by surgically
resected specimens, diagnostic imaging and clinical follow-up.
RESULTS: 60 malignant and 12 benign pancreatic lesions were determined. The
diagnostic sensitivity, negative predictive value and accuracy (90.0%, 66.7% and
91.7%) of CB with immunostaining were significantly higher than those of SC
(70.0%, 30.0% and 75.0%, P 5 0.05), LBC (73.3%, 31.6% and 77.8%, P 5
0.05). The combination of CB and SC, or CB and LBC did not significantly
increase the efficiency compared to CB with immunostaining alone (P 4 0.05).
Table: Diagnostic efficiency of SC, LBC and CB methods in pancreatic lesions
SC LBC CB SCCB LBCCB
Sensitivity,% (n) 70.0 (42/60) 73.3 (44/60) 90.0 (54/60)* 91.7 (55/60) 93.3 (56/60)
Spcificity, % (n) 100 (12/12) 100 (12/12) 100 (12/12) 100 (12/12) 100 (12/12)
PPV, % (n) 100 (42/42) 100 (44/44) 100 (54/54) 100 (55/55) 100 (56/56)
NPV, % (n) 30.0 (12/40) 31.6 (12/38) 66.7 (66/72)* 70.6 (12/17) 75.0 (12/16)
Accuracy, % (n) 75.0 (54/72) 77.8 (56/72) 91.7 (66/72)* 93.1 (67/72) 94.4 (68/72)
CONCLUSION: The CB with immunostaining technique presents a higher diag-
nostic efficiency than both of SC and LBC without on-site cytopathologist in
patients with pancreatic lesions who had undergone EUS-FNA.
United European Gastroenterology Journal 2(5S)
Disclosure of Interest: None declared
P0096 EFFECT OF TELOMERASE PEPTIDE VACCINATION, GV 1001
COMBINED WITH GEMCITABINE IN PANCREATIC DUCTAL
ADENOCARCINOMA
J.K. Park1,*, H. Kim2, Y. Kim2, S.-H. Lee1, J.K. Ryu1, W.J. Lee2, J.S. Kang2
1
Internal Medicine, Seoul National University Hospital College of Medicine,
2
Anatomy, Seoul National University College of Medicine, Seoul, Korea, Republic
Of
Contact E-mail Address: mdsophie@gmail.com
INTRODUCTION: Pancreatic ductal adenocarcinoma (PDAC) shows dismal
prognosis due to early metastasis, frequent recurrence and chemo-resistance.
However, there is no effective treatment to overcome these problems. GV1001
is a telomerase-based cancer vaccine made of a 16-mer TERT peptide and human
telomerase reverse transcriptase (hTERT), the rate-limiting subunit of the telo-
merase complex, is therefore an attractive target for cancer vaccination.
AIMS & METHODS: AIMS: The aim of this study was to evaluate the combi-
nation benefit of telomerase peptide vaccination, GV1001 combined with
Gemcitabine in PDAC.
METHODS: Human PDAC cell lines (Panc-1 and AsPC-1) and PDAC stem
cells (CD133) were used in in vitro experiments. Also, a PDAC xenograft mice
model was established using PDAC cell lines (Panc-1 and AsPC-1) and PDAC
stem cells (CD133). Treatment groups were divided as follows; control,
Gemcitabine alone, GV 1001 alone and Gemcitabine and GV 1001 combination.
The changes of weight and tumor size were evaluated in regular intervals before
and after the treatment. The inflammatory cytokines (IL-6, TNF-, INF-),
leptin and ghrelin were measured from the serum of xenograft PDAC mice
model.
RESULTS: In vitro experiments: GV1001 alone did not affect the proliferation of
PDAC cells.
Almost 100% of the population of each PDAC cell line was positive for
Epithelial Specific Antigen (ESA, Epithelial Cellular Adhesion Molecule). The
positive results in PDAC cells ranged from as few as 0.5% to as many as 3% for
ESACD133 cells.
In vivo experiments: Mean tumor volume and size were decreased in treatment of
Gemcitabine only group and Gemcitabine with GV 1001 group, and there were
no significant differences between the two groups. However, Gemcitabine only or
Gemcitabine with GV 1001 treatment groups had significantly small tumor size
and volume compared to control group (P 5 0.001). Interestingly, there was
significant difference in mean body weight between the groups with
Gemcitabine only vs. Gemcitabine with GV 1001 combination groups. Mice of
Gemcitabine with GV 1001 treatment group did not have significant weight loss
compared to Gemcitabine only group although they have decreased tumor size
and volume. There was no mortality of mice until the end of the treatment.
CONCLUSION: GV1001 showed beneficial effects combined with Gemcitabine
in the PDAC xenograft mice model, preventing emaciation and increasing anti-
inflammatory effects. Moreover, GV 1001 combined with Gemcitabine treatment
showed significant loss of fibrosis in tumor tissue. Therefore, further investiga-
tion of GV1001s effect may give us useful insights to understand the biology of
PDAC progression and the synergistic effects of anti-cancer drug delivery in
PDAC treatment.
Disclosure of Interest: None declared
P0097 PRDX1 PROMOTES PANCREATIC CANCER CELL MOTILITY
AND INVASION BY MODULATING P38 MAPK ACTIVITY
K. Taniuchi1,*, M. Furihata1, S. Iwasaki1, S. Shimizu1, T. Shimizu1, M. Saito1,
T. Saibara1
1
Kochi Medical School, Kochi University, Nankoku, Japan
Contact E-mail Address: ktaniuchi@kochi-u.ac.jp
INTRODUCTION: Previous reports describe that Prdx1 is an antioxidant
enzyme that participates in the regulation of hydrogen peroxide-mediated
signal transduction, and is also implicated in the immune response, cell prolif-
eration, differentiation, and apoptosis. Prdx1 interacts with apoptosis signal-
regulating kinase 1 (ASK1), a member of the mitogen-activated protein kinase
kinase kinase (MAPKKK) family that activates both MKK4/MKK7-JNK and
MKK3/MKK6-p38 MAPK signaling cascades, via the thioredoxin-binding
domain of ASK1; the redox-sensitive catalytic activity of Prdx1 is required for
the interaction with ASK1.
AIMS & METHODS: Pancreatic ductal adenocarcinoma (PDAC) is among the
deadliest cancers because PDAC cells are highly invasive, they easily invade
surrounding tissues, and they metastasize at an early stage. Since the role of
Prdx1 in migration and invasion of cancer cells, including pancreatic cancer
cells, has not been reported, the aim of this study was to investigate the role of
Prdx1 in invasiveness of pancreatic cancer cells. This study describes new and
unique findings regarding the molecule Prdx1.
RESULTS: Prdx1 plays a role in promoting cell motility and invasion by reg-
ulating the activity of p38 MAPK, a member of the MAPK family protein. Prdx1
interacts with active forms of p38 MAPK, and complexes of Prdx1 and phos-
phorylated p38 MAPK localize at the leading edges of migrating PDAC cells.
Suppression of Prdx1 decreases active p38 MAPK and inhibits cell motility and
invasion. Treatment of PDAC cells with a p38 MAPK inhibitor decreases inva-
siveness. The peroxidase activity of Prdx1 was likely not associated with cell
motility and invasion in PDAC. Thus, Prdx1-dependent promotion of cell moti-
lity and invasion is likely associated with increased active p38 MAPK.
Suppression of Prdx1 inhibits membrane ruffling and protrusions and decreases
peripheral actin structures in membrane protrusions. The p38 MAPK inhibitor
A157
also inhibits the formation of membrane protrusions via inhibition of accumula-
tion of Prdx1 in cell protrusions.
CONCLUSION: Prdx1 regulates actin-cytoskeleton rearrangements at mem-
brane protrusions through modulation of the activity of p38 MAPK, which in
turn promotes pancreatic cancer cell motility and invasion. Inhibition of binding
of Prdx1 with active p38 MAPK may be effective for targeted molecular therapy,
because any such therapy would inhibit the formation of cell protrusions and
consequently limit cell motility and invasion of pancreatic cancer cells.
Disclosure of Interest: None declared
P0098 TIME-RESTRICTED ACTIVATION OF PROTEIN KINASE D2
DIRECTS VASCULOGENESIS DURING MOUSE EMBRYONIC
STEM CELL DIFFERENTIATION
M. Muller1,*, J. Schroer1, N. Azoitei1, F. Genze2, A. Illing1, T. Seufferlein1,
S. Liebau3, A. Kleger1
1
Department of Gastroenterology, 2Department of Urology, Universitatsklinikum
Ulm, Ulm, 3Institute of Anatomy, Universitat Tubingen, Tubingen, Germany
INTRODUCTION: The protein kinase D (PKD) isoenzymes PKD1, -2, and -3,
are prominent downstream targets of PKCs and phospholipase D in various
biological systems. Recent data from our laboratory identified PKD isoforms
as novel, essential mediators of tumour cell-endothelial cell communication but
also as regulators of tumour cell motility and metastasis formation. The role of
PKD isoforms during vascular development remains elusive.
AIMS & METHODS: In the current study, we aimed to dissect the contribution
of PKDs to vasculogenesis and angiogenesis in early embryonic development
using mouse embryonic stem (ES) cells as bona fide tool.
RESULTS: First, we identified Protein Kinase D2 as the predominant isoform in
undifferentiated ES cells leading us to particularly focus on this isoform. Time-
restricted PKD2 activation using an inducible knock-in allele in differentiating
mouse ES cells prevented cardiac mesoderm but activated a vascular differentia-
tion program as shown by gene and protein regulation. Interestingly, the prolif-
erative capacity is strongly diminished as a consequence of forced PKD2
expression. Finally, we aimed to underpin our findings in two independent
in vivo models: First, embryoid bodies were transplanted on the chorioallantois
membrane (CAM) of fertilised chicken eggs, a widely used model to study pro-
and anti-angiogenesis. In line, with our in vitro data pronounced vessel formation
was evident in the tumour-like structures arising at day 4 of the CAM assay.
Second, we used the teratoma assay and induced PKD2 in immunodeficient mice
during teratoma formation. While there was no difference in teratoma weight or
size, a strong increase of CD31 expression as an indicator of vasculogenesis was
observed in teratoma lysates.
CONCLUSION: Our data obtained in murine ES cells demonstrate that PKD2
contributes to the regulation of angiogenesis during early development and
ascribes a vascular fate in two independent embryonic tumorgenesis models.
Disclosure of Interest: None declared
P0099 GENISTEIN POTENTIATES THE ANTITUMOR EFFECT OF 5-
FLUOROURACIL BY INDUCING APOPTOSIS AND AUTOPHAGY
IN HUMAN PANCREATIC CANCER CELLS
R. Suzuki1,2,*, Y. Kang3, D. Roife3, X. Li3, J.B. Fleming3
1
Gastroenterology and Rheumatology, Fukushima Medical University School of
Medicine, Fukushima, Japan, 2Gastroenterology, Hepatology and Nutrition,
3
Surgical Oncology, UT MD Anderson Cancer Center, Houston, United States
Contact E-mail Address: rs197857@gmail.com
INTRODUCTION: Although 5-fluorouracil (5-FU)-based combination che-
motherapy (e.g. FOLFIRINOX) has demonstrated effectiveness against pancrea-
tic cancer, novel therapeutic strategies must be developed to enhance increase the
therapeutic window of these cytotoxic agents. Genistein is a soy-derived isofla-
vone with pleiotropic biologic effects that can enhance the antitumor effect of
chemotherapeutic agents.1-3
AIMS & METHODS: To understand how genistein potentiates the antitumor
effects of chemotherapeutic agents, we examined apoptosis and autophagy in the
MIA PaCa-2 human pancreatic cancer cell line and subcutaneous pancreatic
tumor xenograft model. Apoptosis was evaluated using DNA fragmentation
assay and Western blot of poly (ADP ribose) polymerase and caspase-3.
Meanwhile, autophagy was evaluated using Western blot of microtubule-asso-
ciated protein light chain 3 (LC3)-I/II and fluorescent microscopy observation of
green fluorescent protein-LC3B puncta and acidic vesicular organelle formation.
In animal study, induction of apoptosis and autophagy was assessed by TUNEL
assay and immunohistochemistry staining of LC3B, respectively.
RESULTS: We observed that genistein enhanced 5-FU-induced apoptosis by
down-regulating B-cell lymphoma 2 (bcl-2). Moreover, gensitein enhanced 5-
FU-induced autophagy and triggered autophagic cell death by decreasing bcl-2
while inducing beclin-1. In vivo treatment studies demonstrated that the combi-
nation of 5-FU and genistein significantly decreased final tumor volume compar-
ing to genistein alone or 5-FU alone by inducing apoptosis as well as autophagy.
CONCLUSION: Genistein can potentiate the antitumor effect of 5-FU by indu-
cing apoptotic cell death as well as autophagic cell death. These results demon-
strate the potential of genistein as an adjuvant therapeutic agent to enhance the
antitumor effects of current first-line cytotoxic agents against pancreatic cancer.
REFERENCES
1. Banerjee S, Zhang Y, Ali S, et al. Molecular evidence for increased antitumor
activity of gemcitabine by genistein in vitro and in vivo using an orthotopic
model of pancreatic cancer. Cancer Res 2005; 65: 9064-9072.
2. Banerjee S, Zhang Y, Wang Z, et al. In vitro and in vivo molecular evidence of
genistein action in augmenting the efficacy of cisplatin in pancreatic cancer. Int J
Cancer 2007; 120: 906-917.
A158
3. Hwang KA, Kang NH, Yi BR, et al. Genistein, a soy phytoestrogen, prevents
the growth of BG-1 ovarian cancer cells induced by 17beta-estradiol or bisphenol
A via the inhibition of cell cycle progression. Int J Oncol 2013; 42: 733-740.
Disclosure of Interest: None declared
P0100 CHARACTERIZATION OF THE NERVE-STELLATE CELL
INTERACTIONS IN PANCREATIC CANCER
S. Teller1,*, D. Dischl1, R. Go1, I.E. Demir1, H. Friess1, G.O. Ceyhan1
1
Chirurgische Klinik und Poliklinik, Klinikum rechts der Isar, TU Munchen,
Munchen, Germany
Contact E-mail Address: Steffen. Teller@tum.de
INTRODUCTION: Pancreatic stellate cells (PSC) emerged in recent years as the
main actor for the generation of pancreatic fibrosis in pancreatic cancer (PCa).
Subsequent to their activation, PSC start to proliferate, migrate, and produce
several extracellular matrix (ECM) components as well as cytokines. In this
context, neural invasion and pancreatic neuroplasticity is most prominent in
the desmoplastic areas.
AIMS & METHODS: The present study aims at elucidating the characterisation
of the interactions of nerves, carcinoma cells and PSC and the potential impact of
PSC during the generation of neuropathic alterations in PCa.
PSC were isolated from Wistar rats and cultivated under hypoxia, stimulated
with TGF or left untreated as controls. After cell lysis, the expression of neuro-
trophic factors and their receptors (GFR) was determined by Immunoblotting
and by qRT-PCR. For neuroplasticity assays, dorsal root ganglia (DRG) were
isolated from newborn Wistar rats and treated with supernatants of quiescent
and activated PSC. Changes in neurite length, axonal branching, perikaryonal
diameter and glial density were determined.
RESULTS: PSC produce neurotrophic factors as well as their receptors and alter
the expression pattern of neurturin and artemin after activation towards their
active forms, whereas the GFR expression remains unchanged. After treatment
of PSC with hypoxia or TGF, PSC are activated. Cell culture supernatants of
activated PSC lead to an increased neurite and glial density in isolated DRG.
CONCLUSION: Activated PSC alter their expression pattern of neurotrophic
factors, influence neuroplasticity of isolated DRG and therefore may play a
seminal role in the generation of pancreatic neuropathy and pain in PCa.
Disclosure of Interest: None declared
P0101 THE METASTASIS-PROMOTING ROLES OF EXTRAVASATED
PLATELET AGGREGATION IN PANCREATIC CANCER AND
STROMA
T. Miyashita1,*, H. Tajima1, I. Makino1, H. Nakagawara1, H. Kitagawa1,
T. Ohta1
1
Department of Gastroenterological Surgery, KANAZAWA UNIVERSITY
HOSPITAL, Kanazawa, Japan
Contact E-mail Address: tomoharumiya@gmail.com
INTRODUCTION: The last decade has focused attention on the central role of
platelets interacting with tumor cells and the immune system in promoting tumor
progression and distant spread through release of growth factors, such as trans-
forming growth factor beta (TGF-), vascular endothelial growth factor A
(VEGF-A) and plasminogen activator inhibitor-1 (PAI-1), into the tumor micro-
environment. We focused on the potential metastasis-promoting role of extra-
vasated platelet aggregation (EPA) in pancreatic cancer and stroma.
AIMS & METHODS: Resected pancreatic cancer specimens from 40 patients
were used in this study. To examine the expression and localization of platelet
aggregation in the epithelial-mesenchymal transition (EMT) region in cancer and
stroma, CD42b, Snail1 and E-cadherin were assessed using immunohistochem-
istry. We determined the correlation of these expressed proteins with clinical
features and overall survival.
RESULTS: CD42b expression was detected at the invasive front of the tumor,
which was in 73% of the EMT portion, but not in the region of tubular forma-
tion. Increased Snail1 and loss of E-cadherin expression were noted in 85% and
75% of the EMT portion, respectively. There was a significant correlation
between CD42b and Snail1 expression (p 0.02) and CD42b and loss of E-
cadherin expression (p 0.008). No prognostic impact of CD42b, Snail1 or
loss of E-cadherin expression on overall survival was identified using Kaplan
Meier survival analysis.
CONCLUSION: We demonstrate that EPA is associated with the first step in the
formation of the EMT. These data suggest a potential role for antiplatelet agents
to suppress EMT and metastasis by changing the tumor microenvironment.
Disclosure of Interest: None declared
P0102 CATHEPSIN B AND D DRIVE THE FIBROGENIC POTENTIAL OF
PANCREATIC STELLATE CELLS AND MODULATE THE STROMAL
COMPARTMENT IN PANCREATIC DUCTAL ADENOCARCINOMA
(PDAC)
U.M. Mahajan1,*, T. Schwaiger1, F.-U. Weiss1, M. Lohr2, M.M. Lerch1,
J. Mayerle1
1
Department of Medicine A, University Medicine, Ernst-Moritz-Arndt-University,
Greifswald, Greifswald, Germany, 2CLINTEC, Karolinska Institutet, Stockholm,
Sweden
Contact E-mail Address: mayerle@uni-greifswald.de
INTRODUCTION: Remodelled extracellular matrix (ECM) has been implicated
in the resistance of cancer cells to chemotherapy. Stromal-cell-derived proteases,
e.g. cathepsins, are involved in tumorigenesis and tissue invasion but their role in
regulating pancreatic stellate cells (PSCs) and thus ECM formation is unknown.
United European Gastroenterology Journal 2(5S)
We studied whether cathepsin B and D, lysosomal proteases both highly
expressed in pancreatic cancer, contribute to fibrogenesis by activating PSCs.
AIMS & METHODS: Cathepsin B and D activity was measured in serum of
PDAC patients. PSCs were isolated by Nycodenz-gradient from mouse pancreas
for immunoblotting and immunofluorescence staining. TGF1 was measured
using ELISA and LC/MS-mass-spectroscopy.
RESULTS: Serum cathepsin D activity was increased and correlated with poor
survival of patients with PDAC. Expression of cathepsin B and D was negligible
in quiescent PSCs but increased in parallel with PSC trans-differentiation to
myofibroblasts. Silencing or inhibition (Pepstatin, CA074Me) of cathepsin B
and D decreased phenotypic markers of PSC activation. Moreover, latent
TGF1 was cleaved to TGF1 leading to an increase in the PSC fibrogenic
potential in a time-dependent manner. Cathepsin D activated cathepsin B and
both acted directly on latent TGFb1. TGFb1 increased proliferation, invasion
and extracellular matrix remodedelling of PSCs.
CONCLUSION: We show that Cathepsin D activity correlates with poor survi-
val in PDAC patients. Cathepsin B and D expression increases during PSC
activation in vitro and both modulate ECM-formation via proteolytic cleavage
of latent TGF1. Via PSC activation cathepsins B and D regulate fibrogenesis
and stroma development in pancreatic cancer and therefore represent a promis-
ing treatment target.
Disclosure of Interest: None declared
P0103 SRC/STAT3 SIGNALING PATHWAYS ARE INVOLVED IN KAI1-
REDUCED VEGF-C DOWN-REGULATION IN PANCREATIC
CANCER
X. Guo1,*, X. Liu1
1
General Hospital of Shenyang Military Area, Shenyang, China
Contact E-mail Address: guoxiaozhong1962@163.com
INTRODUCTION: To investigate the signaling pathways involved inKAI1-
reduced vascular endothelial growth factor C (VEGF-C) down-regulation and
lymphatic metastasis in MIA PaCa-2 pancreatic cancer cells.
AIMS & METHODS: MIA PaCa-2 pancreatic cancer cells were transfected with
KAI1 by liposomes. The expression level of VEGF-C was assessed by Western
blot. Levels of vascular endothelial growth factor (VEGF)-C secreted by cells
measured by enzyme-linked immunosorbent assay (ELISA). Src and STAT3
phosphorylation was detected by Western blot. Signaling transduction inhibitors,
PP2 and AG490, were used to block Src and STAT3 signaling pathways,
respectively.
RESULTS: KAI1 overexpression decreased VEGF-C expression and inhibited
Src and STAT3 phosphorylation. PP2 pretreatment efficiently reversed the upre-
gulation of Src and STAT3 phosphorylation and VEGF-C expression. AG490
pretreatment efficiently reversed the upregulation of STAT3 phosphorylation
and VEGF-C expression, but not the upregulation in Src phosphorylation.
CONCLUSION: This study identified that Src/STAT3 signaling pathways were
involved in KAI1-reduced VEGF-C down-regulation and suggested their impor-
tant roles in lymphatic metastasis in pancreatic cancer.
REFERENCES
1 Qian CN, Berghuis B, Tsarfaty G, et al. Preparing the "soil": the primary tumor
induces vasculature reorganization in the sentinel lymph node before the arrival
of metastatic cancer cells. Cancer Res 2006; 66: 10365-10376.
2 Stacker SA, Achen MG, Jussila L, et al. Lymphangiogenesis and cancer metas-
tasis. Nat Rev Cancer 2002; 2: 573-583.
3 Miranti CK. Controlling cell surface dynamics and signaling: how CD82/KAI1
suppresses metastasis. Cell Signal 2009; 21: 196-211.
4 Cheng P, Jin G, Hu X, et al. Analysis of tumor-induced lymphangiogenesis and
lymphatic vessel invasion of pancreatic carcinoma in the peripheral nerve plexus.
Cancer Sci 2012; 103: 1756-1763.
5 Liu X, Guo XZ, Zhang WW, et al. KAI1 inhibits HGF-induced invasion of
pancreatic cancer by sphingosine kinase activity. Hepatobiliary Pancreat Dis Int
2011; 10: 201-208.
6 Stacker SA and Achen MG. The VEGF signaling pathway in cancer: the road
ahead. Chin J Cancer 2013; 32: 297-302.
7 Ischenko I, Seeliger H, Camaj P, et al. Src tyrosine kinase inhibition suppresses
lymphangiogenesis in vitro and in vivo. Curr Cancer Drug Targets 2010; 10: 546-
553.
Disclosure of Interest: None declared
P0104 TP53 CODON 72 AND MDM2 SNP309 POLYMORPHISMS IN
PANCREATIC CANCER
Y. Hori1,*, K. Miyabe1, M. Yoshida2, T. Nakazawa1, K. Hayashi1, I. Naitoh1,
S. Shimizu1, H. Kondo1, Y. Nishi1, S. Umemura1, A. Kato1, H. Ohara3, T. Joh1
1
Department of Gastroenterology and Metabolism, Nagoya City University
Graduate School of Medical Sciences, Nagoya, Japan, Nagoya, Japan, 2Division of
Digestive Diseases, Emory University School of Medicine, Atlanta, United States,
3
Department of Community-based Medical Education, Nagoya City University
Graduate School of Medical Sciences, Nagoya, Japan, Nagoya, Japan
Contact E-mail Address: horinei_40847357@yahoo.co.jp
INTRODUCTION: Single-nucleotide polymorphisms (SNPs) of TP53 gene
(codon 72, rs1042522) and mouse double minute 2 (MDM2) promoter
(SNP309, rs2279744), have been associated with increased risk of various
human cancers. However, few studies have analyzed these polymorphisms in
pancreatic cancer.
AIMS & METHODS: We investigated TP53 codon 72 and MDM2 SNP 309
polymorphisms in 32 patients with pancreatic ductal carcinoma (PDAC) and 21
patients with controls (non-neoplastic pancreatic epithelium attached to resected
specimens without pancreatic disease), using paraffin-embedded tissue sections.
United European Gastroenterology Journal 2(5S)
RESULTS: The frequencies of TP53 codon72 arginine (Arg)/Arg, Arg/proline
(Pro), and Pro/Pro were 6, 28, and 66% in PDAC and 29, 52, and 19% in
controls, respectively. The ratio of Pro/Pro genotype to Arg/Arg genotype was
significantly higher in PDAC than controls [p 0.004, adjusted odds ratio
(OR) 15.75; 95% confidence interval (CI) 2.30-107.9]. On the other hand,
those of MDM2 SNP309 TT, TG, and GG genotypes were 22, 44, and 34% in
PDAC and 38, 33, and 29% controls, respectively. There were no significant
differences among them.
CONCLUSION: This is the first study to evaluated the significance of TP 53
codon 72 and MDM2 SNP 309 polymorphism using paraffin-embedded pan-
creas tissue. The proportion of Pro/Pro genotype was significantly higher in
PDAC, while the proportion did not differ in MDM2. This finding indicates
that TP53 codon 72 polymorphism is likely to be correlated with increased risk
for pancreatic cancer.
REFERENCES
Grochola LF, et al. Single-nucleotide polymorphisms in the p53 signaling path-
way cold spring. Harb Perspect Biol 2010; 2: a001032.
Disclosure of Interest: None declared
P0105 POSTRANSCRIPTIONAL REGULATION OF HO-1 AND COX-2
EXPRESSION AS NOVEL THERAPEUTIC TARGETS IN
PANCREATIC CANCER
A. Jakstaite1,*, Z. Dambrauskas1, A. Gulbinas1, G. Barauskas2, J. Pundzius2
1
Institute for Research of Digestive System, 2Department of Surgery,
LITHUANIAN UNIVERSITY OF HEALTH SCIENCES, Kaunas, Lithuania
Contact E-mail Address: zilvinas.dambrauskas@gmail.com
INTRODUCTION: Pancreatic cancer is a rapidly invasive, metastatic tumor,
which is resistant to standard therapies, thus only 1015% of patients are candi-
dates for potentially curative surgery. None of the currently available chemother-
apeutic agents have an objective response rate of over 10%. Recent studies show
that RNA binding proteins regulate post transcriptional gene expression and
play a critical role in RNA stability andtranslation, thus they potentially could
become an important group of new therapeutic targets.
AIMS & METHODS: We examined the association of this postranscriptional
regulation pathway (CUGBP2 and HuR) and the expression of COX-2 and HO-
1, which are known to be associated with inhibition of apoptosis, increased
tumor invasiveness and resistance to oxidative stress and/orchemotherapy, and
promotion of angiogenesis. Western blot analysis, immunohiostochemistry and
quantitative RT-PCR were employed to show the expression of mRNA and
protein in normal pancreas (from organ donors), cancer tissue (surgical
specimens).
RESULTS: RT-PCR analysis showed 10.3 and 14 fold lower HuR and CUGBP2
mRNA levels in pancreatic cancer compared to normal tissue (p50.05), COX-2
levels were 1.5 times higher and HO-1 expression on average was upregualted 6-
fold in the pancreatic cancer samples, compared to the normal pancreatic tissue
(p50.05). Western blot analysis showed very low levels of HuR and CUGBP2 in
pancreatic cancer compared with the normal tissue (p 5 0.05). Expression of
COX-2 protein levels was 2-fold higher in pancreatic cancer. Western blot ana-
lysisrevealed 3.5 times higher (p50.017) expression of HO-1 in pancreatic cancer.
CONCLUSION: The decreased or altered activity of CUGBP2 and HuR could
be associated with high chemoresistance and early dissemination of pancreatic
cancer through the HO-1 and COX-2 mediated cytoprotective and carcinogenesis
pathways. These results mandate further functional studies and evaluation of
postranscriptional regulation as a new potential therapeutic target.
Disclosure of Interest: None declared
P0106 DIAGNOSTIC VALUE OF A PANCREATIC MASS ON
COMPUTED TOMOGRAPHY IN PATIENTS UNDERGOING
PANCREATODUODENECTOMY FOR PRESUMED PANCREATIC
CANCER
A. Gerritsen1,2,*, T.L. Bollen3, C.Y. Nio4, I.Q. Molenaar1, M.G. Dijkgraaf5, H.C.
van Santvoort6, G.J. Offerhaus7, L.A. Brosens8, K. Biermann9, E. Sieders10, K.P.
de Jong10, R.M. van Dam11, E.van der Harst12, H.van Goor13,
B.van Ramshorst14, B.A. Bonsing15, I.H. de Hingh16, M.F. Gerhards17, C.H.
van Eijck18, D.J. Gouma2, I.H. Borel Rinkes1, O.R. Busch2, M.G. Besselink2 on
behalf of the Dutch Pancreatic Cancer Group
1
Dept of Surgery, University Medical Center Utrecht, Utrecht, 2Dept of Surgery,
Academic Medical Center, Amsterdam, 3Dept of Radiology, St Antonius Hospital,
Nieuwegein, 4Dept of Radiology, 5Clinical Research Unit, Academic Medical
Center, Amsterdam, 6Department of Surgery, 7Dept of Pathology, University
Medical Center Utrecht, Utrecht, 8Dept of Pathology, Academic Medical Center,
Amsterdam, 9Dept of Pathology, Erasmus Medical Center, Rotterdam, 10Dept of
Surgery, University Medical Center Groningen, Groningen, 11Dept of Surgery,
Maastricht University Medical Center, Maastricht, 12Dept of Surgery, Maasstad
Ziekenhuis, Rotterdam, 13Dept of Surgery, Radboud University Medical Center,
Nijmegen, 14Dept of Surgery, St Antonius Hospital, Nieuwegein, 15Dept of
Surgery, Leiden University Medical Center, Leiden, 16Dept of Surgery, Catharina
Hospital, Eindhoven, 17Dept of Surgery, OLVG, Amsterdam, 18Dept of Surgery,
Erasmus Medical Center, Rotterdam, Netherlands
Contact E-mail Address: a.gerritsen@dpcg.nl
INTRODUCTION: Preoperative differentiation between malignant and benign
pancreatic tumors can be difficult. Consequently, some 5-14% of patients under-
going pancreatoduodenectomy for suspected malignancy are ultimately diag-
nosed with benign disease.
AIMS & METHODS: We aimed to determine the diagnostic value of a pancrea-
tic mass on computed tomography (CT) in patients with presumed pancreatic
cancer and the additional value of reassessment by expert-radiologists.
A159
We performed a multicenter retrospective cohort study in 1629 consecutive
patients undergoing pancreatoduodenectomy for suspected malignancy (2003-
2010). All patients with unexpected benign disease at postoperative pathological
diagnosis were included in a 1:3 ratio with random patients with (pre)malignant
disease. The preoperative CT scan was reassessed by two expert-radiologists
separately and subsequently (after defining a mass as a measurable space occupy-
ing soft tissue density, except for an enlarged papilla or focal steatosis) in
consensus.
RESULTS: 86 patients with benign and 258 patients with (pre)malignant disease
were included. A mass was reported in the original CT report in 66% of patients
versus 48% and 50% on reassessment by the two expert-radiologists, respec-
tively. Interobserver agreement among expert-radiologists was moderate
(kappa 0.47, 95%CI 0.38-0.56); they disagreed on the presence of mass in
29% of patients. The incidence of mass decreased to 44% after consensus reading
(P50.001 vs. original report). 167/212 (79%) masses identified in the original
report proved to be malignant after pancreatoduodenectomy versus 139/150
(93%) masses identified by expert-radiologists in consensus (P50.001). The sen-
sitivity, specificity, positive predictive value, negative predictive value and accu-
racy of masses identified in the original CT report were 68%, 42%, 79%, 7%,
and 67%, respectively. For masses identified by expert-radiologists in consensus
these were 54%, 87%, 98%, 12%, and 56%, respectively.
CONCLUSION: In patients with presumed pancreatic cancer, the diagnostic
value of a pancreatic mass on CT is high, whereas the absence of a mass
cannot rule out malignancy. Expert-radiologists less frequently identified a pan-
creatic mass as compared to the original CT-report, with doubled specificity for
malignancy.
Disclosure of Interest: A. Gerritsen Financial support for research from:
Unrestrictred grant from Ipsen Farmaceutica B. V., T. Bollen: None declared,
C. Y. Nio: None declared, I. Q. Molenaar: None declared, M. Dijkgraaf: None
declared, H. van Santvoort: None declared, G. J. Offerhaus: None declared, L.
Brosens: None declared, K. Biermann: None declared, E. Sieders: None declared,
K. de Jong: None declared, R. van Dam: None declared, E. van der Harst: None
declared, H. van Goor: None declared, B. van Ramshorst: None declared, B.
Bonsing: None declared, I. de Hingh: None declared, M. Gerhards: None
declared, C. van Eijck: None declared, D. Gouma: None declared, I. Borel
Rinkes: None declared, O. Busch: None declared, M. Besselink: None declared
P0107 FARNESOID X RECEPTOR (FXR) EXPRESSION IN HUMAN
PANCREATIC ADENOCARCINOMA: ASSOCIATIONS WITH
CLINICOPATHOLOGICAL PARAMETERS, TUMOR
PROLIFERATIVE CAPACITY, PATIENTS SURVIVAL AND
RETINOID X RECEPTORS (RXRS) EXPRESSION
I. Koutsounas1,*, K. Giaginis2, A. Zizi3, G. Kouraklis4, E. Patsouris1,
S. Theocharis1
1
First Department of Pathology, Medical School, National and Kapodistrian
University of Athens, Athens, 22Department of Food Science and Nutrition, School
of the Environment, University of the Aegean, Myrina, Lemnos, 3Department of
Pathology, Tzanion General Hospital, Piraeus, 42nd Department of Propedeutic
Surgery, Laikon General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
Contact E-mail Address: john_koutsounas@yahoo.gr
INTRODUCTION: Farnesoid X Receptor (FXR) belongs to the group of
nuclear receptors (NRs). As a transcription factor, it binds to DNA either as a
monomer or as an heterodimer with Retinoid X Receptor (RXR). FXR affects
several metabolic pathways, including development of atherosclerosis, intestinal
bacterial growth and liver regeneration. Additionally, FXR is involved in the
pathogenesis of cholestatic diseases, non-alcoholic fatty liver disease, inflamma-
tory bowel disease and cancer. Although many studies have investigated FXR
expression in various cancer types, a few data exist, so far, on the clinical sig-
nificance of this receptor in pancreatic cancer.
AIMS & METHODS: The expression levels of FXR and its heterodimeric part-
ners RXR-, - and - were assessed immunohistochemically on histopatholo-
gical samples obtained from pancreatic adenocarcinoma patients, and associated
with various clinicopathological parameters, tumor proliferative capacity (Ki-67
labeling index), and patients survival.
RESULTS: Moderate/strong FXR expression was noted in 27 (49.1%) out of 55
pancreatic adenocarcinoma cases, being at borderline level associated with earlier
histopathological stage (p 0.054). Moderate/strong FXR/RXR- expression
was significantly correlated with low tumour histopathological grade of differ-
entiation (p 0.017). Moderate/strong FXR/RXR- and FXR/RXR- expres-
sion was significantly correlated with smaller tumor size (p 0.037, p 0.005,
respectively) and earlier histopathological stage (p 0.017, p 0.004, respec-
tively), while moderate/strong FXR/RXR- expresssion was also significantly
correlated with the absence of lymph node metastases (p 0.018).
Furthermore, patients presenting moderate/strong FXR expression showed sig-
nificantly longer survival times compared to those with negative/weak (log-rank
test, p 0.013). In multivariate analysis, FXR expression and histopathological
stage were identified as independent prognostic factors for patients survival
(Cox-regression analysis, p 0.044 and p50.001). Patients presenting moder-
ate/strong FXR/RXR- or FXR/RXR- expression showed significantly
longer survival times compared to those with negative/weak (log-rank test,
p 0.021, p50.001, respectively).
CONCLUSION: FXR, FXR/RXR-, FXR/RXR- and FXR/RXR- expres-
sion levels in pancreatic cancer are associated with important histopathological
parameters and better patients outcome.
Disclosure of Interest: None declared
A160
P0108 CLINICAL SIGNIFICANCE OF PREGNANE X RECEPTOR (PXR)
AND RETINOID X RECEPTORS (RXRS) EXPRESSION IN HUMAN
PANCREATIC ADENOCARCINOMA: AN
IMMUNOHISTOCHEMICAL STUDY
I. Koutsounas1,*, K. Giaginis2, A. Zizi3, G. Kouraklis4, E. Patsouris1,
S. Theocharis1
1 1
First Department of Pathology, Medical School, National and Kapodistrian
University of Athens, Athens, 2Department of Food Science and Nutrition, School
of the Environment, University of the Aegean, Myrina, Lemnos, 3Department of
Pathology, Tzanion General Hospital, Piraeus, 42nd Department of Propedeutic
Surgery, Laikon General Hospital, National and Kapodistrian University of
Athens, Athens, Greece
Contact E-mail Address: john_koutsounas@yahoo.gr
INTRODUCTION: Pregnane X Receptor (PXR) is a member of the nuclear
receptor (NR) superfamily, expressed mainly in the liver and intestine, exerting
its transcriptional regulation by binding to DNA response elements as an hetero-
dimer with Retinoid X Receptor (RXR). PXR is involved in the homeostasis of
numerous endobiotics, as well as in inflammatory bowel disease, bone home-
ostasis, liver steatosis and antifibrogenesis. Additionally, PXR has a multifactor-
ial impact on cancer, either by directly affecting cell proliferation and apoptosis
or by inducing chemotherapy resistance. Even though many studies have inves-
tigated PXR implication in various types of cancer, data on the clinical signifi-
cance of this receptor in pancreatic cancer are still very limited.
AIMS & METHODS: The expression levels of PXR and its heterodimeric part-
ners RXR-, - and - were assessed immunohistochemically on histopatholo-
gical samples obtained from pancreatic adenocarcinoma patients, and associated
with various clinicopathological parameters, tumor proliferative capacity (Ki-67
labeling index), and patients survival.
RESULTS: Moderate/strong PXR expression was noted in 24 (43.6%) out of 55
pancreatic adenocarcinoma cases, being positively correlated with tumour histo-
pathological grade of differentiation (p 0.023). Moderate/strong PXR/RXR-
and PXR/RXR- expression was significantly correlated with smaller tumor size
(p 0.005, p 0.012, respectively) and earlier histopathological stage (p 0.003,
p 0.014, respectively). Additionally, pancreatic adenocarcinoma patients pre-
senting moderate/strong PXR/RXR- or PXR/RXR- expression showed longer
survival times compared to those with negative/weak, at non significant levels
though (log-rank test, p 0.278, p 0.053, respectively).
CONCLUSION: In our study, PXR and PXR/RXRs expression was for the first
time examined in human pancreatic cancer cases, being correlated with favour-
able histopathological parameters and associated with longer patients survival.
Disclosure of Interest: None declared
P0109 UROKINASE-TYPE PLASMINOGEN ACTIVATOR (UPA)-
POSSIBLE PANCREATIC CANCER DIAGNOSTIC AND
PROGNOSTIC MARKER?
K. Winter1,*, M. Pawlowski2, P. Szczes niak3, A. Ga siorowska1, D. Orszulak-
Michalak3, E. Malecka-Panas1
1
Department of Digestive Tract Diseases, 2Department of Diabetes and Internal
Diseases, 3Biopharmacy Institution, Medical University of Lodz, Lodz, Poland
Contact E-mail Address: katarzyna.winter@vp.pl
INTRODUCTION: Urokinase-Type Plasminogen Activator (uPA) is a serine
proteinase, which transforms inactive plasminogen to the active plasmin. UPA
is involved in cancer progression, growth and metastasis through degradation of
extracellular matrix (ECM), growth factors FGF, IGF, VEGF release and cel-
lular migration activation. UPA overexpression was confirmed in many human
cancers including pancreatic cancer and was connected to the poor survival. UPA
expression was found in the vessels of tumor stroma, which suggests that it can be
detected in serum.
AIMS & METHODS: The aim of this study was to evaluate the uPA serum
concentration in patients with pancreatic cancer (PC) and chronic pancreatitis
(CP) in order to determinate its possible diagnostic and prognostic value.
The study group included 90 patients: 40 with pancreatic cancer, 30 with chronic
pancreatitis and 20 healthy individuals (control group). Serum level of uPA was
analyzed using an enzyme-linked immunosorbent assay (ELISA). Pancreatic
cancers were classified according to the TNM classification. Criteria for resect-
ability included: absence of distant metastases, lack of evidence of tumor invol-
vement of major arteries, and (if there is venous invasion) a suitable segment of
portal vein (above) and superior mesenteric vein (below) the site of venous
involvement to allow for venous reconstruction.
RESULTS: We revealed threefold increase in uPA serum level in patients with
pancreatic cancer (3.23ng/ml) and twofold increase in patients with chronic pan-
creatitis (2.18ng/ml), with was significant higher than in control group (1.01ng/
ml) (p50.05 PC vs CP; PC vs control; CP vs control). We observed significantly
higher level of uPA in patients with pancreatic cancer and CA19-94 500 IU/l
compared to patients with CA19-9 5500 IU/l 3.98 ng/ml vs 2.8 ng/ml
(p50.03). We noticed lower level of uPA in patients with resectable pancreatic
cancer: 2.28 ng/ml vs 3.4 ng/ml in patients with unresectable pancreatic cancer
but difference was not significant (p 0.14). In addition there was no correlation
between uPA level and pancreatic cancer stage. We found the significant correla-
tion between high serum uPA concentration and shorter survival (p50.05); mean
survival in patients with uPA 4 2 was 181 days 155.11 and in patients with
uPA 5 2 ng/ml- 335 days 313.75 (p 0.04).
CONCLUSION: The results suggest the possible use of serum uPA in pancreatic
cancer diagnosis and differentiation from chronic pancreatitis. Significant corre-
lation between serum uPA concentration and decreased survival, may indicate on
the role of uPA as a prognostic marker in pancreatic cancer.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0110 PARTIAL COVERED BILIARY METALLIC STENT WITH/
WITHOUT DUODENUM METAL STENT AND NEOADJUVANT
CHEMORADIATION THERAPY PROVIDES SYMPTOMATIC
BORDERLINE RESECTABLE PANCREATIC HEAD CANCER WITH A
CHANCE FOR R0 SURGERY
Y. Sekino1, K. Kubota1, K. Hosono1, A. Nakajima1, Y. Fujita1,*
Gastroenterology, Yokohama City University, Yokohama, Japan
Contact E-mail Address: kubotak@yokohama-cu.ac.jp
INTRODUCTION: Neoadjuvant chemradiationtherapy (NACRT) may lead to
successful margin-negative resection (R0) in pts with borderline resectable pan-
creatic head cancer (BRPHC). NACRT using a covered metallic biliary stent has
been attempted in pts with BRPHC, however, the efficacy of this therapy with/
without metallic duodenal stent (MDS) and the influence of using partially cov-
ered metallic stent (PCMS) for its delivery in the treatment of BRPHC has not
been evaluated.
AIMS & METHODS: To evaluate the efficacy of and complications associated
with the use of PCMS with/without MDS during NACRT and the surgical
period.
We reviewed the outcomes of consecutive pts with BRPHC had histopathologi-
cally proven pancreatic adenocarcinoma, who presented with symptomatic bili-
ary obstruction, and divided the patients chronologically, in terms of the period
of stent placement into two groups: group A; plastic stent (PS) deployment plus
NACRT between August 2009 and October 2010; group B; prospectively PCMS
deployment with/without MDS plus NACRT between November 2010 and
December 2013. The pts were categorized as having borderline resectable
cancer based on the NCCN clinical practice guideline established in 2013.
Data on the pts demographics, complications, non re-intervention rate (NRR),
surgical time, operative blood loss, length of hospital stay, complications after
resection, the rate of R0 and prognosis were studied. Safe R0 surgery was defined
as R0 surgery without the need for re-intervention or postoperative
complications.
RESULTS: There were a total of 57 pts with LAPHC (group A and B: 29 and 28
pts, respectively). The median time from stent placement to surgery in the overall
subject population were 130.5 Days in group A and 130.7 days in group B. MDS
was deployed in one pts with group A and three pts with group B. NPR for the 1st
30 days in group A (PS) and B (PCMS) were 48% and 96%, respectively. NPR
for the 2nd 30 days in group A and B were 23% and 92%, respectively. NPR for
the 3rd 30 days in group A and B were 15% and 92%, respectively. Regarding
NPR, PCMS is superior to group using PS (p50.05). No severe complications
including gastrointestinal bleeding after irradiation were noted in any pts. There
were no significant differences between groups regarding surgical time, operative
blood loss, length of hospital stay. The rates of achievement of R0 surgery in
groups A and B were 68.9% (20/29) and 89.3% (25/28), respectively. The PCMS
and MDS did not interfere with the conduct of the NACRT and pancreatico-
duodenectomy in any patients. The rates of achievement of safe R0 surgery in
groups A and B were 10.3% (3/29) and 70.4% (20/28), respectively (p50.05).
Multivariate analysis showed that odds ratio for safe R0 surgery was 18.426
(p50.0001) for PCMS placement.
CONCLUSION: Insertion of PCMS should be considered for the relief of biliary
and/or duodenum obstruction in pts with BRPHC scheduled to receive NACRT,
in view of the minimize need for re-intervention for recurrent biliary obstruction,
and a potentially high rate of achievement of safe R0 surgery, as compared to the
results obtained with PS deployment.
Disclosure of Interest: None declared
P0111 BRANCH DUCT INTRADUCTAL PAPILLARY NEOPLASMS
WITH CYSTS LARGER THAN 3 CM WITHOUT HIGH-RISK
STIGMATA: SHOULD WE RESECT THESE NEOPLASMS OR NOT?
K.T. Lee1,*, M.J. Lee1, Y.J. Lee1, J.K. Lee1, K.H. Lee1
1
Department of Medicine, Samsung Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: happymap@skku.edu
INTRODUCTION: In 2012, revised international consensus guidelines were
published, and they suggested a more conservative approach for the management
of BD-IPMN with cysts larger than 3 cm without other high-risk stigmata.
But, several recent studies have challenged the safety of this guideline. The aim of
this study is to compare the prognosis in patients who underwent surgical resec-
tion because of the cyst size and the prognosis in patients who chose close
observation.
AIMS & METHODS: We retrospectively reviewed the data of 48 BD-IPMN
patients with a cyst size  3cm, without any other suspicious features, between
March 1995 and October 2013. We divided the patients into 2 groups (21 patients
underwent surgery, and 27 patients chose close observation), and compared the
patients characteristics and prognosis.
RESULTS: The patients in the observation group were older than the patients in
the surgery group and they had severe co-morbidities (2 ACE-27 co-morbidity
score (moderate)). None of the patients developed new worrisome features or
high-risk stigmata during the follow-up period, and the causes of death were
not related to IPMN. Among the 21 patients who underwent resection; 4 patients
(19%) were diagnosed with invasive carcinoma, and 1 patient (4.8%) was diag-
nosed with intestinal type of invasive carcinoma. No surgery-related death and
major postoperative complications were noted.
CONCLUSION: While making a decision regarding the management of BD-
IPMN with a cyst size  3cm in the absence of high-risk stigmata, we should
consider the risk of surgery in patients, but we should not hesitate to perform
resection in surgically fit patients especially in high-volume centers with experi-
enced surgeons.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0112 FOLLOW UP HIGH-RISK INDIVIDUALS FOR EARLY
DETECTION OF PANCREATIC CANCER
R. Ashida1,*, T. Ioka1, N. Ishida1, H. Sueyoshi2, R. Takada2, N. Fukutake2,
H. Uehara2, K. Katayama1
1
Departments of Cancer Survey and Gastrointestinal Oncology, 2Department of
Hepato-Biliary and Pancreato Oncology, Osaka Medical Center For Cancer And
Cardiovascular Disease, Osaka, Japan
Contact E-mail Address: rashida@goo.jp
INTRODUCTION: For the detection of pancreatic cancer in early stage, it is
important to identify high-risk individuals and follow up those patients periodi-
cally. We have started an early detection system for pancreatic cancer since 1998,
and revealed that individual with either pancreatic cyst (45mm) or dilated main
pancreatic duct (42.5mm) is high-risk for pancreatic cancer. Follow up of high-
risk individuals (HRIs) with imaging tests, such as trans abdominal ultrasound
which is specialized to pancreato-billiary area (pancreatic US: pUS), endoscopic
ultrasound (EUS) and computed tomography (CT) or magnetic resonance ima-
ging (MRI), can lead to the detection and treatment within asymptomatic
patients, however usefulness of the optimal imaging approach is not known.
AIMS & METHODS: Between June 2007 and January 2014, 535 asymptomatic
HRIs were examined periodically at single center, using pUS (every 3 or 6 month)
and CT or MRI (once a year). EUS was performed when any changes such as
hypoechoic mass, new nodule or rapid change in cyst size were detected by pUS.
ERCP was recommended for cytology when the size of cyst become bigger than
3cm or main pancreatic duct was dilated bigger than 3mm or a newly narrowed
part appeared, or the size of cyst or main pancreatic duct changed rapidly. EUS-
FNA was performed when an invasive nodule or hypoechoic mass was detected.
Contrast harmonic pUS/EUS was also performed if necessary.
RESULTS: Sixteen patients with pancreatic cancer have been confirmed as
malignancy during follow up (2.99% incidence rate), 8 males and 8 females
(mean age 69.1 yrs). Eight patients had an intraductal papillary mucinous
neoplasms (IPMNs) with an associated carcinoma (2: invasive, 6: non-invasive),
six had an invasive ductal adenocarcinoma, and two had ductal carcinoma in situ
(PanIN3). Mean total follow up period until the detection of cancer was 34.8
months (range 6.6 - 64 mo). Fourteen patients were asymptomatic. The number
of patients with cancer stage of 0, IA, IIA, IIB, III, was 7, 4, 2, 1 and 2, respec-
tively. Ten cases were brought to further examination by the findings detected by
pUS, two with symptoms such as abdominal pain, one with tumor marker eleva-
tion, one with MRI finding, one with CT finding and one with EUS finding
which was found by chance during further examination for another lesion. All
invasive pancreatic cancers (smaller than 10mm) were detected only by either
pUS or EUS but not by CT nor MRI. Invasive cancer showed hypo-vascularity
in pUS/ CE-EUS. Three cases were comfirmed as malignant by EUS-FNA and
twelve cases by ERCP. Thirteen cases had surgical resection and three cases had
chemotherapy.
CONCLUSION: Periodical examination of asymptomatic HRIs frequently
detects small pancreatic cancer with early stage. EUS and pUS could detect
invasive pancreatic cancer in early stage better than CT or MRI and are thought
to be important modalities in surveillance.
Disclosure of Interest: None declared
P0113 THE INFLUENCE OF NEURAL INVASION ON SURVIVAL AND
TUMOR RECURRENCE IN PATIENTS WITH PANCREATIC DUCTAL
ADENOCARCINOMA A SYSTEMATIC REVIEW AND META-
ANALYSES
S. Schorn1,*, I.E. Demir1, B. Haller2, H. Friess1, G.O. Ceyhan1 on behalf of
Pancreatic Neuropathy and Pain
1
Department of Surgery, 2Institute of Statistics and Epidemiology, Klinikum
Rechts der Isar der TU Munchen, Munchen, Germany
Contact E-mail Address: Stephan. Schorn@tum.de
INTRODUCTION: The aim of this study is to assess the true impact of peri-
neural invasion/Pn on survival and tumor recurrence in pancreatic ductal ade-
nocarcinoma/PDAC.
Pn is a histopathological hallmark of PDAC, which affects overall survival/OS
and tumor recurrence. Until now, recent studies could demonstrate that Pn
influences disease-free-survival-time/DFS and progression-free-survival-time/
PFS. However, at this time point, there is still no consensus on the real impact
of Pn in PDAC.
AIMS & METHODS: Pubmed, Cochrane library, Ovid and Google Scholar
were scanned for the terms pancreatic ductal adenocarcinoma, pancreatic patients underwent pancreatic resection in our hospital from 1982 to 2003.
cancer, survival, tumor recurrence and perineural invasion. Using the Seventy-four patients died from a known cause. Patients with intraductal papil-
Preferred Reporting Items for Systematic review and Meta-Analysis/PRISMA
guidelines, a systematic review/SR and meta-analyses was performed. All articles
meeting the predefined criteria were critically analyzed on relevance and meta-
analyses were performed by pooling univariate and multivariate hazard ratios/
HR.
RESULTS: 23 studies for the influence of Pn on tumor recurrence and a total of
101 studies analyzing the influence of Pn on survival were identified by the SR.
The performed analyses revealed the prognostic influence of Pn on PDAC
patients. The pooled HR of the univariate (1.86; CI 1.67-2.08; p50.00001) and
multivariate analyses (1.50; CI 1.36-1.65; p50.00001) showed a strong negative
impact of Pn on OS in PDAC. Interestingly, Pn was also closely linked to
decreased DFS (HR: 2.23, CI 1.13-4.41; p50.05) and PFS (HR: 2.82; CI 1.97-
4.04; p50.00001) in the pooled multivariate analyses.
CONCLUSION: This is the first systematic review and meta-analyses focusing
on the prognostic impact of Pn on OS, DFS and PFS in PDAC. Here we could
demonstrate that Pn is an independent prognostic factor among PDAC patients,
which decreases OS, PFS and DFS. Therefore, Pn should receive increased
A161
attention for improved patient stratification and be considered much more inten-
sively in the development of novel therapeutic algorithms in PDAC.
Disclosure of Interest: None declared
P0114 OBESITY IS A RISK FACTOR FOR PANCREATIC
PRECANCEROUS LESIONS
V. Rebours1,*, S. Gaujoux2, G. dAssignies3, A. Sauvanet2, P. Levy1,
P. Ruszniewski1, A. Couvelard4
1
Pancreatology Unit, 2Surgery Unit, 3Radiology Unit, Beaujon Hospital, Clichy,
4
Pathology Unit, Bichat Hospital, Paris, France
Contact E-mail Address: vinciane.rebours@bjn.aphp.fr
INTRODUCTION: Obesity was described as a risk factor of pancreatic cancer in
combination with metabolic abnormalities. The respective roles of intravisceral
and subcutaneous fat are unknown and the prevalence of precancerous lesions in
obese patients was never evaluated.
AIMS & METHODS: To characterize the frequency and severity of pancreatic
intraepithelial neoplasia (PanIN) in patients with fatty pancreas, to correlate
pathological findings with metabolic abnormalities, tobacco intake and type of
fat. Consecutive pancreatic specimens of patients operated on for benign neu-
roendocrine tumors were analyzed. The pancreatic parenchyma was analyzed at
least 2 cm apart from the tumor. Fatty infiltration and fibrosis of the parench-
yma in intra- and extralobular locations were assessed. Dysplastic lesions were
described according to the PanIN classification. General characteristics of the
patients were collected, including body mass index (BMI), diabetes and tobacco
intake. Liver steatosis was assessed by CT scan (mean of 3 regions of interest,
threshold 458UH). The subcutaneous and intravisceral fat (% of the total area)
was estimated on CTscan by the ImageJ software (1.47, NIH, USA).
RESULTS: 110 patients (males: 57%) were included (median surface of pancrea-
tic specimen: 7.5 cm2). Median age at surgery was 53.8 [17-85] years. Arterial
hypertension, diabetes, tobacco intake were found in 19, 9 and 23%, respectively.
Median BMI was 24 [16-37], (BMI525: 45%, 25-530: 24%, 430: 11%).
Overall, PanIN lesions were found in 65% of the patients, Type 1, 2 and 3
PanIN were observed in 62, 38 and 1% of the cases, respectively. Fibrosis and
fatty pancreas (intra- and extralobular locations) were found in 1% and 24% and
in 30% and 51%, respectively. Liver steatosis was observed in 27%. A correla-
tion was observed between the presence of PanIN lesions on one hand and fatty
pancreas [extra- (0.01) and intralobular (50.0001)], intralobular fibrosis (0.003),
high BMI (p 0.02), liver steatosis (p 0.03) and subcutaneous (p 0.02) and
intravisceral fat (p 0.02) on the other. Presence of PanIN was not influenced by
tobacco intake or diabetes. The number of PanIN lesions was correlated with the
severity of liver steatosis (r -0.25, p 0.02), the percentage of intravisceral fat
(r 0.22, p 0.04) but not with the percentage of subcutaneous fat (r 0.14,
p 0.22) or patient age at surgery.
CONCLUSION: Obesity -and especially android obesity with increased intra-
visceral fat- is a risk factor for precancerous lesions of the pancreas. These results
suggest that fatty infiltration per se plays a specific role in pancreatic oncogenesis.
Disclosure of Interest: None declared
P0115 MUCIN PHENOTYPE PREDICTS THE SITE OF METASTASIS
AFTER RESECTION OF PANCREATIC DUCTAL
ADENOCARCINOMA
Y. Hamada1,*, K. Maeshiro2, Y. Nakayama3
1
Pathology, FUKUOKA UNIVERSITY, Fukuoka, 2Surgery, St. Maria Hospital,
Kurume, 3Laboratory Medicine, National Medical Center, Fukuoka, Japan
Contact E-mail Address: yhamada@fukuoka-u.ac.jp
INTRODUCTION: Prognosis after surgical resection of pancreatic ductal ade-
nocarcinoma remains poor because of the high incidence of recurrence. Some
studies have described the sites of metastasis after resection of pancreatic ductal
adenocarcinoma, but little is known about the relationship between clinicopatho-
logical features of the primary carcinoma and site of recurrence. Both normal
and malignant epithelial cells of a variety of organs contain mucous substances
that are rich in very high molecular weight glycoproteins called mucins, which
contain many serine- and threonine-linked carbohydrate chains. However, few
studies examine the relationship between mucin phenotype of primary pancreatic
ductal adenocarcinoma and the site of metastasis.
AIMS & METHODS: The current study focused on clinicopathological features,
including mucin phenotype, in primary pancreatic ductal adenocarcinoma and
their relationship to sites of metastasis after surgical resection. A total of 323
lary mucinous neoplasm were excluded. The follow-up period was 61 to 288
months. Clinical data were obtained from patients charts, and pathological
factors were assessed according to the WHO classification. A control group
comprised 13 patients who had survived more than 10 years after surgery for
carcinoma of the pancreas (10 group). Sections were stained with hematoxylin
and eosin and high iron diamine blue stain for detection of sulfomucin and
sialomucin. The staining pattern was classified into three groups: pure sialomucin
type (Si type), pure sulfomucin type (Su type), and mixed type. With regard to
immunohistochemical staining for MUC1, MUC2, MUC5AC and MUC6, stain-
ing of more than 10% of the carcinoma was defined as positive. Neurovascular
invasion was deemed to be present if involvement of more than five sites on a
typical section was seen.
RESULTS: Of the 74 patients with an obvious cause of death, 45 died of peri-
tonitis carcinomatosa following local recurrence (P group), 25 died of liver metas-
tasis (L group), 2 died of lung metastasis, and 2 died of bone metastasis. We
compared the clinicopathologic features between the L group, P group, and 10
group. Clinicopathologic features of each group are as follow: L group: frequent
A162
Si type of carcinoma (vs. P group, p 5 0.0001; vs. 10 group, p 0.0002), high
rate of venous invasion (vs. P group, p 5 0.0001; vs. 10 group, p 5 0.0001), and
shorter prognosis (334 months, vs. P group, p 0.0257). P group: advanced pT
factor (vs. 10 group, p 0.0015) and high rate of R1 status (vs. L group,
p 0.0370; vs. 10 group, p 0.0243). 10 group: lower grade of pT factor (vs. L
group, p 0.0086; vs. 10 group, p 0.0015) and lower stage (vs. P group,
p 0.0037).
CONCLUSION: We might be able to predict the occurrence of liver metastasis
by preoperative histochemical mucin staining of carcinoma cells that were clas-
sified as Si type preoperatively using EUS-FNA or biopsy.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
ENDOSCOPY AND IMAGING I POSTER EXHIBITION HALL
XL_____________________
P0116 EUS-FNA FOR SMALL GASTROINTESTINAL SUBMUCOSAL
LESIONS: USEFULNESS OF FORWARD-VIEWING
ECHOENDOSCOPE ATTACHED WITH CAP DEVICE
A. Yamabe1,*, A. Irisawa1, G. Shibukawa1, Y. Abe1, K. Imbe1, K. Hoshi1,
R. Igarashi1
1 NEOPLASMS
Gastroenterology, Fukushima Medical University Aizu Medical Center,
Aizuwakamatsu, Japan
Contact E-mail Address: akaneko@fmu.ac.jp
INTRODUCTION: Previous reports demonstrated endoscopic ultrasound-
guided fine-needle aspiration biopsy (EUS-FNA) for gastrointestinal submucosal
lesion (SML) is feasible and safe with high diagnostic yield. On the other hand,
since it is difficult to perform EUS-FNA for small SML especially less than
15mm, almost small SMLs are observed without EUS-FNA. However, because
SMLs include malignant lesions even though a tumor is small, it is desirable to
perform EUS-FNA when possible.
AIMS & METHODS: The aim of this study is to evaluate feasibility and safety
of EUS-FNA using forward-viewing echoendoscope attached with a cap device
to the tip of scope for the small SML. Eight patients who had small SML less
than 15mm I upper GI were enrolled in this study. EUS-FNA was done using
forward-viewing EUS scope (XGIF-UCT160J-AL5; Olympus, Tokyo, Japan)
and needle devices (22G, 25G), with rapid on-site evaluation. To fix the SML
at the needling, a cap device was attached to the tip of scope. We evaluated the
rate of sampling, accuracy, and complication.
RESULTS: Mean diameter of SMLs was 10.6 mm2.94mm (meanSD, range
8-15mm). The puncture could be done in all 8 cases, and mean number of FNA
passes was 4.61.59 (meanSD, range 3-7). The adequate materials were
obtained in 6 (87.5%) for cytology, in 4 (50%) for histological examination
with immunostaining. In 1 (12.5%) patient, adequate sample for both cytology
and histology was not obtained. As final diagnosis, 6 patients were gastrointest-
inal stromal tumor (2 in definition, 3 in suspicion), 2 patients were leiomyoma.
No complication was noted.
CONCLUSION: Although the rate of definitive diagnosis was 50%, EUS-FNA
using forward-viewing echoendoscope attached with a cap device for small SML
was feasible and safe.
Disclosure of Interest: None declared
P0117 ENDOSCOPIC CHARACTERISTICS OF EARLY GASTRIC
CANCERS MIXED WITH WELL AND POORLY DIFFERENTIATED
ADENOCARCINOMA
A. Takahashi1,*, T. Oyama1
1
Endoscopy, Saku Central Hospital Advanced Care Center, Nagano, Japan
Contact E-mail Address: aurevoireurope@yahoo.co.jp
INTRODUCTION: The risk of lymph node metastasis of superficial gastric
cancer depends on histological type, invasion depth and the size. Sometimes,
well differentiated gastric adenocarcinoma has poorly differentiated component
partially. And, the incidence of lymph node metastasis is higher than that of the
well differentiated type. Therefore, endoscopic diagnosis of histological type is
important. However, the endoscopic characteristics of such a histologically
mixed gastric adenocarcinoma are unknown.
AIMS & METHODS: The aim of this study is to investigate the endoscopic
characteristics of early gastric cancers partially with poorly differentiated type.
One hundred eighty-two gastric adenocarcinomas from 172 patients treated by
ESD from January to December 2012 were enrolled in this study. All of the
examination was performed by Olympus H260Z with Lucera. And, narrow
band imaging (NBI) magnified observation was performed after white light ima-
ging (WLI) observation. Magnified endoscopic findings were divided into surface
and vascular pattern. Surface pattern was divided into villous, pit and unclear.
The gross type was classified into 0-I, 0-IIa, 0-IIb and 0-IIc type, and the number
was 9, 67, 7, and 99, respectively. The histology was classified into well and
poorly differentiated type. When the cancer had only well differentiated type,
it was classified as pure well differentiated type. And, when the well differentiated
adenocarcinoma had a poorly differentiated component, it was classified as
mixed type. And when the cancer was composed of only poorly differentiated
adenocarcinoma, it was classified as pure poorly differentiated type.
RESULTS: 1. The numbers of pure well differentiated type, mixed type and pure
poorly differentiated type were 157, 23 and 2, respectively.
2. 0-I type: Seven of 9 lesions were pure well differentiated type, and two of 9
lesions were mixed type. The size of these two lesions was more than 20mm.
3. 0-IIa type: Sixty three and 4 of 67 lesions were well differentiated and mixed
type, respectively. The incidence of mixed type has relationship with the size.
When the lesions were divided three groups depends on the size such as 1-9, 10-
United European Gastroenterology Journal 2(5S)
19, 20-29, 30mm or bigger, the incidence of mixed type was 0% (0/15), 8% (2/24)
and 0% (0/15), 15% (2/13), respectively.
4. 0-IIb type: All of seven lesions were pure well differentiated type.
5. 0-IIc type: 80, 17 and 2 of 99 lesions was pure well, mixed and pure poorly
differentiated type, respectively. And when the size was subclassified into four
groups 2-9, 10-19, 20-29, 30mm or bigger, 0% (0/30), 25% (12/48), 27% (4/15)
and 50% (3/6) were mixed type.
6. The surface pattern of well differentiated adenocarcinoma observed by mag-
nified endoscopy showed irregular villous or pit pattern. However, the surface
pattern of mixed type was unclear in some cases. However, sometimes the surface
was covered by thick mucus, and magnified endoscopic observation was
impossible.
CONCLUSION: The incidence of mixed type depends on the size and macro-
scopic type of the superficial gastric cancer. Magnified endoscopy was sometimes
useful to detect mixed type from the surface pattern.
REFERENCES
NONE
Disclosure of Interest: None declared
P0118 SUBMUCOSAL FIBROSIS AFFECTS THE OUTCOME OF
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) FOR GASTRIC
A. Shimozato1,*, N. Ogasawara1, Y. Kondo1, Y. Ito1, H. Noda1, K. Yanamoto1,
M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University, Nagakute City Aichi, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) is an effective
treatment for gastric neoplasms. However, because of its technical difficulty, it
takes longer, and there is a greater risk of complications such as bleeding and
perforation. The success of ESD depends on the technical proficiency of the
endoscopist and the condition of the gastric tumor. Even for a skilled endosco-
pist, however, submucosal fibrosis can be an obstacle to success of ESD.
Submucosal fibrosis, which usually results from inflammation or tumor invasion,
makes it harder to lift the tumor tissue from the muscle layer. This in turn
lengthens the procedure time, creates risk of complications such as perforations,
and reduces the success rate of complete en bloc resection. Despite its impor-
tance, there has been little investigation of the relationship between the degree of
submucosal fibrosis and outcomes of ESD in early gastric tumors. Accordingly,
the aims of this study were 1), to examine the association between endoscopic and
pathologic findings and submucosal fibrosis in gastric neoplasms; 2), to examine
the association between degree of submucosal fibrosis and outcomes of ESD.
AIMS & METHODS: Two hundred forty six patients with gastric neoplasms (52
cases of adenomas and 194 cases of early gastric cancers) were treated by ESD
from November 2008 to September 2013. Endoscopically, the degree of submu-
cosal fibrosis was classified as follows, based on the findings obtained after a
solution including indigo carmine was injected under the submucosal layer: F0,
no fibrosis, which appeared as a blue transparent layer; F1, mild fibrosis, which
appeared as a white web-like structure in the blue submucosal layer; and F2,
severe fibrosis, which appeared as a white muscle-like structure without a blue
transparent layer.
RESULTS: The presence of endoscopic submucosal fibrosis was not significantly
related to tumor size, ulceration, histological findings, submucosal invasion, and
en bloc resection rates in univariate analysis. However, posterior walls of the
stomach harbored higher frequency of submucosal fibrosis compared with ante-
rior wall regardless of upper, middle or lower portion of the stomach (p50.05).
The procedure time according to the degree of endoscopic submucosal fibrosis
were as follows (mean SD): F0, 82.142.1 minutes; F1, 146.681.6 minutes,
and F2, 171.4106.7 minutes, showing significant difference between groups (p
50.01). The severity of endoscopic submucosal fibrosis was associated with
abundant immediate bleeding which required hemostasis using hemoclips
during ESD procedure (p50.05). However, delayed bleeding was not signifi-
cantly related to the degree of submucosal fibrosis.
CONCLUSION: Submucosal fibrosis of gastric neoplasms is closely related to
tumor location, procedure time, and severe bleeding during ESD. Moreover, the
more advanced the endoscopic submucosal fibrosis, the longer the time required
for ESD and the higher the frequency of immediate bleeding. Further develop-
ment of endoscopic devices and peripheral equipments are needed for safe and
complete resection of lesions with severe fibrosis.
Disclosure of Interest: None declared
P0119 NEW ENDOSCOPIC TECHNIQUE FOR SECONDARY
PLACEMENT OF VOICE PROSTHESIS
A.M. Seraphim , A. Pelosof , L. Kowalski , J. Vartanian , C.Z. Sztokfisz1
1,* 1 2 2
1
endoscopy, 2head and neck surgery, AC Camargo Cancer Center, Sao Paulo,
Brazil
Contact E-mail Address: alvaroseraphim@yahoo.com.br
INTRODUCTION: The functional speech rehabilitation in laryngectomized
patients after total laringectomy remains as one of the most challenging matters
for head and neck surgeons and speech therapists.
The use of voice prostheses has been considered the gold standard in voice
rehabilitation for the last 25 years. Insertion can be performed either as a primary
procedure during laryngectomy or as a secondary procedure with rigid esopha-
goscope or trocar. In some patients these procedure became technically impos-
sible due to some post treatment cervical abnormalities such as necks reduced
hyperextension (post surgery or radiotherapy) anastomotic reduced diameter
(post surgery), trismus and other impairments situations.
AIMS & METHODS: Objective: To present an endoscopic technique for sec-
ondary placement of Provox prosthesis using the flexible endoscope, a plastic
United European Gastroenterology Journal 2(5S)
pliable overtube (to keep the virtual esophageal lumen open so the traqueoeso-
phageal puncture could be performed safely, avoiding unexpected lesions on the
posterior esophageal wall), a 14 gauge intravenous catheter to perfomed the
puncture, and a flexible guidewire. Furthermore, using the flexible endoscope
instead of the rigid esophagoscope we can avoid some of the major complications
of the classical technique i.e.: mediastinitis, cervical cellulitis, fracture of cervical
vertebra, and esophageal perforation
Methods: 7 patients referred to voice rehabilitation with Provox II vocal pros-
thesis in a secondary placement, in which the classic technique could not be
performed, underwent a new surgical technique, performed with a flexible endo-
scope, a plastic pliable overtube, a 14 gauge intravenous catheter and a flexible
guidewire,
RESULTS: The procedure was successfully performed in all seven patients.
There were no complications related to the surgical technique.
CONCLUSION: In patients where the classic technique for secondary insertion
of the Provox prosthesis is technically impossible, this new technique could be a
good alternative
Disclosure of Interest: None declared
P0120 ARE OUTCOMES FOLLOWING ENDOSCOPY FOR
EMERGENCY UPPER GI BLEEDING WORSE AT NIGHT AND
WEEKENDS?
A. Rehman1,*, P. Mundre1, B. Rembacken1
1
Leeds teaching hospital Leeds, Leeds, United Kingdom
Contact E-mail Address: bjorn.rembacken@leedsth.nhs.uk
INTRODUCTION: Patients admitted out of hours or at weekends may have an
excess mortality due to the fact that they undergo emergency endoscopy by junior
staff. We retrospectively looked at the predictors of mortality in patients under-
going emergency endoscopy for severe bleeding in Leeds.
AIMS & METHODS: The survival of patients with the most significant upper
GI bleeding lesions who underwent emergency endoscopy in Leeds between end
of April 2008 and middle of June 2012 were selected for retrospective analysis
using data from our endoscopy reporting system and hospital records.
RESULTS: A total of 509 significant emergency gastroscopies were carried out
with the finding of 197 duodenal ulcers, 105 gastric ulcers, 161 oesophageal
varices, 26 gastric varices, 12 Dieulafoys and 9 other bleeding lesions (bleeding
biopsy site, bleeding EMR site, gastric lymphoma, 3 PHG, 3 angioectasia).
After 22% of procedures (114/509), the patient died within 30 days. As expected,
patients who died had a significantly higher Rockall score (7.6 vs. 6.0 p50.0001),
a higher ASA level (3.5 vs. 2.7 p50.001) and a lower systolic BP at the time of
the examination (94.8 vs 103 p 0.025). Patients who died following endoscopy
for bleeding ulcers were significantly older than those who survived (77.7 vs. 67.5
yrs, p 0.006). There was no significant difference in mortality with the type of
bleeding lesion, Hb (8.0 vs. 7.8) or heart rate (100 vs. 102 bpm) at the time of the
endoscopy between those who survived and those who died. Patients who died,
were transfused significantly more blood than those who survived (5.9 units vs
3.8). Of the patients who suffered a re-bleed, 52 patients died and only 62 sur-
vived. A total of 28 patients required emergency angiography and embolisation
of a bleeding vessel. This small group had suffered a significantly greater blood
loss (21 had suffered a re-bleed) and had an average Hb of only 6.9 in spite of
having received an average of 12.9 units of blood. In spite of this, 22 patients
survived following embolisation.
Undergoing an emergency gastroscopy at night or during the weekend or a bank
holiday was not associated with an increased risk of death (p 0.50, p 0.32
respectively). Whether the examination was carried out by a SpR or a Consultant
made no difference to the survival of the patient (p 0.40).
CONCLUSION: Our study had the statistical power to detect all the recognised
risk factors for death following admission with an acute upper GI bleed including
advancing age, increasing comorbidity, hypotension, re-bleeding and transfusion
requirement. We found no evidence that undergoing an emergency endoscopy at
night or during the weekend or a bank holiday had any adverse effect on out-
comes. Similarly, the level of seniority of the endoscopist did not affect outcomes.
Disclosure of Interest: None declared
P0121 LONG-TERM OUTCOMES OF PATIENTS WITH MALIGNANT
DYSPHAGIA THAT HAVE UNDERGONE STENTING
A. Gaglia1,*, H. Smart2, P. OToole1, N. Haslam1, S. Sarkar1
1
Gastroenterology, 2Royal Liverpool University Hospital, Liverpool, United
Kingdom
Contact E-mail Address: gagliam2000@hotmail.com
INTRODUCTION: Oesophageal stenting with fully covered self-expanding
metal stents (SEMS) has transformed the care of patients with malignant dys-
phagia. SEMS are easily removable and have fewer reported long-term compli-
cations of tumour ingrowth although possibly more migration. However,
predictive factors for favourable outcomes are yet to be fully defined for those
with malignant dysphagia.
AIMS & METHODS: The aim of this retrospective study was to evaluate the
complications, the re-intervention rate and the survival after insertion of fully
covered SEMS for malignant dysphagia and to identify any predictive factors for
outcomes other than tumour stage. All SEMS procedure data were retrieved
from Royal Liverpool University Hospital patient database retrospectively in a
2-year inclusion period and analysed regarding SEMS characteristics, procedural
events, re-interventions and survival on a standard proforma.
RESULTS: A total of 96 fully covered SEMS were inserted in 74 patients (47
males) with a median age of 73 (range 36-89) years. Technical success was 99%
(95/96), with no complications of perforation or bleeding. Minor (n 6) compli-
cations included chest pain, vomiting & severe GORD. The 30-day mortality was
A163
12% but was not directly related to the SEMS insertion. The 7-day readmission
rate following SEMS placement was 5% as result of symptoms caused by SEMS
including pain & vomiting. The median survival was 125 (range 4-910) days. 26
(35%) of the patients needed re-intervention due to recurrence of dysphagia due
SEMS migration or tumour overgrowth. The SEMS migration rate was 18%
(n 14/96) occurring after a median of 120 (range 10-365) days. 87% of the
migrated SEMS were from tumours of the lower oesophagus and GOJ.
Tumour overgrowth occurred in 16% (n 15/96) at a median of 120 (range
28-210) days. In 19/26 (73%) cases palliation was successfully achieved with
re-intervention; further SEMS placement in 17 & APC in 2. Interestingly, the
patients with recurrence of dysphagia had significantly (p00.5) prolonged sur-
vival (median 156 (range 30-790) days) compared to patients who did not need
any intervention (median 125 (range 4-910) days).
CONCLUSION: Fully covered SEMS are safe and offer extremely effective
palliation of malignant dysphagia for up to 3-4 months. Re-intervention
beyond this point is for recurrence of dysphagia due to SEMS migration and/
or tumour overgrowth that may be due to increased patient survival. The major-
ity of patients can be re-palliated successfully with further endotherapy.
Disclosure of Interest: None declared
P0122 HIGH DIAGNOSTIC YIELD OF EUS-ASSISTED SINGLE
INCISION-NEEDLE KNIFE (SINK) BIOPSY FOR HISTOLOGICAL
ANALYSIS OF UPPER GASTROINTESTINAL STROMAL TUMORS
C.de la Serna- Higuera1,1,*, P. Diez- Redondo1, F. Santos1, I. Penas1, P. Gil1,
H. Nunez1, M. Perez-Miranda1
1
Gastroenterology, Rio Hortega Hospital, Valladolid, Spain
Contact E-mail Address: csernah@hotmail.com
INTRODUCTION: Gastrointestinal stromal tumors (GIST) are the most fre-
quent type of mesenchymal neoplasms of the upper gastrointestinal tract and
may be malignant regardless their echopattern or size, therefore, histologic and
immunohistochemical (IH) analysis are crucial for diagnostic and pronostic pur-
poses. EUS- guided FNA provides a low diagnostic yield, specially for smaller
GIST. EUS - assisted SINK biopsy is an alternative method with promising
preliminary results.
AIMS & METHODS: We aimed to evaluate the diagnostic yield of SINK sam-
ples for IH analysis and mitotic index (MI)assessement.
Retrospective evaluation of a prospectively-mantained database, including all
patients with upper gastrointestinal subepithelial tumors (SETs) who underwent
EUS-assisted SINK biopsy since April 2010 to March 2014. All patients under-
went previous radial/linear EUS for size measurement and morphological char-
acterization; then a needle-knife was used in blended current at 30W to 60W
settings and a 6 to 12 mm linear incision was made along the highest convexity
zone of the lesion. Then, 3 to 5 biopsy samples were obtained from the exposed
tissue with a standard biopsy forceps and included in formalin. When histologic
analysis revealed features of mesenchymal origin (spindle cells), specific IH mar-
kers for GISTs (cKit- CD 117, CD 34) and mitotic count per 50 high- power
fields (HPF) to assess malignant potential were performed.
RESULTS: 72 patients (M/F: 38/34) were included (mean age 63.66, range 22-
89). There were 27 mesenchymal lesions (27/72: 37.5%); GIST 23, leiomioma 4.
Median size: 3.53 mm (1.34-5.90). IH analyses for SINK samples was positive in
25/ 27 GISTs (92.59%) and MI determination was feasible in 21/ 27 (77.77%).
16/21 showed 5 5 mitoses per 50 HPF and were categorized as very low risk
according to the NIH classification-all these lesions with diameters under 30 mm.
There were no procedure-related complications.
CONCLUSION: EUS-assisted SINK-biopsy of upper GISTs appears to be an
easy and safe technique and provides sufficient tissue samples for IH diagnosis
and assessment of malignancy by means of an accurate MI calculation.
REFERENCES
1.-Philipper M, Hollerbach S, Gabbert HE, et al. Prospective comparison of
endoscopic ultrasound-guided fine needle aspiration and surgical histology in
upper gastrointestinal submucosal tumors. Endoscopy 2010; 42: 300-305.
2.-Fernandez-Esparrach G, Sendino O, Pellise M, et al. Endoscopic ultrasound-
guided fine needle aspiration and trucut biopsy in the dignosis of gastric stromal
tumors: a randomized crossover study. Endoscopy 2010; 42: 292-299.
3.-Hoda KM, Rodriguez SA and Falgel DO. EUS-guided sampling of supected
GI stromal tumors. Gastrointest Endosc 2009; 69: 1218-1223.
4.-De la Serna C, Perez-Miranda M, Diez-Redondo P, et al. EUS-guided single-
incision needle-knife biopsy: description and results of a new method for tissue
sampling of subepithelial GI tumors. Gastrointest Endosc 2011; 74: 672-676.
Disclosure of Interest: None declared
P0123 PENTAX I-SCANTM WITH MAGNIFICATION FOR THE
IDENTIFICATION OF UNDERDIAGNOSIS ORGANIC
ESOPHAGEAL LESIONS (BARRET ESOPHAGUS AND
ESOPHAGITIS) IN PATIENTS WITH FUNCTIONAL DYSPEPSIA: A
PROSPECTIVE STUDY
C. Robles-Medranda1,*, R. Del Valle1, M. Soria1, G. Bravo1, H. Lukashok1,
C. Robles-Jara1
1
ENDOSCOPY, INSTITUTO ECUATORIANO DE ENFERMEDADES
DIGESTIVAS, UNIVERSITY HOSPITAL OMNI, ESPIRITU SANTO
UNIVERSITY, Guayaquil, Ecuador
Contact E-mail Address: carlosoakm@yahoo.es
INTRODUCTION: Functional dyspepsia (FD) is a highly prevalent gastroin-
testinal disorder characterized by symptoms originating from the gastroduodenal
region in the absence of underlying organic disease as defined by Roma III
criteria. Upper endoscopy (UE) associated to digital chromoendoscopy (DC),
magnification (M) and high definition (HD) had shown excellent results for
A164
the diagnosis of Barret esophagus (BE) and esophagitis. However, not all patients
are investigated with this kind of technology, where UE results are considered as
absence of organic lesions, thus diagnosed as FD.
AIMS & METHODS: Based on the hypothesis that HD UE associated to DC
and M can detect more mucosal details than standard UE, we evaluate the
effectiveness of i-ScanTM (HD UEDCM) in patients with functional dyspep-
sia for the identification of organic esophageal lesions. After approval by the
ethics committee and signing of an informed consent, a prospective study was
performed in consecutive patients undergoing for UE from Nov 2012 to June
2013. Inclusion criteria: Criteria of FD in accordance to ROMA III criteria,
normal standard UE in the last 3 months previous to the inclusion in this
study. Exclusion criteria: age 518, pregnancy, history of: gastritis, GERD, gas-
trointestinal cancer, H pylori infection, pancreatic disease, choledocolitiasis,
alcohol or smoke abuse, use of medications (IBP, NSAIDs, Antibiotics). HD
UEDC and M was performed using the EPK-i processors with i-ScanTM from
Pentax. Under sedation patients underwent HD UE, analyzing all the mucosa
aspects using initially white light (WL), with especial regard in the Z-line at the
level of the cardia. Then DC was performed using i-Scan. Any alteration in the
mucosa pattern (color, pitt or vascular pattern) was analyzed and then classified
as inflammation or BE using Los Angeles and Prague classifications respectively.
Finally acetic acid was performed and a target biopsy was done as the gold
standard method to confirm i-Scan findings.
RESULTS: 491 patients were included. 48% were men with a mean age of 47
(ranges: 18-87). 151/491 patients (30.7%) had an organic esophageal lesion
detected at i-Scan. 45/151 patients were detected initially by HD-UE-WL.
Biopsy confirm the esophageal lesions in 125 cases. i-Scan detect 94 cases of
short BE (C51,M51), 25 cases of esophagitis (Grade A), and 6 cases where
considered to have a mixed disease (BE and esophagitis). The accuracy to predict
BE for i-Scan was 95% and 100% for esophagitis.
CONCLUSION: HD UEMDC (i-ScanTM) could detect an important
number of organic esophageal lesions as BE and esophagitis in patients initially
overdiagnosed as a functional disease.
Disclosure of Interest: C. Robles-Medranda Consultancy for: Pentax Medical,
MaunaKea technologies, R. Del Valle: None declared, M. Soria: None declared,
G. Bravo: None declared, H. Lukashok: None declared, C. Robles-Jara: None
declared
P0124 COMPARATIVE STUDY OF ESD AND SURGICAL RESECTION
FOR GASTRIC SETS ORIGINATED FROM MUSCULARIS PROPRIA
C.B. Ryu1,*, M.S. LEE2, J.Y. BAE3, J.Y. SONG4
1
Department of Internal Medicine, Soon Chun Hyang University School of
Medicine, 2Department of Internal Medicine, SOON CHUN HYAN
UNIVERSITY SCHOOL OF MEDICINE, BUCHEON, 3SEOUL MEDICAL
CENTER, SEOUL, 4SUWON MEDICAL CENTER, SUWON, Korea, Republic
Of
INTRODUCTION: Endoscopic resection for gastric subepithelial tumors (SETs)
originated from the muscularis propria (GSET-PM) has offered less invasive
alternatives to surgical resection. The aims of this study were to compare endo-
scopic subtumoral dissection (ESD) with surgical resection for the removal of
GSET-PM.
AIMS & METHODS: This study involved 17 patients with GSET-PM removed
by ESD and 76 patients who underwent curative surgical resection. ESD was
attempted in GSET-PM with well marginated tumors which was below 5cm and
showed an endoluminal growth pattern according to endoscopic ultrasound
(EUS) finding.
RESULTS: ESD group were more likely to have upper portion (10/17, 58.8%)
and surgery group were more likely to have mid portion (41/76, 53.8%)
(p 0.039). ESD group had smaller median tumor size (25.6 mm vs 35.9 mm,
p 0.037) and higher endoluminal ratio (58.59.1% vs 45.815.4%, p 0.002).
ESD group mostly had Yamada type III (10/17, 58.8%) and the surgery group
were mostly Yamada type I (52/76, 68.4%) (p50.001). Complete resection by
ESD was lower than by surgical resection (82.4% vs 100%, p50.001). In ESD
group, 3 performed surgical resection after ESD (1 incomplete resection and 2
uncontrolled bleeding) and 1 showed perforation which was completely resected
with endoscopic closure. In the surgery group, complications occurred in 6
patients (1 leakage, 1 stricture, 1 hernia and bowel obstruction, 1 wound infection
and 2 worsened general condition after surgery). Although surgery group were
lower in complication rate than ESD group (p 0.006), severity of complications
were higher in the surgery group and there were no mortalities in the ESD group
compared with 2 in the surgery group. There was no statistical difference of
recurrence and the follow-up period between the two groups.
CONCLUSION: ESD can be a good option for the resection of endoluminal
GSET-PM and could replace treatment by surgical resection in Yamada type III
with a high endoluminal ratio.
Disclosure of Interest: None declared
P0125 NON-CURATIVE ENDOSCOPIC RESECTION DOES NOT
ALWAYS LEAD TO GRAVE OUTCOMES IN SUBMUCOSAL
INVASIVE EARLY GASTRIC CANCER
C. Jun Young1,*, J. Seong Woo1, C. Kwang Bum2, P. Kyung Sik2, K. Eun Soo2,
P. Chang Keun3, C. Yun Jin3, K. Joong Goo4, J. Jin Tae4, K. Eun Young4,
K. Kyeong Ok5, J. Byung Ik5, L. Si Hyung5, P. Jeong Bae6, Y. Chang Hun6
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Kyungpook National University Medical Center, 2Internal Medicine, Keimyung
University College of Medicine, 3Internal Medicine, Fatima Hospital, 4Internal
medicine, Daegu Catholic University School of Medicine, 5Internal Medicine,
Youngnam University School of Medicine, Daegu, 6Internal Medicine, Dongkuk
United European Gastroenterology Journal 2(5S)
University School of Medicine, Gyeongju, Korea, Republic Of
Contact E-mail Address: sentiwalk@naver.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely
performed for the treatment of early gastric cancer (EGC).
AIMS & METHODS: The aim of this study is to confirm the effectiveness of
ESD in submucosal invasive gastric cancers (SM-GC), with a special focus on
patients who underwent non-curative resection.
Data for 1,246 patients who underwent ESD for treatment of EGC at six medical
centers in Daegu-Gyeongbuk, Korea, between February 2003 and May 2010
were collected. After retrospective analysis of ESD databases, 118 patients
were enrolled in the study. The corresponding EGC lesions were classified into
three groups based on the results of pathological examination: 1) gastric cancers
with submucosal invasion less than 500mm (SM1-GC) that met the expanded
criteria (EC) (SM1 EC group, n 42); 2) SM1-GC that did not meet the EC
(SM1 non-EC group, n 38); and 3) gastric cancers with submucosal invasion
greater than 500mm (SM2-GC group, n 38).
RESULTS: The en bloc resection rate (SM1 EC group/SM1 non-EC group/
SM2-GC group: 85.7%/94.7%/97.4%, respectively) and complete resection
rate (SM1 EC group/SM1 non-EC group/SM2-GC group: 81.0%/81.6%/
71.1%, respectively) did not differ significantly among the three groups.
However, the curative resection rate was significantly better in the SM1 EC
group (69.0%) compared to that in SM1 non-EC and SM2-GC groups (0% in
both cases). Out of a total of 118 patients, 89 (75.4%) underwent non-curative
resection. Cancer recurrence was observed in 9 patients (9/89, 10.1%) during the
median follow-up period of 40 months (range: 3-99). We analyzed the overall
survival and disease-free survival in non-curative patients that underwent or did
not undergo additional surgery. The overall survival and disease-free survival did
not differ significantly between patients that were treated with additional surgical
resection and those that were simply followed up after ESD.
CONCLUSION: Non-curative resection in SM-GC does not always lead to
cancer recurrence. Thus, if additional surgery cannot be performed because of
the patients unsuitable condition (due to age, underlying disease, etc.) or refusal,
a close follow-up with endoscopy can be considered as an alternative for carefully
selected patients. Moreover, as the ESD technology continues to evolve, it might
be possible to expand the criteria for curative ESD in patients with SM-GC.
Disclosure of Interest: None declared
P0126 PROSPECTIVE LONG-TERM OBSERVATION TRIAL OF ARGON
PLASMA COAGULATION (APC) FOR SHORT-SEGMENT
BARRETTS ESOPHAGUS IN AN OUTPATIENT SETTING
D. Schadlich1,*
1
Universitat Erlangen-Nurnberg, Erlangen, Germany
Contact E-mail Address: e-mail@daniela-hascher.de
INTRODUCTION: Barretts esophagus (BE) is the only known precursor lesion
to esophageal adenocarcinoma of the distal esophagus. There are various endo-
scopic treatments to ablate BE to generate a neo-squamous epithelium such as
radiofrequency ablation (RFA), cryotherapy and argon plasma coagulation
(APC). However, there is limited data available for APC in an outpatient setting.
AIMS & METHODS: Prospective long-term observation trial of Argon Plasma
Coagulation in an outpatient setting.
Patients of a gastroenterology practice were considered for entry into this trial.
At the initial endoscopy a chromoendoscopy was undertaken and biopsies were
taken (bioptic mapping). Then the patients were treated with a high frequency
pulsed APC (16 boosts/sec) in order to ablate BE completely. One session was
necessary for tongue-shaped and complete covering epithelium, more than two
sessions for distal circular BE. Follow-ups were scheduled after six weeks, six
months, one and two years.
RESULTS: 73 patients (17% women, median age: 71 years, range: 34 -82 years)
were enroled but only 70 patients were finally included in this trial. Other than
rare minor retrosternal pain after large ablations there were no other treatment-
associated complications. Of all patients treated with APC-ablation 87.5%
showed a stable complete eradication with regenerated neo-squamous epithelium
in the follow up. During the 2-year follow up 4.3% showed a macroscopic and
histological recurrence. However, the clinical role of residual or recurrent BE in
form of so called Buried glands (10%) is still uncertain and worth discussing.
CONCLUSION: In this trial it was shown the first time that APC was a safe and
efficient endoscopic treatment to ablate short-segment non-dysplastic BE espe-
cially in an outpatient setting.
Disclosure of Interest: None declared
P0127 FUNCTIONAL ESOPHAGOSCOPY VIA TRANSNASAL ACCESS
ALLOWS NEW INSIGHTS IN PATIENTS WITH NEUROGENIC
DYSPHAGIA
D. Domagk1,*, P. Lenz1, K. Heuwing1, I. Suttrup2, H. Heinzow1, J. Wessling3,4,
R. Dziewas2, I.F. Herrmann5, T. Warnecke2
1
Department of Medicine B, 2Department of Neurology, University of Muenster,
3
Department of Radiology, Clemens Hospital Muenster, 4Department of Clinical
Radiology, University of Muenster, Muenster, 5Reflux Center Duesseldorf,
Duesseldorf, Germany
Contact E-mail Address: domagkd@uni-muenster.de
INTRODUCTION: Patients suffering from neurogenic dysphagia often get
caught in the trap: they find themselves somewhere in the space between different
specialists. This dilemma might be due to a lack of pathophysiological knowledge
of the complex swallowing process from the oral cavity to the stomach and an
inability to directly visualize the esophageal phase of deglutition.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: In a multidisciplinary setting, 31 consecutive patients with
suspected neurogenic dysphagia were evaluated by transnasal access applying an
ultrathin video endoscope with an outer diameter of 3.8 mm (BF-3C160,
Olympus Europe). Patients were examined in sitting position while ingesting
water and food of different consistencies. Diagnostic was completed by video-
fluoroscopy and high-resolution manometry. The study was approved by the
local Ethics Committee.
RESULTS: Functional endoscopy was successfully performed in all patients. We
were able to show that functional endoscopy is a feasible and safe method; no
adverse events were noted. Endoscopic findings correlated well with the clinical
signs of the patients and the other diagnostic modalities. A variety of disorders
was documented by functional endoscopy and recorded as video files: Incomplete
and delayed closure of the upper esophageal sphincter (in retroflex view), clear-
ance disturbance of tubular esophagus, esophageal hyperperistalsis and hypomo-
tility. The most common findings in the oral and pharyngeal phase were bolus
leakage, delayed swallowing reflex, vallecular residues, and, aspiration during
food intake.
CONCLUSION: By interdisciplinary cooperation with additional assessment of
the esophageal phase of deglutition using the innovative method of functional
endoscopy, the diagnostic of neurogenic disorders including dysphagia may be
tremendously improved leading to a better clinical understanding of complex
dysfunctional patterns. To our best knowledge, this is the first study to show
that a retroflex view of the ultrathin video endoscope within the esophagus may
be safely performed. This diagnostic comprehensive approach should be helpful
to apply focused prophylactic and therapeutic actions.
Disclosure of Interest: D. Domagk Lecture fee(s) from: Olympus Europe,
Consultancy for: AbbVie, P. Lenz: None declared, K. Heuwing: None declared,
I. Suttrup: None declared, H. Heinzow: None declared, J. Wessling: None
declared, R. Dziewas: None declared, I. Herrmann: None declared, T.
Warnecke: None declared
P0128 REPEATED BOLUS INJECTION VERSUS SLOWLY
CONTINUOUS INFUSION OF PROTON PUMP INHIBITOR FOR
THE MANAGEMENT OF BLEEDING AFTER ENDOSCOPIC
SUBMUCOSAL DISSECTION
D.K. Kang1,*, D.H. Kang1, H.W. Kim1, C.W. Choi1, S.B. Park1, S.J. Kim1,
Y.S. Shin1, Y.Y. Choi1, H.K. Lim1, S.K. Oh1, H.S. Nam1
1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
INTRODUCTION: Elevated intra-gastric pH is important in management of
bleeding and healing the artificial ulcer after endoscopic submucosal dissection.
The Proton Pump Inhibitor (PPI) has powerful acid suppression. At present, the
standard treatment of choice for the prevention of gastric ulcer bleeding is con-
tinuous infusion of PPI after intravenous bolus loading.
AIMS & METHODS: Our aim is to compare the effects of repeated bolus
injection and slowly continuous infusion of PPI for the management of delayed
bleeding after gastric ESD.
From March 2012 to Feb 2013, 273 patients with gastric superficial epithelial
neoplasm were enrolled. The group was divided into two. One is the repeated
bolus group, the other one the slowly continuous-infusion group. All patients are
undergod ESD. In slowly infusion group After initial pantoprazole 80mg bolus
loading for 30 min before ESD, 8mg/hr continuous infusion for 72 hours is done
after initial 80mg bolus loading for continous infusion group. For repeated bolus
group (n 136), pantoprazole 40mg bolus is injected q 12 hours for 72 hours.
After 72 hours, Oral pantoprazole 40 mg daily for 4 to 8 weeks. Follow-up
endoscopy is performed 2 days and 4 weeks after ESD. (In case of incomplete
ulcer healing, 8 week endoscopy and pantoprazole 8 wk medication was done.)
RESULTS: No difference on clinical characteristics were seen between two treat-
ment groups. Bleeding events occurred in 8.4% (23/273) of all patients. In follow
up endoscopic findings, high risk of stigma was found in 15.8% (43/273) of all
patients. No difference in bleeing event was seen between repeated bolus group
and slowly continous infusion group. Submucosal invasive, gross type of lesion
and coronary disease were significant risk factors for rebleeding events rather
than the method of PPI administration.
CONCLUSION: The method of PPI administration was not significantly differ-
ent to predict post ESD delayed bleeding. Submucosal invasive, gross type of
lesion and coronary disease were more important to predict post ESD delayed
bleeding.
Disclosure of Interest: None declared
P0129 A NOVEL STRATEGY IN THE ENDOSCOPIC TREATMENT OF
REFRACTORY UPPER GI-BLEEDING IN ANTICOAGULATED
PATIENTS WITH THE OVER-THE-SCOPE-CLIP (OTSC) ARE WE
ENTERING TO A NEW ARA IN THE TREATMENT OF UPPER GI-
BLEEDING?
E. Wedi1,*, A. Sportes2, T.M. Reiig2, J. Hochberger1
1
Departement of Gastroenterology and Interventional Endoscopy, 2University
Hospital Strasbourg, Strasbourg, France
Contact E-mail Address: edris1@web.de
INTRODUCTION: The OTSC (OVESCO, Germany) is a novel endoscopic
device successfully applied for severe GI bleedings, perforations, fistulas and
experimental NOTES procedures.
We performed a retrospective analysis of all OTSC applications for acute gastro-
intestinal bleeding from February 2009 to March 2014 using our endoscopy
database and individual patient records.
A165
AIMS & METHODS: Over a 5 year period 55 patients [median 73 y (29-97) 17
w, 38 m, ASA 2-4] with acute severe upper gastrointestinal bleeding (hemoglobin
5 7 g/dl at admission for acute bleeding or as emergency endoscopy for hospi-
talized patients) using 56 OTSCs (n 54 T-type 12/6 17.5 mm OD; n 2 T-type
14/6 21 mm OD).
RESULTS: In 48/55 cases (87.2%) acute bleeding was related to peptic ulcer
disease, in 2 cases due to bleeding from a malignant ulcer (1x gastric AC, 1x
gastric lymphoma), 2 cases due to recurrent bleeding after polypectomy and clip
in the stomach. In 1 case a heavily bleeding Mallory Weiss tear and in 1 case a
bleeding ulcer at a gastro-jejunal anastomosis was treated. One patient bled
heavily from a deep muscle laceration after balloon dilatation for achalasia.
18/55 (32.7%) were treated due to a failure of a previous hemostasis methods
(standard hemoclips, injection or radiologic embolization).
Of the 55 patients 44 (80%) were on pre-existing anticoagulation, 9/55 (16.4%)
took warfarin, 24/55 (43.6%) aspirin, 10/55 (18.2%) heparin/enoxaparin and 1
(1.8%) was anti-coagulated with a combination of aspirin plus clopidogrel.
In 46/55 of all cases, primary treatment with the OTSC was successful (83.6%), in
all the cases without re-bleeding events. In 7/55 (12.7%) surgical treatment was
necessary due to insufficient hemostasis. However, 4 of those 7 patients died
during the hospital stay. 2 multi-morbid patients not fit for surgery passed away.
CONCLUSION: The OTSC system is a promising new tool for the management
of acute severe GI-bleeding. Especially patients with pre-existing anticoagulation
and multi-morbidity seem to profit from this system.
Disclosure of Interest: None declared
P0130 CLINICAL OUTCOMES OF ENDOSCOPIC RESECTION FOR
GASTRIC NEOPLASMS IN THE PYLORUS
E.J. Gong1,*, D.H. Kim1, H.-Y. Jung1, H. Lim2, K.-S. Choi1, J.Y. Ahn1,
J.H. Lee1, K.D. Choi1, H.J. Song1, G.H. Lee1, J.-H. Kim1
1
Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center,
Seoul, 2Gastroenterology, Hallym University Sacred Heart Hospital, Anyang,
Korea, Republic Of
INTRODUCTION: Endoscopic resection (ER) for gastric neoplasms in the
pylorus is a technically difficult procedure.
AIMS & METHODS: We investigated clinical outcomes to determine the feasi-
bility and effectiveness of ER for gastric neoplasm in the pylorus. Subjects who
underwent ER for gastric neoplasm in the pylorus at Asan Medical Center
between January 1997 and February 2012 were eligible. The clinical features of
patients and tumors, histopathologic characteristics, adverse events, results from
ER, and survival were investigated.
RESULTS: A total of 227 subjects underwent ER for 228 gastric neoplasms in
the pylorus. Median age was 62 years (interquartile range [IQR]: 53-68 years),
and the male to female ratio was 2.2:1. Median tumor size was 14 mm (IQR: 10-
22 mm), and median procedure time was 23 minutes (IQR: 15-33 minutes). En
bloc resection was achieved for 193 lesions (84.6%), including complete resection
(CR) of 195 lesions (85.5%), and curative resection (CuR) of 167 lesions (73.2%).
Rates of CR and CuR were significantly lower for pyloric and postpyloric lesions
than for prepyloric lesions (p 0.002 and p 0.006). Adverse events occurred in
19 patients, including delayed bleeding in 12 (5.3%) and stricture in 7 (3.1%).
During a median follow-up period of 79.0 months, local tumor recurrence was
detected in 2.6%. The 5-year overall and disease-specific survival rates in the 83
patients with gastric cancer were 81.5% and 96.9%, respectively.
CONCLUSION: ER appears to be a feasible and effective method for the treat-
ment of gastric neoplasms in the pylorus, on the basis of these favorable clinical
outcomes.
Disclosure of Interest: None declared
P0131 THE ROLE OF NONCONTRAST COMPUTED TOMOGRAPHY
(CT) PRIOR TO THE ENDOSCOPIC INTERVENTION FOR THE
SUSPICIOUS ESOPHAGEAL FISH BONE (FB)
E.K. Choi1,*, S.U. Jeong1, H.U. Kim1, S.-J. Boo1, S.-Y. Na1, H.J. Song1, Y.-
K. Cho1, B.-C. Song1
1
Internal Medicine, Jeju National University Hospital, Jeju-Do, Korea, Republic
Of
Contact E-mail Address: suhmok@gmail.com
INTRODUCTION: Accidental foreign body ingestion is not uncommon among
patients of all ages. The immediate risk to the patient ranges from negligible to life
threatening. In Asian countries, fish bones (FB) are the most prevalent esophageal
foreign bodies and they are usually ingested accidentally together with food. The
FBs have sharp polygonal or pin-like pointed structure and they can perforate or
tear the esophageal wall. Therefore, endoscopic intervention should be performed
if FB is impacted in the esophagus. However, it is difficult to diagnose esophageal
FB with symptom, sign or plain radiography in most cases. Computed tomogra-
phy (CT) has been proven to be accurate and noninvasive technique for evaluating
the structures of esophagus. There are few reports or practical guidelines for using
CT scan for the diagnosis of esophageal FB till now.
AIMS & METHODS: The aim of this study was to evaluate the usefulness of CT
scan for the diagnosis of esophageal FB. Between March 2009 and March 2014,
consecutive patients with suspected esophageal FB at Jeju National University
Hospital were identified. Among those, patients with normal plain radiography
were included, and medical records were abstracted for CT scan and endoscopy
with outcomes. In some patients, noncontrast neck CT scan was performed prior
to endoscopic intervention. We evaluated the outcome in two groups (pre-endo-
scopic CT or No CT).
RESULTS: During the study period, 134 patients (M:F 55:79) who were
strongly suspected of FB ingestion with normal plain radiography were enrolled.
The mean age was 54.515.6. Of those 134 patients, 91 (68%) underwent CT
A166
scan, and 43 (32%) underwent endoscopic intervention without CT scan. Among
91 patients with pre-endoscopic CT scan, 57 patients had positive CT findings of
FB. The subsequent endoscopic procedure showed FB in 56 (98%), and FB was
removed in all patients successfully. Among 34 patients who had negative finding
of FB on the CT scan, 20 patients underwent endoscopy because of patients
request. However, FB was found in only 2 (10%) patients at the inlet of esopha-
gus. In these two patients, artifacts which were made by dental prosthesis inter-
fered with detecting FB on the CT scan. Among 43 patients without pre-
endoscopic CT scan, 31 patients (72%) had esophageal FB in endoscopic exam-
ination. The sensitivity, specificity, positive predictive value, and negative pre-
dictive value of CT scan for the detection of FB was 98.2%, 90.1%, 96.5%, and
94.7%, respectively.
CONCLUSION: Pre-endoscopic CT scan is accurate and noninvasive diagnostic
modality for the detection of ingested esophageal FB. Moreover, CT scan prior
to endoscopic procedure is very useful to avoid unnecessary endoscopic proce-
dure. Further studies are needed about the advantages of pre-endoscopic CT scan
for the evaluation of pre-endoscopic complication and for the planning of endo-
scopic removal method.
Disclosure of Interest: None declared
P0132 ENDOSCOPIC THERAPY IN UPPER GI BLEEDING: ARE WE
FOLLOWING THE GUIDELINES?
G. Goodchild1,*, S. Subramaniam1, K. Besherdas1
1
Gastroenterology, Barnet and Chase Farm NHS Trust, London, United Kingdom
INTRODUCTION: Acute upper gastrointestinal bleeding (UGIB) is a common
medical emergency that carries a 10% inpatient mortality. Acute peptic ulcer
disease is the most common aetiology followed by variceal bleeding. Mortality
has not significantly improved over the last 50 years, highlighting the need to
follow best practice guidelines in order to improve outcomes.
Upper GI endoscopy allows us to diagnose and treat the cause of UGIB as well
as to help prevent re-bleeding. The 2012 NICE guidance on the management of
non-variceal UGIB states that adrenaline as monotherapy should be avoided. It
suggests that only mechanical therapy (e.g clips) be used as monotherapy and
that adrenaline should always be used as dual therapy with either clips or thermal
coagulation (APC).
The aim of our study was to audit our practice and compliance with NICE
guidance in delivering appropriate endoscopic therapy for non variceal UGIB
and to ascertain the rate of re-bleeding.
AIMS & METHODS: A retrospective analysis of all patients who underwent
upper GI endoscopy for melaena or haematemesis as a primary symptom over an
eight year period (2006-2013) was performed within a large district general North
London NHS trust. Data was obtained from the Unisoft Endoscopy reporting
software. The therapies used at endoscopy for UGIB were scrutinized.
RESULTS: 3759 patients were referred for upper GI endoscopy with melaena or
haematemesis. 594 patients received endoscopic therapy (102 for variceal bleeds
and 492 for non-variceal bleeds).
Table 1: Therapies in non-variceal upper GI bleeding:
Therapy Number of patients (%)
Adrenaline monotherapy 172 (34.9%)
Adrenaline Endoclip* 117 (23.8%)
APC monotherapy 94 (19.1%)
Adrenaline APC* 53 (10.8%)
Endoclip monotherapy* 32 (6.5%)
Adrenaline APC endoclip* 18 (3.7%)
Endoclip APC 6 (1.2%)
Total 492
A total of 26 patients (5.3%) diagnosed with non-variceal upper GI bleeding
experienced re-bleeding (defined as the re-appearance of melaena/haematemesis
with repeat endoscopy within 7 days). Of these patients 14 (53.8%) had received
optimal (NICE recommended) therapy whilst 12 (46.2%) had received sub-opti-
mal therapy (7 had adrenaline monotherapy and 5 had APC monotherapy).
There was no associated increase in mortality compared to the national average.
CONCLUSION: This study demonstrates poor adherance to current NICE gui-
dance on dual therapy in non variceal UGIB as only 45% of patients received
optimal intervention. Endoscopic monotherapy for acute UGIB either with
adrenaline (35%) or APC (19%), though no longer recommended was still evi-
dent within our trust. The type of therapy given did not influence the risk of re-
bleeding in our population and our overall mortality rates fell within expected
levels.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0133 PRIMARY OBESITY SURGERY ENDOLUMENAL METHOD FOR
THE TREATMENT OF 162 OBESE PATIENTS WITH A FOLLOW UP
TIME OF 1 YEAR
G. Lopez-Nava1,*, I. Bautista-Castano1, A. Jimenez-Banos 1, T.de Grado-
Manchado 1, J.P. Fernandez-Corbelle1
1
Bariatric Endoscopy Unit, Sanchinarro University Hospital, Madrid, Spain,
Madrid, Spain
Contact E-mail Address: inmaculadabautista60@gmail.com
INTRODUCTION: Obesity is at epidemic proportions and rising1. Bariatric
surgical procedures have demonstrated better durable weight loss than diet and
exercise. However risk may limit adoption of these procedures2. Endoscopic
procedures like the Primary Obesity Surgery Endolumenal (POSE), may offer
less risk and satisfactory results, however, limited safety and outcome data is
available3.
AIMS & METHODS: The objective of the study was to describe the POSE
procedure, perioperative care, one year safety and weight loss outcomes for a
single center.
Methods: 162 patients undergoing the POSE procedure between July 2011 and
April 2013 were followed for one year. Overall patient status and weight data was
collected at baseline and at 1 year (n 130). Outcomes included adverse events,
change in total body weight (TBWL), percentage of TBWL (%TBWL) and
percentage of excess weight loss (%EWL).
RESULTS: Patients tolerated the procedure well with no serious short or long
term adverse events. All but one patient was discharged within 24 hours of
procedure. Mean age was 43.711.0 years and baseline BMI was 38.0  4.9
kg/m2. Initial body weight (106.7 18.0 kg) was significantly reduced at 1
year: mean TBWL was 16.010.2 kg and mean % TBWL was 14.48.2%. At
1 year of follow up %EWL was 43.425.6%
CONCLUSION: The POSE method can be considered an effective, safe and well
tolerated for the treatment of patients with obesity, at least at 1 year of follow-up.
REFERENCES
1- World Health Organization. Obesity: preventing and managing the global
epidemic. Report of a WHO Consultation (WHO Technical Report Series
894), http://www.who.int/nutrition/publications/obesity/WHO_TRS_894/en/
(accessed 5 March 2014).
2- Gloy VL, Briel M, Bhatt DL, et al. Bariatric surgery versus non-surgical
treatment for obesity: a systematic review and meta-analysis of randomised con-
trolled trials. BMJ 2013; 347: f5934.
3- Espinos JC, Turro R, Mata A, et al. Early Experience with the incisionless
operating platform (IOP) for the treatment of obesity: The primary obesity sur-
gery endolumenal (POSE) procedure. Obes Surg 2013; 23: 1375-1383.
Disclosure of Interest: None declared
P0134 A KOREAN MULTI-CENTER STUDY TO EVALUATE THE
EFFICACY OF THE OTSC SYSTEM FOR TREATMENT OF GI
FISTULA, PERFORATION AND NOTES ENTRY SITE CLOSURE
H.L. Lee1,*, J.Y. Cho2, J.-H. Cho2, J.J. Park3, S.H. Kim4, J.-H. Han5
1
Gastroenterology, HANYANG UNIVERSITY HOSPITAL, 2Gastroenterology,
Soonchunhyang University, 3Gastroenterology, Korea University,
4
Gastroenterology, Eulji University, Seoul, 5Gastroenterology, Chungbuk National
University, Cheongju, Korea, Republic Of
Contact E-mail Address: alwayshang@hanyang.ac.kr
INTRODUCTION: Recently, a new over-the-scope clip (OTSC) (Ovesco
Endoscopy, Tuebingen, Germany) system has been developed and used for the
primary non-surgical closure of GI tract perforations and fistulas.
AIMS & METHODS: The aims of this study were to investigate the therapeutic
yield of endoscopic management by the OTSC system. We performed a multi-
center prospective study. In total six experts (five centers) performed OTSC
procedure.
RESULTS: This study involved in total 17 patients (median age 55 years (range
32-77 years), 12 men) with GI leaks from anastomotic dehiscence, fistulas, and
esophageal perforation due to Boerhaaves syndrome: Three gastrojejunostomy
site, three esophagojejunostomy site, three esophagogastrostomy site, two
Boerhaave syndrome, two gastrobronchial fistula, one gastrocolonic fistula,
one endoscopic full thickness resection site closure, one jejuno-jejunal fistula,
one colonopseudocyst fistula. The diameter of leaks ranged between 5 and 20
mm. Mean procedure time was 18.3 min. Technically, all procedures were succss-
ful. Complete sealing of leaks was achieved by using OTSC alone in 14 of 17
patients. For one OTSC fail patient, closure was completed by placing one
additional covered stent. Two fistula cases required surgical repair.
CONCLUSION: The OTSC system is very useful in the management of GI leaks
especially in case of anastomotic leakage after bowel surgery.
Disclosure of Interest: None declared
P0135 THE TISSUE EFFECT OF ARGON-PLASMA COAGULATION
WITH PRIOR SUBMUCOSAL INJECTION (HYBRID-APC) VERSUS
STANDARD APC: A RANDOMIZED EX-VIVO STUDY
H. Manner1,*, A. Neugebauer2, M. Scharpf3, K. Braun1, C. Ell4, F. Fend3,
M.D. Enderle2
1
HSK Wiesbaden, Wiesbaden, 2Erbe Elektromedizin, 3Institute of Pathology,
University Tuebingen, Tuebingen, 4Sana Klinikum, Offenbach, Germany
Contact E-mail Address: HSManner@gmx.de
INTRODUCTION: Thermal ablation for Barretts esophagus has widely been
established in gastrointestinal endoscopy during the last decade. The mainly used
methods of radiofrequency ablation (RFA) and argon-plasma coagulation
United European Gastroenterology Journal 2(5S)
(APC) carry a relevant risk of stricture formation of up to 5-15%. Newer abla-
tion techniques that are able to overcome this disadvantage would therefore be
desirable.
AIMS & METHODS: The aim of the present study was to compare the depth of
tissue injury of the new method of Hybrid-APC versus standard APC within a
randomized study in a porcine esophagus model. Using a total of 8 explanted pig
esophagi, 48 esophageal areas were ablated either by standard or Hybrid-APC
(APC with prior submucosal fluid injection) using power settings of 50 and 70W.
The depth of tissue injury to the esophageal wall was analysed macroscopically
and histopathologically.
RESULTS: Using 50 W, mean coagulation depth was 937469mm during stan-
dard APC, and 477271mm during Hybrid-APC (p 0.064). Using 70 W, coa-
gulation depth was 1096320mm (standard APC) and 468136 mm (Hybrid-
APC; p 0.003). During all settings, damage to the muscularis mucosae was
observed. Using standard APC, damage to the submucosal layer was observed
in 4/6 (50 W) and 6/6 cases (70 W). During Hybrid-APC, coagulation of the
submucosal layer occurred in 2/6 (50 W) and 1/6 cases (70 W). The proper muscle
layer was only damaged during conventional APC (50W: 1/6; 70W: 3/6).
CONCLUSION: Hybrid-APC reduces coagulation depth by half in comparison
with standard APC, with no thermal injury to the proper muscle layer. It may
therefore lead to a lower rate of stricture formation during clinical application.
Disclosure of Interest: H. Manner: None declared, A. Neugebauer Other:
Employee of Erbe Elektromedizin, M. Scharpf: None declared, K. Braun:
None declared, C. Ell: None declared, F. Fend: None declared, M. Enderle
Other: Employee of Erbe Elektromedizin
P0136 EVALUATION OF GASTRIC SUBMUCOSAL TUMORS BY
ENDOSCOPIC VISUALIZED FEATURES ON SUBMUCOSAL
ENDOSCOPY
H. Kobara1,*, H. Mori1, S. Fujihara1, N. Nishiyama1, T. Matsunaga1, M. Ayaki1,
T. Yachida1, T. Masaki1
1
Gastroenterology and Neurology, Kagawa University, Kagawa, Japan
Contact E-mail Address: kobara@med.kagawa-u.ac.jp
INTRODUCTION: Although the macroscopic characteristics of submucosal
tumors (SMTs), such as gastrointestinal stromal tumors (GISTs), have been
characterized, the assessment of SMTs by their endoscopic visualized features
(EVF; which are observed by endoscopic imaging under direct view) remains
unevaluated.
AIMS & METHODS: The aim of the present study was to investigate the
potential of endoscopic diagnostics for SMTs using EVF. The EVF of 26 gastric
SMT cases, in which the final pathological diagnosis was obtained by bloc biopsy
using the submucosal endoscopy with mucosal flap method, were retrospectively
reviewed. Each type of SMT was classified according to the following five EVF:
Color, clarity, shape, tumor coating and solidity. Additionally, the EVF of 13
low-risk GISTs and 13 benign submucosal tumors (BSTs) were comparatively
evaluated for the five abovementioned EVF.
RESULTS: Similar trends were identified between the low-risk GISTs, granular
cell tumors and the schwannoma with regard to EVF. While these tumors exhib-
ited cloudy EVF, leiomyomas tended to exhibit clear EVF. Among SMTs of the
heterotopic pancreas type, the EVF demonstrated particularly small nodules of
the pancreatic tissue itself. Although the sample size included in the present study
is small, a classification system for gastric SMTs was proposed according to the
EVF. When compared with the BST group, the GIST group demonstrated a
significantly higher frequency of tumors that exhibited a combination of three
EVF (white, cloudy and rigid) that are consistent with all gastric GISTs
(P50.05).
CONCLUSION: Gastric SMTs may be classified based on the EVF, which
indicates that the EVF possess potential diagnostic value for the differentiation
of GISTs from BSTs.
REFERENCES
1. Kobara H, Mori H, Masaki T, et al. Bloc biopsy by tunneling method using
the endoscopic submucosal dissection for upper gastrointestinal submucosal
tumor. Endoscopy 2012; 44: E197-E198.
2. Kobara H, Mori H, Fujihara S, et al. Bloc biopsy by using submucosal endo-
scopy with a mucosal flap method for gastric subepithelial tumor tissue sampling
(with video). Gastrointest Endosc 2013; 77: 141-145.
3. Kobara H, Mori H, Masaki T, et al. Gastric heterotopic pancreas can be
identified by endoscopic direct imaging with submucosal endoscopy. J
Gastrointestin Liver Dis 2013; 22: 345-348.
Disclosure of Interest: None declared
P0137 MIXED HISTOLOGICAL-TYPE (INTESTINAL AND DIFFUSE
TYPE) EARLY GASTRIC CANCER PATIENTS TENDED TO BE
NON-CURATIVE RESECTION BY ENDOSCOPIC SUB-MUCOSAL
DISSECTION
H. Osumi1,*, J. Fujisaki1, M. Igarashi1
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: hiroki.osumi@jfcr.or.jp
INTRODUCTION: It is well known that the histological types of gastric cancer
are intestinal and diffuse type (by Lauren1). Intestinal type mucosal gastric
cancer will be cured by ESD. However, Diffuse type gastric cancers have
lymph node metastasis and even intramucosal cancer. Intestinal type was divided
into well (tub1) differentiated adenocarcinoma and moderately (tub2) differen-
tiated adenocarcinoma according to their structure abnormality by Japanese
Classification of Gastric carcinoma (JCGC). Intestinal type is equal to differen-
tiated adenocarcinoma and Diffuse type is equal to undifferentiated
A167
adenocarcinoma by JCGC. Mixed-histological type (Intestinal and Diffuse)
early gastric cancer sometimes yields different results in pre-endoscopic sub-
mucosal dissection (ESD) biopsy diagnosis and post-operative ESD diagnosis.
This complicates the diagnosis of the cancer region using narrow band imaging
(NBI).
AIMS & METHODS: The purpose of this study is to evaluate the clinical char-
acteristics and tendencies of mixed-histologic-type early gastric cancer, and bring
up points of consideration of pre-operative ESD diagnosis. 1259 patients who
were diagnosed with predominantly differentiated early gastric cancer (M: 1026
cases, SM: 233 cases) and who were treated with ESD between 2005 and 2012
without previously being treated at the Cancer Institute Hospital were retrospec-
tively studied. The histological type of the cancer tissue, the criteria used to
determine the stump, and the degree of SM invasion were determined based on
the Japanese Classification of Gastric Carcinoma (JCGC). The Chi-square test
and logistic regression analysis were used as univariate and multivariate analysis
respectively to statistically compare the test groups.
RESULTS: Mixed-histologic-type early gastric cancer was defined as showing
10% or more undifferentiated adenocarcinoma in the post-operative ESD diag-
nosis. 94.6% of well (tub1) differentiated adenocarcinoma diagnosed by biopsy
accorded with final ESD specimens pathology. However, 68.2% of moderately
(tub2) differentiated adenocarcinoma diagnosed by biopsy accorded with ESD
specimens. Mixed-histologic-type adenocarcinoma tended to be bigger in size and
had a higher positive rate of sub-mucosal invasion than pure differentiated ade-
nocarcinoma. (Size: 23.2 mm (13.2) vs14.7 mm (9.8), p50.05 SM: 45% vs
26%, p50.05) The rates of lateral margin involvement (LM), Lymphatic inva-
sion (ly) and Lymph node metastasis (LN) were significantly different between
groups of pure differentiated adenocarcinoma and mixed-histologic-type
adenocarcinoma.(LM: 5.4% vs 1.0%, p 0.003 ly: 18% vs 3.1%, p50.05 LN:
3.6% vs 0.3%, p 0.003) In the multivariate analysis, all the above factors are
significantly different between groups.
CONCLUSION: If pre-operative histological diagnosis using biopsy specimens
before ESD shows tub2, there is the possibility that it is mixed-histologic-type
early gastric cancer. We consider it necessary in such a case to conduct a careful
pre-operative diagnosis of the cancer region using NBI or a biopsy of the sur-
rounding area, while keeping in mind the clinical characteristics of mixed-histo-
logic-type adenocarcinoma avoiding non- curative resection by ESD.
REFERENCES
1 Lauren T. The two histological main types of gastric carcinoma. Acta Pathol
Microbiol Scand 1965; 64: 34.
Disclosure of Interest: None declared
P0138 A MORPHOLOGICAL CLASSIFICATION OF WHITE OPAQUE
SUBSTANCE WITHIN GASTRIC NEOPLASIA VISUALIZED BY
MAGNIFYING ENDOSCOPY WITH NARROW-BAND IMAGING
H. Ueyama1,*, A. Nagahara1, K. Matsumoto1, Y. Nakagawa1, K. Matsumoto1,
T. Yao2, S. Watanabe1
1
Gastroenterology, 2Human Pathology, Juntendo University School of Medicine,
Bunkyo-Ku, Japan
Contact E-mail Address: psyro@juntendo.ac.jp
INTRODUCTION: White opaque substance (WOS) identified within gastric
neoplasias is a unique finding visualized in magnifying endoscopy with
narrow-band imaging (ME-NBI) and represents intramucosal accumulation of
lipid droplets. The morphological classification of WOS within gastric neoplasia
has not been investigated in detail.
AIMS & METHODS: The aim of the current study was to establish the mor-
phological classification of WOS and investigate whether it can be used to dis-
criminate between adenoma and early carcinoma. This study retrospectively
investigated two hundred twenty-seven patients with 242 gastric neoplasias (29
adenomas and 213 early carcinomas) who underwent ME-NBI before endoscopic
resection in our hospital between January 2010 and December 2013. We studied
the frequency of WOS within gastric neoplasias and identified the following
morphological patterns: 1) dotted pattern, scattered and distributed as dots; 2)
linear pattern, shaped like a line composed of aggregated dots; 3) reticular pat-
tern, shaped like a honeycomb composed of connected lines; 4) speckled pattern,
mottled and composed of aggregated dots; and 5) diffuse pattern, diffusely dis-
tributed by dense WOS in the intervening part. We also investigated the irregu-
larity of WOS within adenomas and early carcinomas. We defined irregular WOS
as disorganized and asymmetrical distribution of WOS in all patterns.
RESULTS: WOS was more frequently observed in adenomas (13/29: 44.8%)
than in early carcinomas (62/213: 29.1%). WOS within adenomas showed a
symmetrical distribution with a regular reticular pattern because the intervening
part has no severe structural abnormalities. The WOS within carcinomas showed
an asymmetrical distribution with an irregularly dotted or speckled pattern
because the intervening part has severe structural abnormalities.
Adenoma (13) Carcinoma (62) P value
Dotted pattern 2 (15.4%) 30 (48.4%) 50.05
Linear pattern 5 (38.5%) 13 (21.0%) NS
Reticular pattern 8 (61.5%) 9 (14.5%) 50.01
Speckled pattern 4 (30.8%) 40 (64.5%) 0.053
Diffuse pattern 1 (7.69%) 8 (12.9%) NS
Irregular WOS 3 (23.1%) 60 (96.8%) 50.01
A168
CONCLUSION: In gastric neoplasias containing WOS, the morphological clas-
sification of WOS is useful in discriminating between adenoma and early
carcinoma.
Disclosure of Interest: None declared
P0139 ESTABLISHMENT OF AN ENDOSCOPIC DIAGNOSIS FOR
GASTRIC ADENOCARCINOMA OF THE FUNDIC GLAND TYPE
(CHIEF CELL PREDOMINANT TYPE) USING MAGNIFYING
ENDOSCOPY WITH NARROW-BAND IMAGING
H. Ueyama1,*, K. Matsumoto1, A. Nagahara1, Y. Nakagawa1, K. Matsumoto1,
T. Yao2, S. Watanabe1
1
Gastroenterology, 2Human pathology, Juntendo University School of Medicine,
Bunkyo-Ku, Japan
Contact E-mail Address: psyro@juntendo.ac.jp
INTRODUCTION: Gastric adenocarcinoma of the fundic gland (chief cell pre-
dominant type, GA-FG-CCP) has recently been proposed as a new and rare
variant of gastric adenocarcinoma. We previously described the clinicopathoplo-
gical and endoscopic features of GA-FG-CCP using conventional endoscopy
(CE) in 2010 and 20141-2. If this tumor type is not recognized by a physician,
it may be misdiagnosed as a submucosal tumor or fundic gland polyp or it may
be overlooked. Therefore, the endoscopic diagnosis of GA-FG-CCP using mag-
nifying endoscopy with narrow-band imaging (ME-NBI) may be useful; how-
ever, this technique has not been investigated in detail.
AIMS & METHODS: The aim of the current study was to evaluate the endo-
scopic features of GA-FG-CCP using ME-NBI. A total of 17 GA-FG-CCPs were
evaluated retrospectively between January 2008 and December 2013. The endo-
scopic and clinicopathological features of the lesions were analyzed to provide
information of diagnostic value.
RESULTS: A total of 17 patients [median age 66 y (57-75), 10 men, 7 women]
with 17 lesions were treated as follows: 12 were treated with ESD, 3 were treated
with EMR, and 2 underwent surgery. Except for 2 cases that underwent addi-
tional surgery, all of the cases underwent an endoscopic removal without further
treatment. Twelve of the lesions were detected in the upper stomach, 4 in the
middle stomach, and 1 in the lower stomach. Macroscopically, 9 lesions were
submucosal tumors in shape, whereas 5 were depressed, 1 was flat-elevated, 1 was
protruded and 1 was flat in shape. The mean tumor size was 11.8 (3-39) mm.
Histopathologically, there were 5 intramucosal cancers and 12 submucosal inva-
sive cancers. The mean depth of the submucosal invasion was 337.5 (50-1200)
mm. Lymph node metastasis was observed in one case (25%, 1/4). The most
common features of the 17 lesions with CE were 1)submucosal tumor shape in
10(58.8%) cases, 2) whitish color in 12(70.6%) cases, 3)dilated vessels with
branching architecture in 9(52.9%) cases and 4)background mucosa without
atrophic change in 15 (88.2%) cases. The endoscopic findings for a GA-FG-
CCP using ME-NBI did not meet the criteria for carcinoma. However, we
detected the four most frequently occurring features using ME-NBI to be 1)an
indistinct line of demarcation between the lesion and the surrounding mucosa 8/
8(100%), 2)a dilatation of the crypt opening 7/8(87.5%), 3)a dilatation of the
intervening part between the crypts 5/8(62.5%) and 4)the presence of microves-
sels without distinct irregularities 7/8(87.5%).
CONCLUSION: GA-FG-CCP has distinct endoscopic characteristics, especially
in terms of its shape, color, vessels and background mucosa using CE and in its
demarcation lines, the shape of the crypt opening, the shape of the intervening
part between the crypts and the microvessels observed with ME-NBI. Further
investigations should include collecting cases using CE and ME-NBI based on
these endoscopic features.
REFERENCES
[1] Ueyama H, et al. Gastric adenocarcinoma of fundic gland type (chief cell
predominant type): proposal for a new entity of gastric adenocarcinoma. Am J
Surg Pathol 2010; 34: 609619.
[2] Ueyama H, et al. Gastric adenocarcinoma of the fundic gland type (chief cell
predominant type). Endoscopy 2014; 46(02): 153-157.
Disclosure of Interest: None declared
P0140 DIAGNOSTIC AND THERAPEUTIC EFFICACY OF ENDOSCOPIC
ENUCLEATION FOR SMALL GASTRIC MUSCULARIS PROPRIA
LAYER TUMOR
H. Kim1,*, B. Bang1, K. Kwon1, Y. Shin1
1
Internal Medicine, Inha University Hospital, Incheon, Korea, Republic Of
INTRODUCTION: Gastric subepithelial tumors originated from muscularis
propria (MP) are partly benign tumors, but some gastric stromal tumors have
malignant potential, especially gastrointestinal stromal tumors (GISTs). PM
tumors are usually treated by surgical intervention and endoscopic treatment
remains controversial. The aim of this study was to retrospectively evaluate the
utility of endoscopic enucleation for diagnosis and treatment of MP tumors.
AIMS & METHODS: From January 2010 to June 2013, forty patients with
gastric MP tumor ( 20 mm) underwent endoscopic enucleation. Before endo-
scopic resection, all patients performed endoscopic ultrasound to determine the
layer of origin and the accurate size. Small PM tumor (512 mm) was resected by
using band ligation method and PM tumor (range 12-20 mm size) was enucleated
by endoscopic submucosal resection (ESD) technique using various endo-knifes.
Tumor characteristics, tumor size, procedure technique, complete resection rate
and recurrence were analyzed.
RESULTS: A total 40 patients (16 men, 24 women; mean age 50.3 years) were
eligible for inclusion in this study. The histologic diagnosis was leiomyoma
(n 24), GIST (n 15) and schwanoma (n 1). Band ligation method was
used in 20 patients. Median procedure time was 8 min (5-26) and complete
resection rate was 95% (19/20). Two patients developed perforation, which
United European Gastroenterology Journal 2(5S)
was closed by endoscopic methods with metallic clips. ESD method was used
in 20 patients. The mean procedure time was 41.1 minutes (range 10 260) and
complete resection rate was 60% (12/20). Four cases were complicated by per-
foration, and the perforations were closed with metal clips. The mean follow-up
time was 9.8 months (range 3-35). No recurrence was developed during follow-up
period.
CONCLUSION: Endoscopic enucleation appears to be effective method for the
histologic diagnosis and removal of small MP layer tumors (52cm). Although
there is a risk of perforation which has become manageable endoscopically.
REFERENCES
Park YS, Park SW, Kim TI et al. Endoscopic enucleation of upper-GI submu-
cosal tumors by using an insulated-tip electrosurgical knife. Gastrointest Endosc
2004; 59: 409-415.
Huang WH, Feng CL, Lai HC, et al. Endoscopic ligation and resection for the
treatment of small EUS-suspected gastric GI stromal tumors. Gastrointest
Endosc 2010; 71: 1076-1081.
Jeong ID, Jung SW, Bang SJ, et al. Endoscopic enucleation for gastric subepithe-
lial tumors originating in the muscularispropria layer. Surg Endosc 2011; 25: 468-
474.
Disclosure of Interest: None declared
P0141 COMPARISON OF DEXMEDETOMIDINE VERSUS
MIDAZOLAM FOR PROCEDURAL SEDATION DURING
ENDOSCOPIC SUBMUCOSAL DISSECTION OF GASTRIC TUMOR
I.-K. Sung1,*, H.S. Park1, J.H. KIM1, S.-Y. Lee1, S.-P. Lee1, C.S. Shim1
1
Konkuk university medical center, Seoul, Korea, Republic Of
Contact E-mail Address: inksung@kuh.ac.kr
INTRODUCTION: Endoscopic submucosal dissection (ESD) is nowadays com-
monly performed as a treatment for gastric tumor. However, the sedation with
midazolam (MDZ) often did not reach a satisfactory sedation during the proce-
dure and the drug could suppress respiration and blood pressure also.
AIMS & METHODS: To investigate the safety and efficacy of dexmedetomidine
(DEX) in comparison with midazolam (MDZ) as a sedative during an endo-
scopic submucosal dissection (ESD) of gastric tumor.
Design: Prospective, randomized, double-blind study.
Setting: Tertiary-care institution.
Patients: Scheduled patients undergoing ESD of gastric tumor.
Main Outcome Measurements: The depth of sedation by using a MOAA/S score
(Modified Observers Assessment alertness/sedation), interfering actions of
patients, sedation related-adverse events, and the satisfaction degree of the
doctors.
RESULTS: Eighty patients were randomly assigned to one of two treatment
regimens (40 patients of each). There was no statistically significant difference
between the two groups regarding age, sex, body mass index, ASA classification,
and tumor characteristics. Appropriate sedation rate and the satisfaction degree
of the doctors were significantly high in the DEX group. There were more move-
ments of patient leading to an interruption of the procedure in the MDZ group
than in the DEX group. There was no difference in the adverse events between
the two groups.
CONCLUSION: DEX for the sedation during gastric ESD is as safe as MDZ
and the sedation effect of DEX is superior to that of MDZ.
Key words: Procedural sedation; Endoscopic submucosal dissection; Sedative
agents; Dexmedetomidine; Midazolam
Disclosure of Interest: None declared
P0142 A NEW METHOD TO PERFORM DIRECT PERCUTANEOUS
ENDOSCOPIC JEJUNOSTOMY USING DOUBLE BALLOON
ENTEROSCOPY AND FLUOROSCOPY
J. Velazquez1,2,*, R. Beyer2, K. Kabir Baig2, K. Monkemuller2
1
ENDOSCOPY, UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO,
MEXICO, Mexico, 2ENDOSCOPY, UNIVERSITY OF ALABAMA,
Birmingham, United States
Contact E-mail Address: jacovelazquez@gmail.com
INTRODUCTION: Direct percutaneous endoscopic jejunostomy (DPEJ) is
usually performed using traditional push enteroscopes or pediatric colonoscopes.
The success rate of DPEJ in expert hands is about 68%. Herein we present a new
method to perform DPEJ using DBE and fluoroscopy.
AIMS & METHODS: To report on the efficacy and safety of DBE-assisted
DPEJ with simultaneous use of fluoroscopy.
The DBE was performed by using the standard push-pull-technique after the
balloon enteroscope was advanced beyond the ligament of Treitz. During
advancement, a site in the jejunum was sought for PEJ tube placement by tran-
sillumination and finger indentation. In addition we confirmed the site of inden-
tation by placing a radio-opaque marker on the skin and verifying that the small
bowel loop was closed to the skin. After a suitable site was identified, DPEJ
placement was performed by using the Ponsky-method (pull-type-percutaneous
gastrostomy tube technique and 20 Fr PEG-kit.
After placing the DPEJ we administered water soluble contrast through the tube
to clearly confirm intraluminal jejunal positioning.
RESULTS: The study included 24 patients (11 females, 13 males, mean age 55
years, age range 31-79). The indications for DPEJ were feeding in 23 patients and
venting for malignant small bowel obstruction in one. The technical success was
91.6%. In two patients no transillumination was possible. The mean distance of
DPEJ was 74 cm (range 50 to 90 cm) past the pylorus or the anastomosis. One
jejunostomy site got infected (4.1%). There were no major complications asso-
ciated with the procedure.
United European Gastroenterology Journal 2(5S)
CONCLUSION: DBE-DPEJ using fluoroscopic assistance seems an efficacious,
safe and successful approach for patients requiring jejunal enteral feeding.
Nevertheless, studies comparing the double balloon enteroscopy technique to
the standard push enteroscopy technique are needed to establish potential advan-
tages of this technique.
REFERENCES
1. Maple JT, Petersen BT, Baron TH, et al. Direct percutaneous endoscopic
jejunostomy: outcomes in 307 consecutive attempts. Am J Gastroenterol 2005;
100: 2681-2688.
2. Zhu Y, Shi L, Tang H, et al. Current considerations of direct percutaneous
endoscopic jejunostomy. Can J Gastroenterol 2012; 26: 92-96.
3. Kwon RS, Banerjee S, Desilets D, et al. Enteral nutrition access devices.
Gastrointest Endosc 2010; 72: 236-248.
4. Jovanovic I, Vormbrock K, Zimmermann L, et al. Therapeutic double-balloon
enteroscopy: a binational, three-center experience. Dig Dis 2011; 29: 27-31.
5. Monkemuller K, Vormbrock K, Kassalik M, et al. A. Direct percutaneous
endoscopic jejunostomy tube placement using double-balloon enteroscopy.
Gastrointestinal Endoscopy 2012; 75: 463465.
Disclosure of Interest: None declared
P0143 ENDOSCOPIC CLOSURE OF COMPLEX FISTULAS IN POST-
BARIATRIC SURGERY PATIENTS USING THE OVER-THE-SCOPE-
CLIP (OTSC) SYSTEM
J. Velazquez1,2,*, H. Neumann2, C. Diaz2, K. Monkemuller2
1
ENDOSCOPY, UNIVERSIDAD NACIONAL AUTONOMA DE MEXICO,
MEXICO, Mexico, 2ENDOSCOPY, UNIVERSITY OF ALABAMA,
BIRMINGHAM, United States
Contact E-mail Address: jacovelazquez@gmail.com
INTRODUCTION: The novel over-the-scope-clip (OTSC) allows for excellent
apposition of tissue, potentially permitting closure of various types of GI defects.
AIMS & METHODS: To evaluate the usefulness and safety of OTSC for endo-
scopic closure of fistulas and leaks and perforations in patients with post-obesity
surgery altered upper GI anatomy
Case series of all patients with post-obesity surgery altered upper GI anatomy
referred for attempted endoscopic closure over a 14-months period. Data analy-
sis included clinical characteristics, demographics, indication, and type of baria-
tric surgery, primary closure, recurrence, complications, and long-term follow-up
clinical outcome.
RESULTS: Seven consecutive patients with fistulas and leaks associated with
previous bariatric surgery, four men, three women, were included. The mean age
was 50.3 years (range 29-66), mean ASA score of 3 (range 2-4). The most
common surgery was gastric sleeve (n 4), followed by gastric bypass (n 3).
Four patients had a gastropleural fistula; three patients had a gastro-peritoneo-
cutaneous fistula. Endoscopic closure was achieved in 6/7 (85.7%). Whereas 4
patients had resolution of the fistula after one endoscopic session, two patients
required two sessions and one patient required three sessions. On long-term
follow-up there was one recurrence, which was treated with another OTSC.
There were no complications associated with OTSC-applications.
CONCLUSION: This is the largest series reported so far on the utility of OTSC
for closure of fistulas associated with bariatric surgery. OTSC represents an
effective, easy to perform and safe endoscopic therapeutic modality for various
types of fistulas. This therapy should be added to the armamentarium of ther-
apeutic endoscopists.
REFERENCES
1. Nishiyama N, Mori H, Kobara H, et al. Efficacy and safety of over-the-scope
clip: including complications after endoscopic submucosal dissection. World J
Gastroenterol 2013; 19: 2752-2760.
2. Junquera F, Mart nez-Bauer E, Miquel M, et al. OVESCO: a promising
system for endoscopic closure of gastrointestinal tract perforations.
Gastroenterol Hepatol 2011; 34: 568-572.
3. Kirschniak A, Subotova N, Zieker D, et al. The Over-The-Scope Clip (OTSC)
for the treatment of gastrointestinal bleeding, perforations, and fistulas. Surg
Endosc 2011; 25: 2901-2905.
4. Sandmann M, Heike M and Faehndrich M. Application of the OTSC system
for the closure of fistulas, anastomosal leakages and perforations within the
gastrointestinal tract. Z Gastroenterol 2011; 49: 981-985.
5. Weiland T, Fehlker M, Gottwald T, et al. Performance of the OTSC System in
the endoscopic closure of iatrogenic gastrointestinal perforations: a systematic
review. Surg Endosc 2013; 27: 2258-2274.
Disclosure of Interest: None declared
P0144 IMPROVING OUTCOMES FROM UPPER GASTROINTESTINAL
BLEEDING IN ENGLAND BETWEEN 2001 AND 2012
J. Rees1,*, F. Evison2, R. Vohra3, N. Trudgill1
1
Gastroenterology, Sandwell General Hospital, 2Health Informatics Department,
3
General Surgery, Queen Elizabeth Hospital, Birmingham, United Kingdom
Contact E-mail Address: jamesrees@doctors.org.uk
INTRODUCTION: Upper gastrointestinal bleeding (UGIB) is a common med-
ical emergency with significant mortality. UGIB management has changed in
recent years with early therapeutic endoscopy and interventional radiology
(IR) rather than surgery for uncontrollable bleeding. We have therefore exam-
ined outcomes for patients with UGIB over the last decade in England.
AIMS & METHODS: Hospital attendances in England are collated using
Hospital Episode Statistics (HES). ICD-10 coding was used to identify admis-
sions to hospital with UGIB between 2001 and 2012. Death in hospital, 30 day
mortality, emergency readmission within 30 days, median time to endoscopy,
need for surgery or IR and length of stay were examined.
A169
RESULTS: 679,505 episodes were examined involving 378057 men and 301448
women. 51.9% were coded as undergoing inpatient endoscopy. The overall in-
hospital mortality and 30-day mortality for UGIB was 12.2% and 16.1% respec-
tively. Both in hospital and 30-day mortality fell over the 10 year period exam-
ined (2001-2003 14.4% and 18.1% vs. 2009-2012 10.2% and 14.3%, p50.001).
There has been a large fall in age-adjusted in-hospital mortality (81.7 per 1000
(95% CI 79.1-84.3) in 2001-2002 vs. 56.5 (95% CI 56.5-58.3) in 2011-2012). Age-
adjusted 30-day mortality has also fallen from 102.9 per 1000 (95% CI 99.9-
105.9) in 2001-2002 to 79.9 (95% CI 77.7-82.1) in 2011-2012. In-hospital mor-
tality for bleeding varices has fallen by 21.8% from 235.6(95% CI 207.8-265.5)
per 1000 in 2001-2003 to 184.3 (95% CI 165-205) in 2009-2012 and for bleeding
peptic ulcer it has fallen by 18% from 82.2 per 1,000 in 2001-2003 (95% CI 76.7-
88) to 67.4 (95% CI 62.4-72.7) in 2009-2012. For patients who were not coded as
undergoing endoscopy, overall in-hospital and 30-day mortality was higher
(16.4% and 21% respectively) but also fell over the decade. During the same
period there has been a significant fall in the number of patients undergoing
surgery (2001-2003 1.84% vs. 2009-2012 0.75%, p50.001) and a rise in the
proportion of patients undergoing an IR procedure (2001-2003 0.04% vs.
2009-2012 0.18% p50.001). Median time to endoscopy did not change signifi-
cantly (2001-2003 1(IQR 1-3) days vs. 2009-2012 1(IQR 0-3)days) and the per-
centage of patients undergoing endoscopy within 48 hours of admission remained
55% over the same time period. Average length of stay fell from 5 (range 2-12)
days in 2001-2003 to 4 (range 1-9) days in 2009-2012 but rates of emergency
readmission within 30 days have significantly increased (2001-2003 18.2% vs.
2009-2012 27.8% p50.001).
CONCLUSION: Outcomes for patients with UGIB have improved over the past
decade with significant reductions in associated mortality and age-adjusted mor-
tality. There has been a reduction in surgery and increase in IR for UGIB.
Disclosure of Interest: None declared
P0145 ROUTINE CONFOCAL ENDOMICROSCOPY IN A CLINIC
SPECIALIZED IN THE MANAGEMENT OF THE DIGESTIVE
PATHOLOGY WITH MUCOSECTOMY, SUBMUCOSAL
DISSECTION, PROSTHESIS AND PUNCTURE: RESULTS OF THE
FIRST MONTHS OF USE
J.M. Canard1,*
1
Gastro Enterology, Clinique du Trocadero, Paris, France
Contact E-mail Address: jm.canard@hotmail.fr
INTRODUCTION: Probe-based Confocal Laser Endomicroscopy (pCLE) is an
imaging technique that allows the achievement of an extemporaneous micro-
scopic exam of a lesion before the treatment or to control the quality of the
endoscopic treatment.
The aim of the study is to appreciate the real indication of Cellvizio in routine in
a clinic specialized in the management of the digestive pathology.
AIMS & METHODS: In 5 months of practice (from May 16th until November
23rd 2013) during 436 endoscopies, 51 procedures of pCLE were performed. In
all cases, the pathologist exam supports the conclusions of the probe-based
microscopic exam.
Among these 51 procedures, 6 are presented:
- One in the esophagus showing the utility of pCLE to find a dysplasia area on a
Barretts Esophagus before mucosectomy followed by a BARRX destruction.
- One in the colon showing the utility of pCLE to differentiate serrated polyps
from hyperplasic polyps so as to realize an immediate resection.
- One in the stomach showing the utility of pCLE to find a gastric dysplasia area
inside relief abnormalities and treat it by submucosa dissection.
- One in the duodenum showing the utility of pCLE to differentiate an inflam-
matory granuloma from an adenomatous residue which would justify an
ARGON treatment and/or a mucosectomy on a duodenal scare or a right
colic that could initiate major complications.
- One in the biliary duct showing the utility of pCLE for the immediate diagnosis
of cholangiocarcinoma (1) allowing to choose the most appropriate prosthesis.
- One in the pancreas showing the utility of pCLE for the differential diagnosis of
pancreas cysts (serous, mucinous, pseudocysts, cystic forms of neuroendocrine
tumors)
RESULTS: For the first 51 procedures the repartition was: 2 cases in the eso-
phagus (4%), 3 in the cardia (6%), 3 in the stomach (6%), 2 in the duodenum
(4%), 1 in the small bowel (2%), 3 in the biliary duct (6%), 3 in the Vater papillia
(6%), 1 in the pancreas and 33 in the colon (64%).
In 43 cases (84%), the pCLE diagnosis was consistent with those of the pathol-
ogist. In 6 cases (12% of cases, 1 in cardia BE, 1 in the stomach, 1 in colonic
mucosectomy scares, 1 at the Vater papillia and 2 colonic polyps). pCLE over
evaluated the lesion. In 2 cases (4% of cases, 2 cases with colon polyp) pCLE
didnt concur with the diagnosis of the pathologist.
CONCLUSION: Optical biopsies have been useful in the management of the
lesions in the whole digestive tract in 51 cases out of 436 (11.7% of cases) before
E. M. R, E. S. D., installation of biliary prosthesis, pancreatic cysts treatment
and to control the nature of potential residues on an E. M. R or E. S. D. scares.
REFERENCES
(1) Giovannini M, et al. Emid study: final results of a prospective bicentric study
assessing Probe-Based Confocal Laser Endomicroscopy (pCLE). Impact in the
management of biliary strictures. Gastrointest Endosc 2013.
Disclosure of Interest: None declared
A170
P0146 HIGH-PRESSURE INJECTION OF GLYCEROL WITH
HYBRIDKNIFE FOR ESD IS FEASIBLE AND INCREASES THE
EASE AND SPEED OF THE PROCEDURE: AN IN VIVO STUDY IN
PIGS
J. Jacques1,*, D. SAUTEREAU1, P. CARRIER1, C.-Y. COUQUET2,
M. DEBETTE-GRATIEN1, A.L.-sidaner1, T. TABOURET1,
V. VALGUEBLASSE1, V. LOUSTAUD-RATTI1, R. LEGROS1
1
Hepato-gastro-enterology, CHU Limoges, 2laboratoire departemental, conseil
general de haute vienne, Limoges, France
Contact E-mail Address: jeremiejacques@gmail.com
INTRODUCTION: The HybridKnife water-jet system (ERBE, Tubingen,
Germany) has been shown to increase dissection speed and decreased the risk
of perforation during endoscopic submucosal dissection (ESD). Glycerol mixture
is a viscous, long-lasting solution preferentially used by Japanese ESD experts.
The combination of the HybridKnife system with a glycerol solution has not
been evaluated to date.
AIMS & METHODS: A prospective non-randomised comparative study of ESD
with HybridKnife injecting of either a glycerol mixture or normal saline was
performed. Twenty dissections (ten per group) were performed on four anaes-
thetised domestic mini-pigs. Dissection speed (mm2/min), size of the specimen
(mm2), duration (min), en bloc resection rate, and bleeding and perforation rates
were prospectively recorded. An evaluation of operator comfort and perception
of safety (dissection score) was performed using a visual analogue scale with 0
being the worst score and 10 the best.
RESULTS: High-pressure injection of the glycerol mixture and dissection with
the HybridKnife was feasible without complications. Dissection was significantly
more rapid (1.67-fold) with glycerol injection than normal saline injection (27.44
vs. 16.44 mm2/min; p50.001). The dissection score was significantly higher in the
glycerol group than in the normal saline group (5.9 vs. 2.9; p50.001) indicating
that both operators felt more comfortable and safe performing ESD with the
glycerol mixture injection. No differences were observed in the rates of en bloc
resection, bleeding and perforation.
Table 1: Results
Solution Glycerol (n 10) NaCl 0.9% (n 10) p
Mean surface (mm ) 2
1495 (/- SD 430.3) 976 (/- SD 117.8) 0.0127
Mean time (min) 54 (/- SD 9.43) 62.6 (/-SD 17.08) 0.082
Mean speed (mm2/min) 27.44 (/- SD 5.70) 16.44 (/- SD 3.43) 50.001
Perforation 0% 0% NS
Bleeding 20% 20% NS
En bloc resection 100% 100% NS
Dissection score 5.9 (/- SD 0.7) 2.9 (/- SD 0.78) 50.001
Preliminary incision 5 4 NS
CONCLUSION: In an in-vivo pig model, high-pressure jet injection of glycerol
with HybridKnife for ESD is feasible and increases the speed and safety of the
procedure compared with use of normal saline.
REFERENCES
Lingenfelder T et al. Combination of water-jet dissection and needle-knife as a
hybrid knife simplifies endoscopic submucosal dissection. Surg Endosc 2009; 23:
15311535.
Pioche M, et al. High-pressure jet injection of viscous solutions for endoscopic
submucosal dissection: a study on ex vivo pig stomachs. Surg Endosc. Epub
ahead of print 3 January 2014.
Disclosure of Interest: None declared
P0147 VALIDATION OF A FRENCH TRAINING PROGRAM OF
ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD) IN LIVE PIGS
AIMING TO START EFFICIENT AND SAFE HUMAN RECTAL ESD
J. Jacques1,*, R. LEGROS1, C.-Y. COUQUET2, V. VALGUEBLASSE1,
F. BOULANGER1, A.L.-Sidaner1, R. DALOKO1, A. BOUYGUES1,
P. CARRIER1, M. DEBETTE-GRATIEN1, V. LOUSTAUD-RATTI1,
D. SAUTEREAU1
1
Hepato-gastro-enterology, CHU Limoges, 2laboratoire departemental, conseil
general de haute-vienne, Limoges, France
Contact E-mail Address: jeremiejacques@gmail.com
INTRODUCTION: ESD is a beneficial procedure that allows higher rates of en
bloc and complete resection for large precancerous lesions or superficial cancer.
However, training in ESD requires numerous sessions to become efficient, and so
takes time and patience especially in Western countries. A well-structured train-
ing program is essential, because the outcome of ESD is dependent of the experi-
ence of the endoscopist. European experts recommend structured training
programs with animal models to overcome the initial learning curve.
Afterwards, constant practicing of ESD is required to increase success and
decrease the procedure time and complications. We report the sucessful experi-
ence of a standardized local training program for ESD in a french tertiary center
with a starting recruitment.
AIMS & METHODS: Between March and December 2013, 31 pig gastric ESD
were performed by two operators. After the 11 initial pig gastric ESD, operators
began human rectal ESD and 8 rectal human ESD were performed during the
same period. The 20 next animals ESD were performed in parallel in order to
keep a constant exposure to ESD cases. All procedures were performed with a
hybridknife type T (Erbe medical, Erlangen, Germany). Glycerol mixture and
physiologic serum were used for submucosal injection. Live, 20 kg, domestic
United European Gastroenterology Journal 2(5S)
mini-pigs, fasted for 48h prior to the procedure, were used. The duration of
the procedure, size of the specimen, speed of the dissection, en bloc resection
rate, complete resection rate and complications rate were prospectively recorded.
RESULTS: In the pig model, the en bloc resection rate was 96.7% (29/30). The
speed of dissection increased with the experience of the operator to reach a
plateau (30 mm2/min) after 10 dissections. The speed of dissection for the 15
last ESD was significantly higher than the 16 first ESD (16.6 vs 28.2 mm2/min;
p50.001). The mean size of the resected specimen was 1072.8 mm2, the mean
dissection time was 47.9 min and the mean speed of dissection was 22.4 mm2/min.
Only 1 perforation occurred and 6 (19.3%) per procedure bleedings imposed the
use of a coagulation forceps.
In human rectal ESD, en bloc and complete resection rate were 100%. The mean
specimen size was 1909.2 mm2, the mean procedure time was 256 min. The
average speed of dissection was 8.6 mm2/min: 5.8 mm2/min for the first 4
cases vs 10.9 mm2/min for the last 4 cases (p 0.03) No perforation occurred
and 2 patients presented per procedure bleeding considered as a complication. 2
patients presented post procedure bleeding at day 7 and day 17 successfully
treated with hemoclips.
CONCLUSION: A local training program with a pig model allows starting
human dissection with high safety and efficiency. Initial training accelerates the
learning curve and the continuous practice in pig model allows maintaining
constant training until the recruitment of patients becomes sufficient.
REFERENCES
Deprez P, et al. Current practice with endoscopic submucosal dissection in
Europe: position statement from a panel of experts. Endoscopy 2010; 42: 853
858.
Disclosure of Interest: None declared
P0148 BURIED BUMPER SYNDROME - MANAGEMENT BASED ON
ACCURATE STAGING
J. Cyrany1,*, R. Repak1, T. Douda1, S. Rejchrt1, M. Kopacova1, J. Bures1
1
2nd Department of Internal Medicine - Gastroenterology, Charles University in
Prague, Faculty of Medicine in Hradec Kralove; University Hospital Hradec
Kralove, Hradec Kralove, Czech Republic
Contact E-mail Address: jiri.cyrany@fnhk.cz
INTRODUCTION: Buried bumper syndrome (BBS) is one of the major com-
plications of percutaneous endoscopic gastrostomy (PEG). Until now there is no
universal diagnostic and therapeutic algorithm based on the degree of disc
submersion.
AIMS & METHODS: to assess safe and effective algorithm for diagnosis and
therapy of BBS based on easy-to-use classification of severity. Methods: retro-
spective analysis of an endoscopic database, composition and evaluation of BBS
severity scale
RESULTS: We have identified 40 cases of BBS in 38 patients (pts.) out of 1248
procedures of PEG performed from 01.01.2002 to 31.12.2012 at our endoscopy
unit. The cohort consisted of 27 men and 11 women of 22-84 years of age (mean
age 64 years). The most frequent indications for gastrostomy were neoplasma (18
cases) and neurological impairment (16 cases). Duration of gastrostoma to the
diagnosis of BBS varied from 2 weeks to 64 months (mean 13 month). The
incidence of BBS was 3.2% and it has almost tripled between subsequent five-
year intervals - from 1.8% in group A (year 2003-2007) to 5% in group B (year
2008-2012). Potential reasons for the increase we found in more frequent detec-
tion of asymptomatic BBS (0 in group A, 8 in group B, p 0.05), often in
patients with already minimal or no use of the stoma (0 in group A, 9 in
group B, p 0.03). New classification of the depth of disc migration was com-
posed based on clinical examination, gastroscopy and abdominal ultrasound
(Table). Endoscopic component of this classification was validated with a high
inter-rater agreement ( 0.93) and abdominal ultrasound showed favourable
parameters in the localisation of the buried bumper inside the stomach (sensi-
tivity, specificity, positive and negative predictive value were 100%, 90%, 92%
and 100%, respectively). Spectrum of severity in our cohort according to this
classification was: grade 1 - 6 pts., grade 2 - 5 pts., grade 3 - 15 pts., grade 4 - 0
pt., grade 5 - 13 pts., grade 6 - 1 pt. 13 patients with grade 3 were treated
endoscopically by various techniques of dissection, only one case was compli-
cated by pneumoperitoneum. From 13 patients with BBS grade 5, six underwent
laparotomy - bumper was localized outside the stomach in all cases.
STAGE gastroscopy/abdominal ultrasound (US)/clinical finding
0 normal
1 ulcer below the disc and/or partial overgrowth of the disc (less than a
half of disc area covered)
2 disc components still visible (more than a half of disc area covered)
3 disc completely covered, guide wire can be introduced; US: disc
localized inside the stomach
4 disc completely covered, guide wire cannot be introduced; US: disc
localized inside the stomach
5 disc completely covered; US: disc localized out of the stomach
6 disc protrudes out of the skin or palpable just below the skin
CONCLUSION: Incidence of BBS in our series was 3.2% with significant rise
during 11 year period. New BBS severity classification based on gastroscopy and
abdominal ultrasound is easy tool for stratification of patients for surgical and
endoscopic therapy. Acknowledgement: Supported by the project PRVOUK 37-
08.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0149 ENDOSCOPIC SUBMUCOSAL RESECTION FOR
METACHRONOUS TUMOR IN THE REMNANT STOMACH AFTER
SUBTOTAL GASTRECTOMY
J. Lee1,*, B.-H. Min1, J.H. Lee1, J.J. Kim1, P.-L. Rhee1, K.-M. Kim2
1
Department of Internal Medicine, 2Department of Pathology, Samsung Medical
Center, Seoul, Korea, Republic Of
INTRODUCTION: Subtotal gastrectomy is one of the most common procedures
to resect gastric cancer curatively. However, if the patients have a remnant
stomach after the surgery, the risk of metachronous gastric tumor remains.
Because early gastric cancer (EGC) patients have a good prognosis after curative
surgery, the incidence of metachronous tumor in the remnant stomach is now
problematic. When the metachronous gastric tumor is detected, endoscopic sub-
mucosal dissection (ESD) can be considered as an alternative treatment option
than an additional operation.
AIMS & METHODS: Little information exists concerning the optimal treatment
of metachronous tumor in the remnant stomach. The aim of this study was to
assess the clinical outcomes and safety of ESD for this lesion. We retrospectively
enrolled patients who had undergone ESD for metachronous tumor in the rem-
nant stomach after subtotal gastrectomy from December 2007 to January 2013 at
the Samsung Medical Center in Seoul, Korea. A total of 18 lesions in 12 patients
with EGC and 6 patients with high grade dysplasia (HGD) were treated by ESD.
The patient characteristics, endoscopic findings and histopathological features
and technical outcomes of ESD were investigated.
RESULTS: A total of 18 patients had previously undergone 17 Billoth-I (94%), 1
Billoth-II (6%) gastrectomies. The median period from the previous gastrectomy
to the subsequent ESD for metachronous tumor in the remnant stomach was
71months (range 13-207 months), the median tumor size was 13mm (range
4-22mm). En block resection with curative resections achieved for 16 lesions
(88.9%). Adverse events showed 1 case of perforation (5.6%) and there was
neither case of requiring emergent surgery nor treatment-related mortality
during this study period. The patients who requiring additional surgery for cura-
tive treatment due to deep submucosal invasion were 2 (11.2%).
CONCLUSION: ESD for the metachronous tumor in a remnant stomach after
subtotal gastrectomy showed a high en bloc resection rate and very low compli-
cation rate. Therefore, we suggest that ESD is an effective and safe treatment
method for metachronous tumor in the remnant stomach if it is performed by
highly qualified experts. It is less invasive than additional surgery. Therefore, it
can give a better quality of life to the patients, and the treatment outcome is
excellent, with no treatment-related mortality in this study.
Disclosure of Interest: None declared
P0150 EFFICACY OF REBAMIPIDE IN THE HEALING OF IATROGENIC
ULCERS POST ENDOSCOPIC SUBMUCOSAL DISSECTION: A
META-ANALYSIS
J.-A. V. Bisnar1,*, I.H. Cua1
1
Institute of Digestive and Liver Disease, St. Lukes Medical Center, Quezon City,
Philippines
Contact E-mail Address: joannebisnar@gmail.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) is a treatment
option for early gastric cancer (EGC). It is less invasive, however, it is associated
with larger, deeper ulcers post-procedure. Combined use of mucosal protective
anti-ulcer drugs such as rebamipide and proton pump inhibitors (PPI) was
reported to promote ulcer healing.
AIMS & METHODS: The study aims to determine the efficacy of rebamipide in
the healing of post ESD associated ulcers.
PubMed, Cochrane Database and bibliographies of retrieved articles were
searched for eligible articles. Randomized controlled trials involving patients
with EGC who underwent ESD and were given rebamipide monotherapy or as
adjunct to PPI were included in this meta-analysis. 2 reviewers extracted the data
and assessed the quality of the studies included. Review Manager 5 software was
used to analyze data from the studies included. Random effects model was used
for combining quantitative data.
RESULTS: 6 studies with a total population of 758 were included in the review.
356 patients were randomized to the treatment group (rebamipide alone or as an
adjunct to PPI). 354 patients were randomized to the control group (PPI or H2-
RA). Rebamipide monotherapy or as an adjunct to a PPI compared to placebo
(PPI or H2-RA) significantly improved healing with a p value of 0.0002 (RR
1.50, 95% CI 1.21-1.87).
CONCLUSION: Rebamipide improves the healing of post ESD associated
ulcers especially when administered with PPI for 4 weeks.
REFERENCES
Rembackes BJ, et al. Endoscopic mucosal resection. Endoscopy 2001; 33: 709-718.
Uedo N, et al. Effect of a proton pump inhibitor or an H2-receptor antagonist on
prevention of bleeding from ulcer after endoscopic submucosal dissection of early
gastric cancer: a prospective randomized controlled trial. Am J Gastroenterol
2007; 102: 1610-1616.
Terano A, et al. Rebamipide, a gastro-protective and anti-inflammatory durg,
promotes gastric ulcer healing following eradication therapy for Helicobacter
pylori in Japanese population: a randomized, double-blind, placebo-controlled
trial. J Gastroenterol 2007; 42: 690-693.
Park SH, et al. Comparison of prevention of NSAID-induced gastrointestinal
complications by rebamipide and misoprostol: a randomized, multicenter, con-
trolled trial STORM STUDY. J Clin Biochem Nutr 2007; 40: 148-155.
Kato, et al. Clinical trial: rebamipide promotes gastric ulcer healing by proton
pump inhibitor after endoscopic submucosal dissection a randomized con-
trolled study. J Gastroenterol 2010; 45: 285-290.
Disclosure of Interest: None declared
A171
P0151 ENDOSCOPIC SUBMUCOSAL DISSECTION IN THE
TREATMENT OF GASTROINTESTINAL NEOPLASIAS: INITIAL
RESULTS IN 31 PATIENTS
A. Herreros de Tejada1,2,*, M. Hernandez Conde1, J.L. Calleja1,2, A. Sanchez
Movilla1, C. Salas1, P. Matallanos1, E. Blazquez1, J.C. Fernandez-Rial1,
S. Gonzalez2, J.F. Garc a2, L. Abreu1,2
1
Hospital Universitario Puerta de Hierro Majadahonda, 2M. D. Anderson Cancer
Center, Madrid, Spain
Contact E-mail Address: marta.hernandez.conde@gmail.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) is an advanced
technique used for en-bloc curative resection of early neoplasms of the gastro-
intestinal tract. Main advantages are high rate of curative resection and low
recurrence rate, avoiding in most cases the need of surgery.
AIMS & METHODS: Initial training on Animal Research facilities was carried
out for 2 years before starting ESD in humans. Prospective analysis of ESD
performed for suspected early neoplasia of GI tract. The interventions were
performed mostly in the endoscopy suite, full equipped to provide general anaes-
thesia in selected cases (all cases on the oesophagus and stomach, as selected
colorectal cases). Flush knife BT (Fujifilm Co. Japan) was the main knife used,
both in versions BT 1.5mm (oesophagus, colon and rectum) and 2.0mm (sto-
mach); occasionally other knifes were applied, such as Hook-knifeand Dual-
Knife (Olympus Co, Japan)
RESULTS: From January 2012 to February 2014 ESD was completed in 31
patients. The mean age was 64.4 years (SD12), with a male proportion of
55%. Over 60% of the cases were performed in colorectal location (colon 12
(39%); rectum 7 (22%)); other locations were stomach (9 (29%)) and oesophagus
(3 (10%)). Initial success of ESD was 93.5%, with 2 cases requiring surgery due
to failure or severe complication (both colonic cases). The en-bloc resection rate
was 96.5%, the average specimen size 18.1 cm2 (max. length on average 46.4mm),
with a median of 114 minutes (34-256) to complete the procedure. Regarding the
morphology, 16 cases were 0-IIa, 5 cases 0-Is, 3 cases 0-IIa/0-IIc, 2 cases 0-IIb, 2
cases 0-Is/IIa 1 case 0-IIa/0-IIb and 1 case 0-IIb/0-IIc. Lateral spreading tumors
(LSTs) distribution was: LST granular mixed type 5 cases, LST granular homo-
geneous type 7 cases, and 1 case of LST non-granular type. The R0 resection rate
for successful ESD was 90% (26 cases). There were 12 cases (39%) with perfora-
tion (38%), of which 10 (80%) were managed successfully with local endoscopic
treatment (closure with clips). There were 2 cases of late complications (splenic
rupture and mild lower gastrointestinal bleeding), with no mortality associated.
We analyzed the population according to chronological inclusion and divided
into 3 similar periods. The average dissection speed during the initial phase was
0.36mm/min, compared to 0.49mm/min and 0.44mm/min during the intermedi-
ate and the final phase respectively, with no statistically significant differences
(p 0.2) due to the small sample size.
CONCLUSION: ESD is an effective technique in the treatment of early neoplas-
tic lesions in the digestive tract, particularly in cases of flat-depressed morphol-
ogy, with a size greater than 20mm and/or the presence of submucosal fibrosis.
The technical difficulty, along with the prolonged time of endoscopy and the risk
of serious complications (essentially perforation) are the main constraints of
ESD. However, in our own experience, high en-bloc and R0 resection rate can
be achieved, along with remarkable technical progress during the learning curve
and successful endoscopic management of perforation. Our results demonstrate
the possibility of successful adoption of ESD in Europe after completing proper
training.
Disclosure of Interest: None declared
P0152 ENTONOX DURING COLONOSCOPY; HOW SHOULD IT
BE USED?
A. Ball1,*, S. Din1, M. Donnelly1, K. Smith1, S.A. Riley1
1
Gastroenterology, Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield,
United Kingdom
Contact E-mail Address: alex.ball@sth.nhs.uk
INTRODUCTION: Entonox can be used to ease the discomfort associated with
colonoscopy but the optimal mode of administration is unknown. We have
compared continuous and as required Entonox use during screening colonoscopy
examinations.
AIMS & METHODS: Patients attending for screening colonoscopy were invited
to participate. Eligible patients were randomised to using Entonox as required or
continuously. Procedural and demographic details including HADS score were
collected. Examinations were performed by three experienced colonoscopists.
Patients rated pain on a 10 point numerical ratings scale (0 no pain and
10 extreme pain) every 2 minutes during colonoscopy, prior to discharge and
1-3 days following colonoscopy. The colonoscopist and specialist screening prac-
titioner (SSP) also rated the patients overall pain severity and the technical
difficulty of colonoscopy.
Continuous and categorical data were compared using a t test and chi-squared
test respectively. Correlations were assessed using Pearsons correlation coeffi-
cient and the agreement between observers was assessed using the intra-class
correlation coefficient (ICC).
RESULTS: 157 patients were screened and 49 were excluded (34 opted for intra-
venous sedation, 13 declined and 2 had a cardiac pacemaker). 108 patients were
randomised and 8 patients were withdrawn (7 had a cancer and 1 was unable to
activate Entonox). Study participants had a mean age of 67 years and 75% were
male. 46 patients were randomised to continuous and 54 to as required use.
15/54 (27.7%) patients in the as required group did not use Entonox and 7/46
(15.2%) of patients in the continuous group reverted to as required use due to side
effects. The number of patients requiring additional analgesia was not significantly
different between continuous use and as required use (4/46 vs 3/54, p 0.54).
A172
There was no significant difference in the overall pain scores given by patients
who used Entonox continuously and as required (mean score 2.4 vs 3.2,
p 0.08 and peak score 4.2 vs 4.8, p 0.26). Overall patient satisfaction was
high with the continuous and as required methods (mean 9.9 vs 9.7, p 0.23) as
was willingness to undergo a repeat examination (mean 9.2 vs. 9.7, p 0.09).
A HADS anxiety score of 7 was associated with higher overall pain scores
(mean score 2.1 vs 3.6, p 0.004 and peak scores 3.7 vs 5.6, p 0.003). Edinburgh, Edinburgh, United Kingdom, 2Endoscopy Unit, Department of
Patient with a HADS anxiety score 57 who were allocated to continuous
rather than as required use had lower pain scores (mean 1.4 vs 2.5,
p 0.045) but there were no significant differences between strategies in the
patients with a HADS score 7 (3.3 vs 3.8, p 0.6) There was no significant
difference in the pain ratings according to gender.
Patients overall rating of pain prior to discharge correlated highly with the mean
intra-procedural pain score (r 0.84) and peak rating of pain (r 0.84). There
was also a very high correlation between the patients overall pain rating prior to
discharge and 1-3 days later (r 0.94). There was good agreement between the
patients and the SSPs (ICC 0.79) and endoscopists (ICC 0.76) overall pain
rating.
CONCLUSION: Overall, the method of Entonox administration did not influ-
ence pain ratings. However, continuous Entonox use was more effective in
patients with a low anxiety level.
Disclosure of Interest: None declared
P0153 NON-ANAESTHESIOLOGIST ADMINISTERED PROPOFOL IN
COLONOSCOPY INTERIM ANALYSIS OF A RANDOMIZED
CONTROLLED TRIAL
A.O. Ferreira1,2,*, J. Torres1, S. Pereira1, S. Dias1, M. Rocha1, R. Pinto3,
V. Schuler3, M. Neves3, C. Castanheira3, A.A. Santos3, F. Silva3, M. Cravo1
1
Department of Gastroenterology, Hospital Beatriz Angelo, Loures, 2Department
of Gastroenterology, Centro Hospitalar do Algarve, Portimao, 3Department of
Anesthesiology, Hospital Beatriz Angelo, Loures, Portugal
Contact E-mail Address: alex.gastrohep@gmail.com
INTRODUCTION: Propofol allows the best sedation in colonoscopy. There is
only one Randomized Controlled Trial (RCT) comparing Non-Anaesthesiologist
Administered Propofol (NAAP) with sedation by an anaesthesiologist.
AIMS & METHODS: Our goal was to compare the incidence of sedation-related
adverse events (AE), colonoscopy quality, and patient satisfaction between
NAAP and anaesthesiologist sedation. We performed a single blinded RCT
with two parallel intervention groups (group A NAAP; group B anaesthe-
siologist sedation). In group A, a 40-60 mg propofol bolus was administered
followed by 10-20 mg bolus as needed. In group B propofol was administered
under the anesthesiologist indication. The primary endpoint was the incidence of
AE as defined by the World SIVA International Task Force on Sedation.
Secondary endpoints were propofol dose, patient satisfaction, and pain assessed
by a 10-point visual analogue scale, procedure and recovery time, and colono-
scopy quality indicators (cecal intubation rate, withdrawal time, adenoma detec-
tion rate). A sample size of 330 (1:1) cases was calculated for a power of 90% at a
5% level of significance, and based on the AE incidence in our preliminary
experience. Patients aged 18-80 with low anaesthetic risk (ASA I-II) were
included (patients characteristics presented in table 1). Herein we present the
interim analysis of the first 100 cases. Statistical analysis was performed with
SPSS version 21. Chi-square, Fischers exact, t-tests and logistic regression were
used as appropriated.
RESULTS: The incidence of AE was 34.3% on group A and 42.4% on group B
(odds ratio 0.709; 95% CI 0.302-1.668; p 0.43). There were no severe (sentinel)
AE events. The following interventions were necessary: atropine administration
(0% vs 6.1%); airway repositioning (14.9% vs 9.1%); increase in O2 adminis-
tration (8.9% vs 6.1%); increase in fluids rate (4.5% vs 0%). Mean propofol
dose: group A 222  84 mg vs group B 245  118mg (p 0.276). Procedure times
were 22.24  13.12 and 21.39  10.78 min (p 0.75), withdrawal time was 11.97
 10.36 vs 11.84  6.15 min (p 0.949) and recovery time was 62  44 vs 61  22
min (p 0.856) in group A and group B respectively. Patients had no pain (0) in
84.5% vs 88.5% (p 0.946) and reported complete satisfaction with the sedation
in 84.8% vs 81.2% (p 0.58). Procedural amnesia was reported in 88 vs 93.8%
(p 0.49). All the patients were willing to repeat the colonoscopy under propofol
sedation. Cecal intubation rates were 95.5% vs 93.9% (p 1.0), adenoma detec-
tion rates were 30.4% vs 31.3% (p 0.93).
Patient characteristics Group A(n 67) Group B(n 33) p
Male sex, n (%) 24(35.8) 14(42.5) n.s.
Mean age, years (sd) 57(14) 51(18) n.s.
ASA I/II, n 6/61 7/26 n.s.
Cardiovascular disease, n (%) 10(14.9) 5(15.2) n.s.
Smoking, n (%) 15(22.4) 5(15.2) n.s.
Snoring history, n (%) 4(8.0) 2(6.0) n.s.
CONCLUSION: In the interim analysis NAAP was equivalent to anaesthesiol-
ogist sedation in the rate of adverse events in a low risk population.
Clinicaltrials.gov (NCT02067065).
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0154 MACROSCOPIC COLONOSCOPY FINDINGS OF
COLLAGENOUS COLITIS; A THREE-CENTRE EXPERIENCE
A. Koulaouzidis1,*, K. Sjoberg2, L. Bartzis1, M. MacNeill3, A. Nemeth2,
G. Wurm Johansson2, P. Finneron3, A.J. Lucendo4, E. Toth2
1
Endoscopy Unit, Centre for Liver & Digestive Disorders, The Royal Infirmary of
Gastroenterology, Skane University Hospital, Malmo, Sweden, 3Pathology
Department, Western General Hospital, Edinburgh, United Kingdom, 4Endoscopy
Unit, Hospital General de Tomelloso, Tomelloso, Spain
INTRODUCTION: Microscopic colitis (MC) encompasses 2 entities, collage-
nous colitis (CC) and lymphocytic colitis (LC).1 Although (by definition) a his-
topathological diagnosis, there are occasions when colonoscopy reveals findings
such as alteration of the vascular mucosal pattern/innominate grooves, mucosal
nodularity and a sequence of mucosal changes from defects/lacerations to cica-
tricial lesions that are thought to be characteristic of MC, and especially CC.1,2
The aim of this study was to evaluate the frequency and type of endoscopic
findings in patients diagnosed with CC in two University Hospitals.
AIMS & METHODS: Retrospective study. The database of the Pathology
Department of 2 university hospitals in Edinburgh (Scotland) and Malmo
(Sweden), and a district general hospital in Spain (general Hospital de
Tomelloso) were searched for patients who have been diagnosed with CC
between May 2008 and August 2013. Endoscopy reports & endoscopic images
were retrieved and reviewed; data on lesions, sedation, bowel preparation (type
and effect) and endoscopists experience were abstracted. Categorical data are
reported as mean SD. The Fischers exact, the chi-square and the t (unpaired)
tests were used to compare datasets. A two-tailed P value of 50.05 was consid-
ered statistically significant.
RESULTS: A total of 416 patients (96M/320F; mean age: 67.112.1 years) case
notes, who were diagnosed with CC, were collected and reviewed.
The colonoscopies had been carried out by senior medical/surgical staff (consul-
tants or associate specialists) in 331 (79.6%). A total of 81 (19.5%) patients had a
mix of findings, previously described as being suggestive of CC in endoscopy,
such as mucosal erythema/oedema (mosaic pattern): 65, colonic mucosa linear
defects (lacerations, tears, ulcers/fractures, mucosal furrows): 10, cat-scratch
mucosa: 4, and cicatricial lesions: 3.
Although the use of polyethylene glycol (PEG) offer superior quality of bowel
prep effect (as compared to other pre-colonoscopy preparations; P50.0001), this
was not associated with higher detection rate of (all types) macroscopic findings
and/or colonic mucosal defects in specific (P 1.0). Furthermore, mucosal colo-
nic defects had no association with either the experience of the colonoscopist
(P 0.812), or the use of general anaesthesia/propofol (P 0.53), and/or the use
spasmolytic (hyoscine butylbromide/glucagon), P 0.568.
CONCLUSION: A substantial minority of patients with CC (19.5%) had endo-
scopic findings indicative of CC. The presence of these findings is not associated
with procedural factors such as endoscopists experience, quality of bowel prep,
and/or use of spasmolytic during colonoscopy.
REFERENCES
1. Koulaouzidis A and Saeed AA. Distinct colonoscopy findings of microscopic
colitis: not so microscopic after all? World J Gastroenterol 2011; 17: 4157-4165.
2. Suzuki et al. Usefulness of colonoscopic examination with indigo carmine in
diagnosing microscopic colitis. Endoscopy 2011; 43: 1100-1104.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
FalkPharmaUK, Other: Travel support: Dr FalkPharma, Abbott, MSD, K.
Sjoberg: None declared, L. Bartzis Other: Grant from the Hellenic Society of
Gastroenterology, M. MacNeill: None declared, A. Nemeth: None declared, G.
Wurm Johansson: None declared, P. Finneron: None declared, A. Lucendo:
None declared, E. Toth: None declared
P0155 A TAILORED SEDATION FOR COLONOSCOPY BY NON-
ANESTHESIOLOGISTS: USE OF PROPOFOL TARGET
CONTROLLED INFUSION FOR SAFELY ERASE PATIENTS PAIN
A. Della Rocca1,*, A. Scatto2, P. Tresin3, S. Gallo1, E. Rosa-Rizzotto1,
L. Peraro1, E. Guido1, D. Caroli1, B. Licata3, F. De Lazzari1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
2
Anesthesiology, Azienda Ospedaliera, 3Anesthesiology, St Anthony Hospital,
Padua, Italy
INTRODUCTION: Pharmacokinetics and pharmacodinamic of both
Midazolam(M) and Pethidine(P) (the most common drugs for procedural seda-
tion) dont allow during colonoscopy to rapidly adjust dosage according to
patient response and to the complexity and length of the procedure. As result
patients may be too much or not enough sedated. Propofol sedation overcomes
these limitations but may expose the patient to dangerous side effetcs such as
hypotension and respiratory depression.
AIMS & METHODS: Demonstrate that Propofol Target Controlled Infusion
(PTCI) enables properly modified infusion rate (ie total drug dose) in order to
perform a zero pain colonoscopy and without affecting safety. 3 types of sedation
were utilized in this trial: PTCI, MP, Propofol titration (PT). Propofol infusion
was controlled by a TCI pump set on Schnider protocol. Propofol administration
and monitoring was performed by a nurse trained on recognizing adverse effects
and on basic resuscitation maneuvers; an anesthesiologist was always on call.
Colonoscopy started 1 min after infusion was begun. Initial Effect Site Target
Concentration was 2.5 mg/ml, increments of 0.5 mg/ml/min were allowed until
total pain relief. We monitored pts ETCO2, SpO2, NIBP, ECG. At the end of the
procedure pts were transferred to recovery room only when Observers
Assessment of Altertness/Sedation (OAA/S) scale was 4 3 and then discharged
when ALDRETE score was 4 8. Satisfaction was established by Numeric Visual
United European Gastroenterology Journal 2(5S)
Scale (NVS, pain evaluation from 1 to 10). A control group (treated with MP)
followed the same protocol.
RESULTS: 721 consecutive pts undergoing both diagnostic and operative colo-
noscopy were included. No exclusion critheria were stipulated. 345 pts PTCI at
an average drug dosage (ADD) of 156.869.6 mg; 376 pts MP at an ADD,
respectively, of 4.181.3 mg and 47.55.5 mg; The 2 groups were clinically
homogeneus (M 55.4%; F 44.6%; ASA 1-2 90%, ASA 3 10%) Adverse Contact E-mail Address: benjamin.walter@lrz.tum.de
events: Hypoxemia (So2590%): PTCI 0.Mp 8 (p50.05); Apnea:
PTCI 3, Mp 26 (p50.001); Hypotension (SBP590mmHg): PTCI 44, INTRODUCTION: High quality preparation is essential for colonoscopy. A
Mp 36 (p ns); Bradycardia (540 bpm) PTCI 5, Mp 11 (p ns). sufficient colon cleaning improves adenoma detection rate and reduces rates of
Apnea was treated successfully with neck extension. Outcome and satisfaction:
mean NVS (all procedures) PTCI 0.361.2 vs 1.072.1 MP (p50.001); mean
NVS (only difficult proceures) PTCI 0.241 vs 1.972.8 MP (p50.001); mean
cecal intubation time (intubation rate was 98.4%) PTCI 6.143.6 min vs MP
7.524.8 min (p50.01), mean time for the entire procedure (colonoscopy
recovery time): PTCI 38.7615.1 min vs MP 53.9514.6 min (p50.001).
PTCI total mean dosage was compared with the mean dosage of 50 colonosco-
pies in propofol titration, at the univariate analysis less total propofol (adjusted
for BMI, Sex, Age, Endoscopist, Abdominal surgery) was administered using
PTCI than the titration method: 156.8569.63 vs 212.5085.70 (p50.0001).
CONCLUSION: Propofol TCI provide a extremely flexible technique which
ensures a sedation tailored to the individual patient and gives the possibility to
guarantee an effective sedation for long lasting procedures without affecting
recovery time. The final results are the opportunity to totally relieve pain, high
performance (time length and quality of recovery) and less operator-dependent
process.
Disclosure of Interest: None declared
P0156 HOW WELL DOES RADIOLOGY PREDICT COLITIS?
CORRELATING IMAGING WITH ENDOSCOPY; A
RETROSPECTIVE STUDY
A. Sinha1, J. Gulliver1,*, M. Shaw2, R. Makins1
1
Gastroenterology, 2Radiology, Gloucestershire Hospitals NHS Trust,
Cheltenham, United Kingdom
Contact E-mail Address: ashish.sinha@glos.nhs.uk
INTRODUCTION: A common indication for endoscopic assessment of the large
intestine is to clarify an abnormal finding on either cross sectional or contrast
radiological imaging. Our aim was to assess how often a positive diagnosis of
colitis of any form was made following either CT scanning or barium enema. We
then aimed to correlate these radiological findings with those seen at a subse-
quent endoscopy.
AIMS & METHODS: The endoscopy database at Gloucestershire Hospitals
NHS Foundation Trust was reviewed for procedures performed between
January 2008 and June 2013. Cases where endoscopy was performed for the
indication of abnormal radiological findings were selected. The patients radi- P0158 WHY DONT WE RETRIEVE ALL THE ENDOSCOPIC RESECTED
ology reports were reviewed and the cases where colitis or inflammation was POLYPS?
described as possible differentials were selected. We then compared these radi-
ological findings with those seen on endoscopy for positive correlation. The
endoscopic finding of diverticular disease was taken as a positive correlation
where relevant. Histology reports from the biopsies taken during the endoscopic
procedures were also reviewed to confirm the endoscopic findings.
RESULTS: Between January 2008 and June 2013, 562 colonoscopies or flexible
sigmoidoscopies were performed as a result of an abnormality seen on radiolo-
gical imaging. In 168 (30%) a positive diagnosis of colitis was mentioned on the
radiology report. Demographics showed a fairly even sex distribution with 53%
of patients female, 47% male. The ages ranged from 22-98 with a mean age of
60.9 years. A total of 5 cases were excluded, with the colonoscopy failing to reach
the region of interest in 4 cases.
Endoscopy confirmed mucosal inflammation in 60 of the 163 cases (37%)
whereas the endoscopy was reported as normal in the remaining 103 cases (63%).
In patients with positive endoscopic correlation, biopsies were taken in 34 (57%)
of cases. Biopsies were not taken in cases where diverticular disease was identified
and considered a positive diagnosis.
In those with histological specimens 28 of the 34 (82%) showed histology con-
sistent with an inflammatory process. Of these the majority (57%) showed
Crohns disease. 6 specimens showed no inflammatory change on histology
despite a macroscopic impression of inflammation.
Interestingly 2 biopsy series were taken despite negative endoscopic correlation,
of which 1 was confirmed as lymphocytic colitis on histology. Another showed
features of Crohns on histology (this patient had known Crohns).
CONCLUSION: 37% of the cases in our series referred for endoscopic evalua-
tion after the finding of colitis on radiological imaging were confirmed to have 1) deficient bowel preparation, 2) a colorectal surgery history, 3) a greater number
colonic inflammation at endoscopy. This suggests that there is a limited correla-
tion between radiological and endoscopic imaging when a diagnosis of colitis is
being considered.
Further studies are required to determine whether a number of parameters con-
sidered together to create a scoring system would increase the likelihood of a
positive pick up at endoscopy following colitis identified on radiological imaging,
thereby improving diagnostic yield and reducing the number of unnecessary
procedures. Interestingly, with one diagnosis of lymphocytic colitis made on
samples from endoscopically normal colon, an argument could be made for
taking biopsy series in all cases to exclude microscopic colitis.
Disclosure of Interest: None declared
A173
P0157 SHORT MESSAGE SERVICE (SMS) IN COLONOSCOPY
PREPARATION - PERICLES-I -A FEASIBILITY STUDY
B.M. Walter1,*, P. Klare1, B. Neu1, R.M. Schmid1, S.von Delius1
1
II. Medizinische Klinik und Poliklinik, Klinikum rechts der Isar, Munchen,
Germany
necessary re-colonoscopies due to invalid preparation. Several studies showed
importance of patients education and correct pre-colonoscopy diet. Only few
studies have evaluated feasibility of using new media such as SMS in high quality
preparation. The PERICLES-project (prospective studies for improvement of
colonscopy preparation by optimized visualisation) aims to optimize patient gui-
dance by reminding the most important steps during colonoscopy preparation.
AIMS & METHODS: Objective: To assess the feasibility of colonoscopy pre-
paration using SMS (short message service) starting 4 days prior colonoscopy
appointment and to assess sufficient colonoscopy preparation.
Design: A feasibility study Setting: Tertiary care center, university hospital.
Subjects: Patients scheduled for out-patient colonoscopy at a university hospital.
Interventions: Patients enrolled in the SMS study group get SMS information at
different timepoints according to the next step of colonoscopy preparation and
diet information. Data of out-patient colonoscopies with regular preparation
procedure were collected as control group during time of SMS study.
RESULTS: Colonoscopy could be performed in all patients included in the study.
Overall patient satification receiving SMS based information was high. Asked if
the SMS reminder system was helpful to get the colonoscopy preparation done (1
not helpful to 10 very helpful) an average score of 7.8 was counted (n 18). On the
contrary asked if the SMS reminder system was inhibitory (1 not inhibitory to 10
very inhibitory) an average of 1.1 was counted (n 19). The average total BBPS
was significantly higher than in the control group (MeanSEM 7.316  0.2967
(SMS-group), MeanSEM 6.269  0.1925 (control group); good bowel prepara-
tion for colonoscopy 5). BBPS calculated for the different colon regions.
LC Left colon (MeanSEM 2.5000.1357 (SMS group) MeanSEM
2.1380.06530 (control group)), TC transverse colon (MeanSEM
2.4000.1124 (SMS group) MeanSEM 2.1150.06875 (control group)),
RC right colon (MeanSEM 2.4000.1124 (SMS group) MeanSEM
2.0150.07325 (control group)) were higher than in the control group.
CONCLUSION: A SMS (short message service) system in colonoscopy prepara-
tion works is stable and effective. Quality of colonoscopy preparation was higher
than in regular preparation procedure. Patients were highly satisfied by using the
SMS system during colonoscopy preparation.
Disclosure of Interest: None declared
C. Fernandes1,*, R. Pinho1, S. Leite1, L. Proenca1, A. Rodrigues1, L. Alberto1,
I. Ribeiro1, T. Pinto-Pais1, A. Ponte1, J. Silva1, J. Fraga1, J. Carvalho1
1
Gastroenterology, C. HOSPITALAR VILA NOVA GAIA, V N Gaia, Portugal
INTRODUCTION: Colonoscopy is able to diagnose, resect and retrieve colonic
polyps. The latter is of major importance to allow an accurate histological eva-
luation. Factors associated with failed polyp retrieval are not yet clear.
AIMS & METHODS: To evaluate the prevalence of failed polyp retrieval; to
define factors associated with polyp retrieval failure.
A single center retrospective study that considered all the resected polyps by
snare in consecutive colonoscopies performed between September 2011 and
December 2012. Eleven gastroenterology specialists and 3 residents were consid-
ered as endoscopists. Demographic and endoscopic data obtained through the
colonoscopy report.
Statistical analysis (SPSS v.19): Chi-square, t-student.
RESULTS: 496 colonoscopies were evaluated, corresponding to 484 patients
(male gender 66.1%, mean age 63.4 years [10.2]). Considering a total of 1111
resected polyps, 52 (4.7%) were not retrieved. A deficient bowel preparation
(p 0.0006), a coloretal surgery history (p 0.008), a higher number of resected
polyps (p50.0001), a smaller size of resected polyps (p50.0001), a right-side
location (p 0.0006) and a cold snare resection versus current snare resection
(p 0.0007) were factors associated with failed polyp retrieval. Colonoscopy
performed by a resident (p 0.81), under deep sedation (p 0.94) or with diver-
ticulum (p 0.44) were not related with failed polyp retrieval.
CONCLUSION: In our study the polyp retrieval failure prevalence was 4.9%. A
of resected polyps, 4) a smaller size of the resected polyps, 5) a righ-side location
and 6) a cold snare resection were associated with polyp retrieval failure.
Disclosure of Interest: None declared
P0159 FUSE COLONOSCOPY YIELDS HIGHER DETECTION OF
ADVANCED AND MULTIPLE ADENOMAS AS COMPARED TO
STANDARD FORWARD VIEWING COLONOSCOPY: A POST-HOC
PER PATIENT ANALYSIS FROM A RANDOMIZED COMPARATIVE
TRIAL
C. Hassan1,*, I. Gralnek2
1
ONRM Hospital, Rome, Italy, 2Rambam Health Care Campus, Haifa, Israel
Contact E-mail Address: cesareh@hotmail.com
INTRODUCTION: As compared with Standard Forward Viewing (SFV) colo-
noscopy, Full Spectrum Endoscopy (Fuse) colonoscopy has been shown to sig-
nificantly increase the yield of adenomas detected (per lesion analysis) [1].
A174 United European Gastroenterology Journal 2(5S)
However, the accuracy of FUSE based upon a per-patient analysis has not fully Table to abstract P0160
been addressed.
AIMS & METHODS: We performed a post-hoc analysis of the data from a Patient demographics
recently completed international, multicentre, randomized trial (NCT01549535)
in which 197 patients underwent same-day, back-to-back tandem colonoscopy Sex (%)
with SFV- and FUSE-colonoscopes. The per-patient detection rate of polyp/
advanced adenoma was calculated for each of the two colonoscopy techniques Male 66 (66%)
according to polyp size and multiplicity (3 polyps). The relative detection rate Female 34 (34%)
was defined as the ratio between the number of patients classified by either SFV Disease extent (%)
or FUSE colonoscopy in each lesion category and the cumulative detection with Extensive 87 (87%)
both of the colonoscopy techniques (SFVor FUSE) for the same lesion category.
Statistical analysis was performed by Chi-square test. Left-sided 13 (13%)
RESULTS: We found 111, 23 and 9 patients presenting with at least one 5mm, Disease duration (years) (Median, 24 (13 33)
6-9mm, or 10mm polyp respectively, while 22 and 27 additional patients had as interquartile range)
their most severe lesion an advanced adenoma or multiple adenomas, respec- Age at the time of dysplasia diagnosis 61 (54 69)
tively. The relative sensitivity of SFV and FUSE for each type of lesion is (years) (Median, interquartile range)
shown in Table 1. In detail, the sensitivity of FUSE was statistically significantly
superior to SFV for all categories except for polyps 10mm. As compared to
SFV colonoscopy, FUSE detected an additional 9 patients with multiple adeno-
mas, resulting in a relative per-patient sensitivity of 94%, as compared with 27% CONCLUSION: Patients with endoscopically resectable, well-circumscribed
for SFV colonoscopy. dysplastic lesions within the segment of colitis may be appropriately managed
CONCLUSION: As compared to SFV colonoscopy, FUSE colonoscopy appears with endoscopic resection. However, close surveillance is necessary given the
to be more effective in identifying patients with multiple polyps and polyps up to relatively high rate of recurrence.
9 mm in size, including 6-9mm advanced adenomas. These data appear to further Disclosure of Interest: None declared
demonstrate the clinical relevance of the additional adenoma detection of FUSE
as previously shown at a per lesion level [1].
REFERENCES P0161 LOW-GRADE DYSPLASIA IN ULCERATIVE COLITIS: IMPACT
[1] Gralnek IM, et al. Standard forward-viewing colonoscopy versus full-spec- OF LESION SHAPE AND SIZE ON PROGRESSION TO HIGH-
trum endoscopy: an international, multicentre, randomised, tandem colonoscopy GRADE DYSPLASIA OR COLORECTAL CANCER
trial. Lancet Oncol 2014; 15: 353-360. C.H. R. Choi1,*, A. Askari1, A. Ignatovic-Wilson1, J. Warusavitarne1,
Disclosure of Interest: None declared M. Moorghen1, S. Thomas-Gibson1, B. Saunders1, T. Graham2, A.L. Hart1
1
Academic Institute, St. Marks Hospital, 2Tumour biology, Barts Cancer Institute,
Queen Mary University of London, London, United Kingdom
P0160 DISCRETE DYSPLASTIC LESIONS IN ULCERATIVE COLITIS Contact E-mail Address: pacoblue@gmail.com
MAY BE ADEQUATELY MANAGED ENDOSCOPICALLY: A LONG
TERM FOLLOW-UP STUDY INTRODUCTION: One of the most challenging aspects of managing low-grade
C.H. R. Choi1,*, A. Ignatovic-Wilson1, A. Askari1, J. Warusavitarne1, dysplasia (LGD) in ulcerative colitis (UC) is the identification of patients who
M. Moorghen1, S. Thomas-Gibson1, B. Saunders1, A.L. Hart1 will progress to high-grade dysplasia (CRC) or colorectal cancer (CRC). The aim
1
Academic Institute, St. Marks Hospital, London, United Kingdom of this study was to identify risk factors associated with progression to HGD or
Contact E-mail Address: pacoblue@gmail.com CRC in UC patients diagnosed with LGD.
AIMS & METHODS: Patients with UC who were diagnosed with LGD between
INTRODUCTION: While there is evidence to support endoscopic resection of 1990 and 2012 were identified from the UC surveillance database of a large
adenoma-like mass (ALM) occurring in patients with ulcerative colitis (UC), its tertiary centre in the UK and followed up to 1st January 2013. Data on patient
long-term follow up data is currently limited. The aim of this study is to evaluate demographics, endoscopic and histological variables at the time of the first LGD
the long-term outcomes of patients with UC who have had an endoscopic resec- episode were collected and correlated with progression to HGD or CRC, our
tion of dysplasia within segment of bowel affected by colitis. primary outcome measure. Time to event analysis was performed using Cox
AIMS & METHODS: All patients who had their dysplastic lesions resected proportional hazards methods with a Bonferroni adjusted significance level
endoscopically between 1998 and 2008 were retrospectively identified from the (p 0.0022).
endoscopic and histology databases. Patients who were immediately referred to RESULTS: A total of 189 patients were evaluated during 1,100 patient-years of
colectomy were excluded. Medical records, endoscopy and histology reports were follow up from the date of the first LGD diagnosis (median, 53 months; inter-
reviewed to determine the primary study outcome, which was defined as no quartile range, 19 92 months). Overall, 38 (20.1% of study population) had
further dysplasia episode, recurrence of dysplasia, or development of colorectal progressed to HGD (16 patients) or CRC (22 patients). Table 1 shows the variables
cancer (CRC). significantly associated with progression to HGD or CRC on univariate analysis.
RESULTS: A total of 100 patients underwent endoscopic resection for 121 dis- A statistically non-significant trend towards the progression to HGD or CRC was
crete dysplastic lesions during the study period (table 1). The median follow-up observed in those patients with history of primary sclerosing cholangitis (hazard
duration from the time of dysplasia resection was 70 months (interquartile range ratio (HR), 3.54; p 0.018), a shortened colon (HR, 2.75; p 0.024), multiple
(IQR), 53 89 months). The Paris classifications of the resected lesions were: Ip episodes of dysplasia (HR, 2.59; p 0.005), and histological active inflammation
(60 lesions, 50.4% of 121 lesions), Is (36, 29.8%), IIa (3, 2.5%), IIb (4, 3.3%), in the segment of LGD (HR, 2.20; p 0.025). At the multivariate level, only non-
IIa/c (1, 0.8%), and lateral spreading tumour (1, 0.8%). Remaining 16 lesions polypoid shape (HR, 7.3; 95% confidence interval (CI), 2.4 21.8; p50.001),
(13.2%) were described as appearance suspicious for dysplasia associated lesion lesion size one centimeter (cm) or bigger (HR, 4.2; 95% CI, 1.3 13.3;
or mass (DALM), where Paris classification was not recorded. Median size of p 0.015) remained significant variables contributing to HGD or CRC.
the resected lesions was eight millimetres (IQR, 4 15 millimetres). Lesions were
removed using snare polypectomy (66 lesions, 54.5% of 121 lesions), EMR (30, Hazards 95% confidence
24.8%), hot biopsy (21, 17.4%) or ESD (4, 3.3%) techniques. Histology showed Variables Categories ratio (HR) interval (CI) P
low-grade dysplasia (LGD) in 111 (91.7% of 121 lesions) and high-grade dyspla-
sia (HGD) in 10 lesions (8.3%). Pathologists interpretations on the lesions were Lesion shape Polypoid x 1 10.0 58.1 50.001
as follows: histological features favour DALM (36 of 121 lesions, 29.8%) favour Non-polypoid 24.1 1.5 22.6
sporadic adenoma (56, 46.3%), or distinction not possible on histological Invisible] 5.8
grounds alone (29, 23.9%). Overall, 23 patients (23% of study population) Lesion size 51cm 1 4.8 41.3 50.001
had developed recurrent episode of dysplasia in median of 41 months since the 1cm 14.1
time of resection (IQR, 16 55 months). Seven of these patients underwent Stricture No 1 2.4 21.1 50.001
colectomy: cancer was detected in two patients (Dukes A and C), but no Yes 7.1
other patients had HGD or CRC in surgical specimen. The patient who devel- Previous indefinite No 1 1.9 8.4 50.001
oped Dukes C cancer did not have surveillance colonoscopy for five years prior dysplasia Yes 4.0
to the cancer diagnosis. The cumulative incidence of recurrent episode of dyspla- Pathologists interpretation Adenoma more likely 1 1.4 109.4 50.001
sia following endoscopic resection was 3.1% in 1 year, 7.4% in 2 years, 11.9% in on histological features Distinction not 12.2 5.1 273.6
clear 37.2
3 years, 16.7% in 4 years and 22.0% in 5 years.
UC associated dys-
plasia more likely
Multifocal dysplasia No 1 1.6 6.0 .001
Yes 3.1

Table 1: Results of Univariate Analysis (only significant variables are shown). x:

Discrete pedunculated or sessile polyps (Paris classification type I). : Flat,
depressed (Paris type II), irregular, diffuse, plaque-like or lesions with poorly
defined edges. ]: LGD with no evidence of endoscopic abnormality.
CONCLUSION: Low-grade dysplastic lesions that are non-polypoid or large
(1cm) have a high-risk of progression to HGD or CRC in patients with UC.
Patients harboring these lesions require careful counseling of management
options including colectomy. Conversely, small polypoid low-grade dysplastic
United European Gastroenterology Journal 2(5S)
lesions may be appropriately managed with endoscopic resection and close
surveillance.
Disclosure of Interest: None declared
P0162 A PILOT STUDY OF FLUORESCENT IMAGING
COLORECTAL TUMOR USING -GLUTAMYL-TRANSPEPTIDASE
(GGT) FLUORESCENCE ACTIVITY PROBE
C. Sato1,*, S. Abe1, E. So1, M. Yamada1, M. Makazu1, H. Takamaru1,
H. Sasaki1, Y. Matsuyama1, T. Sakamoto1, T. Nakajima1, T. Matsuda1,
R. Kushima2, M. Kamiya3, Y. Urano3,4, Y. Saito1
1
Endoscopy Division, 2Pathology Division, National Cancer Center Hospital,
3
Laboratory of Chemical Biology and Molecular Imaging, University of Tokyo,
4
Accelerated research enhancement program of Japan Science and Technology
Agency (JST), Tokyo, Japan
Contact E-mail Address: csato@ncc.go.jp
A175
were carcinoma. Profound bleeding occurred in 1 patient with whole nodular
type LST, who changed to piecemeal resection and was needed transfusion
during ESD. Perforations developed in 2 patients after ESD, which were mana-
ged by endoscopic clipping treatment. The duration of hospitalization in the
giant colorectal LST was 5.6 day (range: 2-12 day). During a mean follow-up
OF period of 18.5 mo (range: 5.9-27.4 mo), no local recurrence and distant metastasis
occurred. The complication rate was higher in giant colorectal LST than others
(42.9% vs 8.7%, p 0.026). The en-bloc resection and curative resection rate of
ESD for the giant colorectal LST was 85.7% and 100%, respectively, and these
rates were comparable with that of ESD for LST smaller than 10 cm. (en-bloc
resection rate 92.1%, and curative resection rate 92.9%)
CONCLUSION: The ESD of giant colorectal LSTs appears to be a feasible and
curative treatment, even if, it endure the higher complication rate, higher tech-
nical difficulty and longer procedure time.
Disclosure of Interest: None declared

INTRODUCTION: New endoscopic technologies improve visibility of early col-
orectal cancers. However, flat lesions especially in lateral spreading tumor of the
non-granular type (LST-NG) are sometimes hard to detect even with such mod-
alities. -glutamyl-transpeptidase (GGT) is poorly expressed in normal tissue,
but overexpressed on the cell membrane of various cancer cells in vivo. The
use of -glutamyl hydroxymethyl rhodamine green (gGlu-HMRG) has been
reported to show specific and immediate fluorescence activity with overexpressed
GGT in tumor. This fluorescence active probe is expected to be applied to a new
modality for cancer-selective fluorescence imaging1).
AIMS & METHODS: This pilot study aimed to evaluate ex-vivo fluorescent
imaging of colorectal tumor using the GGT fluorescence activity probe. 30
endoscopically resected colorectal tumors from March 2013 to March 2014
were included in this study. 1000l of gGlu-HMRG in a concentration of
either 50M or 500M was sprayed on the freshly resected specimen fixed on
a black board. Fluorescent images of the resected specimen were taken after
spraying gGlu-HMRG every 30 seconds for 15 minutes using a dedicated ima-
ging machine providing 550nm of blue excitation light (Discovery; INDEC Inc.).
The fluorescence image 7 minutes after spraying (when fluorescence activity had
almost reached equilibrium) was evaluated by 3 endoscopists. The fluorescence
activity was judged positive or negative. Lesions showing partial fluorescence
activity were considered positive. This pilot study assessed the proportion of
lesions positive for fluorescence and correlation with their clinicopathological
characteristics.
RESULTS: The clinicopathological features were; mean age was 687, male/
female 15 /15, mean tumor size: 3913mm, macroscopic type: lateral spreading
tumor of the granular type (LST-G)/LST-NG 20/10, adenoma/ carcinoma in
adenoma 13/17. 20 (67%) of images after 7 minutes were positive for fluores-
cence activity and 10 (33%) were negative. The mean tumor size of lesions
positive for fluorescence activity was 42mm and that of negative was 32mm.
Of 13 adenoma, 7 (54%) lesions were positive and 6 (46%) were negative. Of
17 carcinoma in adenoma, 13 (76%) lesions showed positive and 4 (24%) were
negative. 16 LST-G lesions (80%) and 4 LST-NG lesions (40%) revealed posi-
tive. 18 (75%) of 24 lesions in 50M gGlu-HMRG and 2 (33%) of 6 lesions in
500M revealed positive.
CONCLUSION: Topically spraying gGlu-HMRG to identify GGT activity in ex
vivo colorectal tumors provides rapid and selective fluorescent imaging.
REFERENCES
1) Urano Y et al. Sci Transl Med 2011.
Disclosure of Interest: None declared
P0163 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR GIANT
COLORECTAL LATERAL SPREADING TUMORS LARGER THAN
10 CM: IS IT FEASIBLE?
D.H. Jung1,*, Y.H. Youn1, J.-H.K. 1, J.J. Park1, H. Park1
1
Yonsei University College Of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: leah1004@yuhs.ac
P0164 ANALYSIS OF THE BLEEDING AFTER THE ENDOSCOPIC
SUBMUCOSAL DISSECTION (ESD) AND THE ENDOSCOPIC
MUCOSAL RESECTION (EMR) OF COLORECTAL NEOPLASMS
FOR THE PATIENTS TAKING ANTI-THROMBOTIC AGENTS
D. Okamoto1,*, M. Tosa1, D. Komazawa1, H. Ito1, N. Dairaku1, T. Ikeda1, S.-
I. Ikeya1, H. Nakayama1, N. Hiwatashi1, S. Takahashi1
1
Gastroenterology, Iwaki Kyoritsu General Hospital, Iwaki city, Fukushima, Japan
Contact E-mail Address: oka1572@gmail.com
INTRODUCTION: Recently, EMR and ESD for the patients with many com-
plication has been increasing. Anti-thrombotic therapy is usually provided to
prevent cerebro-cardiovascular events. In 2012, the endoscopic treatment guide-
lines for the patients taking anti-thrombotic agents were published from Japan
Gastroenterological Endoscopy Society. Thereafter, in our institution, we per-
form endoscopic treatment in accordance with the guidelines. Delayed bleeding is
one of the major complications of EMR and ESD, but little is known about the
influence of anti-thrombotic therapy.
AIMS & METHODS: In this study, we analyzed the delayed bleeding rate after
colorectal EMR and ESD for the patients taking anti-thrombotic agents. This is
a retrospective study for the consecutive patients treated in our center from
February 2014 to January 2013. Furthermore, we divided the patients taking
anti-thrombotic agents into three groups, and compared the bleeding rate and
the clinical background with control group. [A]: anti-coagulant continuation
group, [B]: heparin or anti-coagulant single agent replacement group, [C]:anti-
coagulant discontinuation group. Statistical analysis was made by Chi-squared
test (significance: p50.01).
RESULTS: We treated 328 patients with 633 colorectal neoplasms by EMR, and
the delayed bleeding rate was 1.9% (12/633). Male/Female ratio was 237:91 and
the mean age was 64.5 years. 63 patients (19.2%) with 129 neoplasms (20.4%)
received anti-thrombotic therapy and divided into three groups, [A]:16/28, [B]:21/
45, [C]:26/56 (patients/neoplasms). Patients taking the anti-coagulant agents were
significantly older than control group (P50.01). The delayed bleeding rate was 1/
28(3.6%) in group A, 2/45(4.4%) in group B and none (0/56) in group C. We
found no significant differences about the delayed bleeding rate when we com-
pared each group with the control group (9/504; 1.9%). On the other hand, we
treated 47 patients with 47 neoplasms by ESD. Male/Female ratio was 32:15 and
the average age was 68.7 years. 11 patients (23.4%) received anti-thrombotic
agent and divided into three groups, [A]:4, [B]:2, [C]:5. In ESD, patients taking
anti-thrombotic agents were significant older (P50.01), and the delayed bleeding
was not recognized in all cases. In addition, cerebro-cardiovascular events did not
occur in all cases during the clinical course of EMR and ESD.
CONCLUSION: We found no significant differences about the delayed bleeding
rate between patients taking anti-thrombotic agents and control group. Although
this is a single institutional study, we thought that EMR and ESD for the patients
taking anti-thrombotic agents could be performed without increased risk of
delayed bleeding in accordance with the guidelines.
Disclosure of Interest: None declared

INTRODUCTION: Colorectal endoscopic submucosal dissection (ESD) has

recently been used for the resection of large colorectal neoplasms that could
not be completely resected by conventional endoscopic mucosal resection
(EMR). The colorectal ESD technique has an advantage of high en bloc resection
rates, but is not accepted as a standard procedure due to several limitations, such
as relatively high perforation rate and very high technical difficulty. However,
ESD was applied to the lesions such as the giant colorectal lateral spreading
tumor (LST) larger than 10 cm by some expert ESD-endoscopist. Thus, we
investigated the feasibility and safety of ESD of giant colorectal LST over 10 cm.
AIMS & METHODS: A total of 133 patients received colorectal ESD between
March 2009 and August 2013 by a single expert ESD-endoscopist at Gangnam
Severance Hospital, Seoul, Korea. Among them, 7 patients had giant colorectal
LSTs larger than 10cm. The tumor features, complete resection rate, and com-
plications of ESD of giant colorectal LST were evaluated. We compared the
clinicopathologic factors of ESD between giant colorectal LSTs and others. All
patients underwent regular follow-up to evaluate for any local recurrence or
distant metastasis.
RESULTS: The colorectal LSTs larger than 10cm were categorized as the giant
colorectal LST. The locations of the 7 giant colorectal LST lesions as follows:
cecum (n 1), sigmoid colon (n 2), and rectum (n 4). The average maximal
diameter of the giant colorectal LST lesions was 124.3 mm (range: 110-160 mm),
and the procedure time was 294.3 min (range: 146-570 min). 2 lesions were whole
nodular types and 5 lesions were focal nodular lesions by the Japanese
Classification of Colorectal Carcinoma. According to the World Health
Organization classification system, histologic diagnosis determined that 1
lesion was low grade dysplasia, 2 lesions were high grade dysplasia, and 4 lesions
P0165 SESSILE SERRATED ADENOMA (SSA): QUALITATIVE
ENDOSCOPIC IDENTIFICATION USING ACETIC ACID, FICE AND
IMAGE MAGNIFICATION
L.A. R. Oliveira1, D.S. D. Oliveira2,*, R. Delisa3
1
Endoscopic Advanced Center (CEA), 2Pontifica Universidade Catolica de
Campinas, 3Pathology, Endoscopic Advanced Center (CEA), Campinas, Brazil
Contact E-mail Address: uniendolix@terra.com.br
INTRODUCTION: Sessile Serrated Adenoma may be the precursor of 30% of
colorectal cancers. The colonoscopy finding and identification of this type of
lesion can reduce the incidence of colorectal cancer.
The correct approach on the search of this specific type of lesion is known to be a
true challenge for the colonoscopists nowadays, and the precise identification, in
number and type, of these lesions is associated to the quality of the colonoscopy
exam.
Not much can be found in the literature about the combined use of acetic acid,
FICE and image magnification in the identification of this specific type of lesion.
AIMS & METHODS: 150 lesions in the right colon were prospectively evalu-
ated: the lesions were larger than 10mm, had a mucus cap and their morphology
suggested sessile serrated adenoma, by the analysis of these lesions, crypts pat-
tern. The study was performed by an endoscopist with extensive experience in
chromoendoscopy and magnification and a single pathologist with extensive
experience in this type of lesion. The lesions were classified into three types of
Pits: type II Classic (Pit II - C), Pit II Open Shape (Pit II - O), and Pit II Fat
A176
Shape (Pit II - F). The crypts were evaluated after instillation of acetic acid,
chromoscopy (FICE), and image magnification.
RESULTS: From all the 150 lesions, 122 were classified as SSA. The Pit pattern
II C was found in all of the lesions analyzed, revealing a low specificity in the
association of this pattern with SSA. However, the Pit II O pattern was found
in 120 lesions, and 118 of these were classified as SSA form, showing a stronger
association of this pattern and SSA than the Pit II- C pattern. When it comes to
the Pit II F, it was found in 122 lesions, and 120 of these were classified as SSA.
All lesions containing the association of Pit II- O and Pit II F pattern, were
classified as SSA.
CONCLUSION: The strong correlation between the colonoscopic findings of
SSA with the use of acetic acid, FICE and image magnification and histological/
molecular alterations of the suspicious lesions, reveals the importance of this
technique in this type of lesions management decision and in the participation
on the colorectal cancer prevention.
REFERENCES
A novel pit pattern identifies the precursor of colorectal cancer derived from
sessile serrated adenoma. Am J Gastroenterol 2012; 107: 460469.
Serrated lesions of the colorectum: Review and recommendations from an expert
panel. Am J Gastroenterol 2012; 107: 13151329.
Disclosure of Interest: None declared
P0166 THE USEFULNESS OF INTRAVENOUS CIMETROPIUM
BROMIDE ON POLYP/ADENOMA DETECTION DURING
COLONOSCOPY WITHDRAWAL
D.K. Kang1,*, D.H. Kang1, H.W. Kim1, C.W. Choi1, S.B. Park1,1, S.J. Kim1,
B.J. Song1, Y.Y. Choi1, Y.S. Shin1, H.K. Lim1
1
Division of Gastroenterology, Department of Internal Medicine, School of
Medicine Pusan National University, Pusan National University Yangsan Hospital,
Yangsan-si, Korea, Republic Of
Contact E-mail Address: shadam@naver.com
INTRODUCTION: Colorectal cancer can be prevented effectively by colono-
scopy, because it can detect polyps and adenoma. It can miss from 5 to 32% of
polyps, and proximal colon cancers are not efficiently prevented by colonoscopy
screening. Cimetropium bromide has antispasmodic activity and improves polyp
detection, especially in the right side colon.
AIMS & METHODS: We studied the effect of cimetropium bromide on detec-
tion of adenoma in colonoscopy.
Patients undergoing colonoscopy for screening and diagnostic examinations were
included and received 5 mg cimetropium bromide at cecal intubation in Pusan
National University Yangsan Hospital during 2 months in 2013 and 2014, respec-
tively. We studied retrospectively polyp detection rate (PDR), adenoma detection
rate (ADR), advanced adenoma detection rate (AADR), and sessile serrated
adenoma detection rate (SADR) in right side colon as well as in whole
colorectum.
RESULTS: A total of 1025 patients were analyzed in this study. Cimetropium
group consisted of 214 patients and control group consisted of 811 patients.
ADR, AADR in whole colorectum were significantly higher in cimetropium
group, respectively (38.2% vs 28.4% (p 0.03), 10.5% vs 5.3% (p 0.026)).
Also, PDR, ADR, and AADR in right side colon were significantly higher in
cimetropium group, respectively (25.6% vs 19.4% (p 0.015), 23.4% vs 15.6%
(p 0.023), 7.2% vs 3.5% (p 0.024)). But, PDR in whole colorectum and
SADR in right side colon between two groups were not different. In non-right
side colon, PDR and ADR were not significantly higher in cimetropium group,
respectively (31.6% vs 27.8% (p 0.487), 25.0% vs 21.0% (p 0.154)).
CONCLUSION: Cimetropium bromide can improve ADR and AADR in right
side colon as well as colorectum in colonoscopy.
Disclosure of Interest: None declared
P0167 CORRELATION BETWEEN ENDOSCOPIC AND
ENDOMICROSOPIC SCORES IN CROHNS DISEASE PATIENTS IN
DETECTING RELAPSE AFTER SURGERY
D. Moussata1,2,*
1
Gastroenterology, Lyon Sud Hospital, Pierre Benite, 2CREATIS, CNRS,
Villeurbanne, France
Contact E-mail Address: driffa.moussata@chu-lyon.fr
INTRODUCTION: As clinical relapse risk is well correlated with the endoscopic
appearance in operated Crohns disease (CD) patients, its recommended to per-
form an endoscopy in the year following the surgery in order to adapt treatment.
In endoscopy, the relapse is based on Rutgeerts score superior to i2 defined by
the presence of more than 5 ulcerations. Confocal Laser Endomicroscopy (CLE)
can detect inflammation on a macroscopic healing mucosa (whereas macrosco-
pically the mucosa appears normal). Inflammation is evaluated by CLE accord-
ing to percentage of gaps reported to total villous perimeter and to Watsons
score based on shedding and luminal signal.
AIMS & METHODS: Aim: To evaluate inflammation with CLE into the ileum
above the anastomosis (ileocolic anastomosis) and compare with Rutgeerts score.
Patients and methods: In the year following the surgery, under sedation, an
endoscopy with CLE (EC3870K Pentax, Tokyo) was performed after 3 ml fluor-
osceine injection. Relapse was scored endoscopically with Rutgeerts score and
endomicroscopically with percentage of gaps and Watsons score, which were
quantified as calprotectine in stools, urinary neopterine and C-reactive protein
(CRP). We compared Harvey Bradshaw score, Watsons score, calprotectine,
neopterine, CRP and histology (Gomes score) with Rutgeerts score.
RESULTS: 26 patients (12 men, mean age 36  11 years ( SD)) were included
prospectively. The endoscopy was performed in 9  3 (range 6 to 13) months
after the surgery. 9 patients relapsed with a mean Rutgeerts score 2.7  0.8 after
United European Gastroenterology Journal 2(5S)
10  2.5 months and 17 patients did not relapse with a mean Rutgeerts score 0.4
 0.5 after 8  3 months. 5, 2 and 2 patients presented a Rutgeerts score i2, i3, i4,
and 10 and 7 presented a Rutgeerts score i0 and i1, respectively. The mean
percentage of gaps was 11.5  17 (range 0 to 55). Watson score was 1.7  0.9
(range 0 to 3). The mean HB was 1  1.1 (range 0 to 4). Mean Gomes score was
1.1  0.9 (range 0 to 3). Mean CRP, calprotectine and neopterine were 5.4  9.3
(range 52 to 44 mg/l), 811  2207 (range 35 and 9200) and 553  287 (range 142
and 992), respectively. The correlation was significantly positive between
Rutgeerts and Watson score and percentage of gaps (Rho 0.65). The correlation
was positive but not significantly with CRP, Gomes and calprotectine (Rho 0.47,
0.35 and 0.27, respectively). However, in 5/10 and 2/7 patients with i0 and i1
Rutgeerts score, respectively, CLE detected inflammation (Watson score 2).
CONCLUSION: There is a good correlation between CLE score and Rutgeerts
but CLE detected inflammation in 5 patients without endoscopic relapse. The
follow-up of these patients would be interesting to evaluate CLE in predicting
relapse in CD patients.
Disclosure of Interest: None declared
P0168 ENDOSCOPIC SELF-EXPANDABLE METAL STENTS IN ACUTE
MALIGNANT LARGE BOWEL OBSTRUCTION SINGLE CENTER
EXPERIENCE
E. Rodrigues-Pinto1,*, P. Pereira1, A. Peixoto1, S. Lopes1, A. Ribeiro1,
G. Macedo1
1
Gastroenterology, Centro Hospitalar Sao Joao, Porto, Portugal
Contact E-mail Address: edu.gil.pinto@gmail.com
INTRODUCTION: Endoscopic self-expanding metal stents (SEMS) may be
used in acute malignant large bowel obstruction (AMLBO) emerging as an alter-
native to surgery.
AIMS & METHODS: Characterize the population of patients with AMLBO
that placed endoscopic SEMS in clinical practice. Cross-sectional study of
patients with AMLBO that placed SEMS in a tertiary center in a 3 year period.
RESULTS: We placed SEMS in 47 patients, with a mean age of 7113 years.
The distal top of the tumor was located in the descending colon in 12.8%, in the
sigmoid colon in 61.7% and in the rectum in 25.5%. Eighty-one percent of
patients had lymph node invasion and 68.1% had metastasis. The location of
the tumor did not influence the presence of lymph node involvement (p 0.764),
metastasis (p 0.885) nor the extent of the stent used (p 0.511). Fluoroscopy
was used in 57.4% of the procedures. There was need for placement of a second
stent in 6.4% of patients due to migration during the opening. The rate of early
complications was 11% and late complications was 4.6%. The use of fluoroscopy
did not influence the occurrence of immediate complications (p 0.385), early
complications (p 0.950) or late complications (p 0.057). Thirty-three percent
of patients underwent surgery at a later time, with neo-adjuvant therapy in
17.8%. The median time of follow-up was 150 days (P25-75: 23 437), with a
mortality rate at first year of 60.6%. The survival was significantly higher in
patients submitted later to combined therapy in relation to chemotherapy, sur-
gery or symptomatic treatment (838.5 days [ 35.0] vs 387.6 days [ 87.7] vs
354.3 days [ 80.2] days vs 222.3 [ 104.6 therapy], p50.001).
CONCLUSION: The majority of patients with AMLBO had advanced disease.
SEMS have a high success rate with a low complication rate, reducing the high
morbidity and mortality associated with emergency surgery and creation of a
stoma.
Disclosure of Interest: None declared
P0169 COLONIC CHICKEN SKIN MUCOSA IS AN INDEPENDENT
ENDOSCOPIC PREDICTOR OF DISTALLY LOCATED ADVANCED
COLORECTAL ADENOMA
E.J. Chung1,*, J.Y. Lee1, S.-J. Myung2
1
Health promotion and screening center, 2Gastroenterology, Asan medical center,
Seoul, Korea, Republic Of
INTRODUCTION: Chicken skin mucosa (CSM) surrounding colorectal ade-
noma is described as an endoscopic finding with pale yellow-speckled mucosa
and aggregations of lipid-filled macrophages in the lamina propria noted on
histopathology. However, its clinical significance is unknown.
AIMS & METHODS: The aim of this study was to evaluate the prevalence,
clinical characteristics of CSM, and association between colorectal carcinogenesis
and CSM. This cross-sectional study was performed on 733 consecutive patients
who underwent endoscopic polypectomy for colorectal adenoma after screening
colonoscopy at the Asan Health Promotion Center between June 2009 and
December 2011. The colonoscopic and pathological findings of colorectal ade-
noma including number, size, location, dysplasia, and morphology, and clinical
parameters were reviewed.
RESULTS: The prevalence of CSM was 30.7% (225 of 733 patients), and most
CSM-related adenomas were located in the distal colon (93.3%). Histological
analysis revealed lipid-laden macrophages in the lamina propria of the mucosa.
According to multivariate analyses, CSM was significantly associated with
advanced pathology, including villous adenoma, high-grade dysplasia, and car-
cinoma in situ (OR 2.078, 95% CI 1.191-3.627, p 0.010), multiple adenomas
(i.e.,  2 adenomas; OR 1.692, 95% CI 1.143-2.507, p 0.009), and a protruding
morphology (OR 1.493, 95% CI 1.027-2.170, p 0.036). There were no signifi-
cant differences found in terms of polyp size or clinical parameters between
patients with and without CSM.
CONCLUSION: CSM-related adenoma was mainly observed in the distal colon.
CSM was associated with advanced pathology and multiple adenomas. CSM
may be a potential marker of the carcinogenetic progression of distally located
colorectal adenomas.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0170 PREVALENCE OF COLORECTAL POLYPS IN A GROUP OF
SUBJECTS WITH AVERAGE-RISK OF COLORECTAL CANCER
UNDERGOING COLONOSCOPIC SCREENING IN TEHRAN, IRAN
BETWEEN 2008 AND 2013
M. Sohrabi1, F. Zamani1,*, M. khonsari1, H. Ajdarkosh1, N. Rakhshani1,
G. Hemmasi1
1
Gastrointestinal and Liver Disease Research Centre, Iran University, Tehran,
Iran, Islamic Republic Of
Contact E-mail Address: sohrab_r@yahoo.com
INTRODUCTION: Colorectal cancer (CRC) is one of the leading causes of
death in different countries. Due to slow progression of GC, detection of CRC
in early stage is important issue. There have been no high quality studies from the
Middle East.
AIMS & METHODS: We aimed to investigate the prevalence of preneoplastic
and neoplastic lesions of the colon in the average risk population.
Eligible asymptomatic, average risk adults between 2008 and 2012, aged older
than 40 years old, in Firoozgar general hospital were involved. They underwent
screening colonoscopy. All polypoid lesions were removed and examined by an
expert gastrointestinal pathologist. The lesions were classified by size, location,
numbers and pathologic findings. Size of lesion was also measured by
endoscopists.
RESULTS: One thousand and eight subjects were enrolled in this study. The
mean age of participants was 56.45  9.59 years and 51.6% subjects were male.
Overall polyp detection rate was 199/1208 (16.5%). Of them 26 subjects had non-
neoplastic polyps including hyperplastic polyps, and 173/1208 (14.3%) subjects
had neoplastic polyps of which, 26 (2.15%) were advanced neoplastic lesion. The
prevalence of colorectal neoplasia was more common among 50-59 years old
(p ); although, prevalence of adenoma was noticeable in 40-49 years old
group. The advanced adenoma was also more frequent among age over 50
years old. Majority of adenomas were detected in distal colon, but a quarter of
advanced adenomas were detected in proximal colon. Most colorectal adenoma
was detected beyond sigmoid. The increasing age and male gender were asso-
ciated with presence of adenoma.
CONCLUSION: It seems that CRC screening among average-risk population
might be recommended in countries such as Iran. However, sigmioidoscopy
alone would have missed many colorectal adenomas. Furthermore, the 50-59
age group could be considered as an appropriate target population for this
purpose.
Disclosure of Interest: None declared
P0171 STANDARD QUALITY ENDOSCOPY REPORT: DELPHI
CONSENSUS TO IDENTIFY QUALITY MEASURES FOR UPPER
AND LOWER GI ENDOSCOPY
F. Iacopini1,*, A. Bella2, G. Costamagna3, L. Baiocchi4, M. Angelico5, A. Kohn6,
M.C. Di Paolo7, L. Tammaro8, E. Grasso4 on behalf of Lazio AIGO-SIED-
SIGE members
1
Gastroenterology and Endoscopy Unit, Ospedale S. Giuseppe, Albano L, Rome,
2
National Center for Epidemiology, Surveillance and Health Promotion, Istituto
Superiore di Sanita`, 3Surgical Digestive Endoscopy, Catholic University,
4
Gastroenterology, Policlinico Tor Vergata, Rome, 5Gastroenterology, Policlinico
Tor Vergata, Roma, 6Gastroenbterology, Ospedale S. Camillo-Forlanini,
7
Gastroenterology and Endoscopy Unit, 8Gastroenterology and Endoscopy,
Ospedale S. Giovanni-Addolorata, Rome, Italy
Contact E-mail Address: federico.iacopini@gmail.com
INTRODUCTION: Efforts to improve quality in endoscopy are ongoing and
quality measures determined by examining the procedure report have been pro-
posed as a mechanism for meeting this goal. Complete documentation is neces-
sary for patient care and appropriate use of endoscopy. However, quality
measures are very numerous and it is undetermined which are really critical for
quality of cure.
AIMS & METHODS: To identify the quality measures to be included in the
upper and lower GI endoscopy report of standard quality. Quality measures were
extracted from the Quality Assurance Task Groups of the US Gastroenterology
Societies (ASGE, AGA, ACG). Measures included in the questionnaire were
divided in three categories: 1) pre-procedural with patient demographics (n.
15); 2) procedural (n. 27); 3) post-procedural (n. 9). A Rand Delphi method
was used to reach the consensus. Participants were asked to label each measure
using a 6 point Likert scale from 0 (not required) to 5 (absolutely required). The
questionnaire was iteratively proposed to via a web-based application with a
feedback of the results observed at the preceding round (median value; % of
patients expressing the median value). Consensus was reached when no signifi-
cant change was observed between values of the last two rounds (median, IRQ
range, P value by Wilcoxon test). Measures with a score-5 were considered to
characterize the standard (minimum) quality.
RESULTS: A total of 72 participants completed the 3 Delphi rounds required to
reach the consensus: mean age 48; working experience (yrs) 11; n. endoscopy/
week 415 in 61%; public employment 61%. A strong consensus was obtained
for 33 (61%) out of 51 metrics. A score-5 was achieved for the following mea-
sures: patient name and birth date; exam indication; date and findings of the
previous endoscopy for follow-up; anti PLT/coagulants use; informed consensus
collection; assistants/anesthesiologist names; sedation drugs and doses; antibiotic
prophylaxis use; causes of incomplete examination; stricture lumen according to
the endoscope diameter; photographic documentation of landmark and findings;
findings localization and biopsies; operative interventions: description of techni-
que and completeness; definition of complete EGD retroversion manouvre; defi-
nition of complete colonoscopy: ileoscopy and retroversion in the rectum;
indications after endoscopy in case of adverse events and follow-up.
A177
CONCLUSION: The availability of a huge number of measures may be one of
the causes of the poor report quality. The identification of the list of measures
defining the endoscopy report of standard quality could provide endoscopists
with an improvement tool and referring physicians with a report that use stan-
dard terms and provide follow-up recommendations. The identification of man-
datory quality measures within their long list will ensure a fair accounting of the
procedure and may encourage broader adoption of quality improvement efforts.
Disclosure of Interest: None declared
P0172 SELF-EXPANDABLE MESH METAL STENTS (SEMS) FOR
ACUTE COLONIC OBSTRUCTION - EXPERIENCE OF A UK
CENTRE
G.H. El Sayed1,*, J. Deepak1, B. Paranandi1, P. Patel1, M. Ryde1, S.P. Pereira1,
M.H. Chapman1, G.J. Johnson1, A. Obichere2, M.J. Obichere3, G. Webster1
1
Gastroenterology & Hepatobiliary medicine, 2Colorectal surgery, University
College London Hospitals, London, 3Colorectal surgery, Luton & Dunstable,
Luton, United Kingdom
Contact E-mail Address: ghassanovii@yahoo.co.uk
INTRODUCTION: Acute intestinal obstruction occurs in up to 30% of patients
with colorectal carcinoma. Historically, emergency surgical decompression was
the treatment of choice. Self-expandable mesh metal stents (SEMS) have been
increasingly used for malignant colonic obstruction. Several studies showed its
efficacy in relieving obstruction, offering good palliation, avoiding emergency
surgery and reducing the need for stoma creation.
AIMS & METHODS: A password-protected database of prospectively recorded
endoscopic activity in our UK centre was analysed. Endoscopic records of
patients undergoing SEMS for colonic obstruction from April 2007 to April
2014 were assessed. Data parameters included: patient demographics; site and
pathology of obstruction; SEMS details; technical success of SEMS placement
(correct placement of the stent across the stricture); clinical success (colonic
decompression, with relief of obstructive symptoms and no significant complica-
tion); complications and the need for further intervention.
RESULTS: 107 SEMS insertion procedures were performed on 95 patients
during the study period. M: F 46%:54%; median age 70 years (range 20 95);
50% were tertiary referrals. Causes of obstruction were primary colorectal cancer
(CRC) (78%), extrinsic compression (18%) due to other malignancy mainly
gynaecological; unspecified (4%). Obstruction occurred in left colon (distal to
mid transverse) in 87% of cases. The majority of patients (97%) had sedation and
only 3% were done under general anaesthesia. 3 stent types were used: 98%
uncovered (Boston Wallflex (n 27), Cook Evolution (n 78)), 2% fully covered
(Taewoong Medical (n 2)). The median length of SEMS was 80mm (range
60mm 120 mm). A single SEMS was inserted in 92% of patients, with 2
SEMS in the same session in 8 patients, and 3 SEMS in one patient. All
SEMS were inserted under combined endoscopic and fluoroscopic guidance.
Technical success was achieved in 98% of patients, with clinical success in 76%.
Complication Number (%) Post perforation management
Perforation 5/107 (5%) 4/5 (80%)-emergency laprotomy
1/5 (20%)- palliated
Obstruction due 2/107 (2%)
to flat valving
stent migration 6/107 (6%)
Stent occlusion 3/107 (3%)
Median time to perforation from stent insertion was 4.5 days (range 1 15 days).
Median time to death from stent insertion was 8.5 months; 6/107 (6%) died 5 30
days from stent insertion, with one attributed to stent-related perforation. Stent
migration noted to occur more in non-CRC extrinsic obstruction (2/19 (11%))
than primary CRC (4/88 (4.5%)).
CONCLUSION: Our data demonstrate that SEMS insertion for acute colonic
obstruction is technically highly successful. However, technical success does not
guarantee clinical success in all cases, and non-CRC extrinsic compression may
be associated with higher rates of SEMS migration. The 5% perforation rate was
similar to other reported studies, and needs to be considered in conjunction with
the risks of emergency surgery in this patient group. The results of large rando-
mised multicentre trials of SEMS vs surgery in palliating acute colonic obstruc-
tion are awaited.
Disclosure of Interest: None declared
P0173 LEARNING CURVE IN MUCOSAL HEALING (MH) AND
INFLAMMATORY ACTIVITY ASSESSMENT BY USING THE
ERLANGEN MH SCORE FOR CONFOCAL LASER
ENDOMICROSCOPY (EMHS) IN INFLAMMATORY BOWEL
DISEASES
G. Hundorfean1,*, M.T. Chiriac1, A. Nagel1, H. Albrecht1, C. Janson1, R. Gortz1,
C. Weber1, S. Jungbauer1, L. Merkl1, F. Zoicas1, T. Kukiolka1, A.E. Kremer1,
J. Siebler1, M.F. Neurath1
1
Medical Clinic 1, University of Erlangen-Nuremberg, Erlangen, Erlangen,
Germany
Contact E-mail Address: gheorghe.hundorfean@uk-erlangen.de
INTRODUCTION: Confocal laser endomicroscopy (CLE) is a modern imaging
technique that enables real time histology in vivo, during endoscopy, providing
new insights of mucosal pathology. Monitoring histological activity to assess
A178
MH is important in evaluating the therapy response and management of inflam-
matory bowel diseases (IBD). Our group has recently validated an endomicro-
scopic mucosal healing score (eIBD-MHs), which has to be interpreted by skilled
endoscopists.
AIMS & METHODS: Our first aim was to analyze the learning curve (LC) of
MH assessment by CLE in endoscopists na ve to the CLE technique. Secondly,
we comparatively investigated the LC between endoscopists and residents (i.e.
physicians acquainted neither to endoscopic nor to CLE techniques).
Therefore, 4 study groups were established: a.) senior endoscopists (n 3), board
certified (42000 procedures, 42 years of experience); b.) junior endoscopists
(n 3) (significant endoscopic skills, 52 years of experience); c.) internal med-
icine residents (n 4) without endoscopic experience, and d.) a skilled endomi-
croscopist (n 1). Initially, all attendees received a random set of 20 CLE images
from 10 IBD patients with different inflammatory activity and a table with the
eIBD-MHs (9 criteria) for a spontaneous offline assessment (based only on his-
tologic knowledge from medical school and interdisciplinary medical-histo-
pathology meetings). Thereafter, all physicians participated in a short training
session including explanation of the CLE technique, terminology, elementary
CLE lesions, and assessment of IBD cases based on the eIBD-MHs before and
after therapy). Subsequently, the same set of 20 CLE pictures was re-assessed (in
a modified, paired succession, grouped per patient, before and after therapy). All
physicians were blinded regarding patients identity, diagnosis and disease activ-
ity. Assessment scores and duration from the pre- and post-teaching evaluation
were statistically analyzed.
RESULTS: The average evaluation times before and after training for the groups
a; b; c and d were: 25 vs. 12,33; 23 vs. 15; 24,5 vs. 15,25; 14 vs. 9 minutes,
respectively). Overall, the evaluation time before the CLE instruction session
was significantly longer (p50.001) compared to second evaluation times. No
significant differences were observed between the physicians with or without
endoscopic experience regarding assessment duration and quality.
Interobserver agreement of the MH evaluation in the groups (compared to the
assessment results of the skilled endomicroscopist) for group a; b and c were:
0.72; 0.52 and 0.75, respectively.
CONCLUSION: In conclusion, the LC for MH and inflammatory activity
assessment by CLE is fast, can be easily learned and is independent of basic or
advanced endoscopic skills or experience.
Disclosure of Interest: None declared
P0174 COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION:
RESIDUAL/RECURRENT LESIONS VERSUS PRIMARY LESIONS
G. Andrisani1,*, L. Petruzziello1, G. Vitale1, S. Greco1, I. Costamagna1,
C. Spada1, G. Costamagna1
1
Digestive Endoscopy Unit, Catholic University, Rome, Italy
Contact E-mail Address: gianluca.andrisani@gmail.com
INTRODUCTION: Residual/locally recurrent lesions may occur after endo-
scopic resection: endoscopic mucosal resection (EMR) and endoscopic submu-
cosal dissection (ESD) or after transanal endoscopic microsurgery (TEM) for
rectal lesions. ESD may be useful for resection of scar-embedded lesions, not
lifted by standard injection of saline solution, but may be more technically diffi-
cult. We evaluated the feasibility and safety of ESD, as a salvage therapy for
residual/locally recurrent lesions compared to primary lesions.
AIMS & METHODS: From January 2012 to March 2013 we performed 30
colonic ESD. Fifteen patients were on the first endoscopic treatment and the
remaining fifteen had residual/recurrent lesions (median diameter of 21 mm) and
have received at least an attempt at endoscopic resection using standard techni-
ques including snare polypectomy, EMR or argon plasma coagulation, or TEM
(5/15). The tumor size, the procedure duration, complications and early recur-
rence rate were compared between the two groups.
RESULTS: Procedure time was similar between groups (7022 min vs 7235
min). The lesions were significantly smaller (239 mm vs 35 15 mm; P 5 0.05)
in the residual/ locally recurrent group, compared with primary lesions.
Immediate bleeding rate was significantly higher in primary lesions group
(46.6% vs 6.6%; P 5 0.05). However, there were no cases of delayed bleeding
in both groups. Intraprocedural perforations were observed only in residual/
locally recurrent group (3/15: 20%): surgery was needed in one patient, while
two patients were managed using endoclips. Early recurrence, evaluated at three
months, was similar between groups (20%)
CONCLUSION: Endoscopic submucosal dissection for residual/locally recur-
rent lesions was more difficult with higher risk of perforation due to presence
of scar. However, the presence of lesions of smaller size and the low risk of intra-
procedural bleeding, may recommend this procedure for scar-embedded lesions
instead of surgical resection.
REFERENCES
1. Kuroki Y, et al. Endoscopic submucosal dissection for residual/locally recur-
rent lesions after endoscopic therapy for colorectal tumors. J Gastroenterol
Hepatol 2010; 25: 1747-1753.
2. Azzolini F, et al. Endoscopic submucosal dissection of scar-embedded rectal
polyps: a prospective study (Esd in scar-embedded rectal polyps). Clin Res
Hepatol Gastroenterol 2011; 35: 572-579.
3. Hayashi N, et al. Predictors of incomplete resection and perforation associated
with endoscopic submucosal dissection for colorectal tumors. Gastrointest
Endosc 2014; 79: 427-35.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0175 THE USE OF DOUBLE CHANNEL GASTROSCOPE REDUCED
THE PROCEDURAL TIME IN LARGE LEFT-SIDED ENDOSCOPIC
MUCOSAL RESECTIONS
V. Evangelos1, G. Tribonias1, A. Tavernaraki1, A. Theodoropoulou1,
E. Vardas1, G. Chlouverakis2, G. Paspatis1,*
1
Gastroenterology, Venizeleion Hospital, Heraklion, Crete, 2Department of Social
Medicine, University of Crete, Heraklion, Greece
Contact E-mail Address: gpaspatis@gmail.com
INTRODUCTION: Endoscopic mucosal resection (EMR) of large colorectal
lesions is associated with an increased procedural time. Usually the inject and
cut EMR technique is applied for large sessile or flat colorectal lesions. The use
of double channel gastroscope (DCG) might reduce the procedural time in the
rectosigmoid area.
AIMS & METHODS: To evaluate the effect of DCG use in the procedural time
of injection-assisted EMR performed in the rectosigmoid area. To the best of our
knowledge this is the only comparative study on this subject. All EMRs for
sessile or flat rectosigmoid lesions larger than 2cm performed from July 2012
to September 2013 were retrospectively analyzed. The use of DCG was mainly
dependent on the availability.
RESULTS: There were 55 lesions 2cm or larger in the rectosigmoid area in 55
patients, of which 26 were removed by EMR using a DCG (DC group) and 29 by
using an ordinary colonoscope or gastroscope (OS group). The mean size of the
removed polyps was not statistically different between the two groups (4.3cm
1.86 & 3.9 cm  1.9 in DC and OS group respectively). The Paris classification
was similar between the two studied groups. The mean procedural time in the DC
group (24.418.3 min) was significantly lower compared to that of OS group
(36.324.4 min) (p50.05). Moreover, in the subgroup of patients with polyps
larger than 40mm the statistical difference in the mean procedural time between
the DC group (3321min) and OS group (58.720.6 min) (p50.01) was even
more pronounced. Outcome parameters such as recurrence rate (12 months
follow-up), post-procedural bleeding rate and hospital stay were similar between
the two groups. No case of perforation was observed. Multivariate linear regres-
sion analysis revealed that the polyp size (b 0.92, p50.001) and use of DCG
(b 15.5, p50.001) were significantly associated with the procedural time.
CONCLUSION: Our data suggest that the use of DCG for large sessile or flat
rectosigmoid lesions significantly reduces the procedural time. The use of DCG
seems to be more effective in larger polyps. These results should be confirmed in
a prospective study.
Disclosure of Interest: None declared
P0176 ADENOMATOUS HISTOLOGY IN COLONIC POLYPS:
INFLUENCE OF POLYP LOCATION, SIZE AND PARIS-
CLASSIFICATION
H.F. Hammer1,2, J.L. Klein1,*, M. Okcu3, K.H. Preisegger3
1
Gastroenterology and Hepatology, Medical University Graz, 2Privatklinik,
Kastanienhof, 3IMAH, Graz, Austria
Contact E-mail Address: heinz.hammer@medunigraz.at
INTRODUCTION: Published data on the likelihood of a polyp being an ade-
noma in relation to its location in the colon, size and form are incomplete.
AIMS & METHODS: To evaluate these factors in a consecutive patient group
all histologically verified colonic adenomas which were removed by one endos-
copist between 01-01-2011 and 31-12-2013 were included into this analysis.
Before polypectomy polyps were classified as protruded (Paris classification
type I) or flat (Paris type II), their size was estimated as compared to an open
biopsy forceps, and the location in the colon was noted. Polyps were grouped
according to their diameter using groups of sizes published in the literature. In
the study period 698 patients were colonoscoped by one of the authors (mean
patient age 62 years, 392 female). Visibility was reduced by fecal residues in 43
patients (6.2%). In 12 patients (1.7%) the cecum was not reached. In 8 patients
(1.1%) the polyp could not be retrieved.
RESULTS: 1877 polyps were removed and histologically assessed. In 8 patients
(1.1%) the polyp could not be retrieved for histological analysis. In 7 patients
(1.0%) the location of the polyp was not described. In 34 polyps (6% of polyps)
the estimated diameter was not described. Carcinoma of the sigmoid colon was
detected in one patient. Adenoma was detected in 565 polyps (n 222 Paris type
I lesion; n 343 Paris type II lesion). 13% of all adenomas were located in the
coecum (18 Paris I; 56 Paris II), 23% in the ascending colon (52 Paris I; 79 Paris
II), 27% in the transverse colon (71 Paris I; 79 Paris II), 7% in the descending
colon (19 Paris I; 22 Paris II), 22% in the sigmoid colon (43 Paris I; 80 Paris II)
and 8% in the rectum (19 Paris I; 27 Paris II). The table shows the total number
of adenomas in 5 groups according to lesion diameter, and the likelihood of a
polyp having adenomatous histology in % of all removed polyps, again in rela-
tion to diameter and to Paris-classification of the lesion.
Table to abstract P0176
minute small large
Diameter 55 mm 6-7 mm 8-9 mm 410 mm Total
Number of adenomas 270 189 40 10-19 mm 20 mm 531
27 5
Adenoma, % 23% 39.5% 51.3% 82% 100%
of all polyps
Adenoma in Paris I 58% 61% 64% 91% 62%
Adenoma in Paris II 20% 29% 32% 75% 23%
United European Gastroenterology Journal 2(5S)
CONCLUSION: Summary: 63% of adenomas are located oral to the left colonic
flexure. 61% of adenomas are flat lesions. Both in the right and in the left colon
the majority of adenomas are flat. However, in polyps of all sizes protruding
lesions have a significantly higher likelihood of being adenomatous as compared
to flat lesions. In flat and protruding lesions the likelihood of a polyp being
adenomatous increases with polyp size, from 58% to 91% in protruding and
from 20% to 75% in flat lesions. Conclusion: Almost two thirds of colonic
adenomas are flat or are located oral to the left colonic flexure. Although only
a minority of small and flat polyps are adenomatous, they comprise the majority
of adenomas. The high number of lesions in the right sided colon has not been
reported before and may be related to excellent colonoscopy preparation with
only 6% of colonoscopies having been influenced by fecal residues. The clinical
role of the right sided and the small polyps needs to be determined.
Disclosure of Interest: H. Hammer: None declared, J. Klein: none, M. Okcu:
none, K. Preisegger: none
P0177 A HAND-HELD METAL DETECTOR IS AN ACCURATE, LOW
COST ASSESSMENT OF FLEXIBLE SIGMOIDOSCOPY
COMPLETION TO THE SPLENIC FLEXURE
H.C. Matthews1,2,*, G. Sadler2, R. Leicester3
1
Gastroenterology, Kingston Hospital Foundation Trust, 2Gastroenterology,
3 1
Endoscopy, St Georges NHS Trust, London, United Kingdom
Contact E-mail Address: h.matthews1@nhs.net
INTRODUCTION: Flexible sigmoidoscopy (FS) is a validated screening test to
reduce the incidence of colorectal cancer. Bowel scope screening is due to be
implemented in the UK by 2016. There is variability in FS performance between
operators; internal colonoscopic markings are unreliable for colonoscope posi-
tion. Three dimensional (3D) magnetic imaging systems eg Scopeguide
(Olympus, UK) represent real time instrument position but are not widely avail-
able. Hand-held metal detectors (HHMD) can easily localise metal objects within
the body. We assessed use of HHMD to confirm flexible endoscopic tip place-
ment at the splenic flexure (SF).
AIMS & METHODS: Adult subjects undergoing outpatient FS/colonoscopy
were eligible and gave consent. When the operator judged examination complete
to the SF, an independent observer placed the HHMD at the left 10th intercostal
space, anterior-axillary line (corresponding to the internal fixation of the colon at
the SF). A positive resultTMwas recorded if the HHMD beeped. Position was then
assessed by Scopeguide . If the SF could not be reached, the patient was
excluded. We evaluated 3 different HHMD from different manufacturers.
Patient experience was also studied. Ethical review NREC Ref no 13/LO/1065;
IRAS Project ID 121224.
RESULTS: 44 subjects were recruited consecutively: mean age 64 years (range
17-74), 50% male (n 22), mean BMI 27 kg/m2 (range 20-41 kg/m2). Endoscopic
TM
confirmation of position at SF showed concordance with Scopeguide in 95%
(42/44). Subjects 1-6 were examined using BDS200 (Black & Decker) HHMD.
Despite promising results on colonoscopic training models, this proved insensi-
tive in humans and was abandoned. For subjects 7-30 (n 24) studied with
GMS120 (Bosch) HHMD, positive reading at the correct TM
anatomical marking
was recorded in 88% of examinations with Scopeguide validation. Of the 3
2
failures, 2 had a BMI of 430 kg/m . Use of an X-Ray screening trolley improved
specificity. For subjects 31-44, n 14, a detector with increased sensitivity and
directional capabilities, GPP (Garrett Metal Detectors USA), was used on stan-
dard endoscopy trolleys. This showed concordance with 3D imaging in 100% of
cases (n 14) including 4 patients with BMI 430kg/m2. ThereTMwas one true
negative versus endoscopic assessment confirmed by Scopeguide . The techni-
que was further validated by loss of signal on scope withdrawal. Patient ques-
tionnaires showed high acceptability.
CONCLUSION: Use of HHMD in FS has shown excellent concordance with
ScopeguideTM for colonoscope localisation at SF. Specificity and sensitivity are
improved by adapting the specifications of the HHMD. A HHMD is an accurate
and very cheap (E100 per unit) means of assuring quality during FS and further
studies may confirm its role as a useful training tool especially during future
service expansion.
REFERENCES
Atkin W et al. BMJ 2010.
Leicester R et al. Lancet 1981.
Disclosure of Interest: None declared
P0178 CONFOCAL LASER ENDOMICROSCOPY (CLE) DEMASKS
SUBTLE MUCOSAL CHANGES IN PATIENTS WITH IRRITABLE
BOWEL SYNDROME (IBS)
H. Neumann1,*, G.E. Tontini1,2, M. Vieth3, C. Gunther1, S. Zopf1,
M.F. Neurath1, Y. Zopf1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
Bayreuth, Germany
INTRODUCTION: IBS is a symptom-based diagnosis characterized by chronic
abdominal pain, bloating, and alterations of the bowel habits without any
organic cause. CLE allows in vivo visualization of microscopic features of the
intestinal epithelium in real time during endoscopy.
AIMS & METHODS: To assess whether CLE is able to demask microscopic
alterations of the small and large bowel mucosa in patients with established
diagnosis of IBS.
Patients with established diagnosis of IBS according to Rome-III criteria and
control patients underwent ileocolonoscopy. Fluoresceine guided CLE was per-
formed in the terminal ileum and random optical biopsies were additionally
performed in the colon and rectum. Attention was paid to presence or absence
A179
of epithelial gaps, intramucosal bacteria, crypt and vessel morphology, goblet
cells and cellular infiltrate within the lamina propria. Physical biopsies were
additionally taken for histopathological analysis.
RESULTS: Epithelial gap density and the microvascular pattern were increased
in a subgroup (44%) of patients with IBS according to Rome-III as compared to
control patients suggesting an altered intestinal permeability. No differences were
observed regarding the presence of intramucosal bacteria, colonic crypt morphol-
ogy, presence of goblet cells or the cellular infiltrate within the lamina propria (P
40.05).
CONCLUSION: Confocal imaging revealed subtle changes of the mucosa in
patients with IBS. These findings were not visible in every patient with IBS
according to Rome-III criteria suggesting that some IBS patients may have an
organic cause of the disease.
Disclosure of Interest: None declared
P0179 IN VIVO ASSESSMENT OF PORTAL HYPERTENSIVE
COLOPATHY AND CLINICAL OUTCOME OF PATIENTS WITH
LIVER CIRRHOSIS WITH CONFOCAL LASER ENDOMICROSCOPY
(CLE)
H. Neumann1,*, G.E. Tontini2, C. Gunther1, M. Vieth3, Y. Zopf1, M.F. Neurath1,
S. Zopf1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
Bayreuth, Germany
INTRODUCTION: Recent data has highlighted the role of mucosal integrity for
bacterial translocation in the gut which is also discussed as a major cause for
TM
development of spontaneous bacterial peritonitis (SBP) and/ or hepatic encepha-
lopathy (HE) in patients with liver cirrhosis. CLE has emerged as a valuable tool
for real time diagnosis of mucosal integrity and allows in vivo imaging of com-
mensal bacteria in the gut.
AIMS & METHODS: To prospectively assess the value of CLE for in vivo
diagnosis of portal hypertensive colopathy and its association to Child-Pugh
class, Model for End Stage Liver Disease (MELD), HE and development of
SBP. Patients with established diagnosis of liver cirrhosis and portal hypertension
were prospectively included. Clinical, biochemical, and ultrasound criteria,
including portal vein thrombosis, ascites and collateral portosystemic vessels
were assessed in addition to endoscopic criteria (e.g. esophageal varices, portal
gastropathy) and beta-blocker intake. Fluoresceine aided CLE was performed in
every patient in the sigmoid colon, rectosigmoid junction, and rectum.
Afterwards biopsies were taken, unless contraindicated, for corresponding histo-
pathological analysis.
RESULTS: Overall, more than 14,700 CLE images were collected. Confocal
imaging revealed dilation and/or ectasia of microvessels, congestion of blood
flow, edema, and a non-specific increase of the cellular infiltrate within the
lamina propria. These findings were directly correlated to Child-Pugh class and
MELD score with patients at higher scores showing more distinct changes of the
microarchitecture. Of note, disturbed mucosal integrity, as observed by CLE, was
strongly correlated with occurrence of HE and SBP, even in the follow-up of the
patients. The procedure was well tolerated by the patients, and no adverse events
were observed.
CONCLUSION: Fluoresceine guided CLE in patients with liver cirrhosis and
portal hypertensive colopathy is safe and well tolerated. In vivo imaging revealed
similar microscopic changes of portal colopathy as conventional histology with-
out the need of physical biopsies. Of note, confocal imaging corresponds to
clinical outcome parameters, including development of HE and/or SPB.
Disclosure of Interest: None declared
P0180 HIGH-DEFINITION ENDOSCOPY WITH COMPUTED VIRTUAL
CHROMOENDOSCOPY FOR PREDICTION OF FOOD ALLERGY IN
REAL-TIME A PROSPECTIVE, RANDOMIZED STUDY WITH
CROSS-OVER DESIGN
H. Neumann1,*, M. Vieth2, G.E. Tontini1,3, S. Zopf1, C. Gunther1,
M.F. Neurath1, Y. Zopf1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, 2Klinikum
Bayreuth, Bayreuth, Germany, 3IRCCS Policlinico San Donato, San Donato
Milanese, Italy
INTRODUCTION: Food allergy is mediated via IgE and non-IgE mediated
mechanisms. White-light endoscopy is not feasible to detect any specific mucosal
alterations in patients with intestinal food allergy.
AIMS & METHODS: To access the value of advanced endoscopic imaging using
high-definition colonoscopy with computed virtual chromoendoscopy (CVC) for
prediction of mucosal changes in patients with suspected food allergy.
Patients suffering from recurrent abdominal pain and diarrhea were consecu-
tively included. At baseline, patients underwent a standardized clinical interview
in order to contain the diagnosis. Afterwards, patients underwent ileocolono-
scopy with high-definition white-light endoscopy alone followed by CVC or
the reverse. The mucosa of the terminal ileum, caecum and at the rectosigmoid
junction was carefully inspected with or without CVC. Following the endoscopic
inspection, a diagnostic lavage examination was performed at the above men-
tioned locations and analysed by measuring 13 different allergic markers, includ-
ing TNF-alpha, IgE, and eosinophilic cationic protein. Finally, biopsies were
obtained for additional histopathological analysis of the tissue.
RESULTS: 46 patients were randomized of which 39 patients (31 female, mean
age 50 years; Range 21-78 years) completed the study protocol. Based on the
clinical presentation, histopathological results and the lavage diagnosis 61% (24/
39) of patients were diagnosed with intestinal food allergy. High-definition ima-
ging with CVC visualized lymphoid hyperplasia, slight mucosal edema and
A180
blurred mucosal vascular pattern. No mucosal changes were observed with high-
definition endoscopy alone. CVC allowed correct diagnosis in 21 of 24 intestinal
food allergy cases as compared with the criterion standards, giving a sensitivity,
specificity and accuracy of 88%, 87%, and 87%, respectively. Positive and nega-
tive predictive value of CVC to predict food allergy was 91% and 81%,
respectively.
CONCLUSION: High-definition endoscopy with CVC could mimic slight muco-
sal changes in patients with intestinal food allergy which were highly predictive
for the disease. Therefore, advanced endoscopic imaging could add valid new
criteria for diagnosis of intestinal food allergy.
Disclosure of Interest: None declared
P0181 UNDERWATER ENDOSCOPIC MUCOSAL RESECTION OF
LARGE COLORECTAL LESIONS IN A SWEDISH CENTRE
N. Uedo1, A. Nemeth1, E. Toth1, G. Wurm Johansson1, H. Throlacius2,*
1
Department of Gastroenterology, Skane University Hospital, 2Department of
Surgery, Skane University Hospital, Lund University, Malmo, Sweden
Contact E-mail Address: henrik.thorlacius@med.lu.se
INTRODUCTION: Underwater endoscopic mucosal resection (UEMR) without
submucosal injection has recently been reported to be a useful to remove large
colorectal polyps in one single institution (1). The aim of this study was to
examine if UEMR is a safe and effective procedure for removing large colorectal
lesions in our institution.
AIMS & METHODS: Two experienced interventional endoscopists performed
all UEMR cases after observing UEMR procedures. UEMR was performed by
use of a colonoscope with hood and the polyp was fully immersed in water during
the entire procedure. All polyps were removed by en bloc or piecemeal resection
and without submucosal injection. The size of the snare (15 or 33 mm) depended
on lesion size. Patient data were collected prospectively.
RESULTS: A total of 13 consecutive patients (8 men, mean age 74 years, range
52-84) referred for polyp removal of colorectal lesions underwent UEMR.
Totally 16 lesions with a mean size of 17 mm (range 7-30) were removed by
UEMR. Lesions were located in the cecum (n 8), ascending colon (n 2),
transverse colon (n 4) and rectum (n 2). 56% of the polyps were removed
en bloc and the rest by piecemeal technique. All lesions were radically removed as
judged endoscopically. Minor bleeding events occurred during three procedures
which were easily managed with coagulation forceps and clips. No complications,
such as perforation or delayed bleeding, occurred.
CONCLUSION: UEMR seems to be an effective and safe method for removing
colorectal polyps and should be incorporated into the therapeutic arsenal of
institutions managing large colorectal lesions.
REFERENCES
1. Binmoeller KF, Weilert F, Shah J, et al. "Underwater" EMR without sub-
mucosal injection for large sessile colorectal polyps (with video). Gastrointest
Endosc 2012; 75: 1086-1091.
Disclosure of Interest: None declared
P0182 A PREDICTOR OF THE DIFFICULTY OF COLORECTAL ESD
FROM THE STANDPOINT OF DISSECTION SPEED
H. Chiba1,*, D. Kurihara1, T. Suto1, K. Ashikari1, N. Kawano1, S. Seki1,
S. Tsuruta1, A. Takahashi1, T. Ida1, T. Morohashi1, T. Goto1
1
gastroenterology, Omori Red Cross Hospital, Tokyo, Japan
Contact E-mail Address: h.chiba04@gmail.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been applied
to the treatment of large colorectal tumors in Japan. However, the rate of com-
plications is still higher than conventional endoscopic resection. For a manage-
ment of complications, it is so important that we try to predict the difficulty of
ESD in advance. Dissection speed during ESD will be related to the stability of
the intraoperative visual field or ESD procedure itself.
AIMS & METHODS: To evaluate the difficulty of ESD from the dissection
speed, we retrospective analyzed 94 patients who underwent colorectal ESD in
Omori Red Cross Hospital from 2012 April to 2014 March. Because the mean
dissection speed of total cases was 29.415.5(mm2/min), we divided the patients
into two groups: a low speed group (514 mm2/min) (group A) and a control
group (=15 mm2/min) (group B). The two groups were compared with respect to
their clinical background and tumor characteristics predicted as a difficult case.
In this study, for keeping uniform the quality of ESD, ESD procedure with a
needle type device was done by one experienced ESD physician who under took
more than 150 colorectal ESD before this study. In addition, the degree of sub-
mucosal fibrosis was classified into three types (F02) (1) (F0: no fibrosis, F1:
mild fibrosis, F2: whitish submucosa or severe fibrosis). Independent and sig-
nificant predictors were determined by multivariate analysis.
RESULTS: 94 lesions (male/female: 51/43) underwent ESD procedures; 14 in
group A and 80 in group B. In a low speed group (group A), tumor location was
C1/A2/T3/D3/S4/R1, and the mean tumor size was 25.39.8mm (15-50), and 5
cases had a fibrosis (F1; 2 cases and F2; 3 cases), and the rate of en bloc and
curative resection was 100% and 13/14 (92.9%), and the mean operation time
was 73.3min. The mean age, sex, the number of having antithrombotic agents
was similar between two groups. The statistical analysis showed that severe
fibrosis (F2) was predictor of a low speed (OR 36.0; 95%CI 2.46-527.1;
p 0.009), but tumor size (=30mm), depressed tumor (IIc or LST-NG-PD),
total fibrosis, location of tumors in the rectum or cecum, and the straddle of
the fold did not have any significant differences. With respect to the postopera-
tive course, there was also no differences in WBC, CRP, a number of having a
high fever (=38 C), using antibiotic agents, taking a painkiller, and a hospital
period. Otherwise, there was one complication case in all lesions. This case
United European Gastroenterology Journal 2(5S)
(group A) had a thick fibrosis (F2) after severe radiation colitis and resulted in
a delayed perforation the following day.
CONCLUSION: The size or location of tumors will not be related to dissection
speed. This study showed a severe fibrosis was only a predictor, which was
independent of the tumor size, of decelerating a dissection speed during color-
ectal ESD. In a case with severe fibrosis, an operation will take much time
because of the difficulty, so an experienced physician should perform ESD.
Additional cases, while considering dissection speed, will probably be a good
reference for a predictor of the difficulty of colorectal ESD.
REFERENCES
(1) Matsumoto A, et al. Outcome of endoscopic submucosal dissection for color-
ectal tumors accompanied by fibrosis. Scand J Gastroenterol 2010; 45: 1329-1337.
Disclosure of Interest: None declared
P0183 PREDICTIVE FACTORS OF AN INCOMPLETE EN BLOC
RESECTION IN ENDOSCOPIC MUCOSAL RESECTION FOR
COLORECTAL TUMORS
H. Minamino1,*, M. Shiba1, K. Hayashi2, M. Ominami1, S. Fukunaga1,
Y. Nagami1, T. Hayakawa2, K. Aomatsu2, S. Sugimori1, H. Machida3,
T. Watanabe1, K. Tominaga1, Y. Fujiwara1, T. Arakawa1
1
Osaka City University Graduate School of Medicine, Osaka, 2Izumiotsu
Municipal Hospital, Izumiotsu, 3Machida gastrointestinal hospital, Osaka, Japan
Contact E-mail Address: piacere_minaminohiroaki@yahoo.co.jp
INTRODUCTION: En bloc resection by the procedure of endoscopic mucosal
resection (EMR) for colorectal tumors over 2 cm in diameter is difficult accord-
ing to previous reports. However, predictive factors of difficulty of en bloc resec-
tion are not indicated in colorectal EMR.
AIMS & METHODS: The aim of this study is to clarify predictive factors of an
incomplete en bloc resection in EMR for colorectal tumors. From January 2012
to December 2013, a total of 277 patients with 370 colorectal tumors larger than
10 mm in diameter except pedunculated type tumors underwent EMR at
Izumiotsu Municipal Hospital (Osaka, Japan). Age (mean): 70 years, sex: male
169 / female 108, location: right hemicolon 183 / left hemicolon (including the
rectum) 187, macroscopic type: protruding type including sessile (Is) 43 / semi-
pedunculated (Isp) 151 / flat-elevated type (IIa) 156 / IIaIs 20. DRAGONEA
bipolar snare (ZEON Medical Co., Tokyo, Japan) was used and selected width of
snare 13 mm or 26 mm in diameter in reference to the lesion size in EMR
procedures. Standard saline solution was injected into the submucosa in all
cases. We retrospectively analyzed predictive factors of an incomplete en bloc
resection on age, sex, tumor size, location, macroscopic type, and histological
findings by multivariate analysis.
RESULTS: With crude-OR, location was 1.98 (95% Confidence Interval (CI),
1.12 to 3.48) and tumor size 1.11 (95% CI, 1.05 to 1.18) were associated with the
incomplete en bloc resection. Regarding the location, the multivariate-adjusted
OR of the incomplete en bloc resection for the right hemicolon was 1.9 (95% CI,
1.06 to 3.38) compared with the left hemicolon. Regarding the tumor size, the
multivariate-adjusted OR of the incomplete en bloc resection for the highest
tertile was 2.97 (95% CI, 1.53 to 5.75) compared with the lowest tertile (p for
trend 5 0.01, cutoff value: 16 mm).
CONCLUSION: Size (cutoff: 16 mm in diameter) and location (right hemicolon)
of the colorectal tumors are indicated to be predictive factors for an incomplete
en bloc resection by EMR. Especially, when lesion over 16 mm in diameter or
located in right hemicolon is treated by EMR, the consideration of EMR-pre-
cutting technique or endoscopic submucosal dissection may be needed.
REFERENCES
Disclosure of Interest: None declared
P0184 SUBMUCOSAL DISSECTION IN THE COLORECTUM: LOW
RATE OF PIECEMEAL RESECTION AND RECURRENCE
H. Kashida1,*, T. Adachi1, T. Sakurai1, Y. Asakuma1, M. Takayama1, H. Mine1,
S. Matsui1, M. Kudo1
1
Department of Gastroenterology and Hepatology, Kinki University Faculty Of
Medicine, Osaka-sayama, Japan
Contact E-mail Address: kashi-md@xf6.so-net.ne.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) for colorectal neo-
plasms was developed in Japan but is now spreading rapidly. The technique was
started in our institute in the year 2010.
AIMS & METHODS: The aim of this study is to evaluate the results of color-
ectal ESD procedures for the first 4 years. The subjects are 205 consecutive
lesions in 180 patients which were treated with ESD technique. The indications
for ESD in our hospital are; 1. Neoplasms larger than 20mm but confined to the
mucosa or invading minimally to the submucosal layer, 2. Those smaller than
20mm but unable to be lifted by injection due to fibrosis. The instruments used
are PCF-Q260AZI or JI (Olympus), Short ST Hood and Flush Knife (Fujifilm)
and VIO 300D (Erbe).
RESULTS: Male: female ratio was 86:94 and the average age was 68.0 (39-90)
years old. The location was the cecum, ascending colon, transverse colon, des-
cending colon, sigmoid colon and rectum in 36, 51, 48, 6, 24 and 40 of the lesions,
respectively. The final pathological diagnosis was sessile serrated adenoma/polyp
(SSA/P) in 18, adenoma in 63, mucosal cancer in 101, minimally invasive cancer
(SM1) in 15 and deeply invasive cancer (SM2) in 7, and neuroendocrine tumor in
1. The gross appearance of the adenomas and cancers was flat or laterally spread-
ing tumor (LST) in 174, sessile or 0-Is in 9, and depressed or 0-IIc in 3. The LSTs
were subdivided into 53 lesions of homogeneous granular-type (LST-GH), 41
mixed-nodular type (LST-GM), 41 flat-elevated type (LST-NGF), and 39
pseudo-depressed type (LST-NGPD). The average size in LST-GH, LST-GM,
LST-NGF, LST-NGPD, 0-Is, 0-IIc, and SSA/P was 41.1mm, 39.7mm, 30.7mm
United European Gastroenterology Journal 2(5S)
and 25.7mm, 36.4mm, 10.3mm, and 23.9mm respectively. Invasive rates in these
subtypes in order was 1.9%, 14.6%, 9.8%, 20.5%, 22.2%, 33.3%, and 0%. Post-
procedure bleeding occurred in 2 cases (0.98%). Minor intra-procedure perfora-
tion was encountered in 6 cases (2.93%), but no emergency operation was
required. Delayed pneumoperitoneum was witnessed in one case, but it was
attributable to the ileus caused by anal stricture. If we divide the cases into
1st, 2nd, 3rd, and 4th fifty lesions, the en bloc resection rate was 78%, 88%,
98% and 98%. Local recurrence was witnessed in 3 cases (1.46%) in all of which
the ESD procedure had resulted in piecemeal resection due to fibrosis, but the
recurrent lesions were all small and removed endoscopically.
CONCLUSION: Submucosal dissection in the colorectum was successful with
low rate of piecemeal resection and recurrence, but without serious
complications.
Disclosure of Interest: None declared
P0185 COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION
(ESD) PERFORMED BY EXPERTS IN COLONOSCOPY WITH
LITTLE EXPERIENCE OF GASTRIC ESD
H. Shiga1,*, M. Kuroha1, K. Endo1, J. Kusaka1, T. Tadano1, K. Matsushita1,
Y. Kakuta1, Y. Kinouchi1, T. Shimosegawa1
1
TOHOKU UNIVERSITY GRADUATE SCHOOL OF MEDICINE, Sendai,
Japan
INTRODUCTION: The efficacy of colorectal endoscopic submucosal dissection
(ESD) has been reported mainly from Japanese referral centers. However, it is
technically difficult and is associated with a higher risk of adverse events than
endoscopic mucosal resection (EMR), especially for novices in colorectal ESD
with little experience in gastric ESD.
AIMS & METHODS: We aimed to evaluate the results of colorectal ESD during
the clinical learning curve. Colorectal ESD was performed by 2 endoscopists who
had expertise in colonoscopy and colonic EMR but had experience of fewer than
5 cases of gastric ESD. A total of 120 cases consisting of the first 60 cases of each
endoscopist were retrospectively investigated. The main outcome measurements
were procedural time, en bloc resection rate with tumor-free margins (R0 resec-
tion rate) and adverse events rate. From among the clinical characteristics
obtained before the ESD procedure, factors that affected the main outcome
measurements were identified.
RESULTS: (Clinical characteristics) Tumors were located at the rectum, left
colon, right colon and junction (dentate line, SD junction, hepatic flexure, splenic
flexure, ileocecal valve) in 22, 19, 51 and 28 cases, respectively. With regard to the
macroscopic type, 44, 23, 5 and 8 cases were granular-type laterally spreading
tumor (LST), nongranular-type LST, depressed and protruding type, respec-
tively. Of the 120 cases, 20 cases had factors which reflected fibrosis of the
submucosal layer (sporadic localized lesions with ulcerative colitis, local residual
tumors after EMR, etc.). The mean tumor diameter was 38.518.3 mm. The
histological analysis showed 59 adenocarcinomas and 61 adenomas.
(Outcomes) The mean procedural time was 101.765.9 min. A total of 113
cases (94.2%) were resected en bloc, and the R0 resection rate was 80.0% (96/
120). Perforation and postoperative hemorrhage occurred in 8 (6.7%) and 2
(1.7%) cases, respectively. Multivariate analyses revealed that lesions in junction
and lesions with factors reflecting fibrosis were significantly associated with
longer procedural time (90 min) and a lower en bloc resection rate. Larger
lesions (40 mm) and lesions resected in the first half (up to 60 cases) were
also associated with longer procedural time.
CONCLUSION: Colorectal ESD is feasible and safe when performed by experts
in colonoscopy with little experience of gastric ESD. For novices in colorectal
ESD, beginning with lesions in junction and lesions with factors reflecting fibro-
sis may not be advisable.
Disclosure of Interest: None declared
P0186 A VALIDATION STUDY OF 4 TYPE BOWEL CLEANSING SCALE:
ARONCHICK, BOSTON BOWEL PREPARATION, OTTAWA,
HAREFIELD SCALE
S.H. Kim1,1, I.K. Yoo1, J.M. Lee1, S.J. Nam1, H.S. Choi1, E.S. Kim1, B. Keum1,
Y.T. Jeen1, H.S. Lee1,*, H.J. Chun1, C.D. Kim1
1
Department of Internal Medicine, Division of Gastroenterology and Hepatology,
Korea University Anam Hospital, Seoul, Korea, Republic Of
Contact E-mail Address: kimseunghan09@gmail.com
INTRODUCTION: Total colonoscopy is a potent tool for assessing the large
bowel. There are various bowel preparation scale, but few bowel preparation
scale have been validated. Diversity in bowel preperation scales can cause a lot
of confusion on decisions in the clinical environment and much confounding of
results within clinical studies. However there have been no clinical trials that
compared 4 types of bowel preparation scales. The aim of this study is to
assess the compatibility and reliability of 4 different types of bowel preparation
scales.
AIMS & METHODS: This study compared 4 types of bowel preparation scales:
Aronchick scale (AC), Boston bowel preparation scale (BBPS), Ottawa scale
(OS), Harefield cleansing scale (HCS). 5 trainees read 20 total colonoscopy stu-
dies twice, with an interval of 1 month. We used Intraclass correlation coefficient
(ICC) to evaluate Intra-observer (test-retest) consistency and inter-observer relia-
bility of the BBPS and the OS. The unweighted kappa statistic was used to assess
the reliability of the AC and the HCS.
RESULTS: Total 400 ratings were completed in this study. Inter-observer and
intra-observer reliability were assessed by ICC and kappa statistic. ICC for OS
was 0.73 (95% CI, 0.52-0.87, p 5 0.0001), BBPS 0.76 (95% CI, 0.59-0.88, p 5
0.0001), inter-observer kappa for AC was 0.29 (95% CI, 0.19-0.42, p 5 0.0001),
HCS 0.27 (95% CI, 0.15-0.41, p 5 0.0001). Intra-observer scores for OS, ICC
A181
was 0.79-0.96, BBPS, 0.73-0.89. Intra-observer kappa for AC was 0.51-0.79 and
for HCS, 0.36-0.92.
CONCLUSION: Inter-observer agreement values were high in OS and BBPS.
This validation analysis showed that OS and BBPS are reliable, coherent scales so
that they can provide better standardization to evaluate bowel preparation in
both study and clinical practice.
REFERENCES
Thomas-Gibson S, Rogers P, Cooper S, et al. Judgement of the quality of bowel
preparation at screening flexible sigmoidoscopy is associated with variability in
adenoma detection rates. Endoscopy 2006; 38: 456-460.
Brotz C, Nandi N, Conn M, et al. A validation study of 3 grading systems to
evaluate small-bowel cleansing for wireless capsule endoscopy: a quantitative
index, a qualitative evaluation, and an overall adequacy assessment.
Gastrointest Endosc 2009; 69: 262-270.
Disclosure of Interest: None declared
P0187 MANAGEMENT OF LARGE COLONIC POLYPS IN A BOWEL
CANCER SCREENING PROGRAMME
H.Y. Lee1,*, W. Gashau1, R. Willert1
1
Department of Endoscopy, Central Manchester University Hospitals NHS
Foundation Trust, Manchester, United Kingdom
Contact E-mail Address: huiyann.lee@cmft.nhs.uk
INTRODUCTION: Bowel cancer is the third most common cancer in the United
Kingdom forming up to 13.6% of all newly diagnosed cancers(1). Bowel cancer
screening colonoscopy allows early polyp detection at a curable stage. Complete
resection and follow-up of large polyps is crucial to prevent malignant
progression.
AIMS & METHODS: The aim of this study was to review the management of
polyps with diameters  2 cm, particularly of sessile polyps, to assess the enbloc
resection rates, completeness of resection using endoscopic mucosal resection
(EMR) vs surgery and the incidence of malignant polyps.
Patients were identified retrospectively from a regional bowel screening pro-
gramme database. Details of index colonoscopy including polyp characteristics,
method of resection and complications were recorded. Histology results were
reviewed for all polyps. Outcomes from follow-up endoscopic surveillance were
analysed.
RESULTS: One hundred and fifty-eight patients (102 males, 56 females, mean
age 66.2 years) with polyps  2 cm were identified from 2182 screening colonos-
copies from January 2010 to August 2013. Caecal intubation rate was 96.8% in
this group.
Largest polyp size for each patient ranged from 20 to 60 mm (mean 26.6 mm).
The incidence of adenocarcinoma was 11.9% (n 19), all located within the left
colon, with 12 requiring surgical resection.
One hundred thirty nine patients (n 139) had 155 non-malignant large polyps,
mostly tubulovillous or villous histology (n 110, 79%).
Thirty-six patients had 37 sessile polyps which underwent primary resection by
EMR (n 26) or surgery (n 11).
Polyp diameter was larger in the surgery group with mean polyp diameter of 40.4
mm vs 28.0 mm (p50.05).
EMR enbloc resection rate was 11.5% (n 3 out of 26). Completeness of excision
was 38.4% (n 10) at 3 months and 92.3% (n 24) at 1 year. EMR complica-
tions included 1 perforation, 1 post polypectomy syndrome and 1 bleed.
Surgical resection included: anterior resection in 2, TEMS excision in 7 and right
hemicolectomy in 3.
CONCLUSION: Sessile polyps  2 cm are relatively uncommon in an asympto-
matic bowel cancer screening programme (37 in 2182 colonoscopies). They can
be successfully resected by EMR without recurrence in 92.3% at 1 year providing
a 3 month site check is performed in all piecemeal polypectomies.
REFERENCES
(1) Cancer for National Statistics. Office for national statistics, http://www.ons.-
gov.uk/ons/dcp171778_263537.pdf (2010).of InterestDisclosure: None declared
P0188 ARE THERE ANY PARAMETERS TO PREDICT BILE DUCT
STONES IN BILIARY PANCREATITIS BEFORE ERCP
A. Sayilir1,*, B. Odemis1, E. Parlak1, S. Disibeyaz1, Y. Beyazit1, N. Sasmaz1
1
Gastroenterology, TURKIYE YUKSEK IHTISAS TEACHING AND
RESEARCH HOSPI, ANKARA, Turkey
Contact E-mail Address: drabdurrahim@gmail.com
INTRODUCTION: The role of endoscopic retrograde cholangiopancreaticogra-
phy (ERCP) for the management of acute biliary pancreatitis (ABP) remains a
controversial topic. Pre-ERCP detection of biliary stones in patients with ABP
may strengthen the indication for a subsequent ERCP.
AIMS & METHODS: The aim of this study was to determine the value of
several clinical and laboratory parameters as non-invasive pre-ERCP indicators
_
of bile duct stones. Patients presenting to Turkiye Yuksek Ihtisas Teaching and
Research Hospital (TYIH) between 1 January 2010 and 31 August 2011 with
ABP, who underwent ERCP within 72 hours of the onset of symptoms were
screened, and eligible patients were enrolled in the study. Receiver operating
characteristic (ROC) curve analysis was used to determine the optimal cut-off
value of several parameters, such as AST, ALT, GGT, ALP, bilirubin, common
bile duct (CBD) width on USG and duration of syptoms, with the highest sensi-
tivity and specificity for predicting the presence of CBD stones.
RESULTS: A total of 59 patients [20 (33.89%) males and 39 (66.1%) females]
were included in the final analysis. Areas under the curve for CBD width, timing
of ERCP, AST, ALT, GGT, ALP and bilirubin were 0.753, 0.630, 0.548, 0.370,
0.577, 0.568 and 0.495, respectively. As a predictor of the presence of a biliary
stone(s), CBD width was found to have the highest sensitivity, specificity,
A182 United European Gastroenterology Journal 2(5S)
negative predictive value (NPV), positive predictive value (PPV) and general
P0190 VALIDATION OF A RISK SCORE FOR PREDICTING POST-ERCP
accuracy. With a cut-off value of 8.55 mm for CBD width, sensitivity and spe-
PANCREATITIS BASED ON THE EUROPEAN GUIDELINE
cificity were 75% with a NPV of 47.4%, PPV of 90.9% and general accuracy of
75. A summary of ROC analyses for the other parameters is provided in table 1. A. Mariani1,*, M. Di Leo1, A. Ambrosi2, M.L. Grazie1, A. Giussani1,
Table 1. ROC analysis for the value of several labortory and clinical parameters P.A. Testoni1
1
as pre-ERCP indicators of the presence of bile duct stones. Division of Gastroenterology and Gastrointestinal Endoscopy Vita-Salute San
Raffaele University Scientific Institute San Raffaele, Milan, Italy, 2Vita-Salute
San Raffaele University Scientific Institute San Raffaele, Milan, Italy, Milan,
Sensitivity Specificity NPV PPV
Italy
Cut-off AUC (%) (%) (%) (%) Accuracy
Contact E-mail Address: mariani.alberto@hsr.it
CBD width (mm) 8.55 0.753 75 75 47.4 90.9 75
INTRODUCTION: Post-ERCP pancreatitis (PEP) is an important complication
Duration (hours) 25.5 0.630 60.9 61.5 30.8 84.8 61 in biliopancreatic endoscopy, associated with morbidity and mortality. While
AST (u/L) 224.5 0.548 56.5 53.8 25.9 81.3 55.9 clinical and technical risk factors for PEP have been elucidated, the identification
ALT (u/L) 156.2 0.370 43.2 40.0 13.8 76 42.6 of a simple and valid risk score to predict PEP remains a challenge.
GGT (u/L) 263 0.577 69.8 70 35 90.9 69.8 AIMS & METHODS: To develop a model to predict the risk of PEP in patients
undergoing endoscopic retrograde cholangiopancreatography (ERCP).
ALP (u/L) 153 0.568 56.8 60 24 86.2 57.4 Methods: A risk score was created based on the prognostic factors for PEP
Bilirubin (mg/dl) 1.54 0.495 54.8 50 20.8 82.1 53.8 identified on the basis of the ESGE Guideline (1) and validated on 1823
ERCPs from an independent, prospectively assembled database (validation
cohort). The predictive performance of the models was tested by ROC analysis
CBD, common bile duct; AST, Aspartat Aminotransferase; ALT, Alanin to identify patients at low and high risk of PEP.
Aminotransferase; GGT, Gama-Glutamyl Transferase; ALP, Alkaline phospha- RESULTS: A score proportional to its regression coefficient was assigned to
tase; AUC, area under the curve; NPV, negative predictive value; PPV: positive each independent prognostic factor: suspected sphincter of Oddi dysfunction
predictive value (SOD) (4.1 points), female sex (2.2 points), previous pancreatitis (2.5 points),
CONCLUSION: Determination of CBD width on ultrasonography and serum young age (2 points), no chronic pancreatitis (1.9 points), normal serum bilirubin
GGT levels are important parameters that may help predict the presence of (1.9 points), precut sphincterotomy (2.7 points), pancreatic injection (2.2 points),
biliary stones prior to endoscopic intervention. large number of cannulation attempts (2.9 points), pancreatic sphincterotomy
Disclosure of Interest: None declared (3.1 points), biliary balloon sphincter dilation (4.5 points), failure to clear bile
duct stones (3.4 points). The AUC of the ROC curve showed a predictive score
performance of 0.9268 (95% C. I. 0.90-0.95 p50.0001). We identified 9.5 as the
P0189 PROCEDURAL DESCRIPTION AND CLINICAL OUTCOMES OF cut-off between low- and high-risk classes, with 88.5% specificity, 81.6% sensi-
A NOVEL COMBINED RETROGRADE-ANTEGRADE ENDOSCOPIC tivity. Considering only severe PEP (n 12), there was a significant difference
APPROACH USING ERCP AND EUS FOR THE MANAGEMENT OF between the two risk classes (p 0.001).
POSTOPERATIVE BILE-DUCT TRANSECTIONS CONCLUSION: We developed and validated a simple risk score to predict PEP.
A.L. Vargas1,*, N. Aleman1, I. Penas Herrero1, C. De la Serna-Higuera1, It could be useful to clinicians for predicting the individual risk of PEP and
C. Almohalla1, F. Garc a-Pajares1, G. Sanchez-Antolin1, M. Perez-Miranda1 directing prophylactic measures, to researchers for designing and interpreting
1
Gastroenterology & Hepatology, Hospital Universitario Ro Hortega, Valladolid, clinical trials, and to policy-makers for saving healthcare resources.
Spain REFERENCES
Contact E-mail Address: mpmiranda5@hotmail.com 1. Dumonceau JM, Andriulli A, Deviere J, et al. European Society of
Gastrointestinal Endoscopy (ESGE) Guideline: prophylaxis of post-ERCP pan-
INTRODUCTION: Postoperative Bile-duct Transections (POBT) are not amen- creatitis. Endoscopy 2010; 42: 503-515.
able to endoscopic therapy. Preliminary data from combined percutaneous-endo- Disclosure of Interest: None declared
scopic approaches are encouraging. Isolated reports of successful retrograde
canalization are intriguing. We hypothesized that aggressive retrograde
(ERCP) and/or antegrade (EUS) attempts at recanalization may salvage P0191 MONITORING RADIATION EXPOSURE IN HEALTH
POBTs for endotherapy, and subsequent serial stenting would induce remodeling PROFESSIONALS DURING ENDOSCOPIC RETROGRADE
and durable resolution as seen in partial strictures. CHOLANGIOPANCREATOGRAPHY
AIMS & METHODS: To assess the feasibility, safety and efficacy of an endo- A.R. Alves1,*, D. Gomes1, P. Mendes2, T. Laranjeiro2, G. Paulo2, J. Santos2,
scopic treatment algorithm of POBTs and to characterize the heterogeneous N. Almeida1, S. Mendes1, R. Mesquita1, E. Camacho1, F. Portela1, C. Sofia1
techniques used to attempt recanalization. 1
Gastroenterology Department, Coimbra Hospital and University Centre,
Since September 2010, 248 consecutive ERCPs were performed at a tertiary Unit 2
Coimbra College of Health Technology, Polytechnic Institute of Coimbra,
for postoperative complications (strictures/leaks) in 150 patients (69 Liver Coimbra, Portugal
Transplant, 81 Other). POBTs were identified in 17 patients (9 Female; Contact E-mail Address: alvess.anarita@gmail.com
age 59.6 [43-79] years) following liver transplant (LT) /cholecystectomy
(CCx) /Other in 7/7/3. Clinical records were retrospectively reviewed for proce- INTRODUCTION: Use of radiation in endoscopic procedures has been increas-
dural data (success, antegrade Vs retrograde, technique) and clinical outcome ing in Gastroenterology, particularly during endoscopic retrograde cholangio-
(immediate POBT remodeling and mid-term clinical resolution). pancreatography (ERCP). Safety radiation limits have been defined for
RESULTS: Recanalization was achieved in 12/17 POBT (70%), by means of persons with occupational exposure to ionizing radiation. Monitoring the effi-
ERCP alone in 5 (4 LT, 1CCx), of ERCP combined with EUS-guided antegrade cacy of protection measures and quality of x-ray systems are recommended.
approach in 6 (2 LT, 3CCx, 1 Other), and EUS alone in 1. Lack of upstream AIMS & METHODS: The objectives of this study were to measure occupational
biliary dilation precluded EUS attempts in 4, and recanalization failed in 1 radiation doses during ERCP in a Gastroenterology department and evaluate the
despite EUS-hepaticogastrostomy (EUS-HG). 5 initial failures underwent surgi- impact of a real time individual dosimeter system in staff behavior. A prospective
cal repair with/without interval external PTBD. 10/12 recanalizations required study was performed, during three phases, in which radiation doses were mea-
forced antegrade/retrograde techniques: using the hard end of a stiff guidewire, sured with individual dosimeters in health professionals: gastroenterologist,
needle-knife, puncture with intraductal hollow needles, transhepatic peritoneo- endoscopy and circulating nurses, radiology technician and anesthesiologist.
scopy or magnetic compression anastomosis. A mean (range) of 1.5 (1-5) ERCPs Phase 1 25 procedures, dosimeter placed under the protection apron, at thor-
were needed to achieve recanalization. Coincidental bilomas were drained in 2 acic level. Phase 2 18 procedures, dosimeter placed outside the protection
POBTS (one transpapillary by ERCP and one transmural by EUS each). 11 apron, at cervical level, simulating absence of radiation protection. Phase 3
Patients have completed 12 treatment courses of serial stenting (2 plastic alone 12 procedures, dosimeter placed in second phase position, but with real time
& 10 covered metal with/without plastic) after 323(180-503) days of stents in exposure levels displayed in a monitor and staff being able to adapt their
place. After a mean follow-up of 353(30-900) days, there were 3 recurrences (1 position.
surgery, 1 currently undergoing stenting, 1 successfully remodeled endoscopi- RESULTS: In phase 2, the following doses were registered: gastroenterologist
cally). Post-procedural or stent related mild cholangitis ensued in 4, and moder- 6.785.99 Sv, endoscopy nurse 7.6312.88Sv, radiology technician
ate post-sphincterotomy bleeding in 1. 6.866.27Sv, anesthesiologist 6.5811.75Sv and circulating nurse
CONCLUSION: 70% of POBTs can successfully be recanalized endoscopically 4.565.45Sv. In phase 1, protection equipment allowed a significant reduction
by means of forced mechanical (guidewires, needles), thermal or magnetic tech- in exposure doses: gastroenterologist 3.374.00 Sv, endoscopy nurse
niques. Antegrade EUS approaches allow salvage of 60% of ERCP failures. Mid- 0.090.16Sv, radiology technician 0.701.55Sv, anesthesiologist
term treatment ouctomes using this algorithm for POBTs appear comparable to 0.430.95Sv and circulating nurse 1.153.03Sv (p50.05). In phase 3, with
those seen with partial postoperative strictures. the change of health professionals position, according to real time values, there
Disclosure of Interest: None declared was a reduction of 44-71% in radiation levels, except for the gastroenterologist
whose change of position was limited by his role in ERCP.
CONCLUSION: The present study showed occupational exposure doses within
the recommendations, proving the efficacy of radiation protective equipments.
Real time knowledge of radiation doses may have a positive impact in profes-
sionals behavior.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0192 PALLIATIVE BILIARY DRAINAGE FOR KLATSKIN TUMORS:
ENDOSCOPIC OR PERCUTANEOUS?
A.T. Oliveira1,1,*, S. Campos1, S. Giestas1, N. Almeida1, S. Mendes1,
E. Camacho1, R. Mesquita1, D. Gomes1, A.G. Agostinho2, V. Carvalheiro2,
C. Sofia1
1
Gastroenterology, 2Radiology, Centro Hospitalar e Universitario de Coimbra,
Coimbra, Portugal
INTRODUCTION: At the time of the diagnosis only 20% of patients with
Klatskin Tumors have resectability criteria. Thus, the majority will require pal-
liative procedures for maintenance of biliary drainage.
AIMS & METHODS: The aim of this study is to compare two palliative non-
surgical methods (endoscopic and percutaneous approach) in terms of therapeu-
tic efficacy and complications.
We performed a retrospective study of patients newly diagnosed with Klatskin
Tumors, in the period betwen 2010-2012, undergoing endoscopic biliary drainage
(EBD) and/or percutaneous transhepatic biliary drainage (PTHBD). We ana-
lyzed the patient characteristics, technical success (insertion of drain/stent
through the stenosis), therapeutic success (total bilirubin  4mg/dL after the
procedure), duration of patency, complications and need for reintervention.
RESULTS: We included 70 patients with a mean age of 7111 years and a male
predominance (67.1%), of which 32 were submitted exclusively to PTHBD, 30 to
EBD and 8 at both. These eight were initially submitted to EBD, but by impos-
sibility of access to the biliary tract they needed PTHBD, so we considerer 40
patients in the PTHBD group and 30 in the EBD group. The two groups differed
regarding the mean age (PTHBD 68 years; EBD 74 years; p 0.006). No differ-
ence was found in the Bismuth Classification (Type III/IV: PTHBD 82.5%, EBD
70.0%) and technical success rate (PTHBD 75%; EBD 79%). The rate of ther-
apeutic success was PTHBD 57.5%; ERCP 79.3% (p 0.07). The terapheutic
failure was more common in Bismuth III/IV types, in both groups (PTHBD
48.5%; EBD 30.0%). The complication rate was in the PTHBD group 47.5%
(cholangitis in eleven patients and hemorrhage in 8 patients) and in the EBD
group 23.3% (cholangitis in four, pancreatitis in two and perfuration in one)
p 0.038. The patency time was similar: PTHBD 136 days; EBD 133 days. The
reintervention rate was 32.4% in the PTHBD group and 48.3% in the EBD
group (p 0.191).
CONCLUSION: Palliative biliary drainage is possible by endoscopic or percu-
taneous route, although the success rate is limited, especially in patients with
Bismuth types III/IV. Endoscopic biliary drainage seems to show a trend
toward greater treatment success, and it is associated with fewer complications.
Disclosure of Interest: None declared
P0193 ERCP CANNULATION; EVALUATION OF A WIRE-LED
TECHNIQUE FOR BILIARY ACCESS IN A TRAINING CENTRE
C. Shekhar1,*, S. Shetty1, N.C. Fisher1
1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
INTRODUCTION: A range of techniques have been described to achieve suc-
cessful cannulation at ERCP, and when training in ERCP it is often difficult to
select the optimum approach 1. There are potential advantages to a wire-led
approach and we have evaluated this in our unit in a training setting.
AIMS & METHODS: To evaluate cannulation success rates for trainers and
trainees using a wire-led technique as the default approach.
A prospective evaluation was done with 2 experienced trainers and 2 trainees
(previous experience of 50-100 ERCPs each). The sphincterotome was pre-loaded
with a hydrophilic wire (in limited cases loop tip wire was used) and cannulation
started with the wire extending 3-5mm out of cannula. Attempts were then made
to advance the wire deep into the bile duct before injecting any contrast or
pushing the cannula through the ampulla. Trainees were allowed 6 minutes for
cannulation attempts. If the wire-led approach failed then other techniques were
used. Wire-led cannulation was considered successful only if no other techniques
were required. Only cases with a virgin ampulla were including in this study.
RESULTS: 100 cases were included over a 5 month period. Trainees were present
in 62 (62%) cases. Overall biliary cannulation success was 93 (93%). Success rate
was 54/62 (87%) if a trainee was present and 37/38 (97%), if no trainee was
present. Independent success for trainees was 34/62 (55%), mostly using the wire-
led technique 29/34 (85%). In cases where a trainer took over from a trainee, the
wire-led approach was still successful in 14/28 (50%). Overall success with the
wire-led approach alone was 31 (69%); other approaches used in remaining cases
included pre-cut sphincterotomy, locked PD wire, and PD stent. A peri-ampul-
lary diverticulum was the most common cause for failure of wire-led technique;
other common causes included stricture, floppy ampulla, or an impacted stone.
Median cannulation time was 6.5 minutes (IQR 4-10min) overall and 5 minutes
(IQR 3-10min) for consultant-only cases. Immediate complications included false
passage of wire (1 case, no further clinical events) and late complications: post
ERCP pancreatitis (1 case, hospital stay 3 days, no further clinical events).
CONCLUSION: Wire-led biliary cannulation, with selective usage of additional
techniques, may allow a cannulation rate of 490% in cases with a virgin
ampulla. The technique appears to be a useful training tool and has a low
complication rate.
REFERENCES
1.Gastrointest Endosc Clin N Am 2012; 22: 417-434.
Disclosure of Interest: None declared
A183
P0194 DOUBLE-BALLOON OVERTUBE-ASSISTED ENTEROSCOPY
ERCP IN PATIENTS WITH BILLROTH II GASTRECTOMY: A
LARGE SERIES REPORT
C.-L. Cheng1,*, C.-H. Lin1, J.-H. Tang1, M.-C. Yu2, Y.-N. Tsui1, N.-J. Liu1
1
Gastroenterology, 2General Surgery, Chang Gung Memorial Hospital, Taoyuan
County, Taiwan, Province of China
Contact E-mail Address: chiliang.cheng@gmail.com
INTRODUCTION: Data on double-balloon overtube-assisted enteroscopy to
facilitate ERCP (DBE-ERCP) in patients with Billroth II gastrectomy is limited.
AIMS & METHODS: The primary aim was to evaluate DBE-ERCP success in
patients with Billroth II gastrectomy and suspected pancreaticobiliary disease.
The seconday aim was to examine the safety and efficacy of DBE-ERCP.
Patients with Billroth II gastrectomy in whom standard ERCP techniques had
failed underwent ERCP by using DBE with initial therapeutic intent were iden-
tified retrospectively. DBE success was defined as visualizing the papilla, while
ERCP success as completing the intended pancreaticobiliary intervention.
Clinical success was delineated as a greater than 50% reduction in abdominal
pain or level of hepatic enzyme elevations or resolution of cholangitis or complete
extraction of bile duct stone.
RESULTS: From April 2006 through December 2011, 77 patients (59-male,
mean age 73.5 years, range 50-95 years) had 92 DBE-assisted ERCPs. Overall
DBE-ERCP success was 69 of 77 (90%). DBE success was 73 of 77 (95%), of
whom 69 of 73 (95%) achieved ERCP success. Reasons for DBE- ERCP failure
(n 8): tumor obstruction within afferent limb (n 2), peritoneal adhesion
(n 2), cannulation failure (n 3), and bowel perforation (n 1). Diagnosis in
patients with DBE-assisted ERCP success (n 69): choledocholithiasis (n 50),
biliary dilatation (n 9), malignant biliary stricture (n 9), normal study (n 1).
Selective interventions included biliary sphincteroplasty (dilation  cautery,
n 76), stone extraction (n 57), stenting (n 20), nasobiliary drainage
(n 6), and rendezvous (n 3). Complications occurred in 5 of 77 (6.5%). In
those patients who underwent therapeutic ERCP (n 68), 66 patients (97%)
achieved clinical success.
CONCLUSION: DBE permits diagnostic and therapeutic ERCP in patients with
Billroth II gastrectomy with a high success and acceptable complication rates.
DBE-assisted ERCP should be considered as an effective alternate when stan-
dard ERCP failed in such patients.
REFERENCES
1. Lin CH, Tang JH, Cheng CL, et al. Double balloon endoscopy increases the
ERCP success rate in patients with a history of Billroth II gastrecotmy. World J
Gastroenterol 2010; 16: 4594-4598.
2. Shah RJ, Smolkin M, Yen R, et al. A multicenter US experience of single-
balloon, double-balloon, and rotational overtube-assisted enteroscopy ERCP in
patients with surgically altered pancreaticobiliary anatomy (with video).
Gastrointest Endosc 2013; 77: 593-600.
Disclosure of Interest: None declared
P0195 OUTCOMES OF THE ENDOSCOPIC DRAINAGE OF
PANCREATIC COLLECTIONS ACCORDING TO THE NEW
ATLANTA CLASSIFICATION
D. Ruiz-Clavijo 1,*, B. Gonzalez de la Higuera1, C. Prieto1, E. Sainza1, M. Casi1,
F. Bolado1, J. Urman1, I. Fernandez Urien1, F.J. Jimenez1, J.J. Vila1
1
Complejo Hospitalario de Navarra, Pamplona, Spain
Contact E-mail Address: davidruizcla@gmail.com
INTRODUCTION: Endoscopic drainage is considered a minimally invasive
first-line treatment of pancreatic collections (PC). A revision of the Atlanta
classification has been recently published but outcomes of endoscopic therapy
according to this new classification are scarce.
AIMS & METHODS: Our objective was to evaluate the outcomes of the endo-
scopic drainage procedures of PC performed in our center during the last 5 years,
assessing results with regard to morphological characteristics of the PC, techni-
que used, and type of stent placed. A retrospective review of all endoscopically
drained PC at our center from January 2009 to December 2013 was made.
Indications for endoscopic drainage were symptomatic or complicated PC. PC
were retrospectively classified according to the new Atlanta 2012 classification.
Variables analyzed: 1) general variables: sex, underlying pancreatic pathology,
PC type, 2) endoscopic technique: endoscopic intervention, type of stent, techni-
cal success (successful placement of draining stents), number of endoscopic inter-
ventions (including the session to retrieve the stents after PC resolution),
complications, and 3) other variables: clinical success (symptom resolution),
morphological success (resolution of the PC on computed tomography), and
need for subsequent surgery. All drainage procedures were performed under
endoscopic ultrasound guidance. Chi-squared and Fishers exact test were used
for analysis.
RESULTS: Endoscopic drainage was performed in 39 PC in 37 patients (33
men). 46.2% of PC developed in the setting of acute pancreatitis, 38.5% in
chronic pancreatitis, and 12.5% after pancreatic surgery. PC included 17 pseu-
docysts (2 infected) and 19 walled-off necrosis (15 infected). We were unable to
retrospectively classify 3 PC according to Atlanta 2012. The endoscopic
approach was transgastric in 61%, transpapillary in 28%, and mixed in 7.7%.
In 50% of transgrastric drainages a covered biliary metallic stent was deployed
while the others underwent pigtail stents placement. The treatment approach and
stent used were associated with the type of PC since walled-off necrotic PC were
preferentially drained via a transgastric approach (17 of 19) and with metallic
stents (13 of 19) (p50.05). Nasocystic lavage was performed in 38.5% of drai-
nages (13 infected walled-off necrotic PC and 2 infected pseudocysts).
Endoscopic necrosectomy was required in 2 patients. Technical, clinical and
morphological success was achieved in 94.9%, 76.9% and 66.7% of cases per
A184
intention to treat analysis. Type, location, or etiology of PC, drainage technique
and type of stent did not show a significant influence on technical, clinical, or
morphological success. The median number of endoscopic sessions performed
were 2 (range:1-6). There were 30% of complications after the endoscopic drai-
nage including migration of the stents in 7 patients, infection in 2, and perfora-
tion in 1 case. 3 stent migrations and the perforation required surgery while the
infections resolved after new endoscopic drainage procedure.
CONCLUSION: In our series, endoscopic treatment of PC achieved 95% tech-
nical success, 76.9% clinical success per intention to treat, and 66.7% morpho-
logic success. The type of PC according to Atlanta classification determined the
treatment approach and stent placed.
REFERENCES
Disclosure of Interest: None declared
P0196 CAN INITIAL PRECUT FISTULOTOMY IMPLEMENTATION
REDUCE ENDOSCOPIC RETROGRADE CHOLANGIO-
PANCREATOGRAPHYRELATED COMPLICATION RISK?
D. Kim1,1,*, G. Song1, B. Lee1, D. Baek1, J. Seo1, S. Lee1, T. Kim1, K. Lee1, J. Lee
1 gitis, each due to the previous ERCP attempt. The reasons of failed cannulation
1
Department of Internal Medicine, Pusan National University School of Medicine,
Busan, Korea, Republic Of
INTRODUCTION: Precut fistulotomy allows biliary access when standard can-
nulation methods fail. Precut fistulotomy is considered a risk factor for endo-
scopic retrograde cholangiopancreatography (ERCP)related complications;
however whether the complication risk is due to precut fistulotomy itself or to
the prior prolonged attempts is still debated. We aimed at assessing success of
cannulation and complications of an initial precut fistulotomy vs. a classic strat-
egy of precut fistulotomy after a difficult biliary cannulation.
AIMS & METHODS: We conducted a retrospective study from January 2011 to
December 2012. A total of 152 patients without prior sphincterotomy were
enrolled. The patients were classified into two groups: an initial precut fistulot-
omy (Group A, n 72) or a late precut fistulotomy only after a failed difficult
biliary cannulation (precut fistulotomy after 4 10 cannulation attempts, 4 10
minutes, and 4 3 accidental pancreatic duct cannulations, Group B, n 80).
RESULTS: During the study period, total of 1412 ERCPs were performed. Of
these, 152 cases (10.7%) underwent precut fistulotomy. Both groups were com-
parable, with no differences for age, gender or indications and findings. The
overall success of cannulation for Group A and Group B was 95.9% vs 95%;
mean cannulation time: 5.7 vs. 13.0 minutes (p50.001). The overall frequency of
postERCP pancreatitis was 3 patients in Group A vs. 11 patients in Group B
(p 0.041). Other complications developed with 1 perforation and 2 bleeding
presenting in the Group A and Group B, respectively. All resolved conserva-
tively. Finally, the overall complication rates for Group A and Group B were
8.3% (6 cases out of 72 patients) and 17.5% (14 cases out of 80 patients),
respectively.
CONCLUSION: Initial precut fistulotomy provides a higher cannulation success
with significantly less time than late precut fistoltomy, although final overall
success is similar. Initial precut fistulotomy implementation reduces post
ERCP pancreatitis risk but not the overall complication rate.
Disclosure of Interest: None declared
P0197 ENDOSCOPIC TREATMENT OF PANCREATIC FISTULAS DUE
TO ETIOLOGIES OTHER THAN PANCREATITIS
E. Parlak1,*, S. Disibeyaz2, A.S. Koksal1, B. Odemis2, S. Okten3, O. Aydinli2,
N. Sasmaz2, B. Sahin2
1
Gastroenterology, Sakarya University, Sakarya, 2Gastroenterology, 3Radiology,
_
Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey
Contact E-mail Address: koksalas@yahoo.com
INTRODUCTION: Endoscopy is effective in the treatment of pancreatic fistulas
due to pancreatitis.
AIMS & METHODS: We aimed to determine the effectivity of endoscopic
treatment in patients with pancreatic fistulas due to etiologies other than
pancreatitis.
RESULTS: The study group consisted of 44 patients (28 male, 6-80 years).
Etiologies were surgery in 30 and trauma in 14 patients. Thirty-seven patients
were presented with drainage through the drain, 5 with pancreatic ascites, and 2
with pseudocyst. Pancreatic fistulas were located in the blind end in 22 (50%)and
lateral side of the pancreas in 9 (20.5%) patients. Pancreatic fistula could not be
visualized during pancreatography in 6 (13.6%) patients. Six patients had dis-
connected pancreatic duct syndrome. Endoscopic treatments were pancreatic
sphincterotomy (PES) stenting in 35, PES alone in 6, and PES nasopancrea-
tic drain insertion in 2 patients. The success of endoscopic treatment could not be
determined in 9 patients due to lost to follow up in 6 and exitus in 1 patient.
Endoscopic treatment was unsuccessfull in 7 patients due to disconnection in 6
and failure of cannulation in 1 patient. Endoscopic treatment was successfull in
29 patients (65%) and surgically placed drains were withdrawn after a mean time
of 27.3 days (5-90) in fistulas located in the blind end, 11.9 (3-28) days in fistulas
located in the lateral side, and 9.7 (3-18) days in fistulas with undefined location.
CONCLUSION: Endoscopy is effective in the treatment of pancreatic fistulas
due to etiologies other than pancreatitis if the pancreatic duct is not
disconnected.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0198 THE RESULTS OF ERCP IN PATIENTS WITH A HISTORY OF
FAILED CANNULATION
E. Parlak1,*, S. Disibeyaz2, A.S. Koksal1, B. Odemis2, B. Cicek3, H. Yildiz2,
N. Sasmaz2, B. Sahin2
1
Gastroenterology, Sakarya University, Sakarya, 2Gastroenterology, Turkiye
_
Yuksek Ihtisas Hospital, Ankara, 3Gastroenterology, Acbadem University,
_
Istanbul, Turkey
Contact E-mail Address: koksalas@yahoo.com
INTRODUCTION: Cannulation of common bile or pancreatic ducts is a pre-
requisite for biliopancreatic interventions.
AIMS & METHODS: To determine the reasons of failed cannulations and
suggest ways to increase the success rate.
We reviewed the data of the patients who were referred to our ERCP unit after
failed cannulation at another center.
RESULTS: The study group included 71 patients (40 male, mean age:57.2 years).
Sixty-nine patients had biliary and 2 pancreatic pathologies. On admission, 2
patients had retroperitoneal perforation, 1 patient had pancreatitis and cholan-
were unsuccessfull pre-cut in 31 (43.6%), failure to reach papilla due to apical
stenosis in 8, presence of a peripapillary diverticula in 6, altered anatomy in 6 (3
with Billroth II), distal location of the papilla in 2, and failure to identify papilla
in 1 patient. Fifteen patients had no reasons to explain failed cannulation.
Cannulation was not attempted in the patient with retroperitoneal perforation.
Of the remaining 70 patients, cannulation could be achieved in all of them (68/70,
97.1%) other than 2 with Billroth II gastroenterostomy. Cannulation could be
achieved selectively in 50, after pre-cut in 14, dilation of the apical stenosis in 4,
and by using either one channel two accessory method or leaving a guidewire in
the pancreatic channel in 2 (2.9%) patients with peripapillary diverticula.
CONCLUSION: Performing pre-cut in the appropriate direction, realising the
anatomic alterations and anomalies in the location of papilla, and applying
advanced cannulation techniques are required to increase the success rate of
cannulation.
Disclosure of Interest: None declared
P0199 PREVENTION OF POST-ERCP PANCREATITIS: A
RANDOMIZED CLINICAL TRIAL USING RECTAL DICLOFENAC
G.W. Lua1,*, R. Muthukaruppan1, J. Menon1
1
Medical Department, Ministry of Health Malaysia, Kota Kinabalu, Sabah,
Malaysia
Contact E-mail Address: guanway@hotmail.com
INTRODUCTION: Pancreatitis is one of the commonest post ERCP complica-
tions. Preliminary research has evaluated several pharmacologic agents for pre-
vention of post-ERCP pancreatitis (PEP) but none has been proven to be
effective. Non steroidal anti-inflammatory drugs (NSAIDs) have been shown
to reduce the incidence of PEP via inhibition of phospholipase A2. There were
various trials using different routes and dosages of NSAIDs. Meta analysis of
these trials was carried out but the results were inconsistent. Hence, we conducted
a clinical trial to evaluate the efficacy of prophylactic rectal diclofenac for the
prevention of PEP in high-risk patients.
AIMS & METHODS: This was a randomized, open-label, two-arm, prospective
clinical trial.
Only patients at high risk of developing PEP were selected. This was determined
by validated patient- and procedure-related risk factors. All procedures were
performed by gastroenterology trainees under the supervision of senior consul-
tants. They were then assigned to either receive 100mg rectal diclofenac or no
intervention immediately after ERCP. After the procedure, the patients were
admitted to the ward for further observation.
The primary outcome of the trial was the development of PEP, which consisted
of new onset of upper abdominal pain, an increase in pancreatic enzymes to at
least three times the upper limit of the normal range after the procedure, and
requiring at least 2 nights of hospital stay. The patients were also reviewed 1
month after discharge to exclude the occurrence of any adverse event related to
the study drug and ERCP procedure. The difference in incidence of post-ERCP
pancreatitis between the 2 study groups was analysed using Fisher exact test
(2-tailed), with P 50.05 indicating a significant difference.
RESULTS: Among 107 patients who were enrolled and completed follow-up, 62
(57.9%) received diclofenac and 45 (42.1%) were in the control group. Among all
the patients, 4 (3.7%) developed PEP, in which 3 were in the diclofenac group (a
pancreatic stent was deployed for 1 of the patient in this group) and 1 was in the
control (p 0.31). Every cases of PEP was mild. After ERCP, 5 (4.7%) devel-
oped cholangitis and 1 (0.9%) had a perforation in which they were treated
conservatively. No drug related complications or adverse event were noted for
both groups of patients.
CONCLUSION: Among patients at high risk for developing PEP, rectal diclo-
fenac did not significantly decrease the incidence of PEP.
REFERENCES
1. Elmunzer BJ, Scheiman JM, LehmanGA, et al. Arandomized trial of rectal
indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012; 366: 1414-
1422.
2. Ding XW. Nonsteroidal anti-inflammatory drugs for prevention of post-
ERCP pancreatitis: a meta-analysis. Gastrointest Endosc 2012; 76: 1152-1159.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0200 EUS AND ERCP COMBINED WITH IDUS IN THE DIAGNOSIS OF
BILE DUCT STRICTURE
H. Jiang1,*, S.-Y. QIN1, L. TAO1, W. LUO1, S.-B. SU1, X.L.1, H.-J. NING1,
X.-P. LU1, R.-E. LEI1
1
The First Affiliated Hospital of Guangxi Medical University, Nanning, China
Contact E-mail Address: lihuan@erbechina.com
INTRODUCTION: A variety of cholongioscopes have been emerged as a new
tools for diagnosis of different biliary strictures. But these new techniques are not
widely applied clinically because of high price and too easy to damage.
AIMS & METHODS: We evaluated the value of endoscopic ultrasonography
(EUS) and endoscopic retrograde cholangiopancreatography (ERCP) combined
with intraductal ultrasonography (IDUS) in the diagnosis of bile duct stricture.
36 patients with bile duct stenosis were recruited. The findings by endoscopic
ultrasonography and endoscopic retrograde cholangiopancreatography com-
bined with intraductal ultrasonography and the results of bile duct brushing
cytology and liquid-based cytology of these patients were analyzed. The final
diagnosis was based on clinical data, histopathology and follow-up results (6
months).
RESULTS: All of the 36 patients, in whom 21 were diagnosed malignant biliary
diseases, including 9 biliary tract carcinomas, 4 duodenal papilla carcinomas, 4
pancreatic cancers infiltrating common bile duct and 4 liver cancers infiltrating
common bile duct; 15 were diagnosed as benign biliary diseases, including 9 bile
duct stones, 4 liver fluke diseases, 1 cholangitic stenosis and 1 external compres-
sion, were shown to have bile duct stricture. The accuracy rate of EUS, ERCP,
IDUS and EUSERCPIDUS in the differential diagnosis of bile duct stricture
disease were 77.8%, 88.9%, 91.7% and 94.4%, respectively. The accuracy rates
of differential diagnosis of bile duct stricture disease between EUS and ERCP
were similar; while the accuracy rate of EUS and ERCP combined with IDUS
was significantly higher than both EUS and ERCP (P50.05). The sensitivity,
specificity, positive predictive value (PPV) and negative predictive value (NPV) of
EUSERCPIDUS were 95.2%, 93.3%, 95.2%, 93.3%, respectively; the sensi-
tivity, PPV, NPV in EUS ERCP IDUS were higher than that of EUS, ERCP
and IDUS. All of the 36 patients received bile duct brushing cytology and the
liquid-based cytology tests, 19 of which were diagnosed as malignant biliary
diseases, while 17 were diagnosed as benign biliary diseases. The sensitivity,
specificity and accuracy of differential diagnosis of bile duct stricture disease
were 90.5%, 100% and 94.4%, respectively.
Table. Comparison of ERCP and EUS in the diagnosis of bile duct stricture
EUS ERCP IDUS EUSERCPIDUS
sensitivity 71.4%(15/21) 85.7%(18/21) 90.5%(19/21) 95.2%(20/21)
specificity 86.7%(13/15) 93.3%(14/15) 93.3%(14/15) 93.3%(14/15)
PPV 88.2%(15/17) 94.7%(18/19) 95%(19/20) 95.2%(20/21)
NPV 68.4%(13/19) 82.4%(14/17) 87.5%(14/16) 93.3%(14/15)
diagnosis 28 32 33 34
misdiagnosis 8 4 3 2
Accuracy rate (%) 77.8 88.9 91.7 94.4
CONCLUSION: EUS and ERCP combined with IDUS can improve the diag-
nostic accuracy of bile duct disorders. IDUS is carried out under the guidance of
a guide wire, and the operation is simple. It can also make up for the inadequacy
of EUS. With the help of ERCP and IDUS, the bile duct could be directedly
brushed, which could improve the diagnostic positive rate.
Disclosure of Interest: None declared
P0201 ENDOSCOPIC PANCREATIC INTERVENTIONS USING SHORT
DOUBLE-BALLOON ENDOSCOPE IN PATIENTS WITH
SURGICALLY ALTERED ANATOMY
H. Kogure1,*, A. Yamada1, H. Isayama1, N. Takahara1, R. Uchino1,
T. Hamada1, K. Miyabayashi1, D. Mohri1, T. Sasaki1, S. Matsubara1,
N. Yamamoto1, Y. Nakai1, K. Hirano1, M. Tada1, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, The University of
Tokyo, Tokyo, Japan
Contact E-mail Address: kogureh-tky@umin.ac.jp
INTRODUCTION: In patients with surgically altered anatomy, endoscopic
treatment of pancreatic disease such as pancreaticojejunostomy stricture, pan-
creatic fistula, and pancreatic duct stones can be challenging.
AIMS & METHODS: We evaluated the efficacy and safety of endoscopic pan-
creatic interventions using short double-balloon endoscope (DBE) for the treat-
ment of pancreatic disease in patients with surgically altered anatomy.
Between October 2009 and April 2014, we performed endoscopic pancreatic
interventions in 12 patients using a short DBE (152 cm in length with a 2.8
mm working channel; EC-450BI5/EI-530B, Fujifilm Medical, Tokyo, Japan),
enabling conventional ERCP accessories. Previous surgeries included pancreati-
coduodenectomy with Billroth II reconstruction (n 7), pancreaticoduodenect-
omy with Roux-en-Y reconstruction (n 3), and Roux-en-Y gastrectomy (n 2).
Indication for pancreatic interventions were anastomotic stricture (n 8; with
pancreatic duct stones [n 5]), pancreatic fistula (n 3), and pancreatic duct
stones (n 1).
RESULTS: Access to the papilla or the end of afferent loop successful in all 12
patients, but anastomosis site could not be identified in 3 patients. Pancreatic
duct cannulation was achieved using a straight cannula (0.025-inch ERCP-cathe-
ter, MTW Endoskopie, Wesel, Germany) and a 0.035-inch hydrophilic guidewire
(Radifocus, Terumo, Tokyo, Japan), or a metal tip cannula (PR-132Q, Olympus,
A185
Tokyo, Japan). Pancreatic interventions were successful in 9 patients (75%).
Three of 6 patients with anastomotic stricture were treated successfully with
balloon dilation, and the remaining 3 patients required repeated balloon dilation
and long-term pancreatic stent placement. Two patients with pancreatic fistula
were treated successfully with endoscopic nasopancreatic drainage. Pancreatic
duct stones were successfully removed in 4 patients. Complications occurred in
3 (25%) patients, including retroperitoneal air (n 1) and hyperamylasemia
(n 2), but all were asymptomatic.
CONCLUSION: Endoscopic pancreatic interventions using short DBE,
although technically demanding, are effective and safe in patients with surgically
altered anatomy.
Disclosure of Interest: None declared
P0202 SHORT SINGLE-BALLOON VERSUS DOUBLE-BALLOON
ENDOSCOPE FOR PANCREATICOBILIARY INTERVENTIONS IN
PATIENTS WITH SURGICALLY ALTERED ANATOMY
H. Kogure1,*, A. Yamada1, H. Isayama1, N. Takahara1, R. Uchino1,
T. Hamada1, K. Miyabayashi1, D. Mohri1, T. Sasaki1, S. Matsubara1,
N. Yamamoto1, Y. Nakai1, K. Hirano1, M. Tada1, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, The University of
Tokyo, Tokyo, Japan
Contact E-mail Address: kogureh-tky@umin.ac.jp
INTRODUCTION: With the advent of short double-balloon endoscope (DBE),
therapeutic pancreaticobiliary interventions are possible with surgically altered
anatomy. However, because the channel diameter of short DBE is 2.8 mm, only
limited ERCP devices are available and the exchange of devices is both time-
consuming and cumbersome. Recently, a prototype short single-balloon endo-
scope (SBE) with passive bending and high force transmission, which has a 3.2
mm working channel and a 152 cm in length, was specifically developed for
ERCP (SIF-Y0004-V01; Olympus Medical Systems, Tokyo, Japan).
AIMS & METHODS: The aim of this study was to compare the insertability and
procedural efficiency of short SBE and short DBE for pancreaticobiliary inter-
ventions in patients with surgically altered anatomy. Between March 2013 and
Jan 2014, we performed endoscopic pancreaticobiliary interventions using a short
SBE in 20 patients who have successfully undergone short DBE-assisted ERCP.
Previous surgeries included Roux-en-Y (R-Y) gastrectomy (n 7), hepaticojeju-
nostomy (n 5), pancreaticoduodenectomy with R-Y reconstruction (n 3),
Billroth II (B-II) gastrectomy with Brauns anastomosis (n 2), pancreaticoduo-
denectomy with B-II reconstruction and Brauns anastomosis (n 2), and liver
transplantation with hepaticojejunostomy (n 1).
RESULTS: Access to the papilla or anastomosis with SBE failed in 3/20 patients
(15%). Among successful patients, the median time (IQR) required to reach the
target orifice was 26 min (1132.5 min) with SBE and 16 min (1121 min) with
DBE (P 0.10). Pancreaticobiliary interventions with SBE were successful in 17/
17 patients (100%). Therapeutic procedures using SBE included stone extraction
(n 11), biliary plastic stenting (n 5), papillary large balloon dilation (n 3),
balloon dilation of anastomotic stricture (n 3), pancreatic stenting (n 3), bili-
ary metallic stenting (n 1), balloon dilation of biliary stricture (n 1), and
endoscopic naso-pancreatic drainage (n 1). Although almost the same proce-
dures with prior DBE, the median ERCP procedure time (IQR) was shorter with
SBE than with DBE [29 min (2355.5 min) vs 63 min (46.593.5 min), P 0.03].
Aspiration pneumonia as procedure-related complication occurred in 1 patient.
CONCLUSION: Insertability of a short SBE is slightly inferior to that of a short
DBE. However, a short SBE with a 3.2 mm working channel allows most con-
ventional ERCP devices to be used and reduces ERCP procedure time compared
to a short DBE with an only 2.8 mm working channel.
Disclosure of Interest: None declared
P0203 INTER-OBSERVER AGREEMENT AND ACCURACY OF
PREOPERATIVE EUS-GUIDED BIOPSY FOR HISTOLOGIC
GRADING OF PANCREATIC CANCER
A. Larghi1,*, R. Ricci2, I. Abdulkader3, G. Monges4, J. Iglesias-Garcia 5,
M. Giovannini6, F. Attili1, G. Vitale 1, C. Hassan1, G. Rindi2, G. Costamagna1
1
Digestive Endoscopy Unit, 2Department of Pathology, Catholic University, Rome,
Italy, 3Department of Pathology, University Hospital of Santiago de Compostela,
Santiago de Compostela, Spain, 4Department of Pathology, Paoli-Calmettes
Institute, Marseille, France, 5Gastroenterology Department, University Hospital of
Santiago de Compostela, Santiago de Compostela, Spain, 6Endoscopic Unit, Paoli-
Calmettes Institute, Marseille, France
Contact E-mail Address: albertolarghi@yahoo.it
INTRODUCTION: Post-surgical poor differentiation/high grade of pancreatic
cancer (PADC) appears to accurately predict an early unfavourable outcome,
these patients possibly deserving neo-adjuvant treatment. EUS-guided pancreatic
tissue core biopsy (EUS-PTCB) may in theory allow a pre-operative assessment
of PADC-grading. To assess inter-observer pathological agreement and accuracy
of preoperative PADC-grading based on EUS-PTCB.
AIMS & METHODS: 42 post-surgical PADC-cases with preoperative EUS-
PTCB were chosen. Four expert pathologists independently reviewed the EUS-
PTCB slides, reporting tumour grading (well-/moderate-/poor-degree of differ-
entiation). Agreement among pathologists for reporting PADC-grading on pre-
operative EUS-PTCB material was expressed by using Cohens/Fleiss kappa
statistic, as appropriate. Post-surgical PADC-grading was used as gold-standard
to assess the cumulative accuracy of EUS-PTCB in preoperatively predicting
PADG grade.
RESULTS: The k values for PADC-grading on EUS-PTCB material ranged
from 0.09 to 0.41. The total agreement among the four pathologists was only
fair (k 0.27; 95% CI: 0.14-0.38). When tumor grades were grouped as well-/
A186 United European Gastroenterology Journal 2(5S)
moderately differentiated versus poorly differentiated, kappa values ranged from lesions fine needle aspiration was performed initially from the esophagus under
0.19 to 0.50, with only a fair overall agreement (k 0.27; 95% CI: 0.21-0.49). local anesthesia. Cytology examination of the fine needles aspirates was made on
Preoperative EUS-PTCB-based accuracy of preoperative staging was 56% (75/ site. If EUS-FNA (8pts) gives a negative result (8pts) in the on-site cytological
134 readings; 95% CI: 40-65%), with mean sensitivity and specificity to detect a analysis, EBUS-TBNA was performed once.
high grade poorly differentiated tumor of 41% (95% CI: 19-54%) and 78% (53/ RESULTS: Diagnosis was proved in 87.3% of cases in EBUS-TBNA group and
68 readings; 95% CI: 60-99%), respectively. in 85.7% of cases in EUS-FNA group. Definitive morphology diagnosis was
CONCLUSION: Preoperative EUS-PTCB-based pathological grading of PADC made in 96.4% by the combined approach with rapid on-site evaluation of the
is unreliable, arguing against the use of this information in clinical practice. This fine needles aspirates.
appears to be related with both a suboptimal inter-observer agreement among CONCLUSION: Two procedures can be performed with single ultrasound
pathologists and an overall low accuracy in predicting post-surgical staging. bronchoscope and the combined approach with cytology examination on site
Disclosure of Interest: None declared has better diagnostic value than either alone. But EUS-FNA with ultrasound
bronchoscope is easy, safe and doesnt request moderate sedation. Therefore it
can be performed for patients for tissue diagnosis from enlarge 7 and 4L group
P0204 PERFORMANCE OF THE PROCORE 25 GAUGE NEEDLE IN lymph nodes as the first step of examination.
OBTAINING SAMPLES FOR HISTOLOGICAL EXAMINATION IN A Disclosure of Interest: None declared
LARGE AND HETEROGENOUS COHORT OF PATIENTS: A TWO
CENTERS STUDY
A. Larghi1,*, F. Attili1, G. Petrone2, I. Abdulkader3, F. Inzani 2, J. Iglesias- P0206 RESULTS AND LEARNING FROM A THERAPEUTIC
Garcia 4, C. Hassan1, G. Rindi2, G. Costamagna1 ENDOSCOPIC ULTRASOUND PRACTICAL WORKSHOP ON A
1
Digestive Endoscopy Unit, 2Department of Pathology, Catholic University, Rome, SWINE LIVING MODEL
Italy, 3Department of Pathology, 4Gastroenterology Department, University A. Teran Lantaron1,2,*, B. Castro Senosiain1,2, P. Iruzubieta Coz1,2, G. De las
Hospital of Santiago de Compostela, Santiago de Compostela, Spain Heras Castano1,2, J.C. Manuel-Palazuelos2, J.B. Gornals Soler3, J.J. Vila Costa4,
Contact E-mail Address: albertolarghi@yahoo.it M. Perez-Miranda5, J. De la Pena Garcia1,2
1
GASTROENTEROLOGY AND HEPATOLOGY, HOSPITAL
INTRODUCTION: A new 25-gauge Procore biopsy needle has become UNIVERSITARIO MARQUES DE VALDECILLA, 2HOSPITAL VIRTUAL
recently available. Scanty data on its performance are available. We evaluate VALDECILLA, SANTANDER, 3GASTROENTEROLOGY AND
the yield of this needle in obtaining samples for histologic evaluation (EUS- HEPATOLOGY, HOSPITAL UNIVERSITARI BELLVITGE, BARCELONA,
FNB), its diagnostic accuracy and inter-observer agreement between three 4
GASTROENTEROLOGY AND HEPATOLOGY, COMPLEJO
pathologists in a large cohort of patients with heterogenous indication. HOSPITALARIO DE NAVARRA, PAMPLONA, 5GASTROENTEROLOGY
AIMS & METHODS: Consecutive patients who underwent EUS-FNB using the AND HEPATOLOGY, HOSPITAL UNIVERSITARIO RIO HORTEGA,
Procore 25G were retrospectively retrieved. The collected material was placed VALLADOLID, Spain
directly in formalin or in cytolit and sent for histologic evaluation. All samples Contact E-mail Address: altelan@hotmail.com
were independently reviewed by three pathologists and scored for: (i) presence of
an histologic, cytologic specimen or no specimen; (ii) presence or absence of INTRODUCTION: Therapeutic endoscopic ultrasound (T-EUS) has been
neoplasia; (iii) diagnostic or not diagnostic. Diagnostic accuracy and inter- undergoing extensive development in recent years. Although previous experience
rater concordance among pathologists in the evaluation of the above mentioned on EUS-FNA and ERCP is considered to be needed, data on learning curves and
parameters were calculated. the potential benefit of animal models training are lacking.
RESULTS: 94 patients (median age 71 years; 55 male) underwent EUS-FNB of AIMS & METHODS: To train some different T-EUS techniques and to estimate
101 sites. Mass lesions were located in the pancreas (49 patients), abdomen (6), their difficulties and the potential benefit of the swine model in this context.
liver (8), common bile duct (3 masses and 3 wall thickening), stomach (1 sub- Prospective data analysis from a T-EUS practical workshop on a biliary obstruc-
epithelial lesion and 2 wall thickening), mediastinum (2), lung (1), and adjacent to tion porcine model by OTSC clip, addressed to endoscopists with previous
the rectum (1). All the remaining 25 sampled lesions were mediastinal (14) and EUS-FNA and ERCP experience. There were four different T-EUS procedures
abdominal (11) lymph nodes. The median lesion size was 30 mm (range, 15-67 trained: common bile duct drainage (CBDD), cholecysto-gastrostomy (CGS),
mm) and a mean of 2.5 FNA passes (range, 1-6; median, 3; IQR, 2-3) per lesion transrectal urinary bladder drainage (TUBD), simulating a fluid collection drai-
was done. A total of 41 (40.6%) lesions were classified as having a histologic nage, and gastro-jejunostomy (GJS). All animals were sacrificed after T-EUS
specimen either by at least two of the three pathologists. A presence of a cytologic procedures and necropsy studies were performed. Local Ethics Committee
specimen was found by at least two of the three pathologists in 29 (28.7%) cases. approval was obtained.
In the remaining 31 lesions no specimen was present according to all three RESULTS: Thirty three procedures were analyzed (11 CBDD, 5 CGS, 7 TUBD,
pathologists. There was good agreement among pathologists in determining if 10 GJS), performed by 12 endoscopists in 10 pigs (2.83  0.58 proc./endoscopist;
EUS-FNB provided cytologic vs. histologic samples (kappa index, 0.82; 95% 3.3  1.42 proc./animal). Main results are shown in Table 1. Together TUBD
CI:0.74-0.90). When considering non-diagnostic samples as false negative, the and GJS were the procedures more frequently and successfully completed versus
pooled sensitivity of the EUS-FNB for neoplasia was 65% (154 of 237 readings; CBDD and CGS (100% vs. 62.5%, p 0.007 and 82.4% vs. 37.5%, p 0.011).
95% CI: 54.8-75.1%), whereas specificity was 98% (50 of 51 readings; 95% CI: Among the different procedural steps, guidewire management (31.8%), stent
89-100%). The pooled accuracy of the procedure was 70.8 (204 of 288 readings; insertion (25%) and cystotome use (20%) were the most troublesome ones.
95% CI: 62.1-79.6%). In the per-protocol analysis, the overall sensitivity and Table 1. Results by procedure
accuracy of the procedure for malignancy was 93.8 (150 of 160 readings; 95% CI:
88.8-96.9) and 93.9% (170 of 181 reading; 95% CI: 89.3-96.9%), respectively. CBDD CGS TUBD GJS Total *p
Substantial agreement on the presence (or absence) of neoplasia resulted (kappa
index, 0.94; 95% CI: 0.83-1.00). Substantial agreement was seen across the three N 11 5 7 10 33
reviewers in describing diagnostic accuracy, with an overall kappa value of 0.95
(95% CI: 0.85-1.00). At multivariate analysis, histologic samples were more likely Mean time duration (min.) 51.3  48  31.3  21.2  34.7  0.000
than cytologic one to lead to a correct diagnosis (OR, 4.1; 95% CI: 1.2, 15.0; 14.5 7.6 5.9 17.2 18.5
p 0.027). Completed 63.6% 60% 100% 100% 81.8% 0.007
CONCLUSION: EUS-guided FNB with the Procore 25G needle provided sam- Final succes 45.5% 20% 85.7% 80% 60.6% 0.011
ples for histologic examination in about 40% of the cases and showed excellent Trainer intervention needed 18.8% 20% 14.3% 20% 18,8% 0.608
results in term of interobserver variability.
Disclosure of Interest: None declared Inmediate complications 10% 40% 14.3% 10% 15.6% 0.437

P0205 COMBINED ENDOBRONCHIAL AND TRANSESOPHAGEAL
APPROACH OF AN ULTRASOUND BRONCHOSCOPE FOR TISSUE
DIAGNOSIS OF MEDIASTINAL LYMPHADENOPATHY
A. Strunina1,*, R. Kuvaev1, S. Kashin1, A. Levina2, V. Chernyaeva2,
N. Akhapkin3
1
Endoscopy, 2Cytology, 3Administration, Yaroslavl Regional Cancer Hospital,
Yaroslavl, Russian Federation
Contact E-mail Address: kuvaev_roman@mail.ru
INTRODUCTION: Morphological evaluation of mediastinal masses is essential
for diagnostic confirmation and treatment planning of patients (pts) with med-
iastinal abnormalities. EBUS-TBNA and EUS-FNA is a safe and efficacy
method to obtain tissue for morphological diagnosis. The combined approach
reduces the need for additional equipment, the operating costs, and the duration
of the procedure. However it could be difficult to select the order of preference if
both of the techniques are available.
AIMS & METHODS: The aim was to determine the diagnostic value of EBUS-
EUS combined approach by using single ultrasound bronchoscope for evaluation
mediastinal lymphadenopathy. EUS FNA and EBUS TBNA (Olympus Exera
II BF-UC160F, Olympus 21g needles) were compared in 166 patients for tissue
diagnosis from enlarge (40.9cm) 7 and 4L group lymph nodes. 110 lesions were
sampled from the respiratory tract under moderate sedation as first step. For 56
CONCLUSION: Our model appears to mirror the challenges of T-EUS even for
endoscopists experienced in EUS-FNA and ERCP.
Ethical and cost concerns can be minimized by optimizing the number of T-EUS
drainage procedures, up to 4 per animal.
CGS and CBDD, both longer and with higher number of steps and instrument
requirements, are more challenging than TUBD or GJS, which suggests more
demanding training is needed.
This kind of training based on animal model simulation may allow a safer and
probably quicker learning curve on T-EUS.
Disclosure of Interest: A. Teran Lantaron Financial support for research from:
The workshop reported in this abstract was sponsorized by Boston Scientific, B.
Castro Senosiain: None declared, P. Iruzubieta Coz: None declared, G. De las
Heras Castano: None declared, J. Manuel-Palazuelos: None declared, J. Gornals
Soler: None declared, J. Vila Costa: None declared, M. Perez-Miranda: None
declared, J. De la Pena Garcia: None declared
United European Gastroenterology Journal 2(5S) A187

P0207 COMPLICATIONS AND HISTOPATHOLOGICAL ASSESSMENT P0209 ENDOSCOPIC ULTRASONOGRAPHY-GUIDED DRAINAGE OF

OF THE PANCREAS IN A PORCINE MODEL AFTER EUS HEPATIC ABSCESSES AND BILOMAS BY USING SELF-
RADIOFREQUENCY ABLATION EXPANDABLE METAL STENTS (SEMS). A PILOT STUDY
B.S. Ungureanu1,*, L. Sandulescu1, C. Margaritescu1, D. Pirici2, A. Saftoiu1 C. De La Serna Higuera1,*, P. Diez- Redondo1, I. Penas1, F. Santos1, P. Gil1,
1
Gastroenterology, Research Center in Gastroenterology and Hepatology, H. Nunez1, M. Perez-Miranda1
2 1
Gastroenterology, Morphopatology, Craiova, Romania Gastroenterology, Rio Hortega Hospital, Valladolid, Spain
Contact E-mail Address: boboungureanu@gmail.com Contact E-mail Address: csernah@hotmail.com

INTRODUCTION: Treating pancreatic cancer represents a major objective in
research, as it still remains the fourth leading cause of cancer deaths among men
and women, with approximately 6% of all cancer-related deaths. Radiofrequency
ablation uses electromagnetic energy deposition causing thermal lesions and
overheating tissue which leads in a final stage to necrosis.
AIMS & METHODS: We studied the assessment of an EUS-guided RFA probe
through a 19-gauge needle, in order to achieve a desirable necrosis area in the
pancreas. Radiofrequency ablation of the head of the pancreas was performed
using a RITA Medical System device on 10 Yorkshire pigs with a weight between
25 to 35 kg. Using an EUS-guided RFA experimental probe we ablated an area
of 2 to 3 cm wide at 5-10-15-20 watts for one minute a time.
RESULTS: No major complications were noted. High levels of amylase, lipase,
aspartate transaminase and alanine transaminase were found within 3 days from
the ablation. Necropsy pointed out a very well limited area with minimal inva-
sion and inflammatory tissue at about 2 cm surrounding the lesion. No nearby
fibrosis or adhesions were found and no major vessel injuries or adjacent organ
damage was produced. The pathology examination revealed coagulative necrosis,
a local acute inflamatory reaction with structured necrosis of the glandular par-
enchyma, steatonecrosis, and recent thrombosis of blood vessels.
CONCLUSION: EUS-Guided RFA of the pancreas may be a feasible procedure,
however more studies are necessary.
Disclosure of Interest: None declared
P0208 ROLE OF ENDOSCOPIC ULTRASONOGRAPHY IN THE
SELECTION FOR NEOADJUVANT TREATMENT OF GASTRIC
ADENOCARCINOMA
B.M. Goncalves1,*, P. Bastos1, J.-B. Soares1, D. Fernandes1, E. Couto2,
J. Cunha2, C. Rolanda1, R. Goncalves1
1
Gastroenterology, 2Oncology, Hospital de Braga, Braga, Portugal
Contact E-mail Address: brunommgoncalves@gmail.com
INTRODUCTION: Liver abscesses and bilomas are conventionally managed by
means of percutaneous drainage or surgical approach. However, both procedures
have been reported on high morbi-mortality rates. Transgastric EUS-guided drai-
nage of both entities with plastic stents or nasocystic catheters have been excep-
tionally performed. We describe our experience using self expandable metal stents
(SEMS) tubular and lumenapposing metal stents (LAMS) in this setting.
AIMS & METHODS: The aim of the study was to assess the technical feasibility
and clinical outcomes of EUS-guided drainage of liver abscesses and bilomas
using SEMS under mixed fluoroscopic, endoscopic and ultrasonographic
guidance.
Retrospective analysis involving eight consecutive patients (March12 to Oct 13)
with liver abscesses/bilomas not accesible to percutaneous approach and/or dis-
carded for surgery by means of age or comorbidities (Table 1). Procedures were
performed by using linear echoendoscopes, 19G needles under EUS & fluoro-
scopic control, 0.035 guidewires, 8.5F cystotome and tract dilation with 4 mm
biliary balloon. Aspiration of fluid was routinelly performed for culture. Finally,
cSEMS were placed, either tubular or lumen-apposing metal stents (LAMS:
AXIOSTM- Xlumena Inc).
RESULTS: Six patients with liver abscesses and 2 bylomas were included (Table
1) EUS-guided transgastric approach was performed in 6/8 cases (75%) in cor-
respondence with abscesses located on the left hepatic lobe. 6 patients were
managed with LAMS (5 abscesses, 1 biloma). Median diameter of abscesses
was 80.05 mm (range 52.70 - 99). Drainages were successful in all cases and
there were no procedure-related complications. Stents were removed after a
mean of 7 weeks (range 4-12). There were no relapses after a mean follow-up
of 7.5 months (range 1-18)
CONCLUSION: EUS-guided drainage of hepatic abscesses and bilomas by
means of SEMS appears to be a safe, effective and useful procedure in patients
not suitable for radiologic drainage or surgery. However, larger, prospective and
multicenter studies are needed.
Disclosure of Interest: None declared

INTRODUCTION: Gastric remains one of the most common causes of cancer-

related death. Recent studies reveal that neoadjuvant treatment of locally
advanced gastric cancer improves survival of these patients. Endoscopic ultra-
sonography (EUS) staging is recommended in several guidelines, particularly in
the assessment of the T and N stages. However, its role in identifing patient
candidates to neoadjuvant therapy is not known.
AIMS & METHODS: The purpose of the study was to evaluate the accuracy of
EUS in selecting patients for neoadjuvant therapy of gastric adenocarcinoma.
We conducted a retrospective analysis of patients with gastric adenocarcinoma
who underwent EUS staging and were submitted to primary gastrectomy
between 2011 and 2013. We determined the agreement (kappa k) between
EUS and pathological TNM staging and the accuracy (AUROC, sensitivity
and specificity) of EUS to identify patients with indication for neoadjuvant
therapy (defined as stages II and III in the pathological analysis of the surgical
specimen).
RESULTS: Between 2011 and 2013 were performed 141 USE, of which 66 were
excluded (37 patients did not undergo underwent gastrectomy, 16 patients under-
went neoadjuvant therapy, 7 USE were re-staging examinations and 6 cases
werent adenocarcinomas). Of the 75 patients enrolled, the median age was 66
years, 65% were male and 60% had intestinal type adenocarcinoma. The dis-
tribution of patients according to the EUS and pathological staging was: 50.7%
and 46.6% for stage I, 31.1% and 33.3% for stage II, 16% and 21.3% for stage
III. The agreement between EUS and pathologic stages for T, N and TNM was
good (k 0.61), moderate (k 0.44) and fair (k 0.36), respectively, while for
stages II III was good (k 0.63). The accuracy of EUS for stages II III was
high (AUROC 0.82, sensitivity 78% and specificity 86%), especially for intestinal
type adenocarcinoma (AUROC 0.84, sensitivity 86% and specificity 85%).
CONCLUSION: Endoscopic ultrasonography has an important role in the sta-
ging of gastric cancer, showing a good performance in the selection of patients
for neoadjuvant treatment, especially in intestinal type adenocarcinoma.
Disclosure of Interest: None declared
P0210 COULD QUANTITATIVE AND QUALITATIVE EUS-
ELASTOGRAPHY RESULTS BE AFFECTED BY THE
COMPRESSION RATE AND THE DIAMETER OF THE REGION OF
INTEREST?
C. Robles-Medranda1,*
1
ENDOSCOPY, INSTITUTO ECUATORIANO DE ENFERMEDADES
DIGESTIVAS, UNIVERSITY HOSPITAL OMNI, ESPIRITU SANTO
UNIVERSITY, Guayaquil, Ecuador
Contact E-mail Address: carlosoakm@yahoo.es
INTRODUCTION: EUS-elastography (EUS-e) is an alternative method to eval-
uate tissue stiffness (elasticity-index) of solid pancreatic masses, which may be
related to histopathology tissue features (hard blue neoplastic / soft red-
yellow-green non-neoplastic). Recently publications show different results
using EUS-e and a lack of data exist regarding the compression rate of the
probe (CRP) and the diameter of the region of interest (d-ROI) under analysis.
AIMS & METHODS: Based on the hypothesis that EUS-e could be affected by
CRP and the d-ROI this study aimed to evaluate the quantitative strain ratio (q-
SR) and qualitative color (q-C) EUS-e results determined by the CRP and the d-
ROI in normal pancreatic tissue (NPT). After approval by the ethics committee
and signing of an informed consent, a prospective study was performed in 45
patients undergoing for upper-EUS from Oct-Nov 2013. Inclusion criteria: EUS
for evaluate submucosal tumors. Exclusion criteria: age518 or 4 55; pregnancy,
history of: pancreatic disease, choledocolitiasis, symptoms of maldigestion, alco-
hol abuse, increased serum levels of pancreatic enzymes, smokers and EUS signs
of chronic pancreatitis (Rosemont classification). EUSe was performed using
linear Pentax-EUS and Hitachi-Avius. The q-SR and q-C EUS-e was measured
in the body of the pancreas taking in consideration the curve of the CRP high:
0.4 (H-CRP), middle: 0 (M-CRP), low: -0.4(L-CRP) in the largest (LROI) and
smaller ROI (SROI) diameters. Analysis for q-C was obtained by the predomi-
nant color of the pancreatic area studied. Pictures where recorded and q-SR data

P0209
Collection Size Stent Retrieval Follow-Up
type Age/ Sex (mm) Approach type Complications (weeks) (months) Outcome

1 Abscess 71/M 74 Transgastric AXIOS 15 x 10 NO 8 6 Resolution

2 Abscess 92/M 91,6 Transgastric AXIOS 15 x 10 NO 12 14 Resolution
3 Abscess 65/M 85 Transgastric HotAXIOS 15 x 10 NO 9 3 Resolution
4 Abscess 34/M 99 Transgastric AXIOS 10 x 10 NO 4 2 Resolution
5 Abscess 84/F 52,7 Transgastric AXIOS 10 x 10 NO 6 1 Resolution
6 Abscess 49/F 78 Trans-duodenal Tubular SEMS 60 X 10 NO 9 3 Resolution
7 Biloma 74/F 72 Trans - duodenal AXIOS 15 x 10 NO 4 13 Resolution
Plastic pig-tail
8 Biloma 53/F 69.4 Transgastric Tubular SEMS 60 x 10 NO 4 18 Resolution
Plastic pigtail
A188
were calculated comparing EUS-e of pancreatic tissue with soft tissue (normal
mucosal layer: red). Finally, a comparative analysis was performed between the
results with the mean normal value (NV) of 1.68 for q-SR previously published
for NPT, and between the different CRP.
RESULTS: 60 images were analyzed and 10 patients were included, 6 females,
mean age 50 (ranges: 32-55). LROI q-C analysis: showed a predominant green
(G) color in H-CRP in 90%, M-CRP in 50% and L-CRP in 70% of cases. SROI
q-C analysis: showed a predominant G-color in H-CRP in 100%, L-CRP in 50%
and M-CRP in 66.6% of cases. In LROI-quantitative showed a mean SR of 7.2
(range: 2.7-24) for H-CRP, 11.03 (range: 3.3-42) for M-CRP and 8.8 (range: 2.6-
36) for L-CRP being p50.05 for H-CRP and L-CRP when compared with NV q-
SR, and for H-CRP when comparing with M-CRP. For SROI q-SR analysis
showed a mean SR of 6 (range: 5.5-6.6) for H-CRP; 8 (range: 5-12) for M-CRP
and 77 (ranges: 2.3-224) for L-CRP, being p50.05 in all cases when compared
with NV q-SR.
CONCLUSION: EUS-e (q-C and q-SR) results in NPT could be affected by
CRP and d-ROI. These data suggest that a standardization of the measurements
parameters is required to determine the best results and application of this tech-
nology in pancreatic diseases.
REFERENCES
Dawwas MF, Taha H, Leeds JS, et al. Diagnostic accuracy of quantitative EUS
elastography for discriminating malignant from benign solid pancreatic masses: a
prospective, single-center study. Gastrointest Endosc 2012; 76: 953-961.
Disclosure of Interest: C. Robles-Medranda Consultancy for: Pentax Medical,
MaunaKea technologies, Other: Key Opinion Leader for Pentax Medical
P0211 ENDOSCOPIC ULTRASOUND-GUIDED FINE NEEDLE
ASPIRATION (EUS-FNA) IN PANCREATIC LESIONS: PREDICTIVE
FACTORS OF ACCURATE DIAGNOSIS
C. Leitao1,*, A. Santos1, H. Ribeiro1, J. Pinto1, A. Caldeira1, E. Pereira1,
A. Banhudo1
1
Servico de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saude
de Castelo Branco, Castelo Branco, Portugal
Contact E-mail Address: catia.f.leitao@gmail.com
INTRODUCTION: Endoscopic ultrasound (EUS) has taken on an important
role in the diagnosis of benign and malignant pancreatic disease. Due to the
proximity of the transducer and reduced acoustic interference, EUS provides
high-resolution ultrasound images of the pancreas with subtle anatomical
detail and has the unique ability to obtain specimens of the pancreas and peri-
pancreatic structures for cytohistological diagnosis.
AIMS & METHODS: The aim of this study is to identify the predictive factors
for an accurate EUS-FNA diagnosis. Methods: Retrospective analysis of medical
records of patients submitted to an EUS-FNA for evaluation of a pancreatic
mass, from January of 2008 to December of 2013. All procedures were performed
by 2 operators, using a linear echoendoscop Pentax EG3870UTK and Hitachi
HI Vision Preirus or EUB-6000 US. Collection of demographic data, ultrasono-
graphic characteristics, technical information on EUS-FNA and cytohistological
results.
RESULTS: A total of 1420 EUS examinations were performed during the
period. 88 patients (with a mean age of 6414 years; 54.5% female) diagnosed
with pancreatic masses underwent EUS-FNA. 81.8% of them had this symp-
toms: epigastric pain (34%), weight loss (23.9%) and jaundice (23.9%). 51.5% of
the lesions were located in head of pancreas and 67% were solid masses. The
median size of the lesion was 31.812.5mm. The mean number of passages was
2.350.97. EUS-FNA was performed with 19 G needle in 7.1% of patients, 22G
needle in 70.6% and with 25G needle in 22.4% of patients. The overall diagnostic
accuracy was 82.9%. In 10 patients procore needle (19G-1;22G-1;25G-5) was
used and the diagnostic accuracy was 100%, although not a statistically signifi-
cant difference. Adenocarcinoma was the most common cytological diagnosis
(62.9%), followed by inflammatory pancreatic disease (21%), endocrine neo-
plasm (6.5%), mucinous neoplasm cystic (6.5%) and IPMN (1.6%). There
were no procedure-related complications. The predictors of diagnostic accuracy
(p5 0.05) were: appearance of lesion (solid mass 90.6% vs. cystc mass 54.4%),
size of lesion (diagnostic 32.6 mm vs non diagnostic 23.6 mm) and location of the
lesion (body 100% vs. head 86.6% vs. neck 70.2% vs. tail 40%). The size of
needle and number of passages did not significantly influenced the diagnostic
accuracy of the procedure.
CONCLUSION: EUS-guided FNA is a safe and reliable technique for establish-
ing a diagnosis in pancreatic mass lesions, especially in solid mass, located in
body or head and with a greater dimension.
REFERENCES
(1) Hewitt MJ et al. EUS-guided FNA for diagnosis of solid pancreatic neo-
plasms: a meta-analysis. Gastrointest Endosc 2012; 75: 319-331.
(2) Iglesias-Garcia J, et al. Influence of on-site cytopathology evaluation on the
diagnostic accuracy of endoscopic ultrasound-guided fine needle aspiration
(EUS-FNA) of solid pancreatic masses. Am J Gastroenterol 2011; 106: 1705-
1710.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0212 LEARNING CURVE FOR ENDOSCOPIC ULTRASONOGRAPHY
IN GASTRIC CANCER T STAGING USING CUMULATIVE SUM
METHOD
C.H. Park1,*, J.C. Park1, E.H. Kim1, D.H. Jung1, H. Chung1, S.K. Shin1,
S.K. Lee1, Y.C. Lee1
1
Department of Internal Medicine, Yonsei University College of Medicine, Seoul,
Korea, Republic Of
INTRODUCTION: One of the most studied tools for the loco-regional staging
of gastric cancer is endoscopic ultrasonography (EUS). The American Society for
Gastrointestinal Endoscopy guideline set 75 examinations as a minimum number
of EUS procedures for mucosal cancer including esophageal, gastric, and rectal
cancer before competency can be determined. The learning curve in the staging of
gastric cancer, however, has not been evaluated.
AIMS & METHODS: We retrospectively reviewed the clinical records of
patients who underwent EUS examinations for gastric cancer, which were per-
formed by trainees, at Severance Hospital, Seoul, Korea, between March 2011
and February 2012. Cumulative summation analysis was applied to assess the
learning curve for EUS T staging in each trainee.
RESULTS: A total of 553 initial EUS examinations for na ve gastric cancer
performed by 4 trainees were enrolled in the study. Final EUS T staging was
determined by experts in 332 gastric cancers, while EUS T staging of other 221
lesions was determined by trainees. Accuracies of EUS examinations performed
by trainees and experts were 72.6% and 84.3%, respectively. Required EUS
examinations for reaching a 1st plateau in each trainee were 20, 41, 60, and 65,
respectively. In addition, poor predictive factors for accurate T staging of gastric
cancer were 2030 mm and 3050 mm of size compared to 20 mm or less of size,
pT2pT4 stages compared to pT1 stage, and EUS T staging by trainees.
CONCLUSION: A threshold number of 75 which is suggested by guidelines may
be acceptable for achieving competency of gastric cancer T staging by EUS.
Disclosure of Interest: None declared
P0213 PROGNOSTIC SIGNIFICANCE OF EUS NON-TRAVERSABILITY
IN PATIENTS WITH LOCALLY ADVANCED SQUAMOUS
ESOPHAGEAL CANCER RECEIVING PREOPERATIVE
CHEMORADIOTHERAPY
C.J. Cho1,*, H.J. Song1, J.S. Lee1, J.Y. Ahn1, J.H. Lee1, D.H. Kim1, K.-S. Choi1,
K.D. Choi1, G.H. Lee1, H.-Y. Jung1, J.-H. Kim1
1
Division of Gastroenterology, Department of Internal Medicine, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: formidable1981@gmail.com
INTRODUCTION: Although endoscopic ultrasonography (EUS) is the most
accurate loco-regional staging modality for squamous esophageal cancer (EC),
approximately 30% of patients cannot complete EUS due to malignant stenosis
(EUS non-traversability). Malignant stenosis has reportedly been associated with
advanced tumor stage. However, to date, no study has assessed clinical implica-
tions of EUS non-traversable EC stenosis in patients with locally advanced EC
receiving preoperative chemoradiotherapy (CRT).
AIMS & METHODS: This study aimed to examine the clinical implications and
prognostic significance of EUS non-traversability in locally advanced EC
patients treated with preoperative CRT. Data from 89 consecutive patients
with locally advanced and resectable EC (stage II or III) planning preoperative
CRT followed by esophagectomy were retrieved. Relevant clinical and cancer-
specific parameters were reviewed retrospectively. Univariate and multivariate
analysis with a Cox model were performed to determine significant factors for
survival.
RESULTS: EUS scope could not pass through EC in 26 of 89 (29.2%) patients.
Between EUS non-traversable and traversable group, dysphagia (88.5% vs.
52.4%; P 0.001), need for stent insertion (30.8% vs. 1.6%; P50.001),
median serum albumin level (3.6 vs. 3.9 g/dL; P 0.028), tumor length (6.0 cm
vs. 4.0 cm; P 0.002), and percentage of stage III disease (65.4% vs. 38.1%;
P 0.019) were significantly different. 79 (88.8%) patients completed preopera-
tive CRT; 22 (84.6%) in non-traversable group and 57 (90.5%) in traversable
group (P 0.426). 70 (78.7%) attained CR or PR. CRT response rates were not
different between non-traversable and traversable group (76.9% vs. 79.4%;
P 0.798). 53 (59.6%) patients underwent esophagectomy; 16 (61.5%) in non-
traversable and 37 (58.7%) in traversable group (P 0.806). Median OS of all
patients was 32.8 months (95% CI, 068.2 months) with 5-YSR of 43.8%. Stage
III (P 0.079), non-response to preoperative CRT (P50.001), incompletion of
esophagectomy (P50.001), weight loss 10% (P 0.047), serum albumin level
53.8 g/dL (P 0.035), EUS non-traversability (P 0.025) and tumor length 5
cm (P 0.069) were negative prognostic factors on univariate analysis. Weight
loss 10% (P 0.042), EUS non-traversability (P 0.007), non-response to pre-
operative CRT (P 0.003), and incompletion of esophagectomy (P 0.002)
remained significant negative prognostic factors of survival in multivariate ana-
lysis. EUS non-traversable EC patients had a significantly lower 5-YSR than
those with EUS traversable EC (30.8% vs. 49.3%, P 0.023). 5-YSR was
50.0% for EUS non-traversable EC patients who attained a clinical response
to CRT and also underwent esophagectomy (vs. 64.5% in EUS traversable EC
patients; P 0.153).
CONCLUSION: EUS non-traversability is a significant negative prognostic
factor in patients with locally advanced, resectable EC receiving preoperative
CRT. The clinical implication may arise from incomplete loco-regional EC sta-
ging and larger tumor burden. We suggest that treatment should not be discon-
tinued for the patients with EUS non-traversable EC stenosis, given the
acceptable compliance to multimodality therapy and the survival of the patients
who attained a clinical response to CRT and underwent surgery.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0214 IS THE CORE BIOPSY NEEDLE (PROCORE TM COOK NEEDLE)
THE ALMIGHTY SOLUTION FOR EUS-GUIDED TISSUE
ACQUISITION? A COMPARISON WITH STANDARD EUS-FNA
NEEDLES
C. De Angelis1,*, S. Gaia1, S.F. Manfre1, A. Andrealli1, M. Bruno1, P. Carucci1,
D. Pacchioni1, A. Cassenti1, R. Senetta1, L. Molinaro1, G. Gatti1, A. Sapino1,
M. Rizzetto1
1
Citta` della Salute e della Scienza, Turin, Italy
Contact E-mail Address: eusdeang@hotmail.com
INTRODUCTION: Fine Needle Aspiration (FNA) under Endoscopic
UltraSound (EUS) guidance is an efficient and safe method to obtain tissue
samples from gastro-intestinal tract and from the nearest structures. Whereas
EUS-FNA provides samples of cells without any tissue structure information,
EUS-Fine Needle Biopsy (FNB) has the theorethical advantage to collect tissue
specimens for histological evaluation. The aim of this study is to compare feasi-
bility and diagnostic yield of the newly-developed FNB device (Cook EchoTip
ProCore) with the standard FNA needles.
AIMS & METHODS: 134 patients (75/59 M/F; 6213.5 years) were consecu-
tively enrolled between April 2011 and June 2013, for a total of 137 lesions (mean
size 33.516 mm, range: 6-100 mm): 81 pancreas, 31 lymph nodes, 8 stomach, 7
gut (including 1 papilla), 4 esophagus, 5 aspecific abdominal masses, 1 nervous
ganglia. For each lesion EUS-guided tissue sampling was performed both with
standard needle and with ProCore needle. An expert cytopathologist evaluated
the material giving out a score (0-4) about the adequacy of the samples and
assessing the feasibility of the diagnosis on the samples from the two types of
needle.
RESULTS: A mean of 3.21.1 (range 1-6) and 2.81.1 (range 1-7) needle passes
per lesion were performed with standard needles and ProCore respectively (p:ns).
A core sample adequate for histological assessment from ProCore biopsy was
achieved in 29% lesions (mean length 1.370.7 mm, range 0.5-3.0 mm), with no
difference among the 22, the 19 and the 25 Gauge needle (25%, 46.7% and
33.3% respectively; p: ns). 37% of lesions however fitted for cytological evalua-
tion, whereas 34% were inadequate. There were no statistical difference in the
pathologists adequacy score between the standard needle and the ProCore
needle (2.31.4 and 2.31.4 respectively, p:ns). A final diagnosis was reached
84% cases; 66% of the ProCore samples and 67% of the standard needle samples
(p:ns; Standard Echo alone versus both: p 0.009; ProCore alone versus both: p
0.005). In 16.5% the diagnosis was reached only on the ProCore sample. No
complications were observed.
CONCLUSION: EUS-FNB is feasible and safe, but only in 29% of cases a core
sample adequate for histological evaluation was obtained. The success rate in
reaching the diagnosis is similar with standard needles and with ProCore needles.
However the best results could be reached significantly better with the combina-
tion of the 2 type of needle than with EchoTip alone or with ProCore alone (p:
0.009 and p:0.005 respectively) and it seems that the ProCore needle could be
useful especially on fibrotic or hard lesions.
Disclosure of Interest: None declared
P0215 NATURAL HISTORY OF PANCREATIC INTRADUCTAL
PAPILLARY MUCINOUS NEOPLASMS: CLINICAL EVALUATION
OF SENDAI CRITERIA IN A LARGE COHORT OF PATIENTS
E. Dabizzi1,*, M.C. Petrone1, M.E. Traini1, S.G. G. Testoni1, P.A. Testoni1,
P.G. Arcidiacono1
1
Gastroenterology and Digestive Endoscopy, San Raffaele Scientific Institute-
Universita` Vita e Salute, Milano, Italy
Contact E-mail Address: dabizzi.emanuele@hsr.it
INTRODUCTION: Intraductal papillary mucinous neoplasms (IPMN) are
mucin-producing, pancreatic cystic tumors, with a long-term potential for pro-
gression to adenocarcinoma. The revised Sendai criteria, based on imaging
features, can differentiate the lesions into high and low risk of progression,
influencing the patient management. However, few data are still available
about clinical management and a better understanding in natural history is
critical.
AIMS & METHODS: To evaluate the natural history of IPMN throughout
clinical follow-up. Second end-point was to assess the clinical correlation between
endoscopic ultrasound features and malignant histology, in order to validate the
Sendai Criteria in our clinical practice. All the patients with pancreatic IPMN,
referred to our tertiary referral center between March 2003 and April 2013 were
enrolled in the study. We divided patients into 3 groups, according to Sendai
criteria: patients with cysts without signs of malignancy (1), patients with cysts
with worrisome features (2) and patients with cysts with high risk stigmata (3).
Data were analyzed using uni variate and multivariate logistic regression, to
assess the risk factors of malignant progression at diagnosis (T0) and at 2
years of follow up (T2).
RESULTS: 371 patients were enrolled in the study period (171 M, mean age 67
years), with a mean follow up of 38 months from 1 up to 106 months (mean 38
mo). 191/371 (52%) pts presented cysts without signs of malignancy, 105/371
(28%) pts cysts with worrisome features and 75/371 (20%) pts cysts with high
risk of malignancy. At multivariate analysis, the features significantly associated
with a higher risk of progression at diagnosis included mass size, pancreatic duct
dilation (p50.001), with an accuracy of 78% and a specificity of 88%. Whereas,
the features with a significantly higher risk of progression at 2 year-follow up
included the pancreatic dilation and the presence of mural nodules (OR 40.01)
(P50.001), with an accuracy of 84% and a specificity of 93%.
CONCLUSION: Our results validated Sendai Criteria in clinical practice.
Therefore, patients with no sign of malignancy and unchanged EUS imaging
can be followed up with a lengthened interval. Due to a high progression rate,
A189
a strict follow up is recommended in pts with worrisome features. Patients with
high risk stigmata need surgery at diagnosis.
Disclosure of Interest: None declared
P0216 AUTOMATIC DETECTION OF SUSPICIOUS CAPSULE
ENDOSCOPY VIDEO SEGMENTS
A. Koulaouzidis1,*, S. Tsevas2, D.K. Iakovidis3
1
Centre for Liver & Digestive Disorders, The Royal Infirmary of Edinburgh,
Edinburgh, United Kingdom, 2Department of Computer Engineering, Technogical
Educational Institute of Central Greece, 3Department of Computer Engieering,
Technological Educational Institute of Lamia, Lamia, Greece
INTRODUCTION: Manual review and annotation of capsule endoscopy (CE)
videos requires a considerable amount of reviewing time. Furthermore, the diag-
nostic accuracy of this process over lengthy reviewing sessions may decrease
due to reviewers tiredness. Recent studies showed an average detection rate for
the clinically significant findings as low as 40%.[1] We present a generic com-
putational framework for automatic detection of abnormalities in CE videos.
AIMS & METHODS: A CE video (MiroCam, InrtoMedic Co Ltd, Seoul,
Korea), depicting inflammatory changes (aphthae, mucosal breaks, ulcers,
erythema) was reviewed and manually annotated by experienced CE reader. A
total of 1,984 frames, depicting any type of pathology, were thumbnailed. The
proposed framework considers video frames as members of a vector space repre-
sented by their colour information. An unsupervised data reduction algorithm,[2]
which does not require any prior knowledge about the data, was then applied on
each segment. This algorithm clusters together frames that exhibit similar char-
acteristics e.g. colour distributions. Its output is a subset of video frames
extracted from each cluster by applying a threshold to the clustering result.
The extracted frames are characteristic of the particular video segment and as
a result representative of possible lesions.
RESULTS: The evaluation of the proposed framework aimed to determine its
accuracy, in terms of the ratio of the neighbourhoods represented by at least one
frame in the systems output and the neighbourhoods that were manually anno-
tated as suspicious for containing lesions. The parameters considered include
clustering from 2 to 6 clusters and thresholds[2] varying from 0.004 to 0.6. The
obtained accuracy ranged between 76% and 98% depending on the desired
sensitivity level of the algorithm, controlled by the threshold. Furthermore, the
automatic selection of the representative CE video segments performed by the
proposed approach, the number of video frames to be thoroughly examined can
be reduced from 30% to 60% of the original video, depending on the clustering
and threshold settings.
CONCLUSION: The application of the proposed framework to the evaluation
of CE videos may reduce the rate of false negative evaluations by attracting the
attention of the reviewer to automatically identified video segments (or single
frames) of interest which are likely to contain lesions.
REFERENCES
1. Zheng Y, Hawkins L, Wolff J, et al. Detection of lesions during capsule
endoscopy: Physician performance is disappointing. Am J Gastroenterol 2012;
107: 554-560.
2. Iakovidis DK, Tsevas S and Polydorou A. Reduction of capsule endoscopy
reading times by unsupervised image mining. Comput Med Imaging Graph 2010;
34: 471478.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
FalkPharma, S. Tsevas: None declared, D. Iakovidis: None declared
P0217 WIRELESS CAPSULE ENDOSCOPE LOCALIZATION BASED ON
VISUAL ODOMETRY
A. Koulaouzidis1,*, D.K. Iakovidis2, E. Spyrou2
1
Endoscopy Unit, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom,
2
Dept of Computer Engineering, Technological Educational Institute of Central
Greece, Lamia, Greece
INTRODUCTION: The localization of a wireless capsule endoscope (WCE)
within the small-bowel is typically performed by wearable radiofrequency sensors
triangulation. The accuracy of this approach is low.[1] Only a few approaches
have been proposed for localisation of WCE based on visual features. These
include methods addressing the estimation of the rotation angle of the capsule
[2,3] & temporal video segmentation methods.[4] We present a WCE localization
method, based only on visual information extracted from conventional WCE
recording.
AIMS & METHODS: to check the accuracy of visual odometry in WCE with ex-
vivo data.
Methods: Automatic detection of points of interest (POI) in WCE video frames,
matching of the detected POI between consecutive frames, and determination of
actual correspondences between subsets of these POI based on the random
sample consensus (RANSAC) algorithm was performed. Instead of the speeded
up feature extraction (SURF) algorithm, a maximally stable extremal regions
(MSER) algorithm was used. Based on the scaling & the rotation of the content
of the consecutive WCE frames, it is possible to estimate the displacement & the
rotation of the capsule within the GI tract.
For the ex-vivo experiment a standard simulated intestinal environment was
created. Markers were sewn onto the luminal surface of porcine small-bowel
through which a capsule endoscope (MiroCam, IntroMedic Co Ltd, Seoul,
Korea) was propelled.
RESULTS: Comparative experiments using both SURF and MSER features,
which indicated the superiority of the former over the latter, were conducted.
We worked on a corpus of 1070 WCE frames (634 indicating forward motion,
436 indicating backward motion). The accuracy using SURF features was 81.5%
A190
(87.2% on forward motion, 73.2% on backward motion), while using MSER was
67.2% (79.8% on forward motion, and 48.9% backward motion). Noteworthy,
the proposed algorithm often fails when using MSER (6.7% of frames while
50.1% when using SURF) and a transform is not estimated due to the lack
of adequate correspondences between POI.
CONCLUSION: Visual odometry is a promising technique and -potentially- a
feasible alternative to other localization approaches in WCE.
REFERENCES
1. Than TD, et al. A review of localization systems for robotic endoscopic cap-
sules. IEEE Trans Biomed Eng 2012; 59: 2387-2399.
2. Spyrou E and Iakovidis D. Homography-based orientation estimation for
capsule endoscope tracking. In: Imaging Systems and Techniques (IST), 2012
IEEE International Conference on, 2012, pp. 101105.
3. Mackiewicz M, et al. Wireless capsule endoscopy color video segmentation.
IEEE Trans Med Imaging 2008; 27: 1769-1781.
4. Spyrou E and Iakovidis DK. Video-based measurements for wireless capsule
endoscope tracking. Meas Sci Technol 2014; 25: 015002.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
Given Imaging ESGE research grant 2011, Lecture fee(s) from: Dr
FalkPharmaUK, Other: Material support for research from SynMedUK, D.
Iakovidis: None declared, E. Spyrou: None declared
P0218 UTILITY OF THREE-DIMENSIONAL IMAGE
RECONSTRUCTION IN THE DIAGNOSIS OF OESOPHAGEAL
VARICES
A. Koulaouzidis1,*, A. Karargyris2, Y.L. Ang3, S. Douglas1, E. Rondonotti4,
A.J. Bathgate1, P.C. Hayes3, J.N. Plevris1,3
1
Endoscopy Unit, The Royal Infirmary of Edinburgh, Edinburgh, United Kingdom,
2
National Library of Medicine, National Institutes of Health, Bethesda, MD,
United States, 3Medical School, The University of Edinburgh, Edinburgh, United
Kingdom, 4Gastroenterology Unit, Ospedale Valduce, Como, Italy
INTRODUCTION: Oesophagogastroduodenoscopy (OGD) remains the gold
standard for the diagnosis of oesophageal varices (OVs). Oesophageal capsule
endoscopy (OCE) is a non-invasive alternative. However, recent studies showed
that OCE is lagging behind OGD in diagnostic accuracy [1]; it can be an accep-
table alternative though in certain situations such as those who cannot tolerate
OGD or are at risk of variant CreutzfeldtJakob disease (vCJD)[2]. Application
of innovative 3D reconstruction software may improve OCE accuracy in the
diagnosis of OVs [3].
AIMS & METHODS: 14 patients, intolerant or with contraindications for con-
ventional OGD e.g. risk for vCJD (for public health purposes), underwent OCE
with PillCamESO1/2. The OCE video recordings (from one of the 2 CE domes)
from the entry in the oesophagus to exit in the stomach were deconstructed to
individual frames. Following 3D reconstruction, the frames were stitched back to
3-D videos. Ten reviewers; 6 GI trainees (novice in CE review), 3 GI specialists
with experience between 20 and 100 CE reviews and 3 expert CE reviewers read
the OCE first in 2-D and then in a GUI (graphic user interface) offering (side-to-
side) 2-D & 3-D. Furthermore, the consensus opinion of 3 senior hepatologists,
with wide endoscopy experience in patients with liver disease, who reviewed the
OCEs with the GUI was used as reference standard (RS). Interobserver agree-
ment for each of the above groups was checked with kappa () statistics.
When the RS for C2 (i.e. varices requiring treatment) was taken into account, the
negative predictive value (NPV) of the entire group (10 reviewers) for C2 variceal
diagnosis with2-D and 2D3D was calculated.
RESULTS: The interobserver agreement for the entire group, novice, experi-
enced and experts CE reviewers with 2-D was 0.145, 0.118, 0.125 and 0.025,
respectively. The interobserver agreement for the entire group, novices, experi-
enced and expert reviewers with 2-D & 3-D was 0.215, 0.104, 0.222 and 0.372,
respectively. For C2 varices diagnosis (RS), the NPV of 2-D and 2-D & 3-D
review was 66.6% and 80%, respectively.
Limitations: the use of subjective RS.
CONCLUSION: In oesophageal capsule endoscopy, the use of a GUI that
incorporates 2-D and 3-D reconstructed videos leads to improved diagnostic
agreement; furthermore, it improves significantly he NPV of OCE for C2 varices.
Acknowledgement: we thank all those in the 3-D in capsule endoscopy assess-
ment group.
REFERENCES
1. Laurain A, et al. Oesophageal capsule endoscopy versus oesophago-gastro-
duodenoscopy for the diagnosis of recurrent varices: a prospective multicentre
study. Dig Liver Dis 2014 Mar 12.
2. Millar CM, et al. Risk reduction strategies for variant Creutzfeldt-Jakob dis-
ease transmission by UK plasma products and their impact on patients with
inherited bleeding disorders. Haemophilia 2010; 16: 305-315.
3. Rondonotti E, et al. Utility of three-dimensional image reconstruction in the
diagnosis of small-bowel masses in capsule endoscopy. Gastrointes Endosc 2014,
in press.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
ESGE-Given Imaging Research grant 2011, Lecture fee(s) from: Dr
FalkPharmaUK, Other: Material support for research from SynMedUK, A.
Karargyris: None declared, Y. L. Ang: None declared, S. Douglas: None
declared, E. Rondonotti: None declared, A. Bathgate: None declared, P.
Hayes: None declared, J. Plevris: None declared
United European Gastroenterology Journal 2(5S)
P0219 LATERAL-VIEWING CAPSULE ENDOSCOPY EXPERIENCE
FROM AN ACADEMIC CENTRE IN SCOTLAND
A. Koulaouzidis1,*, L. Bartzis1, S. Douglas1, J.N. Plevris1,2
1
Endoscopy Unit, The Royal Infirmary of Edinburgh, 2Medical School, The
University of Edinburgh, Edinburgh, United Kingdom
INTRODUCTION: CapsoCamSV1 represents a major departure from conven-
tional wireless capsule endoscopy (CE). This CE system utilises on-board data
storage, which necessitates retrieval of the device for data collection. Four lenses
in the middle of the device, offering panoramic views of the bowel lumen, have
replaced a forward-facing lens. Battery life is also increased to 15h by virtue of
a variable image capture rate. Furthermore, the reviewing software provides 4
rectangular panels in a linear sequence, departing from conventional CE reading
software.
AIMS & METHODS: Aim: To report our experience on the clinical use of
CapsoCamSV1 CE.
Setting: An academic hospital, tertiary referral-centre for CE for the South-East
of Scotland.
Methods: Retrospective, single centre, observational study.
RESULTS: Since May 2012, 12 patients (4M/8F, mean age: 67.75 13.5 years; 8
inpatients) underwent CE with CapsoCam following the standard protocol of
our unit. In 80% of patients, the examination was performed for obscure GI
bleeding.
The mean time from capsule ingestion to data upload was 5.6 8.5 days. Two
patients underwent successful endoscopic placement with the AdvanCE delivery
device. The gastric transit time (GTT), small-bowel transit time (SBTT) was 50.9
51.2 min and 5.46 3.15 h, respectively. The mean total working time for
CapsoCam was 14 3 h. Caecal entry was confirmed in 10/12 examinations.
The ampulla of Vater (AoV) was visualised in 2/12 i.e. 20% of cases after cor-
recting for quality of bowel prep (10 good). Diagnostic yield for findings was
33.3%.
CONCLUSION: A significant time interval between capsule ingestion and data
upload is noted. However, capsule retrieval eliminates the need for radiologic
confirmation of capsule excretion in cases of incomplete enteroscopy. The
AdvancCE delivery can be used for CapsoCam endoscopic placement. The
diagnostic yield and the rate of identification of the AoV is comparable to for-
ward-viewing CE devices.
REFERENCES
1. Friedrich K, et al. First clinical trial of a newly developed capsule endoscope
with panoramic side view for small bowel: a pilot study. J Gastroenterol Hepatol
2013; 28: 1496-1501.
2. Pioche M, et al. French Society of Digestive Endoscopy (SFED). Prospective
randomized comparison between axial- and lateral-viewing capsule endoscopy
systems in patients with obscure digestive bleeding. Endoscopy. Epub ahead of
print 27 November 2013.
Disclosure of Interest: A. Koulaouzidis Financial support for research from:
ESGE Given Imaging research grant 2011, Lecture fee(s) from: Dr
FalkPharma UK, Other: Dr FalkPharmaUK, Abbott, MSD,Almiral, L.
Bartzis Other: grant from the Hellenic Society of Gastroenterology, S.
Douglas: None declared, J. Plevris: None declared
P0220 OPTIMAL TIMING OF VIDEO CAPSULE ENDOSCOPY IN
OVERT OBSCURE GI BLEEDING PATIENTS
S.H. Kim1, I.K. Yoo1, J.M. Lee1, S.J. Nam1, H.S. Choi1, E.S. Kim1, B. Keum1,
Y.T. Jeen1,*, H.S. Lee1, H.J. Chun1, C.D. Kim1
1
Department of Internal Medicine, Division of Gastroenterology and Hepatology,
Korea University Anam Hospital, Seoul, Korea, Republic Of
Contact E-mail Address: kimseunghan09@gmail.com
INTRODUCTION: Video capsule endoscopy (VCE) is crucial examination for
diagnosis of small bowel bleeding. But diagnostic yield of VCE is 38% to 83% in
overt obscure gastrointestinal bleeding (OGIB). For an accurate diagnosis of
cause of overt OGIB, the timing to perform VCE is the valuable factor. This
study is to investigate the diagnostic yield, rate of therapeutic intervention, and
prognosis according to the timing of VCE in the overt OGIB patients.
AIMS & METHODS: We conducted a single center, retrospective study at
Korea University Medical Center Anam Hospital from April 2008 to February
2014. Patients who presented overt OGIB with negative result of initial upper and
lower endoscopy were enrolled. We compared the diagnostic yield, rate of ther-
apeutic intervention, length of hospital stay, and rate of re-bleeding between
patients with VCE performed in 48hrs and 448hrs after the occurrence of
overt OGIB. We defined positive finding as active bleeding or any cause of
small bowel bleeding.
RESULTS: In 111 patients, VCE were performed to evaluate overt OGIB during
the period. Among them, 90 patients were included and 21 patients who lacked of
medical records were excluded. Diagnostic yield was 65.51% in 48hrs group
and 35.59% in 448hrs group (p 0.037). Therapeutic intervention was done in
45% of the 48hrs group and 14% of 448hrs group (p 0.006). The average
day of hospital stay was 5.48 days in 48hrs group and 8.18 days in 448hrs
group (p 0.005). Re-bleeding rate between the 48-hrs group and 448-hrs
group was not significantly different.
CONCLUSION: Early VCE deployment within 48hrs of last overt OGIB may
improved the diagnostic yield, rate of therapeutic intervention and decreased the
length of hospital day.
REFERENCES
Yamada A, Watabe H, Kobayashi Y et al. Timing of capsule endoscopy influ-
ences the diagnosis and outcome in obscure-overt gastrointestinal bleeding.
Hepato-gastroenterology 2012; 59: 676-679.
United European Gastroenterology Journal 2(5S)
Singh A, Marshall C, Chaudhuri B, et al. Timing of video capsule endoscopy
relative to overt obscure GI bleeding: implications from a retrospective study.
Gastrointes Endosc 2013; 77: 761-766.
Disclosure of Interest: None declared
P0221 THROMBOCYTOSIS AND HIPOALBUMINEMIA: A PRIORITY
PASS FOR CAPSULE ENDOSCOPY IN CROHNS DISEASE?
B. Rosa1,*, H. Cardoso2, M.J. Moreira1, P. Boal Carvalho1, S. Lopes2,
S. Rodrigues2, M. Marques2, F. Magro2, C. Dias3, G. Macedo2, J. Cotter1
1
Gastroenterology, Centro Hospitalar do Alto Ave, Guimaraes, 2Gastroenterology,
Hospital Sao Joao, 3Biostatistics and Medical Informatics, Faculty of Medicine of
Porto University, Porto, Portugal
Contact E-mail Address: bruno.joel.rosa@gmail.com
INTRODUCTION: Small bowel capsule endoscopy (SBCE) may identify small
bowel lesions in a large proportion of patients with Crohns disease (CD).
AIMS & METHODS: To identify predictive factors of small bowel involvement
in a cohort of patients with CD. Transversal multicenter study including con-
secutive patients with CD affecting the small bowel over a period of eight years.
Small bowel inflammatory activity at SBCE was assessed with the Lewis Score
(LS), and it was considered clinically relevant if LS135. Univariate analysis and
multivariate regression of patients baseline clinical, analytical and endoscopic
(index ileocolonoscopy) variables were performed to identify pre-test predictors
of relevant (LS135) lesions at SBCE in patients with known or suspected CD.
RESULTS: A total of 158 patients were included, 58% female, mainly with ileal
(42%) or ileocolic (39%) location at ileocolonoscopy, non-stricturing non-pene-
trating behaviour in 74% of cases. SBCE lesions were non-significant (LS5135)
in 34 (22%) patients, mild (135LS5790) in 68 (43%) and moderate to severe
(LS4790) in 55 (35%). Lesions were located in the first tertile of the small bowel
in 38 (24.1%) patients, second tertile in 48 (30.4%) and third tertile in 113
(71.5%) patients. Multivariate regression identified thrombocytosis [OR 1,012
(95% CI: 1.002-1.022), p 0.019] and low serum albumin [OR 0.803 (95% CI:
0.663-0.971), p 0.023] as independent variables predictive of small bowel CD,
[ROC 0.846 (0.767-0.925)]. Clinical features, endoscopic distribution of the
disease at ileocolonoscopy, and biomarkers such as anaemia or C-reactive pro-
tein were not predictive of SBCE lesions.
CONCLUSION: In patients with known or suspected CD, thrombocytosis and/
or hipoalbuminemia are predictive of active small bowel inflammation at SBCE.
Whether these biomarkers should play a role in the selection of patients for
SBCE warrants further prospective evaluation.
Disclosure of Interest: None declared
P0222 DOES CAPSULE ENDOSCOPY WITH ALICE IMPROVE
VISIBILITY OF SMALL BOWEL LESIONS?
C.B. Ryu1,1,*, M.S. LEE1, J.Y. BAE2, J.Y. SONG3
1
Department of Internal Medicine, Soon Chun Hyang University School of
Medicine, Bucheon, 2SEOUL MEDICAL CENTER, SEOUL, 3SUWON
MEDICAL CENTER, SUWON, Korea, Republic Of
Contact E-mail Address: ryuchb@gmail.com
INTRODUCTION: ALICE (Augmented Live-body Image Color-spectrum
Enhancement) refers to a spectral imaging technique for the MiroView (TM)
system to perform medical tests through capsule endoscope (CE) system,
where light of specific blue, green, and red wavelength is used to enhance the
detail of certain aspects of the surface of the mucosa, but the data was limited.
AIMS & METHODS: This study is to evaluate the visibility of CE-ALICE
depending on type of small bowel lesions.
A total of 50 patients who underwent CE at Soon Chun Hyang Bucheon
Hospital from August 2008 to November 2011 were enrolled in this study. The
lesions were classified as elevated (tumor and polyp, n 5), flat (angiodysplasia
and erosion, n 18), depressed (ulcer, n 27) lesions. Two experienced endosco-
pists analyzed CE-ALICE images obtained at setting 1-10 (setting 1: red 415 nm,
green 415 nm, blue 540 nm; setting 2: red 415 nm, green 445 nm, blue 500 nm;
setting 3: red 420 nm, green 470 nm, blue 500 nm; setting 4: red 400 nm, green 445
nm, blue 450 nm; setting 5: red 420 nm, green 480 nm, blue 540 nm; setting 6: red
420 nm, green 480 nm, blue 500 nm; setting 7: red 400 nm, green 500 nm, blue 450
nm; setting 8: red 455 nm, green 455 nm, blue 500 nm; setting 9: red 500 nm,
green 455 nm, blue 455 nm; setting 10: red 455 nm, green 500 nm, blue 455 nm)
compared with conventional images. Physicians rated the visibility of the lesions
on ALICE images as follows: _2(improved visibility), _1 (somewhat improved
visibility), 0 (visibility equivalent to that of conventional video CE visibility), _1
(somewhat decreased visibility), and _2 (decreased visibility). Scores for each
lesion were totaled (per ALICE setting) and evaluated. Intraobserver agreement
was also examined.
RESULTS: In elevated lesion (n 5), with setting 2, 3, 4, 5, 6, 7, 9, 10, improve-
ment was achieved but not significantly statistical (NS). In flat lesion (n 18),
with setting 3, 5, 10, improvement was achieved statistically for 100% (18/18),
100% (18/18), 100% (18/18) (p50.01). In depressed lesion (n 27), with setting
2, 3, 6, 10, improvement was achieved statistically for 89% (24/27), 93% (25/27),
93% (25/27), 85% (23/27)
CONCLUSION: CE-ALICE improves visibility of flat and depressed lesion in
small bowel.
Disclosure of Interest: None declared
A191
P0223 UTILITY OF FECAL CALPROTECTIN IN THE EVALUATION OF
PATIENTS WITH CROHNS DISEASE CANDIDATES FOR CAPSULE
ENDOSCOPY: PRELIMINARY RESULTS
C. Romero Mascarell1,*, C. Rodriguez De Miguel1, I. Ordas Jimenez1, E. Ricart
Gomez1, A. Jauregui Amezaga1, A. Ramirez Morros1, M. Gallego Barrero1,
J. Llach Vila1, J. Panes D az1, B. Gonzalez Suarez1
1
Gastroenterology, Hospital Clinic de Barcelona, Barcelona, Spain
Contact E-mail Address: bgonzals@clinic.ub.es; crromero@clinic.ub.es
INTRODUCTION: Small bowel capsule endoscopy (SBCE) is an expensive but
useful imaging method in the diagnosis and extension of Crohns disease (CD).
Symptomatology and acute phase reactants (CRP and ESR) are not correlated
with the presence of endoscopic activity in small Bowel. Fecal calprotectin (FC)
is a biomarker that correlates well with small bowel inflammation.
AIMS & METHODS: The aim of our study is to assess if fecal calprotectin
correlates with the presence of endoscopic activity in small Bowel, evaluated
by capsule endoscopy (Lewis Score).
We included prospectively patients with suspected or diagnosed Crohns disease
referred for capsule endoscopy. All of them were submitted to SBCE and a
measure of FC, ESR, and CRP. CDAI was also registered.
RESULTS: For this preliminary analysis, 30 patients were included (17 females and
13 males), mean age 38 /- 13 years. The indication for capsule endoscopy was
suspected CD (7 patients), extension study of the illness and/or lack of response to
treatment (21 patients) and mucosal healing assessment (2 patients). One patient was
excluded for the analysis because of the capsule was retained in stomach temporarily.
Only 10% of patients had FC levels less than 100 mcg/g, two of them with no
lesions in capsule endoscopy. FC levels higher than 100 mcg/g correlated more
closely with the presence of lesions in capsule endoscopy (p 0.006).
In our study, there is a slight but positive correlation between FC levels and
Lewis Score (r 0.4; p 0.02). There is no correlation between clinical symp-
toms, CRP or ESR, and the presence of lesions in the capsule endoscopy.
CONCLUSION: Fecal Calprotectin seems to be useful in identifying patients
with Crohns Disease and small bowel involvement. It can be a good tool to select
patients for performing capsule endoscopy
Disclosure of Interest: None declared
P0224 ABSENCE OF MUTUAL INTERFERENCE BETWEEN MIROCAM
CAPSULE ENDOSCOPY, PACEMAKERS AND IMPLANTABLE
CARDIAC DEFIBRILLATORS: A CLINICAL
ELECTROPHYSIOLOGICAL STUDY
D. Moneghini1,*, A. Lipari2, G. Missale1, L. Minelli1, G. Cengia1, L. Bontempi2,
A. Curnis2, R. Cestari1
1
Digestive Endoscopy, 2Electrophysiology and Electrostimulation Lab, SPEDALI
CIVILI - UNIVERSITY OF BRESCIA, Brescia, Italy
Contact E-mail Address: dario.moneghini@spedalicivili.brescia.it
INTRODUCTION: Capsule endoscopy (CE) has recently become one of the
most important tools for small bowel investigation. Once swallowed by the
patient, Mirocam capsule transmits images from the gut to an external recorder
by the Human Body Communication (HBC) system. HBC uses the capsule itself
to generate an electrical field and uses the human body as the conductor for data
transmission. Because of the creation of an electric field, a potential electromag-
netical interference with implantable cardiac devices has been postulated, so their
presence is considered a relative contraindication for CE. Whereas some safety
data are available about Given M2A capsule in patients with pacemakers (PM)
and automatic implantable cardiac defibrillators (AICD), studies in this field
regarding Mirocam capsule are lacking.
AIMS & METHODS: We report the use of Mirocam video capsule system
(Intromedic Co Ltd, Seoul, Korea) in 6 patients with PM and in a patient with
AICD over a 2-years period. Patients swallowed the capsule in the morning after a
overnight fast; a bowel cleansing with 2 litres of polyethylene glycol (PEG) solution
was administered in the afternoon before the procedure. All patients gave their
written informed consent. Three different type of PM from 2 manufacturers
(Altura and Insignia Ultra from Boston Scientific Corporation, Esprit from Sorin)
and Atlas AICD from St. Jude Inc. were tested. A full technical control of the cardiac
devices was performed by electrophysiologists before CE examination, using a man-
ufacturer-specific programmer. This technical control included the evaluation of the
following parameters: battery charge, shock impedance, leads impedance and sen-
sing, leads pacing threshold, arhythmic events. After a cardiac visit and electrocar-
diogram (ECG), each patient was placed in Cardiac Care Unit. AICD electrical
therapies were switched off just before capsule ingestion. During CE the patients
were continuously monitored with cardiac telemetry, performed by Mortara X12
device (Mortara Instrument Inc., U. S. A.). At the end of the endoscopic procedure,
before discharge, the patients repeated cardiac evaluation, ECG and a complete
cardiac device check. The following characteristics were analyzed: changes in
device parameters, inappropriate shocks, inappropriate anti-tachycardia therapy,
inappropriate sensing or pacing, noise detection, device reset, programming changes,
permanent electrical damages. CE records were reviewed by a skilled endoscopist.
RESULTS: For 6 patients indication for CE was obscure gastrointestinal bleed-
ing (OGIB), in one was follow up of intestinal polyposis. Mean age was 74 years;
all the patients were males. Capsule reached ileo-cecal valve in all except two
cases. No complications related to capsule transit were observed. No technical
problems related to imagine transmission were recorded. Causes of OGIB were
found in 50% of cases. No polyps were found in patient with polyposis. No
cardiac devices malfunctions nor interference in sensing or pacing were recorded;
conversely, no malfunctions of CE caused by PM or AICD were registered.
CONCLUSION: Our results suggest that Mirocam capsule endoscopy can be
safely performed in patients with different types of implantable cardiac devices.
Disclosure of Interest: None declared
A192
P0225 SELF-EXPANDABLE METAL STENTS VERSUS PLASTIC
STENTS FOR MALIGNANT BILIARY OBSTRUCTION: CLINICAL
OUTCOME AND COST-EFFECTIVENESS IN POLISH ECONOMIC
CIRCUMSTANCES
A. Budzynska1,*, E. Nowakowska-Dulawa1, T. Marek1, M. Hartleb1
1
Dept. of Gastroenterology&Hepatology, Medical University of Silesia, Katowice,
Poland
Contact E-mail Address: budzynskaagnieszka@poczta.onet.pl
INTRODUCTION: Most patients with malignant biliary obstruction are suited
only for palliation of jaundice by endoscopic placement of a plastic stents (PS) or
self-expandable metal stents (SEMS). The initial higher cost of the SEMS is
considered to be balanced by a decreased need for repeated interventions.
AIMS & METHODS: To compare the clinical outcome and costs of biliary
stenting with SEMS and PS in patients with malignant biliary strictures. A
total of 114 pts (63F, 51M) who underwent 366 endoscopic retrograde biliary
drainage (ERBD) for palliation of unresectable malignant biliary obstruction
between 2009 and 2014 were retrospectively enrolled into the study.
RESULTS: ERBD with placement of PS was performed in 80 patients, with one-
step SEMS insertion (direct placement without a prior plastic stent) in 20 patients
and two-step SEMS insertion (placement of SEMS at second or consecutive
endoscopic retrograde cholangiopancreatography following plastic stent place-
ment, e.g. SEMS after PS) in 14 patients. Significantly less endoscopic procedures
were performed in patients with one-step SEMS than PS alone and two-step
SEMS technique (2.01.12, 3.11.7 and 5.72.1 respectively, p50.0001). The
median hospitalization time was similar for three groups of patient. The patients
survival was longest in SEMS after PS group in comparison to SEMS group and
PS group (596.2270d, 276.1141d and 207.5219d, p50.001). Overall median
stent patency was 89.3159 d for PS and 120.6101 for SEMS (p 0.01). Stent
dysfunction occurred more frequently in PS group than in SEMS groups (76.8%
vs. 62.8%, p 0.05). No significant difference between the two stent types in
terms of technical success and complications was observed. The mean total
cost of hospitalization with drainage procedures was higher for SEMS group,
then for SEMS after PS group and finally for PS group (1448312E, 1152135E
and 977156E, p50.0001). Estimated annual cost of subsequent ERBD due to
recurrent biliary obstruction would be still higher for SEMS group than for PS
group (4618E vs. 3995E). Metal stents would be cost-effective if their patency
exceed 202 days.
CONCLUSION: Biliary decompression by metal stents in patients with malig-
nant jaundice is associated with longer patency and reduced number of addi-
tional biliary procedures, but repeated plastic stents drainage is still more cost-
effective strategy.
Disclosure of Interest: None declared
P0226 OUTCOMES OF PRIMARY AND REVISION EFFICACY OF
COMBINED METALLIC STENTS IN MALIGNANT DUODENAL
AND BILIARY OBSTRUCTIONS
D.F. B. Carvalho1,*, J. Canena1,2, J. Coimbra1, C. Rodrigues2, M. Silva1,
M. Costa1, D. Horta2, A. Mateus-Dias1, I. Seves1, G. Ramos1, L. Ricardo2,
A. Pereira Coutinho3, C. Romao3
1
Gastroenterology, Hospital Santo Antonio dos Capuchos - Centro Hospitalar
Lisboa Central, Lisbon, 2Gastroenterology, Hospital Professor Doutor Fernando
Fonseca, Amadora, 3Gastroenterology, Hospital Pulido Valente - Centro
Hospitalar Lisboa Norte, Lisbon, Portugal
Contact E-mail Address: dianafbcarvalho@gmail.com
INTRODUCTION: Self-expandable metal stents (SEMSs) can be used for pal-
liation of combined malignant biliary and duodenal obstructions. However, the
results of the concomitant stent placement for the duration of the patients lives,
as well as the need for and efficacy of endoscopic revision, are unclear.
AIMS & METHODS: This study evaluated the clinical effectiveness of SEMS
placement for combined biliary and duodenal obstructions throughout the
patients lives and the need for endoscopic revision. This study is a retrospective
multicenter study of 50 consecutive patients who underwent simultaneous or
sequential SEMS placement for malignant biliary and duodenal obstructions.
The data were collected to analyze the sustained relief of obstructive symptoms
until the patients death and the efficacy of endoscopic revision, as well as stent
patency, adverse events, survival and prognostic factors for stent patency.
RESULTS: Technical and immediate clinical success was achieved in all of the
patients. Duodenal stricture occurred before the papilla in 35 patients (70%),
involved the papilla in 11 patients (22%) and was observed distal to the papilla in
4 patients (8%). Initial biliary stenting was performed endoscopically in 42
patients (84%) and percutaneously in 8 patients. After combined stenting, 30
patients (60%) required no additional intervention until the time of their
death. The remaining 20 patients were successfully treated using endoscopic
stent reinsertion: 9 patients needed biliary revision, 3 patients needed duodenal
restenting and 8 patients needed both biliary and duodenal reinsertion. The
median duodenal stent patency and median biliary stent patency were 34
weeks and 27 weeks, respectively. The median survival after combined stent
placement was 12 weeks. A Cox multivariate analysis showed that duodenal
stent obstruction after combined stenting was a risk factor for biliary stent
obstruction (Hazard ratio 6.85; 95% CI 1.43-198.98; P 0.025).
CONCLUSION: Endoscopic bilio-duodenal bypass is clinically effective, and the
majority of the patients need no additional intervention until their death.
Endoscopic revision is feasible and has a high success rate.
Disclosure of Interest: D. Carvalho: None declared, J. Canena Consultancy for:
Boston Scientific, J. Coimbra: None declared, C. Rodrigues: None declared, M.
Silva: None declared, M. Costa: None declared, D. Horta: None declared, A.
Mateus-Dias: None declared, I. Seves: None declared, G. Ramos: None declared,
United European Gastroenterology Journal 2(5S)
L. Ricardo: None declared, A. Pereira Coutinho: None declared, C. Romao:
None declared
P0227 TEMPORARY ENDOSCOPIC INSERTION OF UNILATERAL OR
BILATERAL COVERED SELF-EXPANDABLE METAL STENTS
(CSEMS) ABOVE THE HEPATIC DUCT CONFLUENCE FOR BENIGN
BILE-DUCT DISEASE
P. Gil-Simon1, N. Aleman2, I. Penas Herrero1,*, A. Vargas2, R. Sanchez-Ocana2,
F. Santos1, C.de la Serna1, M. Perez-Miranda2
1
endoscopy, 2Hospital Universitario Ro Hortega, Valladolid, Spain
Contact E-mail Address: pgpaula@hotmail.com
INTRODUCTION: cSEMS appear to enhance therapeutic efficacy for benign
distal bile-duct strictures and leaks. Concerns over the use of cSEMS above the
hepatic duct confluence remain since clinical data are very limited. Aim: To
assess the feasibility and efficacy of cSEMS placement proximal to the hepatic
duct confluence in benign disease.
AIMS & METHODS: Retrospective analysis of prospectively databased patients
undergoing ERCP over a 10-month period at referral Unit. 34 Consecutive
Patients (17 female; age 59 [32-87] years) underwent biliary cSEMS placement
across the hilum for benign disease. Underlying diagnosis, number and type of
cSEMS, presence of associated plastic stents, indication for cSEMS (primary vs.
failed prior plastic stenting), duration of stenting, ease of removal, procedural &
stent related complications, and final therapeutic outcome were determined.
RESULTS: Diagnoses: 28 biliary strictures (13 postcholecystectomy, 11 post-
liver transplant, 4 undetermined) and 6 miscellaneous (2 high output fistulas, 2
with prior embedded uncovered SEMS, 1 sump syndrome, 1 primary sclerosing
cholangitis). In 19.4%, 2 or 3 biliary cSEMS were placed. The contralateral
hepatic duct was stented with a plastic stent in 80.6%. Transhilar biliary
cSEMS were indicated primarily in 14 (41%) and as salvage of prior standard
plastic stenting in the remainder 20. CSEMS used were all 10mm in diameter,
Hanaro 23, Wallflex 8, Bonastent 2, Taewoong 1. There were 2 procedural
complications related to cSEMS, one moderate cholangitis secondary to hepatic
branch occlusion (requiring cSEMS removal), and one mild (pain requiring IV
analgesia 424 hours). After a mean duration of stenting of 5.3 (1-15) months,
removal was attempted in 64.3% and was technically successful in all 20 cases
despite 4 partial migrations (3 proximal/ 1 distal; 2 with cholangitis, 2 asympto-
matic). Strictures/leaks were successfully remodeled/controlled upon removal in
19/20 (1 persistent leak), pending long-term follow-up. 11 patients are still under-
going cSEMS replacement. Transient enlargement of the intrahepatic bile-duct
was documented in 12/31, without any adverse clinical consequences. Overall
complication & short-term success rates are 13% & 95%.
CONCLUSION: If the contralateral hepatic duct is stented and ipsilateral sec-
ondary radicals spared, transhilar cSEMS placement appears safe. Refractory
benign disease can successfully be salvaged with this aggressive approach, with
an acceptable safety profile. Transient intrahepatic duct enlargement was noted.
This encouraging preliminary data warrant further study as the long-term effi-
cacy and reproducibility of this approach remain in question.
Disclosure of Interest: None declared
P0229 PREOPERATIVE BILIARY DRAINAGE WITH A MODIFIED
FULLY COVERED SELF-EXPANDABLE METALLIC STENT FOR
POTENTIALLY RESECTABLE DISTAL MALIGNANT BILIARY
OBSTRUCTION
J.H. Moon1,*, H.J. Choi1, Y.N. Lee1, H.J. Jung1, M.H. Choi1, T.H. Lee1, S.-
W. Cha1, Y.D. Cho1, S.-H. Park1, S.-J. Kim1
1
Department of Internal Medicine, SoonChunHyang University School of
Medicine, Bucheon, Digestive Disease Centerand Research Institute, Bucheon,
Korea, Republic Of
Contact E-mail Address: 95970@schmc.ac.kr
INTRODUCTION: Early biliary decompression is indicated for cholangitis in
patients with malignant biliary obstruction (MBO). However, preoperative biliary
drainage using plastic stents may increase the need of reintervention and periopera-
tive complications. We evaluated the usefulness of a removable fully covered self-
expandable metallic stent (FCSEMS) modified to minimize stent-induced complica-
tions in preoperative biliary drainage for potentially resectable distal MBO.
AIMS & METHODS: From January 2009 to Agust 2013, a total of 51 patients
underwent biliary drainage using a modified FCSEMS (BONASTENT M-
Intraductal, Standard Sci Tech Inc, Seoul, Korea) for suspicious distal MBO
that was potentially resectable or on stage work-up. Further treatment was
decided according to the final assessment; (1) curative intent surgery, (2) neoad-
juvant chemoradiation, (3) palliative treatment with/without chemoradiation, or
(4) removal of stent for finally proved benign biliary stricture.
RESULTS: The overall technical and clinical success rates of the biliary drainage
using a modified FCSEMS were 100% (51/51). Complications related with stent-
ing were developed in 5 patients (1 mild pancreatitis and 4 stent migrations).
Final diagnosis was 46 MBS (24 pancreatic head cancers, 18 CBD cancers, 3
gallbladder cancers and 1 ampullay cancer) and 5 benign biliary strictures (3
chronic pancreatitis and 2 autoimmune pancreatitis). 19 patients had undergone
curative intent pancreaticoduodenectomy. 3 patients had undergone surgical
resection after neoadjuvant chemotherapy. No stent-induced postoperative com-
plication occurred. The median stent patency in patients who had undergone
palliative treatment was 148 days (range, 73-256). Removal of the stent was
successful in all patients confirmed finally benign biliary strictures.
CONCLUSION: The modified FCSEMS may be effective for first line of biliary
drainage in patients with potentially resectable distal MBO without interfere for
further intervention.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0230 DOES CHEMOTHERAPY PROLONG THE STENT PATENCY IN
MALIGNANT DISTAL BILIARY STRICTURE?
M. Kida1,*, S. Miyazawa1, S. Tokunaga1, H. Yamauchi1, K. Okuwaki1, T. Iwai1,
M. Takezawa1, M. Watanabe1, H. Imaizumi1, W. Koizumi2
1
Endoscopy Center, 2Gastroenterology, KITASATO University Hospital,
Sagamihara, Japan
Contact E-mail Address: m-kida@kitasato-u.ac.jp
INTRODUCTION: Metallic stents for malignant distal biliary stricture have
become one of the best palliative treatments in inoperative cases who were gen-
erally treated by chemotherapy; however its influence in stent patency has not
been investigated and consensus is not established.
AIMS & METHODS: From 2002 to 2013, we have inserted metallic stents in
totally 259 cases with malignant distal biliary stricture, and treated 164(63%)
caes with chemotherapy and remaining 95(37%) cases with best supportive care
(BSC). We investigated the efficacy of chemotherapy in its stent patency etc.
retrospectively.
RESULTS: Subjects in this study were consisted of 206 (80%) pancreas cancers,
45(14%) biliary cancers, and 8(3%) papillary cancers. Metallic stents we used
were 152(59%) partially covered Wallstents (P-WS), 54(21%) partially covered
Wallflexs (P-WF), 34(13%) fully covered Wallflexs (F-WF), and 19(7%) fully
covered Bonastents (F-BS). There was no significant difference on base line
characteristics between chemotherapy group and BSC group except for age (68
vs 74 years olds). Chemotherapy we employed was Gemcitabine (GEM) alone,
GEM TS-1, and GEMTS-1CDDP etc. The median stent patency was 328
days in total, and the median stent patency of chemotherapy group was signifi-
cantly longer (354 days vs188 days in BSC, p 0.001). The median stent patency
of biliary cancer in chemotherapy group was significantly longer (341 days vs 119
days in BSC, p 50.001), whereas the median stent patency of pancreas cancer
in chemotherapy group was not significant.
CONCLUSION: We concluded that chemotherapy prolong the stent patency in
malignant distal biliary stricture, especially biliary cancers.
Disclosure of Interest: None declared
P0231 ENDOSCOPIC DOUBLE SELF-EXPANDING METAL STENT
PLACEMENT FOR THE TREATMENT OF MALIGNANT BILIARY
AND GASTRODUODENAL OBSTRUCTION: A LARGE SERIES OF
TREATED PATIENTS FROM A REFERRAL HOSPITAL FOR
PALLIATIVE CARE
R. Di Mitri1,*, F. Mocciaro1, G.M. Pecoraro1
1
Gastroenterology and Endoscopy Unit, ARNAS Civico-Di Cristina-Benfratelli
Hospital, Palermo, Italy
Contact E-mail Address: fmocciaro@gmail.com
INTRODUCTION: Patients with malignant gastroduodenal obstruction often
have coexistent biliary obstruction and require simultaneous endoscopic treat-
ment. The use of self-expandable metal stents (SEMS) is an effective palliative
treatment in patients with unresectable malignant gastroduodenal and biliary
obstructions.
AIMS & METHODS: The aims of this study are to evaluate the efficacy and
safety of double SEMS placement in a large consecutive series of patients with
malignant inoperable gastroduodenal and biliary obstruction. From March 2007
to March 2014 we collected data on all consecutive patients treated with double
SEMS placement (Wallflex Enteral and Biliary by Boston Scientific, Niti-S
Biliary by Taewoong). SEMS were placed under fluoroscopic and endoscopic
guidance. First the scope was allowed to reach the duodenal stricture, then a
guidewire equipped with an imaging catheter was passed through the stricture
allowing the deployment of the duodenal SEMS. The duodenoscope was passed
through the duodenal stent for accessing the papilla through the mesh of the
SEMS. After common bile duct cannulation and cholangiography a guidewire
was placed across the papilla. A balloon dilation to enlarge the spacing of the
tight mesh of the duodenal stent was performed allowing the placement of the
biliary SEMS. If possible balloon dilation of the duodenal stricture was per-
formed allowing the deployment of the biliary SEMS before duodenal SEMS
placement. Technical and clinical success, and adverse events were recorded.
RESULTS: 31 patients (20 male [65%]), with a mean age of 73.69.8 year, were
treated: 27 had pancreatic head cancer (87%), 2 antro-bulbar cancer (7%), 1
cholangiocarcinoma (3%), 1 duodenal obstruction due to colon cancer (3%).
The mean baseline bilirubin level and the median gastric outlet obstruction scor-
ing system (GOOSS) score were 16.73.8 mg/dL and 1 (range 0-3) respectively.
Technical success was achieved in all patients with significant reduction in bilir-
ubin levels (8.43.2 mg/dL) and a satisfactory oral feeding at discharge (GOOSS
score 3 [range 2-3]). No complications related to the SEMS placement were
recorded. Biliary stent occlusion occurred in 2 patients (6%) after 3 and 10
months. In 1 patient (3%) migration of the biliary stent was recorded after 5
months. The median hospital stay was 4 days (range 3-8) with a median survival
time of 6 months (range 3-8). All deaths were due to the natural course of under-
lying malignancy.
CONCLUSION: Endoscopic management of malignant gastroduodenal and
biliary obstructions with double SEMS placement is the treatment of choice in
advanced unresectable gastroduodenal tumors with biliary involvement too. It is
a safe procedure and it enhances patients quality of life. In advanced diseases or
in frail patients palliative surgery should be considered only in case of endoscopic
failure.
Disclosure of Interest: None declared
A193
P0232 COMPARISON OF OUTCOMES BETWEEN INTERNAL STENT
PLACEMENT AND PTBD IN PATIENTS WITH PLANNED CRT FOR
PERIHILAR CHOLANGIOCARCINOMA
S.W. Yi1,*, J.H. Cho2, J.B. Chung3, S.W. Park3, S.Y. Song3, S. Bang3
1
Internal medicine, Division of Gastroenterology, International St. Marys
Hospital, 2Internal medicine, Gachon University Gil Medical Center, Incheon,
3
Internal medicine, Division of Gastroenterology, Yonsei University College of
Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: sinbbori97@naver.com
INTRODUCTION: The optimal biliary decompression method in resectable
perihilar-cholangiocarcinoma has been authorized as percutaneous transhepatic
biliary drainage (PTBD). In case of locally advanced perihilar-cholangiocarci-
noma, malignant biliary obstruction is judged to have palliation of jaundice by
placement of an internal stents or PTBD. We aimed to investigate the efficacy of
internal placement of biliary stent compared with PTBD for patients planned
CRT in locally advanced perihilar-cholangiocarcinoma.
AIMS & METHODS: The patients who are histologically proven locally
advanced perihilar-cholangiocarcinoma between Jan. 1995 and Dec. 2013 at
single tertiary medical center in Korea, analyzed as prospective observational
study. The perihilar cholangiocarcinoma was defined as disease occurring above
the junction of the cystic duct up to the secondary branches of the hepatic duct.
RESULTS: Among one hundred seventy six locally advanced perihilar-cholan-
giocarcinoma patients, CRT was performed in 79 patients; endoscopic biliary
decompression was forty six patients (26.14%), and PTBD was thirty three
patients (18.75%). The mean period of internal stent indwelling is 152 days
whereas 222 days in PTBD group (p 0.675). The R0 operative rate after the
CRT was 23.9% in endoscopic stenting group, and 12.1% in PTBD group
(p 0.174). The median overall survivals were 463 days at endoscopic stenting
group and 439 days in PTBD group, respectively (p 0.874). Repeated biliary
decompression procedure was performed at endoscopic decompression group 26
patients (56.5%), 12 patients in PTBD group (36.4%) (p 0.077).
In the subgroup analysis of endoscopic stenting group, there were 25 cases of
SEMS, and 21 cases of biliary drainage using the plastic stent. The stent dysfunc-
tion was found in 20 patients (80.0%) with plastic stent and 6 patients (28.6%) in
SEMS group (p 0.001). Median stent patency time was 111 days and 402 days
in the plastic stent and SEMS, respectively (p 0.002). Post-operative major
complications were not seen in both cases.
CONCLUSION: The endoscopic placement of internal stent might be useful
method for biliary decompression in patients with planed CRT for locally
advanced perihilar-cholangiocarcinoma, compared to PTBD. In case of biliary
endoscopic drainage, the pre-CRT SEMS had lower rate for repeated endoscopic
procedure than plastic stent in perihilar-cholangiocarcinoma.
Disclosure of Interest: None declared
P0233 ENDOSCOPIC OESOPHAGEAL STRICTUROTOMY AS
PROMISING MODALITY IN THE TREATMENT OF BENIGN
RESISTANT OESOPHAGEAL STRICTURES
A.A. Monged1,*, G. Mohamed1, C.B. OSuilleabhain2, M. Buckley1 on behalf of
Gastroenterology depatment, mercy university hospital, cork, Ireland
1
Gastroenterology, 2Mercy University Hospital, Cork, Ireland
Contact E-mail Address: amongid@yahoo.com
INTRODUCTION: The majority of benign oesophageal strictures result from
long-standing gastroesophageal reflux disease. Treatment usually involves dila-
tion combined with acid-suppressive therapy. Other causes of resistant strictures
include post radiation, oesophageal sclerotherapy, caustic ingestions and surgical
anastomosis. In the majority of patients, this can be accomplished with oesopha-
geal dilation, though in cases of refractory strictures, additional therapy is
required. There is little published data on the treatment of resistant esophageal
strictures (ROS).
AIMS & METHODS: To describe our experience with Endoscopic Oesophageal
Stricturotomy (EOS) for resistant oesophageal strictures. From January 2012 to
July 2013 all patients with oesophageal strictures resistant to treatment with balloon
dilatation /- bougienage were selected for EOS. Data on Age, sex, co-morbidity,
clinical presentation, procedural details, and outcome were retrospectively collected,
anonymized, and analized. Endoscopic Oesophageal Stricturotomy procedures
were exclusively done by an experienced endoscopist (M. B.). Patient with resistant
strictures were assessed for suitability for Stricturotomy. Using Needle knife stric-
turotome (RX Needle Knife Boston scientific/ 5.5 F/1.8mm) Four quadrant inci-
sions were made and tissue excised. Stricturotomy was followed by hydrostatic
balloon dilatation if residual stenosis was present.
RESULTS: A total of five male dysphagic patients, median age 58, (range 29-81),
with resistant oesophageal strictures were treated with EOS, during the study
period. Two patients had strictures due to peptic fibrosis, two due to exposure to
radiotherapy, and one had post surgery for oesophageal atresia. 80% (4/5) had
multiple previous trials of unsuccessful balloon. One session of Stricturotomy
was enough for 80% of patients, however, for one patient (20%) EOS were
needed to be repeated 5 times. Only 40% (2 patients) needed balloon dilatation
following the EOS. In all patients, successful response following initial EOS was
obtained.
CONCLUSION: EOS is highly effective in treating selected patients with resis-
tant benign oesophageal strictures. Initial response has been achieved to all five
patients, refractory oesophageal stricture was noted in one patient, that has
finally showed good response after the 5th Stricturotomy session. Short focal
strictures may be more suitable for EOS. The risk of perforation following
EOS is not yet known, and needs to be elucidated in longer studies.
Stricturotomy is a valuable method in the treatment of patients with resistant
oesophageal strictures.
A194
REFERENCES
Patterson DJ, Graham DY, Smith JL, et al. Natural history of benign esophageal
stricture treated by dilatation. Gastroenterology 1983; 85: 346.
Marks RD and Richter JE. Peptic strictures of the esophagus. Am J
Gastroenterol 1993; 88: 1160.
Riley SA and Attwood SEA. Guidelines on the use of oesophageal dilatation in
clinical practice. Gut 2004; 53(Suppl. I): i1i6.
Standards of Practice Committee, Egan JV, Baron TH, et al. Esophageal dilata-
tion. Gastrointest Endosc 2006; 63: 755.
Hernandez LV, Jacobson JW and Harris MS. Comparison among the perfora-
tion rates of Maloney, balloon and Savary dilation of esophageal strictures.
Gastrointest Endosc 2000; 51: 460462.
Disclosure of Interest: None declared
P0234 LONG-TERM COMPLICATIONS OF SELF-EXPANDABLE
METALLIC STENT IN PATIENTS WITH ADVANCED
ESOPHAGEAL CANCER
B.C. Martins1,*, M.S. I. Ribeiro1, F.A. Retes1, M.S. Lima1, A. V. Safatle-
Ribeiro1, C.C. Gusmon1, C.M. Pennacchi1, F.S. Kawaguti1, R.S. Uemura1,
U. Ribeiro Jr2, F. Maluf-Filho1
1
Endoscopy, 2Gastroenterology, Cancer Institute of the University of Sao Paulo,
Sao Paulo, Brazil
Contact E-mail Address: bcm.bruno@gmail.com
INTRODUCTION: Self-expandable metallic stents (SEMS) are considered the
best palliative treatment of dysphagia of patients with advanced esophageal
cancer. Complications are a major concern, especially in patients with better
prognosis and longer survival.
AIMS & METHODS: The aim of this study was to assess the prevalence of
SEMS-related complications in the follow-up of patients with advanced esopha-
geal cancer who survived longer than 6m. We performed a retrospective analysis
of a prospective collected database of patients with advanced esophageal cancer
submitted to SEMS palliation between February 2009 and December 2012 at the
Cancer Institute of the University of Sao Paulo. Patients with follow-up longer
than 180 days were included in this study.
RESULTS: Of the 145 patients from the database, 32 were selected. There was a
predominance of male patients (78.1%), mean age of 60 years with squamous cell
carcinoma (78.1%). The lesions were mainly located in the middle esophagus
(53.1%). Twenty-nine stents were partially covered (90.6%) and three completely
covered (9.4%). Twenty-two (68.7%) patients received chemo and/or radiother-
apy before and 26 (81.2%) patients after SEMS insertion. Complications
occurred in 20 patients (62.5%): migration (n 9), overgrowth (n 8), ingrowth
(n 4), fistula (n 3), pulmonary infection (n 2), food impaction (n 2),
GERD (n 1), bleeding (n 1) and intractable pain (n 1). Most complications
could be managed endoscopically. Fatal complications occurred in 2 (6.2%)
patients: 1 bleeding and 1 pulmonary infection. The median survival after pros-
thesis was 305 days (range 182-630 days). A mean of 0.9 procedures per patient
(range 0-10) were performed to maintain stent patency. At the end of the follow-
up, 20 patients still had a functional stent, while 12 patients had either retrieved
the stent or received a nasogastric tube.
CONCLUSION: The use of SEMS in patients with advanced esophageal cancer
who live longer than 6m is associated with high complication rate. Most com-
plications are usually nonfatal and are managed endoscopically.
REFERENCES
1. Schoppmann SF, Langer FB, Prager G, et al. Outcome and complications of
long-term self-expanding esophageal stenting. Dis Esophagus 2013; 26: 154-158.
2. Park JJ, Lee YC, Kim BK, et al. Long-term clinical outcomes of self-expand-
ing metal stents for treatment of malignant gastroesophageal junction obstruc-
tions and prognostic factors for stent patency: effects of anticancer treatments.
Dig Liver Dis 2010; 42: 436-440.
Disclosure of Interest: None declared
P0235 RISK FACTORS FOR METALLIC STENTS MIGRATION IN
PATIENTS WITH ADVANCED ESOPHAGEAL CANCER
B.D. C. Martins1,*, F.A. Retes1, M.S. Lima1, A. V. Safatle-Ribeiro1, M.S.
I. Ribeiro1, C.M. Pennacchi1, F.S. Kawaguti1, R.S. Uemura1, U. Ribeiro Jr2,
M.C. Franco1, J.T. Rios1, F. Maluf-Filho1
1
Endoscopy, 2Gastroenterology, Cancer Institute of the University of Sao Paulo,
Sao Paulo, Brazil
Contact E-mail Address: bcm.bruno@gmail.com
INTRODUCTION: Migration is one of the most common complications after
stent placement to palliate dysphagia in patients with inoperable esophageal
neoplasia. It occurs in up to 36% of the cases, so it would be useful to recognize
risk factors associated with this complication as preventive measures could be
taken to prevent it.
AIMS & METHODS: The aim of this study was to identify risk factors for
esophageal stents migration in patients with advanced esophageal cancer.
From 2009 to 2012, patients with advanced esophageal neoplasia who underwent
SEMS placement were followed prospectively and data were collected to evalu-
ated risk factors associated with stent migration. Patients with less than 1 month
follow-up were excluded from the study.
RESULTS: A total of 145 patients with a median age of 63 years (SD10) and
male predominance (79.3%) were enrolled in the study. The most common his-
tology was squamous cell carcinoma (109 cases, 75%) followed by adenocarci-
noma (24 cases, 16.5%), and extra-esophageal cancer (12 cases, 8.5%). The lesion
was located in the distal third of the esophagus in 54 (37.2%), in the mid-eso-
phagus in 70 (48.3%) and in the proximal esophagus in 21 (14.5%) patients.
Mean tumors length was 7.5cm (SD 2.8cm). Fifty-nine (40.7%) patients
United European Gastroenterology Journal 2(5S)
received chemoradiation prior and 13 (9.0%) after the stent implantation.
Partially covered stents were placed in 135 (93%) pts and fully covered SEMS
were placed in 10 (7%) pts. Evolution (n 69, 47.5%), Hanaro (n 44, 30.3%),
Endoflex (n 13, 9%), Wallflex (n 12, 8.2%), Plastimed (n 6, 4.2%) and
Ultraflex (n 1, 0.8%) stents were used. After a median follow-up of 156 days
(range: 31 630 days), the migration rate was 13.1% (19 patients, range: 1-323
days). The mean survival rate after the procedure was 146 days. Univariate
analysis showed that fully covered stents (p 0.049) and body stent diameter
measuring less than 20mm (p 0.004) were significantly associated with higher
migration rate.
CONCLUSION: Fully covered stents and stents with body diameter measuring
less than 20mm are associated with higher migration rate.
REFERENCES
Verschuur EM, Homs MY, Steyerberg EW, et al. A new esophageal stent design
(Niti-S stent) for the prevention of migration: a prospective study in 42 patients.
Gastrointest Endosc 2006; 63: 134-140.
Langer FB, Schoppmann SF, Prager G, et al. Temporary placement of self-
expanding oesophageal stents as bridging for neo-adjuvant therapy. Ann Surg
Oncol 2010; 17: 470-475.
Disclosure of Interest: None declared
P0236 ENDOSCOPIC ULTRASOUND (EUS) GUIDED SELF EXPANDING
METAL STENTS (SEMS) PLACEMENT FOR GASTRIC OUTLET
OBSTRUCTION
C. Shekhar1,*, S. Hebbar2, B. Mahon1
1
Radiology, Queen Elizabeth Hospital, Birmingham, 2Gastroenterolgoy, University
Hospital of North Staffordshire, Stoke on Trent, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
INTRODUCTION: SEMS placement is an effective way of relieving gastric
outlet obstruction, majority of them done endoscopically under fluroscopy gui-
dance. This is known to be superior to surgical bypass with lower morbidity,
mortality, and shorter hospital stay1,2. At times, despite direct vision through the
endoscope and fluroscopy guidance, it can be difficult or unmanageable to posi-
tion a SEMS
AIMS & METHODS: To evaluate use of EUS as an adjunct to safely and
effectively delineate lumen through the obstructing lesion and place SEMS
through EUS scope with / without fluroscopy guidance. All procedures were
done using Olympus linear scope (GF-UCT240) and Evolution (Cook
Medical) SEMS were used (22x 60-120mm).
RESULTS: Between February 2010 to November 2011, 15 patients had duode-
nal/enteral SEMS placement using EUS. All patients had prior CT scan and
endoscopy. All had successful stent placement using EUS technique, when it
was not possible to be done by endoscopic view supplemented with fluroscopy
guidance in previous or done as tandem procedures in same sitting. One patient
had 2 stents placed, one in afferent loop endoscopically and another one in
efferent loop with help of EUS.
One patient had perforation, stent was placed successfully across a tight angu-
lated stricture but caused tear as it expanded across the angulated obstruction,
which was managed surgically.
Endoscopic implantation of SEMS in a malignant gastric outlet obstruction is a
safe and effective method. However, any obstruction beyond direct access of
scope, presence of food/liquid debris and some times contact bleeding obscuring
views are impediments in successful implantation of a stent. Most of the time this
is due to inability to visualise/delineate the lumen beyond direct vision even with
help of fluroscopy. There is high risk of false passage formation/perforation if
wire/catheter are advanced blindly. EUS has an added advantage of visualising
lumen even in above circumstances, especially when endoscopic views are poor.
CONCLUSION: This is first ever case series reporting use of EUS in gastro-
duodenal SEMS placement. We believe this is useful adjunct to existing techni-
ques. However, this needs to be evaluated further in larger comparative studies.
As with any other complex intervention, this is highly dependent on experience of
the operator in endoscopic stent placement as well as EUS modality.
REFERENCES
1. Endoscopy 2004; 36: 73-78.
2. Surg Endosc 2002; 16: 310-312.
Disclosure of Interest: C. Shekhar: None declared, S. Hebbar: None declared, B.
Mahon Financial support for research from: Cook
P0237 EFFICACY AND SAFETY OF A PARTIALLY COVERED
DUODENAL STENT FOR MALIGNANT GASTRODUODENAL
OBSTRUCTION
D. Oh1,*, S.S. Lee1, T.J. Song1, D.H. Park1, D.W. Seo1, S.K. Lee1, M.-H. Kim1
1
Division of Gastroenterology, Department of Internal Medicine, University of
Ulsan College of Medicine, Asan Medical Center, Seoul, Korea, Seoul, Korea,
Republic Of
Contact E-mail Address: dongwook.oh1@gmail.com
INTRODUCTION: Duodenal stent placement has emerged as an effective and
safe palliative treatment for patients with malignant gastroduodenal obstruction.
The uncovered enteral stent is susceptible to re-stenosis due to tumor ingrowth.
Although covering an enteral stent with a membrane almost solves the problem
of tumor ingrowth, stent migration continues to be a major unresolved problem.
Recently, a partially covered metallic stent was introduced for gastroduodenal
obstruction.
AIMS & METHODS: Duodenal stent placement has emerged as an effective and
safe palliative treatment for patients with malignant gastroduodenal obstruction.
The uncovered enteral stent is susceptible to re-stenosis due to tumor ingrowth.
Although covering an enteral stent with a membrane almost solves the problem
United European Gastroenterology Journal 2(5S)
of tumor ingrowth, stent migration continues to be a major unresolved problem.
Recently, partially covered metallic stent was introduced for gastroduodenal
obstruction. Twenty patients with malignant gastroduodenal obstruction
received palliative treatment with partially covered duodenal stents. Technical
success was defined as the placement of the stent successfully. Clinical success
was defined as the relief of obstructive symptoms and/or improvement of the
Gastric Outlet Obstruction Scoring System score to  2 after the procedure.
RESULTS: A total of 20 patients (11 men and 9 women; median age 64.5 years,
range 39-85 years) were enrolled in this study. Ten patients had pancreatic
cancer, four patients had gallbladder cancer, two had cholangiocarcinoma, one
had advanced gastric cancer, one had metastatic rectal cancer, one had liver
sarcoma, and one had ampulla of Vater cancer. Stent placement was successful
in 20 of 20 patients (technical success, 100%). Symptoms improved in 19 patients
after stent placement (clinical success, 95%). The Gastric Outlet Obstruction
Scoring System score improved significantly (P-value 5 0.001). Tumor over-
growth developed in eight patients during patients survival period (40%).
Stent migration did not occur in any case. Median stent patency was 79.5 days
(range 13-198 days). Adverse events occurred in 3 patients, comprising two cases
of transient bacteremia, and one of asphyxia due to impaction of food material
into the stent.
CONCLUSION: Partially covered duodenal stent was effective and safe for the
malignant gastroduodenal obstruction and can prevent tumor ingrowth and stent
migration.
REFERENCES
1. Didden P, Spaander MC, de Ridder R, et al. Efficacy and safety of a partially
covered stent in malignant gastric outlet obstruction: a prospective Western
series. Gastrointest Endosc 2013; 77: 664-668.
2. Tringali A, Didden P, Repici A, et al. Endoscopic treatment of malignant
gastric and duodenal strictures: a prospective, multicenter study. Gastrointest
Endosc 2013.
3. Kanno Y, Ito K, Fujita N, et al. Efficacy and safety of a WallFlex enteral stent
for malignant gastric obstruction. Dig Endosc 2013; 25: 386-391.
4. Jung GS, Song HY, Kang SG, et al. Malignant gastroduodenal obstructions:
treatment by means of a covered expandable metallic stent-initial experience.
Radiology 2000; 216: 758-763.
Disclosure of Interest: None declared
P0238 A NOVEL REINFORCEMENT METHOD FOR THE SURFACE OF
GASTOINTESTINAL METAL STENT: GAS PLASMA TREATMENT
H.S. Choi1,*, E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, H.J. Chun1,
C.D. Kim1, J.-J. Park1, S.W. Lee1, H.B. Kim2
1
Internal Medicine, Korea University College of Medicine, Seoul, 2Institute of
Interventional Medicine, M. I. Tech Co., Ltd, Pyeongtaek, Korea, Republic Of
INTRODUCTION: A gastrointestinal (GI) stent, which is made of Nickel-
Titanium (NiTi) alloy coating with a silicone polymer, has been using for the
relief of obstructive symptom in malignant stenosis of gastrointestinal tract. But
the corrosion and fatigue failures of nitinol devices have been constant subjects of
discussion. Recently, GI nitinol stent use is increasing abruptly, and fractures of
GI stents have been reported. Although coating with the silicone polymer on the
stent plays a key role in corroding, corrosion properties may differ along the
surface of the NiTi alloy wire. The surface modification with plasma etching
technology is a way to improve the physical properties of the target. We system-
atically investigated a reinforcement of nitinol alloy and surface modification to
stick the silicone employing gas plasma treatment.
AIMS & METHODS: The fifteen NiTi alloy stents were treated in a few condi-
tions of the plasma treatment, in which mixture rates of Ar and O2 gas, applied
voltages and duration of exposing time were varied. We prepared three kinds of
stents; normal stent (product by normal process, sample 1), slightly etched
normal stent (product by plasma treatment, sample 2) and natural oxide layer-
eliminated normal stent (product that removed natural oxide regions by plasma
treatment, sample 3). The stents were analyzed with a transmission electron
microscope (TEM) and scanning electron microscope (SEM) to examine surface
topographies of the stents and the interlocking state between wire and silicone
polymer. We performed a potentiodynamic test to compare the corrosion state of
each stent in GI state.
RESULTS: The surface profile of the samples showed that some content of the
oxide layer for the normal stent was formed in thickness of about 100nm, while
the others was 6070nm by TEM analysis. Moreover, the oxide layer for normal
product and slightly etched normal stent was likely to exhibit deposition of
oxygen without interlocking that enhances cohesion, whereas natural oxide
layer-eliminated normal stent showed behavior of strong interlocking between
oxide and nickel. SEM image showed effective modification of nitinol wire to
stick the silicone polymer by plasma etching technology. In a potentiodynamic
test, the sample 3 removed natural oxide regions by plasma treatment, indicating
the strongest corrosion resistance.
CONCLUSION: This result implies that an interlocking between nickel and
oxide layer plays a significant role in corrosion resistance. Natural oxide layer
by normal manufacture process induced micro-crack of nitinol GI, stent and
removing the natural oxide layer by plasma treatment improved reinforcement
and surface modification of nitinol GI stent. These results revealed that the
plasma treatment could be employed to improve the surface property of GI
stent for malignant outlet obstruction.
Disclosure of Interest: None declared
A195
P0239 ENDOSCOPIC ELECTROCAUTERY DILATION OF POST-
SURGICAL BENIGN ANASTOMOTIC COLONIC STRICTURES: A
SINGLE CENTER EXPERIENCE
I. Bravi1,*, D. Ravizza1, G. Fiori1, D. Tamayo1, C. Trovato1, G. De Roberto1,
L. Laterza1, C. Crosta1
1
Division of Endoscopy, European Institute of Oncology, Milan, Italy
Contact E-mail Address: ivana.bravi@ieo.it
INTRODUCTION: Benign anastomotic colonic stenosis sometimes occur after
surgery and usually requires surgical or endoscopic dilation. Endoscopic dilation
of anastomotic colonic strictures by using balloon or bougie-type dilators has been
demonstrated to be safe and effective in multiple uncontrolled series. However, few
data are available on safety and efficacy of endoscopic electrocautery dilation.
AIMS & METHODS: Aim of our study was to retrospectively investigate safety
and efficacy of endoscopic electrocautery dilation of post-surgical benign ana-
stomotic colonic strictures.
Patients with post-surgical benign anastomotic colonic strictures treated with
endoscopic electrocautery dilation between June 2001 and February 2013 were
considered. Anastomotic stricture was defined as a narrowed anastomosis
through which a standard colonoscope could not be passed. Only annular ana-
stomotic strictures were considered suitable for electrocautery dilation which
consisted of radial incisions performed with a precut sphincterotome.
Treatment was considered successful if the colonic anastomosis could be
passed by a standard colonoscope immediately after dilation. Recurrence was
defined as anastomotic stricture reappearance during follow-up.
RESULTS: Sixty-eight patients (43 women and 25 men, median age 63.6 yrs
(22.6-81.7)) were included. Nine had undergone adiuvant radiotherapy and che-
motherapy, 25 adiuvant chemotherapy only. Forty-four patients had a colo-
rectal, 19 had a colo-colic and 5 an ileo-rectal anastomosis. Five patients had a
colostomy and 12 an ileostomy. Two patients were referred for subocclusive
symptoms, nine for stipsis and six for stool shape modification. The time-interval
between colorectal surgery and the first endoscopic evaluation or symptoms
development was 7.3 months (1.3-60.7). Electrocautery dilation was successful
in all the patients. There were no procedure-related complications. Median
follow-up was 35.5 months (2.0-144.0). Anastomotic stricture recurrence was
observed in two patients who were successfully treated with electrocautery dila-
tion and Savary dilation, respectively.
CONCLUSION: Endoscopic electrocautery dilation is a safe and effective treat-
ment for annular benign anastomotic post-surgical colonic strictures.
Disclosure of Interest: None declared
P0240 BIODEGRADABLE STENTS IN PATIENTS WITH ACUTE LARGE
BOWEL OBSTRUCTION SECONDARY TO A RECTAL TUMOR AND
INDICATION FOR FURTHER NEOADJUVANT THERAPY:
OUTCOMES AND SAFETY
J. Jimenez-Perez1,*, I. Fernandez-Urien1, J. Vila1, E. Albeniz1
1
GASTROENTEROLOGY, COMPLEJO HOSPITALARIO DE NAVARRA,
Pamplona, Spain
Contact E-mail Address: jjimenezpster@gmail.com
INTRODUCTION: Colorectal stenting is the first choice treatment in patients
with acute large bowel obstruction due to the presence of a malignant tumor in
the left colon. After colon decompresion, stenting allows accurate tumoral staging
and patient preparation for further surgery. However, stenting is controversial in
rectal tumors. The presence of a metallic stent in a patient undergoing neoadjuvant
therapy increases disperse radiation and collateral inflammation in surrounding
tissues, leading to a higher complication rate and poorer surgical results.
AIMS & METHODS: The aim of this study was to assess the outcomes of
biodegradable stents in patients with obstructing rectal tumors undergoing
neoadjuvant therapy. A prospective observational study was conducted including
patients with acute large bowel obstruction due to a rectal cancer and candidates
to neoadjuvant therapy. After large bowel obstruction was diagnosed, a CT scan
was performed to confirm the etiology of the obstruction and, in patients with a
rectal tumor, to characterize the lesion and to assess the indication of further
neoadjuvancy. A biodegradable stent was inserted in these cases. Patients were
followed until surgery or until death if surgical treatment was dismissed.
Technical success at stent insertion, clinical success, stenting complications and
surgical findings and outcomes (primary anastomosis and postoperative compli-
cations) were documented.
RESULTS: 8 patients [4 men/4 women; mean age: 62.6 yr (51-77)] were enrolled
in the study. Once further neoadjuvant therapy was considered indicated, a
polydioxanone monofilament biodegradable stent (Ella-CS. Czceh Rep) was suc-
cessfully inserted in all patients (100%) [31/25/31 mm; 6 cm (n 2), 8 cm (n 6)
length]. Initial colon decompression was achieved in every case (100%) but the
stent migrated in one patient (12.5%) and a second stent was inserted. Patients
underwent neoajuvant therapy [RT: 50.4 Gy in 28 sessions capecitabine (825
mg/m2/12 h)] and were reevaluated with a CT scan at the end of treatment. 3
patients did not go for surgery after tumoral staging, received chemotherapy and
did not present occlusive symptoms until death (mean follow-up: 220 days). 5
patients were operated 96 days after stent insertion (66-123 days). Primary ana-
stomosis was performed in 3 (60%) whereas colostomy was performed in 2 (40%)
due to severe local inflammation in one case and a silent perforation in the other.
The only post surgical complication was a pneumonia in one patient (12.5%). No
wound or anastomosis complications were registered
CONCLUSION: 1. Biodegradable stents are effective in patients with rectal
tumors and secondary large bowel obstruction. 2. Association with neoadjuvant
therapy causes local inflammation but allows primary anastomosis in 60% of
cases and is not followed by an increased post surgery complication rate.
Disclosure of Interest: None declared
A196
P0241 SELF-EXPANDABLE METAL STENTS FOR MALIGNANT
COLONIC OBSTRUCTION
L.C. Meireles1,*, P. Sousa1, L.C. Freitas2, J. Lopes1, L.C. Ribeiro1, J. Velosa1
1
Department of Gastroenterology, Centro Hospitalar Lisboa Norte, Lisboa,
2
Department of Gastroenterology, Centro Hospitalar do Funchal, Funchal,
Portugal
Contact E-mail Address: lilianeenailil@gmail.com
INTRODUCTION: Tumoral obstructions in almost the entire gastrointestinal
tract can be treated with interventional digestive endoscopy techniques. The use
of self -expanding metal stents (SEMS) is a minimally invasive procedure provid-
ing a relatively simple and effective first- line treatment for the relief of obstruc-
tive symptoms.
AIMS & METHODS: To report data from a single center study on self-expand-
able metal stent (SEMS) placement for malignant colorectal obstruction. One
hundred and six patients (64 males, mean age of 7114 years), in a period of 96
months, were retrospectively evaluated and data on type and size of stent, com-
plications, lesion location, and survival after the procedure were analyzed.
RESULTS: Most lesions were located in the rectum (50%, n 53), 36% (n 38)
in the sigmoid colon, descending colon in 8.4% (n 9) and 5.6%(n 6) in the
transverse colon. The mean length of the lesions was 65  36mm. Most proce-
dures were performed with palliative intent and in 4 patients two or more stents
were placed. The stent was uncovered in 92% of cases and partially covered in
8% of the procedures. Complications were 4 neoplastic ingrowths, 3 stent migra-
tions and 1 perforation. Seventy-five percent of patients were dead by the time of
data collection, with a median interval between stenting and death of 105 days.
CONCLUSION: Colonic obstruction may be treated using endoscopic techni-
ques. The placement of SEMS seems to be a safe and effective treatment.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
SURGERY I POSTER EXHIBITION HALL XL_____________________
P0242 WHAT SWEDISH SURGEONS DO WHEN DETECTING
COMMON BILE DUCT STONES DURING CHOLECYSTECTOMY
F. Swahn1,*, L. Enochsson1, U. Arnelo2, M. Lohr2, R. Noel2
1
CLINTEC, Division of surgery, 2KAROLINSKA INSTITUTET, Stockholm,
Sweden
Contact E-mail Address: fredrik.swahn@ki.se
INTRODUCTION: About 11,000 cholecystectomies are done annually in
Sweden, most of which are completed laparoscopically (about 90%).
Management strategies for common bile duct stones (CBDS) have been discussed
in to an extreme extent and new options are rapidly emerging.
AIMS & METHODS: The aim of the study was to describe the current strategies
applied in routine clinical practice in Sweden. A survey questionnaire was mailed
to all hospitals (70) offering cholecystectomies and we obtained responses from
all of them (100%). The questionnaire captured information on the details of
clinical management strategies in a variety of different clinical manifestations of
CBDS.
RESULTS: 35 (50%) of the hospitals reported a predefined policy regarding the
management of CBDS. 65 (93%) hospitals used intra-operative cholangiography
as a routine, 2 in selective cases and 2 did not. Management of a 3 mm large
CBDS received that; 38 (54.3%) left it untreated, 23 (32.8%) performed some
kind of intra-operative procedure, 3 (4.3%) preferred a post-operative ERCP; In
case of a 6 mm large CBDS, the corresponding figures were; 3 (4.3%), 38
(52.2%), 17 (24.2%) respectively; In case of a 17 mm large CBDS: 23 (32.9%)
preferred open CBD exploration and 4 (4.3%) a laparoscopic CBD-exploration,
6 (8.6%) post-operative ERCP. 40 (57.1%) of the hospitals used intra-operative
ERCP with some kind of rendezvous cannulation technique.
CONCLUSION: Half of Swedens surgical units do not follow a predefined
policy regarding the intra-operative management of CBDS. Intra-operative
ERCP with rendezvous cannulation technique is currently the strategy that is
gaining popularity.
Disclosure of Interest: None declared
P0243 INDEPENDENT PROGNOSTIC FACTORS AFTER RESECTION
OF PERIHILAR CHOLANGIOCARCINOMA: ANALYSIS OF 307
PATIENTS FROM TWO HPB CENTERS
J. Wiggers1,*, B. Groot Koerkamp2, P. Allen2, O. Busch1, M. DAngelica2,
R. Dematteo2, D.-J. Gouma1, P. Kingham2, W. Jarnagin2, T.van Gulik1
1
Surgery, Academic Medical Center, Amsterdam, Netherlands, 2Surgery,
Memorial Sloan Kettering Cancer Center, New York, United States
Contact E-mail Address: j.k.wiggers@amc.nl
INTRODUCTION: The purpose of this study was to determine survival and
independent prognostic factors after resection of perihilar cholangiocarcinoma
(PHC).
AIMS & METHODS: Patients with PHC resected between 1991 and 2012 were
identified from prospectively maintained databases from two institutions (in
Europe and USA). Patients with final pathology other than PHC or in-hospital
mortality were excluded. Prognostic factors were evaluated using univariate
Kaplan-Meier survival analysis with log-rank test and multivariable cox-propor-
tional hazards modelling using backward selection with likelihood ratio test.
RESULTS: 307 patients underwent resection for PHC. The median overall sur-
vival was 38 months, and 5-year survival 37%. In multivariable analysis four
factors were independently associated with a poor prognosis: a positive resection
margin, HR 1.69 [95% CI: 1.25-2.28], p 0.001, one or more positive lymph
United European Gastroenterology Journal 2(5S)
nodes, HR 2.31 [1.66-3.23], p50.001, perineural invasion, HR 1.59 [1.13-2.23],
p 0.008, and moderate or poor differentiation, HR 1.64 [1.15-2.33], p 0.006.
Other traditional factors were associated with a poor prognosis only in univariate
analysis, including lymphovascular invasion, non-papillary tumor, T-stage (7th
edition), and AJCC stage (7th edition). Patients with at least 3 out of 4 poor
prognostic factors (n 90) had a median survival of 19 months [95% CI: 16-22]
versus 52 months [95% CI: 40-64]. Analyzing R0 patients separately resulted in
the same independent prognostic factors.
CONCLUSION: A positive resection margin, one or more positive lymph nodes,
perineural invasion and moderate or poor differentiation are independent prog-
nostic factors after resection of PHC. Based on these poor prognostic factors we
will derive and validate a prognostic nomogram for resected perihilar
cholangiocarcinoma.
Disclosure of Interest: None declared
P0244 SUCCESSFUL ENHANCED RECOVERY PROGRAMME IN
MAJOR LIVER SURGERY
J. Savikko1,*, M. Ilmakunnas2, H. Makisalo1, A. Nordin1, H. Isoniemi1
1
Department of Transplantation and Liver Surgery, 2Department of
Anaesthesiology and Intensive Care Medicine, Helsinki University Central
Hospital, Helsinki, Finland
Contact E-mail Address: johanna.savikko@helsinki.fi
INTRODUCTION: Enhanced recovery protocols after surgery accelerate
patients recovery and shorten hospital stay as a result of the optimization of
perioperative care. In colorectal surgery these protocols show high-level evidence
on reducing primary and total hospital stay without compromising the patient
safety. This increased knowledge of perioperative pathophysiology and care has
also been slowly implemented into liver surgery. However, in liver surgery the
experience of optimized protocols is still limited.
AIMS & METHODS: Here we studied in a prospective way the implementation
of multimodal rehabilitation protocol in a tertiary liver surgery unit within a one
year period. This study involves the first 134 consecutive patients who were
treated according to the enhanced recovery principles in open or laparoscopic
liver surgery. An opioid-sparing pain treatment regimen was chosen for these
patients together with early mobilization and oral feeding as well as avoidance or
quick removal of drains and catheters shortly after surgery. Primary pain control
was achieved either with epidural or locally inserted wound catheter analgesia.
Peroral combination of pregabalin, ibuprofen and slow-release tramadol was also
routinely administered shortly after the operation for pain relief.
RESULTS: All investigated liver resections were performed between April 1st,
2013 and March 31st, 2014. Most of the resections (72%) were major liver
surgery involving 2 or more liver segments. Operations were done due to color-
ectal livers metastases (55% of cases), other liver metastases (9%), hepatocellular
carcinoma (13%), gall bladder carcinoma (7%), peripheral cholangiocarcinoma
(6%), and the rest 10% were done for benign liver tumors. Operations requiring
hepatobiliary reconstructions were excluded from this study. 125 of the opera-
tions were open and 9 laparoscopic surgery.
56 of the operated patients were female, 78 male. Age median was 63 years (range
26-86 years). Only 2 patients were admitted to intensive care unit postoperatively;
1 planned admission, 1 due to perioperative pulmonary embolism. Median post-
operative hospital stay was 4 days (range 2-11 days). 80% of all patients were
discharged by the 5th postoperative day: 35% at the 3rd, 29% at the 4th and
15% at the 5th postoperative day. Two of the laparoscopically-operated patients
were discharged at the 2nd, 6 at the 3rd and 1 patient at the 5th postoperative
day. 5% of all patients were discharged via their own district hospitals.
Only 3 patients were readmitted back to the liver surgery ward; 1 patient (dis-
charged at the 3rd day) because of pain problems and 2 patients (both discharged
at the 5th day) because of elevated liver enzymes seen at the scheduled control
visit few days after discharge.
CONCLUSION: Enhanced recovery protocol for perioperative care was intro-
duced safely and effectively after major liver surgery. Routine discharge 2-3 days
after laparoscopic resection and even 3-4 days after open resection is realistic and
achievable.
Disclosure of Interest: None declared
P0245 HEPATOBILIARY SCINTIGRAPHY USING 99MTC-
MEBROFENIN FOR THE ASSESSMENT OF LIVER FUNCTION
AND BILIARY DECOMPRESSION IN PATIENTS WITH
RESECTABLE HILAR CHOLANGIOCARCINOMA
K.P. Cieslak1,*, J.K. Wiggers1, R.J. Bennink2, O.R. C. Busch1, D.J. Gouma1,
T.M. van Gulik1
1
Surgery, 2Nuclear Medicine, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: k.p.cieslak@amc.nl
INTRODUCTION: Assessment of future remnant liver (FRL) function is crucial
in resectable hilar cholangiocarcinoma (HCCA) while complete biliary drainage
of the FRL is considered essential for postoperative function and regeneration in
extended resections. 99mTc-mebrofenin-hepatobiliary-scintigraphy (HBS) pro-
vides segmental, quantitative information on parenchymal function in the
uptake phase, while the excretion of 99mTc-mebrofenin depends on drainage of
the biliary system.
AIMS & METHODS: The aim of this study was to evaluate the value of HBS in
the preoperative work-up of patients undergoing resection for HCCA.
From 2008 to 2013, 67 patients suspected of HCCA underwent resection (7/67
(10.4%) hilar resection and 60/67 (89.6%) hilar resection in combination with
liver resection). Preoperative HBS was used to generate time-activity curves from
regions-of-interest (total liver and FRL). The excretion rate was calculated as
decrease in mebrofenin activity in time (%/min) in the FRL.
United European Gastroenterology Journal 2(5S)
RESULTS: HBS was performed in 51 of 67 patients. Preoperative biliary drai-
nage had been performed in 44/51 patients. HBS showed sufficient function in
30/44 patients (group A), whereas 14/44 patients required additional procedures
(group B), consisting of revision of biliary drainage (n 8; 18.2%), portal vein
embolization (n 2; 4.5%) or a modified (parenchyma sparing) technique (n 8;
18.2%). Overall excretion rate in group A was 2.17%/min (IQR25-IQR75 1.03-
2.36) vs. 1.15%/min (IQR25-IQR75 0.81-1.50) in group B (p 0.03).
Overall mortality in 67 patients was 7.5%. Morbidity was 50.0% and 42.9% in
group A and B, respectively (p 0.75). Two patients died due to postoperative
liver failure: 1/30 (3.3%) in group A with sufficient FRL-function but low excre-
tion rate and 1/14 (7.1%) in group B despite revision of biliary drainage
(p 0.54).
CONCLUSION: HBS provides combined quantitative assessment of parenchy-
mal function (uptake phase) and biliary decompression (excretion phase) of the
FRL enabling identification of patients who require additional or modified pro-
cedures prior to resection of HCCA.
Disclosure of Interest: None declared
P0246 IATROGENIC BILIARY INJURIES:MULTIDISCIPLINARY
MANAGEMENT IN A MAJOR TERTIARY REFERRAL CENTER
O.H. Abdulsalam1,*, I.A. Salama1, H. Shoreem1, S. Saleh1, K. Aboella1,
M. Hoyseni2, M. Abbasy2, G. Badra3,4, M.S. Hashim4
1
Hepato-pancreatico-biliary surgery, 2DEPARTMENT OF RADIOLOGY,
3
DEPARTMENT OF HEPATOLOGY, 4HEPATOLOGY, National Liver
Institute, sheben elkom, Egypt
Contact E-mail Address: OSHEGAZY2002@YAHOO. COM
INTRODUCTION: Iatrogenic biliary injuries are considered as the most serious
complications during cholecystectomy. Better outcomes have been shown in
cases managed in a specialized center.
AIMS & METHODS: To evaluate the management and outcome of biliary
injuries by multidisciplinary team in major referral hepatobiliary center. From
January 2002 to January 2012,472 patients (302 females & 170 males) with post-
cholecystectomy biliary injuries were managed with multidisciplinary team at
National Liver Institute using endoscopy in 232 patients, in addition to percu-
taneous techniques in 42 patients and surgery in 198 patients.
RESULTS: Endoscopy was very successful initial treatment of 232 patients
(49%) being less invasive in comparison to surgery in treatment of mild/moderate
biliary leakage (68%) and biliary stricture (47%) with increased success by addi-
tion of percutaneous (Rendezvous technique) in 18 patients (3.8%). Surgery was
needed in 198 (42%) for major duct transection, ligation, major leakage and
massive stricture. Surgery was urgently in 62 patients and electively in 156
patients. Hepaticojejunostomy was done in most of cases (96) patients with
transanastomatic stents. There was only one mortality after surgery due to biliary
sepsis, and postoperative stricture was in 3 cases (1.5%) treated with percuta-
neous dilation and stenting.
CONCLUSION: Management outcome of biliary injuries becomes better with a
multidisciplinary care team, with initial minimal invasive technique to major
surgery in major complex injury encouraging for early referral to highly specia-
lized hepatobiliary centers.
REFERENCES
1-Flum DR, Cheadle A, Prela C, et al. Bile duct injuries during cholecystectomy
and survival in medicare beneficiaries. JAMAA 2003; 290: 2168-2173.
2-Tamqvist B, Zheng Z, Ye W, et al. Long-term effects of iatrogenic bile duct
injury during cholecystectomy. Clin Gastroenterology Hepatol 2009; 7: 1013-
1018.
3-Sicklick JK, Camp MS, Lillemoe KD, et al. Surgical management of bile duct
injuries sustained during laparoscopic cholecystectomy. Ann Surg 2005; 241: 786-
795.
4-Wange A and Nilsson M. Iatrogenic bile duct injury: a population-bases study
of 152776 cholecystectomies in the Swedish inpatient registry. Arch Surg 2006;
141: 1207-1213.
5-Khan MH, Howard TJ, Fogel EL, et al. Frequency of biliary complications
after laparoscopic cholecystectomy detected by ERCP: Experience at a large
tertiary referral center. Gatrointest Endosc 2007; 65: 247-252.
6-Ludwing K, Bernhardt J, Steffen H, et al. Contribution of intraoperative cho-
langiography to incidence and outcome of common bile duct injuries during
laparoscopic cholecystectomy. Surg Endosc 2002; 16: 1098-1104.
7-Caroll BJ, Birth M and Phillips EH. Common bile duct injuries during laparo-
scopic cholecystectomy that result in litigation. Surg Endosc 1998; 12: 310-313.
8-Singh V, Narasimhan KL, VermaGR, et al. Endoscopic management of trau-
matic hepatobiliary injuries. J Gastro-enterol Hepatol 2007; 22: 1205-1209.
Disclosure of Interest: None declared
P0247 IMPACT OF SARCOPENIA ON OUTCOMES FOLLOWING
RESECTION OF PERIHILAR CHOLANGIOCARCINOMA
R.J. S. Coelen1,*, J.K. Wiggers1, C.Y. Nio2, S.van Dieren3, M.G. H. Besselink1,
O.R. C. Busch1, T.M. van Gulik1
1
Surgery, 2Radiology, 3Epidemiology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: r.j.coelen@amc.nl
INTRODUCTION: Loss of skeletal muscle mass, sarcopenia, reflects the frailty
status of patients and has recently been associated with worse outcomes follow-
ing surgery for malignancies of gastrointestinal origin. The aim of this study was
to investigate the impact of sarcopenia on postoperative morbidity and survival
following resection of perihilar cholangiocarcinoma (pHCCA).
AIMS & METHODS: Data were retrospectively collected from a prospectively
maintained database including all patients in our institute undergoing major liver
A197
resections for suspected pHCCA between 1998 and 2013. Sarcopenia was
assessed in patients in whom an adequate preoperative CT scan was available,
by measuring total skeletal muscle mass at the level of the third lumbar vertebra.
Sex-specific cut-off values for sarcopenia were determined by optimum stratifica-
tion. Clinicopathological data, postoperative morbidity (Clavien-Dindo grade
3), mortality and long-term survival were analysed.
RESULTS: Sarcopenia was present in 41 (42%) of 97 patients with pHCCA and
was correlated with lower body mass index. Sarcopenia was associated with 30-
day/in-hospital mortality (24% vs. 9%, p 0.037). Overall postoperative com-
plication rate (Clavien-Dindo grade 3) was higher in sarcopenic patients (66%
vs. 46%), though this was not statistically significant (p 0.058). However, sar-
copenia was predictive for sepsis (OR 6.77, 1.67 to 27.43, p 0.007). Estimated
five-year overall survival rate was lower for sarcopenic patients (18 vs. 36%,
p 0.024). After correction for lymph node status, resection margin status,
tumour differentiation grade and postoperative complications in multivariable
analysis, sarcopenia was revealed as an independent predictor for worse overall
survival (HR 1.93, 1.08 to 3.43; p 0.026).
CONCLUSION: Sarcopenia has a negative effect on postoperative outcome and
overall survival following resection of pHCCA and should therefore be consid-
ered in preoperative risk assessment.
Disclosure of Interest: None declared
P0248 RESECTION AND RECONSTRUCTION OF THE HEPATIC
ARTERY FOR ADVANCED CHOLANGIOCARCINOMA: COULD
ARTERIOPORTAL SHUNTING ALTER MICROVASCULAR
RECONSTRUCTION?
T. Noji1,*, T. Tsuchikawa1, T. Nakamura1, E. Tamoto1, K. Okamura1,
T. Shichinohe1, S. Hirano1
1
Gastroenterological Surgery II, Hokkaido University, Graduate School of
Medicine, Sapporo city, Japan
Contact E-mail Address: drnoji@med.hokudai.ac.jp
INTRODUCTION: The anatomic features of the hepatic hilum facilitate inva-
sion of the hepatic arteries by cholangiocarcinoma. To accomplish curative resec-
tion, hepatic artery resection and reconstruction is sometimes required for such
advanced cases. One small study suggested that arterioportal shunting (APS)
might be useful in these patients. Surgical results with more cases and the survival
impact of APS for cholangiocarcinoma have not yet been investigated.
AIMS & METHODS: The aim of this case controlled study was to evaluate the
safety of APS and whether APS could be an alternative to microvascular
reconstruction.
Patients and Methods: Thirty nine patients with intra- or extra-hepatic cholan-
giocarcinoma who underwent hepatic arterial resection were evaluated. There
were 18 patients with APS (APS group) and 21 patients with microvascular
arterial reconstruction (MVR group).
RESULTS: Preoperative statuses of the patients from both groups were similar,
except for a number of patients with preoperative portal embolization. There
were no significant differences in incidences of postoperative complications
(Clavien-Dindo  IIIa) between the two groups. However, the incidence of
liver abscess formation was significantly higher in the APS group (38.9% vs
4.8% p 0.02). Treatments for these liver abscesses were complicated.
Mortality (hospital death) was 6% in APS group, 0% in MVR group, respec-
tively (p 0.46). Cumulative 3- and 5-year survival rates were 53.1% and 22.1%,
respectively, in the MVR group, and22.2% and 11.1%, respectively, in the APS
group (p 0.11).
CONCLUSION: Microvasucular arterial reconstruction should be used as the
first-line strategy for patients with intra/extra-hepatic cholangiocarcinoma. APS
is indicated when the artery cannot be microscopically anastomosed.
REFERENCES
1. Kondo S, Hirano S, et al. Arterioportal shunting as an alternative to micro-
vascular reconstruction after hepatic artery resection. Br J Surg 2004; 91: 248-
251.
Disclosure of Interest: None declared
P0249 SURGICAL OUTCOME OF HILAR PLATE RESECTION:
EXTENDED HILAR BILE DUCT RESECTION WITHOUT
HEPATECTOMY
T. Noji1,*, T. Tsuchikawa1, T. Nakamura1, E. Tamoto1, K. Okamura1,
T. Shichinohe1, S. Hirano1
1
Gastroenterological Surgery II, Hokkaido University, Graduate School of
Medicine, Sapporo city, Japan
Contact E-mail Address: drnoji@med.hokudai.ac.jp
INTRODUCTION: In the treatment of hilar cholangiocarcinoma, several studies
have advocated en bloc major hepatectomy to achieve negative histologic mar-
gins and improved survival. However, we know that there are some patients with
distal cholangiocarcinoma with longitudinal spread remaining in the hilar por-
tion, without infiltration beyond the bile duct wall. We also know that there are a
few patients with Bismuth type I hilar cholangiocarcinoma without infiltration
beyond the bile duct wall. These tumors are likely to have superficial spreading,
which would be difficult to accurately diagnose preoperatively. It remains
unknown whether, for patients with such a non-invasive tumor, extended hepa-
tectomy would be appropriate. We have done extended extrahepatic bile duct
resection at the level of the hilar plate with curative or palliative intention for
selected patients with or without hilar malignant tumors, calling this procedure
hilar plate resection (HPR).
AIMS & METHODS: The results of a retrospective study evaluating the clinical
benefits in patients who underwent HPR for biliary malignancies are reported.
A198
Surgical procedure of HPR: Nodal clearance around the pancreatic head and
skeletonization of the portal vein and the hepatic artery were performed first. The
portal vein and the hepatic artery were then separated from the surrounding
tissue upward to the hilar plate, where the duct cannot be further separated
from the vasculature. This was considered the limit of ductal transection with-
out hepatectomy, which is at the right edge of the posterior portion of the right
portal vein and the right edge of the umbilical portion of the left portal vein.
Then, the gallbladder with the cystic plate was resected toward the hepatic
hilum. Finally, the extrahepatic duct at the hilar plate was resected.
Patients: Fifty-two patients with cholangiocarcinoma underwent HPR. The pro-
cedure was performed in 28 patients with curative resection (cHPR group) and in
24 patients with palliative intention (pHPR group). In the same period, one
hundred twenty-eight patients with cholangiocarcinoma underwent major hepa-
tectomy with intrahepatic cholangiojejunostomy (Hx group). We compared with
these groups in term of post operative complications and survival.
RESULTS: There were no significant differences in the number of patients with
postoperative complications and in postoperative hospital stay. The overall
cumulative survival rates of each procedure (Hx group, cHPR group, and
pHPR group) were 40%, 38%, and 11% at 5 years, respectively. There was no
significant difference between Hx and cHPR group in survival rates (p 0.87).
But the survival rate of the pHPR group was significantly lower than that of the
Hx group (p 0.03). The survival rate of the pHPR group was lower, but not
significantly, than that of the cHPR group (p 0.08).
CONCLUSION: HPR appears to be safe and feasible for selected patients with
cholangiocarcinoma. However, the indications for HPR should be restricted.
Disclosure of Interest: None declared
P0250 LAPAROSCOPIC GASTRECTOMY FOR GASTRIC CANCER:
RESULTS OF IMPLEMENTATION OF A NEW TECHNIQUE
E.J. Jongerius1, M. I.van Berge Henegouwen1, S.M. Lagarde1, S.S. Gisbertz1,*
1
surgery, AMC, Amsterdam, Netherlands
Contact E-mail Address: s.s.gisbertz@amc.nl
INTRODUCTION: Although different (neo)adjuvant strategies are being devel-
oped, surgical treatment remains the cornerstone of curative treatment for gastric
cancer. Standard operative procedure has traditionally been an open (sub)total
gastrectomy with a modified D2-lymphadenectomy. In an attempt to lower peri-
operative morbidity, we designed and standardized a laparoscopic technique to
perform a (sub)total gastrectomy for the treatment of patients with potentially
curable gastric cancer.
AIMS & METHODS: Aim of this study was to describe the short-term results of
the first series of laparoscopic gastrectomies in patients with potentially curable
gastric cancer.
In this prospective cohort trial we evaluated the first series of consecutive patients
with potentially curable gastric cancer who underwent a laparoscopic (sub)total
gastrectomy with a modified D2-lymphadenectomy the first year following intro-
duction of the laparoscopic technique. Primary endpoint was perioperative mor-
bidity and mortality. Secondary endpoints were hospital length of stay, number
of harvested lymph nodes and radicality of surgery (R0 resection rate).
RESULTS: From February 2013 until April 2014 28 patients out of a total of 38
patients underwent a laparoscopic gastrectomy (73.7% of all gastrectomies).
Eighteen patients (64.3%) underwent a total gastrectomy and 10 patients
(35.7%) a subtotal gastrectomy. In 5 patients (17.9%) at least 6 cm of esophagus
was co-resected. 18 patients (64.3%) received neo-adjuvant chemotherapy. There
were 3 conversions (10.7%). Reasons for conversion were tumor involvement of
the duodenum with a narrow relation to the pancreatic head in 2 cases and tumor
ingrowth in the left hemidiafragm necessitating partial diaphragm resection in 1
case. The median operation time was 320 min (SD 66.8), median blood loss 200
cc (SD 269.6) and median hospital stay 8 days (SD 6.3). The overall complication
rate was 21.4% (6 patients). There were 2 complications requiring re-intervention
(7.1%). Both patients had an anastomotic dehiscence for which surgical drainage
was performed. One of these patients eventually died of the septic consequences
(total hospital mortality 3.6%). In 1 patient peri-operatively peritoneal metas-
tases were detected and a palliative resection was performed. In 26 patients the
tumor was radically removed (R0 resection rate 96.3%). Median lymph node
count was 25 (SD 8.5).
CONCLUSION: Laparoscopic surgery for gastric cancer is feasible with good
oncologic results and acceptable peri-operative morbidity and mortality.
Implementation of this technique was evaluated as successful and therefore it
is now standard surgical strategy at our center.
Disclosure of Interest: None declared
P0251 SUBMUCOSAL TUNNEL FOR PERITONEAL ACCESS
ASSOCIATED WITH AN OVER-THE-SCOPE CLIPS (OTSC)
CLOSURE: COMPARISON WITH TWO OTHER METHODS OF
GASTROTOMY CLOSURE AFTER NOTES PROCEDURES
J.-M. Gonzalez1,2,*, K. Saito1, C. Kang1, M. Gromski1, M. Sawnhey1,
R. Chuttani1, K. Matthes1
1
Gastroenterology, Beth Israel Medical Center, Harvard Medical School, Boston,
MA, United States, 2Gastroenterology, Aix-Marseille University, North Hospital,
Marseille, France
INTRODUCTION: Safe transgastric NOTES procedures require a reliable clo-
sure of the gastrotomy. Recently a novel peritoneal access method via a submu-
cosal tunnel has been described with encouraging preliminary results.
AIMS & METHODS: The aim was to compare a submucosal tunnel access plus
over-the-scope clips (OTSC) for closure with two other closure modalities. It was
a prospective ex-vivo study on forty-two specimens equally randomized in three
groups and carried out in an Academic medical center. Fourteen procedures were
United European Gastroenterology Journal 2(5S)
performed in each group including: 1.) Tunnel (6 cm) endoclips; 2.) Knife
balloon dilation access OTSC; 3.) Tunnel OTSC. The main outcome mea-
surements were: pressurized air-leak test was realized to evaluate the strength of
the closure. Stomach volumes, procedure times, number of clips, and incision
sizes were also registered.
RESULTS: The mean air leak pressure was statistically higher in group 3 than in
groups 1 and 2: 95.2  19.3 mmHg vs. 72.5  35.2 and 79  24.5 mmHg
(p50.05). The gastrotomy creation times for groups 1, 2 and 3 were 28.0 
10.1, 4.3  1.4 and 20.1  10.6 minutes, respectively, with significantly lower
time in the group 2 (p50.001). The closure times were 16.1  6.1, 6.5  1.2 and
5.3  3.0 minutes, respectively, and significantly longer in the endoclip group
(p50.001). There was no difference in the volumes and the incision sizes between
the three groups.
CONCLUSION: The combination of a submucosal tunnel access and OTSC
offers a stronger closure than the other methods studied.
Disclosure of Interest: None declared
P0252 NEW MULTICOLORED MULTIMATERIAL BIOELASTIC
ORGAN REPLICATION USING HYBRID MDCT AND 3D PRINTING
TECHNOLOGY FOR TANGIBLE DIGESTIVE SURGERY
SIMULATION
M. Sugimoto1,*
1
Gastroenterology, Kobe University, KOBE HYOGO, Japan
Contact E-mail Address: sgmt@med.kobe-u.ac.jp
INTRODUCTION: Our new technology of Bio-Texture Modeling by hybrid
MDCT and 3D printing system enabled manufacturing patient-specific 3D
organ replicas. We developed the latest generation of 3D printer by simultaneous
jetting of different types of model materials.
AIMS & METHODS: The objective was to develop and evaluate patient-speci-
fic, anatomically accurate, bioelastic 3D replica for simulation, navigation and
training of digestive surgery in 40 clinical cases. Based on DICOM data from
MDCT, after generating its surface polygons using OsiriX application, the inkjet
3D printer created life-size copies of the 3D organs, blood vessels, and abdominal
cavity. We programmed a printer to create clear models made from acrylic resins
that allowed us to visualize and understand the gastrointestinal and hepatobiliary
pancreatic complex internal structures and blood vessels or the exact tumor
locations. We printed liver models compounding the polyvinyl alcohol (PVA)
to make the model a realistic stand-in for ultrasonic diagnosis, hepatic interven-
tion and surgical simulation.
RESULTS: The patient individual multicolored 3D printed models were useful
for visible and tangible surgical simulation and navigation to plan and guide the
successful gastrectomy, colectomy, hapatobiliary pancreatic surgeries in total of
40 patients including 20 laparoscopic surgeries. The 3D objects using a combina-
tion of transparent and soft materials allowed creation of translucent medical
models that show visceral organs and other details that can be handled, over-
coming the limitation of the conventional image-guided navigation. The gel-like
support material, which is specially designed to support complicated geometries,
is easily removed by hand. This provided realistic simulation of suturing and
dissection to provide specific values of bio-texture in gastrointestinal hepatobili-
ary pancreatic organs for tensile strength and elongation to break. The PVA was
available for wet tissue simulation in ultrasonography and intervention in hepatic
surgery.
CONCLUSION: New 3D printing techniques delivered tangible and safe surgery
training and could help younger, less experienced surgeons practice with accurate
copies for digestive surgery. Its combines the advantages of conventional 3D
modeling and precise virtual 3D planning and can be applied advantageously
in personalized surgical simulation and navigation.
Disclosure of Interest: M. Sugimoto Financial support for research from: Fasotec
Inc.
P0253 TRANSRECTAL NOTES VERSUS LAPAROSCOPIC AND OPEN
CHOLECYSTECTOMY IN AN ANIMAL MODEL OF CALCULOSE
CHOLECYSTITIS
O. Ryska1,*, Z. Serclova1, J. Martinek2, R. Dolezel3, J. Kalvach3, T. Henlin4,
E. Laszikova4, S. Juhas5, J. Juhasova6, M. Ryska3
1
Department of Surgery, Horovice Hospital, Horovice, 2Hepatogastroenterology
department, Institute for Clinical and Experimental Medicine, 3Department of
Surgery, 4Department of Anesthesiology, Central Military Hospital, Prague,
5
Institute of Animal Physiology and Genetics, Libechov, 6Institute of Animal
Physiology and Genetics, Prague, Czech Republic
INTRODUCTION: Natural-orifice transluminal endoscopic surgery (NOTES)
as an evolving concept has been studied in several experimental trials. However,
randomized experimental study evaluating NOTES in the area of calculose cho-
lecystitis is missing. Transrectal compared to more frequently used transvaginal
access offers good manipulation in the upper abdomen and is not limited to the
female population. Also the physiologic impact during NOTES may differ from
laparoscopy and open procedures because of presumed longer operation and
need of extensive body positioning.
AIMS & METHODS: The aim of the study was to compare transrectal NOTES,
laparoscopic and open approach to cholecystectomy in animal with calculose
cholecystitis.
Laparoscopy (3-ports) was performed, bile was aspirated from the bladder and 4
gallstones obtained by human cholecystectomy were inserted via cholecystotomy
in all 42 animals four week prior planned intervention. Animals were than ran-
domized into NOTES (N 14), open (N 11), laparoscopic (N 11), and sham
groups (N 6). In NOTES cholecystectomy a double channel endoscope was
used to enter the abdominal cavity via rectotomy performed by needle knife
United European Gastroenterology Journal 2(5S)
and balloon dilatation. A standard laparoscopic grasper was advanced to grip the
fundus. Cystic duct and cystic artery were clipped and the preparation finished
with a hook knife. The access site incision was endosutured by OVESCO clip.
Small (5-6cm) subcostal incision and 3-ports laparoscopy were performed in
open and laparoscopic groups. For hemodynamic monitoring using LiDCO,
central venous and arterial catheter were introduced. After a follow-up period
of 30 days, the animals were euthanized and necropsies were performed.
RESULTS: The procedure time was significantly longer in NOTES than in open
and laparoscopic groups 145 (90-240) vs. 40 (25-65) vs. 63 (40-90) minutes, p
50.001. In 3 animals from NOTES group the bladder dissection was compli-
cated by severe bleeding, which was not treatable endoscopically. NOTES tech-
nique was indicated as unfeasible and these animals could not be evaluated
afterwards. Perforation of the gall bladder occurred in 9/11 in NOTES versus
1/11 (RR: 9.0; 1.36-59; p 0.02) and 4/11 (RR: 2.3; 1.1-5.2; p 0.04) in open and
laparoscopy groups. All followed hemodynamic parameters including heart rate,
mean arterial pressure, cardiac index, central venous pressure and systemic vas-
cular resistance did not differ from sham animals in all groups. Gallstones with
wall inflammation confirmed histologically were present in all extracted bladders.
All rectotomies were healed, however intraabdominal infection occurred more
frequently in NOTES (4/11) than in open (2/11) and laparoscopic (1/11) groups.
CONCLUSION: Despite the technical difficulties and longer operational times,
NOTES did not affect hemodynamic parameters. However, the feasibility rate of
NOTES in the area of calculose cholecystitis did not reach conventional
approaches. There were more intraoperative and postoperative complications
in NOTES group. Transrectal access can be used universally and closed safely
but risk of intraabdominal contamination during the procedure remains an issue.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
IBD I POSTER EXHIBITION HALL XL_____________________
P0254 HCMV AND EBV VIRAL LOAD IN MUCOSA OF PATIENTS WITH
CHRONIC INFLAMMATORY BOWEL DISEASE
R. Ciccocioppo1, A. Gallia1,*, G.A. Petazzi1, E. Betti1, V. Imbesi1,
G.C. Cangemi1, F. Racca1, F. Broglia2, F. Baldanti3, G.R. Corazza1
1
Clinica Medica I, 2Servizio di Endoscopia Digestiva, 3Unita` di Virologia,
Fondazione IRCCS Policlinico San Matteo, Universita` di Pavia, Pavia, Italy
Contact E-mail Address: rachele.ciccocioppo@unipv.it
INTRODUCTION: Immunosuppressants and biologicals are considered the
mainstay of therapy for inflammatory bowel disease (IBD) thanks to the possi-
bility of inducing remission and preventing disease progression. However, the
growing and earlier use of these medications predisposes the patients to an
increased risk of opportunistic infections, which represent an important cause
of morbidity and mortality. Human Cytomegalovirus (HCMV) and Epstein-Barr
virus (EBV) play a prominent role in the development of acute colitis in immune-
compromised patients. In a previous study, our group has defined the spectrum
of conditions associated with infection by HCMV and EBV, associating their
presence with the refractory to conventional therapies and identifying the main
risk factors for reactivation, as well as to detect in quantitative real-time PCR
(RT-PCR), performed on fresh intestinal biopsies, the most sensitive method for
diagnosis.
AIMS & METHODS: We investigated the role of these viruses in IBD patho-
genesis by evaluating the presence of viral DNA within the cells of the intestinal
mucosa, in particular in enterocytes and lamina propria mononuclear cells
(LPMCs). We enrolled 7 IBD patients (5/2 M/F, mean age 47), 1 patient with
profound combined immunodeficiency (M, 28 years) and 8 healthy controls
(HC). All patients underwent lower endoscopy with multiple biopsies.
Enterocytes were separated on a Percoll density gradient and LPMCs obtained
by enzymatic digestion. The viral load was assessed by quantitative RT-PCR on
mucosal specimens, enterocytes and LPMCs. Wilcoxon and Mann-Whitney tests
were applied for statistical analysis.
RESULTS: Viral DNA was found in the mucosa of all the patients and in 2
control subjects, with double positivity for HCMV and EBV DNA in 6 patients,
while EBV DNA alone in the remaining 2 patients and HC. In different colonic
locations, 6 patients showed peak values for EBV DNA above 103 copies/105
cells in at least one location, while only 2 patients had similarly high values for
HCMV DNA. No HC showed peak values exceeding 102 copies/105 cells. Viral
DNA was found within enterocytes in 5 patients and in none of the HC, while
inside of LPMCs was evidenced in all patients and 3 HC. HCMV DNA was
found in enterocytes of only 2 patients, while 6 patients had detectable DNA in
LPMCs; instead 5 patients had EBV DNA in enterocytes and in all cases in
LPMCs. EBV DNA median values in healthy and injured mucosa, both in the
enterocytes (223.5 copies/105 cells) and in LPMCs (3348.5 copies/105 cells), were
significantly higher when compared to the levels of HCMV DNA (0 copies/105
cells; 6.5 copies/105 cells in enterocytes and LPMCs respectively) of both patients
and HC. Finally, in inflamed areas EBV DNA median values were higher than in
healthy mucosa.
CONCLUSION: Our data demonstrated the presence of EBV DNA in colonic
LPMCs and enterocytes of patients with IBD, with higher loads observed in the
first population. We also observed high levels of EBV DNA in enterocytes and
LPMCs in the presence of mucosal inflammation. This shows a preponderant
role of EBV compared with HCMV, with further studies needed to improve the
knowledge of the relationship between this virus and clinical manifestations.
Disclosure of Interest: None declared
A199
P0255 AIEC-RECEPTOR CEACAM6 ABNORMAL EXPRESSION IN
CROHNS DISEASE DEPENDS ON HYPOXIA RESPONSIVE
ELEMENTS METHYLATION STATUS AND CHROMATIN
REMODELLING
J. Denizot1, A. Agus1,*, A. Desrichard2, N. Uhrhammer 2, A. Darfeuille-
Michaud1, N. Barnich1
1
UMR1071 INSERM, Universite dAuvergne, 2Department of Oncogenetics,
Department of Breast Oncology, Centre Jean Perrin, Clermont-Ferrand, France
Contact E-mail Address: allison.agus1@udamail.fr
INTRODUCTION: Abnormal expression of CEACAM6 is observed at the
apical surface of the ileal epithelium in Crohns disease (CD) patients. This
allows Adherent-Invasive Escherichia coli (AIEC) to colonize gut mucosa, lead-
ing to development of inflammation. Our aims were to understand the regulation
of CEACAM6 expression in ileal mucosa of CD patients at the baseline and to
investigate molecular mechanisms involved in AIEC infection-dependent
CEACAM6 overexpression. Since changes in DNA methylation patterns were
reported in CD patients, we analyzed whether epigenetic mechanisms are
involved in the up-regulation of CEACAM6 expression in intestinal epithelial
cells.
AIMS & METHODS: Protein expression and localization were analyzed before
and after AIEC infection using immunofluorescence staining and Western-blot
analysis. HIF-1 and histone H3 Serine 10 phosphorylation (H3S10p) levels were
measured in CEACAM6 promoter region by chromatin immunoprecipitation
(ChIP) in intestinal epithelial cells (IEC). Transgenic CEABAC10 mice expres-
sing human CEACAM6 were orally challenged with 109 AIEC LF82 bacteria. At
3 days post-infection, ileum-associated AIEC were quantified, and mRNA levels
were measured in isolated enterocytes.
RESULTS: Higher expression of CEACAM6 was observed in T84 cells com-
pared to Caco-2 cells. This was associated to high binding of HIF-1 on the
CEACAM6 gene promoter in an open chromatin state region characterized by
increased in H3S10 phosphorylation level. In contrast, Caco-2 cells expressed low
levels of CEACAM6 due to a compact chromatin state in CEACAM6 promoter
(low level of H3S10p). AIEC infection led to increased CEACAM6 expression
related to enhance HIF-1 binding to CEACAM6 promoter. Abnormal H3S10
phosphorylation in CEACAM6 promoter following AIEC infection in IEC
enhanced HIF-1 binding, and subsequent CEACAM6 expression. In vivo,
increased levels of CEACAM6 and HIF-1 proteins were measured in ileal
enterocytes of AIEC-infected CEABAC10 mice, which could be due to high
H3S10 phosphorylation enabling HIF-1 binding to CEACAM6 promoter.
CONCLUSION: AIEC bacteria increased CEACAM6 expression in ileal enter-
ocytes of CEABAC10 mice by stabilizing HIF-1 transcription factor and by
opening chromatin in CEACAM6 promoter. This allowed HIF-1 binding and
subsequent gene transactivation, indicating that abnormal CEACAM6 expres-
sion in ileal mucosa of CD patients could be related to AIEC colonization-
induced epigenetic regulation.
Disclosure of Interest: None declared
P0256 WESTERN DIET IN CEACAM6 EXPRESSING MICE: IMPACT ON
SHORT-CHAIN FATTY ACIDS PRODUCTION AND HOST
SUSCEPTIBILITY TO INTESTINAL INFLAMMATION
A. Agus1,*, J. Denizot1, J. Thevenot1, S. Massier1, E. Billard1, S. Denis1,
A. Darfeuille-Michaud1, N. Barnich1
1
UMR1071 INSERM, Universite dAuvergne, Clermont-Ferrand, France
Contact E-mail Address: allison.agus1@udamail.fr
INTRODUCTION: Recent advances have shown that abnormal inflammatory
response observed in Crohns disease (CD) involves interplay between intestinal
microbiota, host genetic and environmental factors. The escalating consumption
of fat and sugar in Western diets parallels an increased incidence of CD during
the latter 20th century. Western lifestyle could explain the increasing prevalence
of new diseases such as CD.
AIMS & METHODS: We aimed at understanding the multifactorial etiology of
CD by evaluating the modulation of host physiology in response to nutrition. We
analyzed the impact of a High-Fat/High-Sugar (HF/HS) diet in mice on gut
micro-inflammation, selection of E. coli population, concentration of short-
chain fatty acids (SCFA) and expression of their free fatty acid-receptors such
as G-protein-coupled receptor 43 (GPR43). Mouse sensitivity to DSS-induced
colitis was assessed to evaluate the impact of nutrition in the sensibility to che-
mically-induced colitis. Mice fed a conventional or a HF/HS diet during 18 week-
period, fecal lipocalin-2 (Lcn-2) was measured by ELISA to detect low-grade
inflammation during the course of treatment, E. coli populations associated to
colonic and ileal mucosa were quantified, production of SCFA by microbiota
were measured by gas chromatography in fecal samples. GPR43 receptor was
visualized by confocal microscopy after immunostaining of colonic mucosa tis-
sues. The severity of DSS-induced colitis (1% of DSS in drinking water, 10 days)
was evaluated by disease activity index (DAI) measurement, histological score
and cytokine release.
RESULTS: HF/HS diet increased Lcn-2 level in stools from 5 weeks until 18
weeks of treatment, showing that HF/HS diet creates a specific inflammatory
environment in the gut. Interestingly, abnormal proportions of E. coli bacteria
were recovered from colonic and ileal mucosa of mice under HF/HS diet, com-
pared to mice under conventional diet. SCFA concentrations (acetate, propio-
nate, butyrate) were significantly decreased in fecal samples from mice under HF/
HS diet compared to mice fed a conventional diet. Combination of HF/HS diet
led to dysbiosis with an overgrowth of pro-inflammatory E. coli bacteria and a
decrease in protective SCFA producing bacteria. GPR43 receptor expression was
reduced in mice treated with an HF/HS diet compared to mice under a conven-
tional diet. In addition, HF/HS diet led to an exacerbation of gut inflammation
A200
following DSS-induced colitis, with an increase of DAI, histological score and
release of pro-inflammatory cytokines.
CONCLUSION: Western diet creates a low-grade inflammation in the gut with a
decrease of protective SCFA producing bacteria, leading to overcolonization by
E. coli opportunistic pathogen bacteria which could aggravate the inflammatory
process resulting in chronic inflammation. Together, these findings support the
multifactorial etiology of CD and highlight the importance of nutrition factors in
CD pathogenesis.
Disclosure of Interest: None declared
P0257 VITAMIN D REGULATES THE TIGHT-JUNCTION PROTEINS
EXPRESSION IN ACTIVE ULCERATIVE COLITIS
A.G. Bonanomi1,*, V. Annese1, L. Retico1, M. Martinesi2, M. Stio2
1
Gastroenterology Unit 2, Azienda Ospedaliero-Universitaria Careggi Firenze,
2
Biochemical Sciences, University of Florence, Firenze, Italy
Contact E-mail Address: maria.stio@unifi.it
INTRODUCTION: Epithelial barrier function is primarily regulated by the
tight-junction proteins (TJ). Ulcerative colitis (UC) is characterized by Th2
immune response with inflammation and epithelial barrier dysfunction, including
an elevation of claudin-2 protein function (1).
In UC, epithelial leaks appear early due to micro-erosions resulting from upre-
gulated epithelial apoptosis and from a significant IL-13-dependent arrest in
epithelial restitution (2).
Vitamin D is traditionally associated with bone metabolism. Importantly,
recently studies support an important role of vitamin D in the pathogenesis as
well as potential therapy of IBD. Vitamin D deficiency is in fact common in
patients with IBD (3).
AIMS & METHODS: Our aim was to determine whether vitamin D could affect
IL-13 and IL-6 levels, and regulate the activity of tight-junction proteins Claudin-
1, -2, -4 and -7 in the inflamed and non-inflamed colonic mucosa of UC patients.
Methods: Biopsies from the colon (rectum, sigma) of patients with active UC
were studied. Non-inflamed (NI) and inflamed (I) intestine tissues, obtained from
the same patient, were cultured with 10 nM 1,25(OH)2D3. After 24 h incubation
the medium was removed and used for the determination of IL-13 and IL-6 levels
by ELISA test. The lysates of biopsies were used to determine the levels of TJ
protein by Western blot analysis.
RESULTS: Claudin-1 and Claudin-2 proteins were up-regulated in active UC.
The treatment with 1,25(OH)2D3 increases the Claudin-1 levels in the NI tract
and decreases their level in the I tract, while the treatment with 1,25(OH)2D3
remarkably decreases the Claudin-2 protein level in both I and NI tract. Claudin-
4 and Claudin-7 proteins were down-regulated with Western Blot Analysis and
their levels increase when both NI and I tract were cultured in the presence of the
1,25(OH)2D3. IL-13 and IL-6 levels decrease incubating the biopsies with
1,25(OH)2D3.
CONCLUSION: Our study reports a down-regulation of claudin-4 and claudin-
7, and an up-regulation of claudin-2, that might lead to altered TJ structure and
be related to the impaired epithelial function in active UC.
Our results, indicating the inhibition of cytokine levels and the regulation of
Claudin-2, Claudin-4 and claudin-7 by 1,25(OH)2D3, suggest that vitamin D
may represent a potential target for the treatment of IBD.
REFERENCES
1) Hering NA and Schulzke JD. Therapeutic options to modulate barrier defects
in inflammatory bowel disease. Dig Dis 2009; 27: 450-454.
2) Schulzke JD, Ploeger S, Amasheh M, et al. Epithelial tight junctions in intest-
inal inflammation. Ann N Y Acad Sci 2009; 1165: 294-300.
3) Mouli VP and Ananthakrishnan AN. Review article: Vitamin D and inflam-
matory bowel disease. Aliment Pharmacol Ther 2014; 39: 125-136.
Disclosure of Interest: None declared
P0258 SMOKING IS ASSOCIATED WITH WATERY DIARRHEA AND
DECREASED LIKELIHOOD TO ACHIEVE CLINICAL REMISSION
IN COLLAGENOUS COLITIS
A. Munch1,*, J. Bohr2, A. Madisch3, O. Bonderup4, C. Tysk2, M. Strom1,
R. Mohrbacher5, R. Muller5, R. Greinwald5, S. Miehlke6 on behalf of European
Microscopic Colitis Group (EMCG)
1
University hospital, Linkoping, 2University hospital, Orebro, Sweden, 3Siloah
hospital, Hannover, Germany, 4Regional hospital, Silkeborg, Denmark, 5DrFalk
Pharma, Freiburg, 6Center for Digestive Diseases, Hamburg, Germany
Contact E-mail Address: andreas.munch@lio.se
INTRODUCTION: Smoking seems to be a risk factor for microscopic colitis and
smokers develop the disease more than 10 years earlier than non-smokers.
However, the impact of smoking on clinical activity and outcome has not been
elucidated.
AIMS & METHODS: In a post-hoc analysis from pooled data of two rando-
mized controlled trials (BUC-60/COC and BUC-63/COC) we assessed the asso-
ciation of demographical (gender, age, smoking habits, previous and/or
concomitant medication, family history of inflammatory bowel disease) and clin-
ical variables (duration of symptoms, mean number of stools/watery stools per
day, abdominal pain, clinical remission). Moreover, we analyzed the predictive
value of baseline parameters on clinical outcome in a logistic regression model.
RESULTS: Pooled data from 202 patients with active collagenous colitis (CC)
were available thereof 36% current smokers, 29% former smokers and 35% non-
smokers. Current smokers had an increased number of watery stools at baseline
compared to non-smokers (p 0.05). 20/137 (15%) patients treated with bude-
sonide did not achieve clinical remission. The majority of these (85%) were either
smokers or former smokers. An association was found between smoking status
(current smokers vs. non smokers: OR 0.37, 95% CI: 0.14-0.96, p 0.041; former
United European Gastroenterology Journal 2(5S)
smokers vs. non smokers: OR 0.21, 95% CI: 0.07-0.60, p 0.004), mean number
of watery stools per day (OR 0.77, 95% CI: 0.66-0.90, p 0.001) and decreased
likelihood to obtain clinical remission. All other variables showed no significant
association.
CONCLUSION: Smoking is associated with increased number of watery stools
and decreased likelihood to achieve clinical remission in collagenous colitis.
Smoking seems to have an impact on disease activity and treatment outcome
in patients with CC.
Disclosure of Interest: A. Munch Financial support for research from: Abbvie,
Lecture fee(s) from: MEDA, Dr Falk Pharma, MSD, J. Bohr: None declared, A.
Madisch: None declared, O. Bonderup Lecture fee(s) from: Dr Falk Pharma, C.
Tysk Lecture fee(s) from: Tillotts Pharma, Falk Pharma, Ferring, MSD, and
AstraZeneca., M. Strom: None declared, R. Mohrbacher Other: employee of
DrFalk Pharma, R. Muller Other: employee of DrFalk Pharma, R. Greinwald
Other: employee of DrFalk Pharma, S. Miehlke Lecture fee(s) from: Dr Falk
Pharma
P0259 REDUCED MUCOSAL EXPRESSION OF INSOLUBLE KERATINS
8, 18 AND 19 IN ACTIVE COLITIS RELATIVE TO PROXIMAL
INACTIVE COLONIC MUCOSA: VALIDATION OF MASS
SPECTROMETRY DATA
A. Assad-Sangabi1,2,*, C. Evans3, D. Majumdar1, B. Corfe2, A. Lobo1
1
Gastroenterology Department, Royal Hallamshire Hospital, 2Oncology
Department, 3Department of Chemical and Biological Engineering, University of
Sheffield, Sheffield, United Kingdom
Contact E-mail Address: arash.sangabi@gmail.com
INTRODUCTION: Intermediate filaments (IF) are one of the main components
of the human cell cytoskeleton, which mainly consist of keratins (K). K8, K18
and K19 constitute the main keratins in the intestinal epithelial cells. Keratin
alteration may play a role in the pathophysiology of ulcerative colitis (UC). K8
-/- mice develop chronic colitis (1). Heritable predispositions to UC were mapped
to the K8/18 loci in human (2). K8 and K18 play a role in TNF- induced-
apoptosis (3). We have previously shown reduced expression of insoluble K8,
K18 and K19 in active UC (ACT) relative to un-inflamed proximal colonic
mucosa (INACT) using mass spectrometry (MS) analysis in the IF fraction of
pooled patient samples from these two groups. The aim of this study was to use
antibody-based relative quantification of K8, K18 and K19 in individual patient
samples to validate MS results and describe variation in expression across the
cohort.
AIMS & METHODS: IF proteins were extracted from rectal biopsies in patients
with active colitis (n 9) as well as endoscopically and histologically un-inflamed
proximal colonic mucosa in each individual. IF proteins extracted from the
sigmoid colon of a normal individual was used as an internal control. Each
sample was dot-blotted on a membrane followed by immunoblotting for identi-
fication and quantification of keratins (8, 18 &19) sequentially. A control MCF-7
sample was included in all immunoblots to allow normalisation between sample
groups. Relative keratins concentration for each dot- blotted sample was inferred
by determining its signal intensity relative to the MCF-7 keratins signal intensity
measured in turn by densitometry. Statistical analysis to compare the two groups
was made separately for K8, K18 and K19 using Mann-Whitney U test.
RESULTS: Median relative IF protein levels from the active mucosa were 0.18,
0.28 and 1.48 for K8, K18 and K19, respectively were significantly lower than
those from the un-inflamed inactive mucosa: 1.21, 1.16 and 3.59 for K8
(p 0.02), K18 (p 0.03) and K19 (p 0.02), respectively. Median Barons endo-
scopy score in ACT and INACT biopsy samples were 2 (range 2-3) and 0 (range
0-1), respectively. Median histological activity index in ACT and INACT were 2
(range 1-3) and 0 (range 0). Median disease duration was 5 years in the cohort.
CONCLUSION: This study confirms reduced expression of insoluble keratins in
the active colonic epithelial cells relative to the un-inflamed proximal colonic
mucosa and validates our previous MS observations. Insoluble keratin expres-
sion may be used as a tissue marker of disease activity.
REFERENCES
1. Baribault H, Penner J, Iozzo RV, et al. Colorectal hyperplasia and inflamma-
tion in keratin 8-deficient FVB/N mice. Genes Dev 1994; 8: 2964-2973.
2. Owens DW, Wilson NJ, Hill AJ, et al. Human keratin 8 mutations that disturb
filament assembly observed in inflammatory bowel disease patients. J Cell Sci
2004; 117(Pt 10): 1989-1999.
3. Caulin C, Ware CF, Magin TM, et al. Keratin-dependent, epithelial resistance
to tumor necrosis factor-induced apoptosis. J Cell Biol 2000; 149: 17-22.
Disclosure of Interest: None declared
P0260 PANCREATIC EXOCRINE INSUFFICIENCY IS NOT A
CLINICALLY SIGNIFICANT PROBLEM IN PATIENTS WITH
ULCERATIVE COLITIS
B. Lindkvist1,*, B. Jonefall1, H. Strid2, M. Simren1
1
Medicine, 2Sahlgrenska University Hospital, Goteborg, Sweden
Contact E-mail Address: bjorn.lindkvist@vgregion.se
INTRODUCTION: It is not uncommon that patients with ulcerative colitis
report symptoms such as diarrhea, bloating and abdominal discomfort despite
a complete absence of biochemical and endoscopic signs of disease activity. One
possible explanation to this phenomenon is that these patients may suffer from
pancreatic exocrine insufficiency (PEI). One previous study has indicated that the
prevalence of PEI may be as high as 17% in patients with inflammatory bowel
disease (IBD) (1). However, most studies on PEI in IBD including the aforemen-
tioned have used fecal elastase (Fel-1) as the only method to investigate pancrea-
tic exocrine function. Concerns have been raised about the diagnostic accuracy of
Fel-1 to diagnose PEI in IBD due to dilution effects and increased degradation.
United European Gastroenterology Journal 2(5S)
Hence, studies on the prevalence of PEI in IBD patients using more specific tests
of exocrine pancreatic function are warranted. The 13C-mixed triglycerides
(MTG) breath test is a non-invasive pancreatic function test that can be used
to confirm the diagnosis of PEI with high sensitivity and specificity.
AIMS & METHODS: The aim of the present study was to investigate the pre-
valence of PEI and clinical factors associated with PEI in patients with ulcerative
colitis. Cases with ulcerative colitis seen at the out patient clinic of Sahlgrenska
University Hospital were included in the study. Ulcerative colitis disease activity
was evaluated by the Mayo scoring system for assessment of ulcerative colitis
activity, fecal calprotectin, and sigmoidoscopy. Patients were screened for PEI
using the Fel-1 test. Subjects with low Fel-1 were further examined using the 13-
CMTG breath test. Computed tomography (CT) was used to evaluate pancreatic
morphology in cases where the 13C-MTG breath test could confirm the PEI
diagnosis.
RESULTS: In total 192 patients with ulcerative colitis were included in the study
(mean age 44 years, 110 (57%) male, 93 (48%) with active disease). Fel-1 below
the lower limit of normal (200 g/g stool) was observed in 15 (7.8%) patients.
There was no difference in age, ulcerative colitis disease activity, stool frequency
or azathioprine use between patients with low and normal Fel-1 (Table 1).
Further examination of patients with low Fel-1 with the 13C-MTG breath test
revealed normal pancreatic exocrine function in all but one patient. This patient
had signs of atrophy of the pancreas on CT.
Table 1
Fecal elastase Fecal elastase
5200 g/g 4200 g/g p-value
Age, median (inter quartile 43 (39-61) 43 (33-54) 0.21
range)
UC, active disease (Mayo 8/15 (53%) 85/177 (48%) 0.79
score 40)
Self-reported increased 6/15 (40%) 59/177 (33%) 0.58
stool frequency
Calprotectin, median (inter 120 (52 to 390) 64 (18 to 260) 0.30
quartile range)
Azathioprine use 1/15 (7%) 27/177 (15%) 0.70
CONCLUSION: Fel-1 values below normal can be found in a minority of
patients with ulcerative colitis but the vast majority of these patients have no
signs of PEI when further tested with the 13C-MTG breath test. Our diagnostic
strategy using Fel-1 as a screening test followed by the 13C-MTG test as a
confirmatory test indicated that clinically significant PEI is rare in patients
with ulcerative colitis.
REFERENCES
1. Maconi G, et al. Dig Dis Sci 2008; 53: 262-270.
Disclosure of Interest: B. Lindkvist Financial support for research from: Abbott,
Consultancy for: Astra Zeneca, B. Jonefall: None declared, H. Strid: None
declared, M. Simren: None declared
P0261 ENTERIC GLIAL CELLS PRODUCE 15-HETE TO REGULATE
INTESTINAL EPITHELIAL PROPERTIES: DYSREGULATION IN
CROHNS DISEASE
S. Coquenlorge1, C. Pochard1,*, J. Jaulin1, T. Durand1, N. Cenac2,
N. Vergnolle2, M. Neunlist1, M. Rolli-Derkinderen1
1
inserm UMR913, nantes, 2Inserm, U1043, CNRS, U5282, toulouse, France
Contact E-mail Address: malvyne.derkinderen@univ-nantes.fr
INTRODUCTION: Accumulating data demonstrate that under physiological
conditions, enteric glial cells (EGC) positively regulate the intestinal epithelial
barrier (IEB). EGC are necessary for IEB homeostasis, increase IEB healing and
decrease IEB permeability, identifying EGC as a source for soluble factors able
to reinforce the IEB. The most recently discovered prostaglandin 15dPGJ2 is
produced by EGC to regulate intestinal epithelial cell (IEC) proliferation and
differentiation. However nothing is known considering other polyunsaturated
fatty acid (PUFA) metabolites that could also be produced by EGC.
AIMS & METHODS: The PUFA signature of the JUG embryonic cell line as
well as rat adult primary cultures of EGC were established using high sensitivity
liquid chromatography tandem mass spectrometry. Immunohistochemistry was
used to detect the 15-LOX producing enzyme of 15-HETE on rat and human
EGC cultures and on human sub-mucosal plexus. Pharmacological approach
was used to determine 15-HETE impact on Caco-2 monolayer cultivated or
not in presence of EGC. Direct injection of 15-HETE into the colon wall was
used to measure its impact on IEB permeability in vivo.
RESULTS: Among the 24 PUFA metabolite measured, rat EGC mostly pro-
duced 5- and 15-HETE. They also expressed the 15-lipoxygenase 2 (15-LOX2),
whereas the 15-lipoxygenase 1 was undetectable. 15-HETE increased IEC spread-
ing, IEB resistance and decreased IEB permeability without affecting IEC pro-
liferation. In addition, 15-LOX2 was expressed in human EGC in culture but also
in situ in EGC from submucosal ganglia. Interestingly, 15-HETE production by
EGC from CD patients was significantly reduced compared to EGC from control
patients. At the same time, CD EGC were unable to decrease IEB permeability,
but addition of 15-HETE backed up the permeability to control conditions.
In vivo, 15-HETE also reduced the IEB permeability, showing the potential of
15-HETE to reinforce IEB.
A201
CONCLUSION: This study not only presents the first evidence for EGC func-
tional abnormalities in CD, but also reveals that 15-HETE can reduce IEB
permeability
Disclosure of Interest: None declared
P0262 INFLUENCE OF ANTI-TNF THERAPY ON THE BONE
METABOLISM IN PATIENTS WITH INFLAMMATORY BOWEL
DISEASE
C.S. Beatriz1,*, V. Carmen1,2, G.M.Jose1, L. Susana1, F.-G. Pedro1,
G.-U. Mayte3, R. Monserrat1, R.J.Antonio2, C. Javier1
1
Gastroenterology, 2internal medicine, 3Bioquimical, H. U. MARQUES DE
VALDECILLA, SANTANDER, Spain
Contact E-mail Address: digcsb@humv.es
INTRODUCTION: Several studies have concluded that patients with inflamma-
tory bowel disease (IBD) are at increased risk of osteoporosis. The increase of
proinflammatory cytokines, as TNF- and interleukins (IL) appear to mediate,
as a pathogenic mechanism, in the loss of bone mass density (BMD) in these
patients. However, the influence of anti-TNF drugs on the bone metabolism of
patients with IBD is not well known. Our aim is to evaluate the influence of anti-
TNF drugs on bone mineral density and markers of bone remodeling in IBD
patients.
AIMS & METHODS: Prospectively we have enrolled 8 patients (2 men and 6
women) with active IBD, 2 ulcerative colitis and 6 Crohns disease, all with
indication for treatment with anti-TNF drugs. Clinical data were collected on
standardized data forms. BMD values were measured by dual-energy X-ray
absortiometry (Hologic QDR 4500) at the lumbar spine (L1-L4) and femoral
neck (FN) baseline visit and after a year of treatment. We determined serum 25-
hydroxyvitamin D3 (25OHD ng/ml) and intact parathyroid hormone (PTH pg/
ml). Bone turnover markers were measured by fully automated electrochemili-
minescence system (Elecsys 2010, Roche Diagnostic, Germany): aminoterminal
propeptide of type collagen (P1NP) and C-terminal telopeptide of type I collagen
(CTX) at baseline visit, 8 week, 6 month and a year after treatment.
RESULTS: In our study, mean age was 42 years (age range 24-54). Two patients
were treated with infliximab and 6 with adalidumab. All of them had been treated
previously with 5-ASA, Azathioprine in 50% and corticoids in 20%. Mean basal
weight (61 kg) did not change over treatment. The BMD in lumbar spine was
1.031 (0.112) g/cm2 at baseline and 1.037 (0.127) g/cm2 a year after. The BMD in
FN was 0.755 (0.131) g/cm2 and 0.774 (0.120) g/cm2 respectively. The percentage
of change in lumbar spine was 1% (p 0.77) and in FN 2.5% (p 0.15). Data
table show biochemical parameters and different percentages over basal state.
Baseline 8 week 6 month Year
25OHD ng/ml 21 (9) 21 (9) [0%] 24 (12)[14%] 23 (12) [9%]
iPTH pg/ml 27 (11) 37 (13) [37%]* 30 (11) [11%] 38 (19) [40%]
P1NPmg/L 49 (26) 66 (26) [34%]* 61 (17) [24%] 43 (23) [-13%]
-CTX ng/ml 0.421 0.380 (0.328) 0.488(0.326) 0.419(0.332)
(0.210) [-9%] [15%] [-2%]
CONCLUSION: 1. Bone mass in IBD patients with TNF-  inhibitors treatment
were similar at baseline and after a year of treatment.
2. P1NP was increased 8 week after the beginning of treatment but P1NP
returned to basal level after a year. Parathyroid hormone levels seem to increase
early after the beginning of treatment and remains above basal levels over time.
-CTX and vitamin D, bone resorption markers, were stable during treatment.
3. Further studies are required to analyze the relationship between this therapeu-
tic agents and bone metabolism in IBD.
Disclosure of Interest: None declared
P0263 EDUCATION OF PATIENTS WITH CROHNS DISEASE ON THE
RISKS OF SMOKING REMAINS CHALLENGING
C. De Bie1,*, V. Ballet1, G.Van Assche1, S. Vermeire1, M. Ferrante1
1
Department of Gastroenterology, UNIVERSITY HOSPITALS LEUVEN,
Leuven, Belgium
INTRODUCTION: The detrimental effect of smoking on development and pro-
gression of Crohns disease (CD) is generally accepted. Although health care
professionals undoubtedly spend a lot of time in education of patients, the
actual awareness of smoking risks in CD patients is unclear.
AIMS & METHODS: We assessed several smoking behaviour parameters and
patients awareness on different consequences of smoking, through a simple
questionnaire in a single referral centre. During the outpatient clinic of gastro-
enterology, 625 consecutive patients with CD, 238 patients with ulcerative colitis
(UC) and 289 patients without an inflammatory bowel disease (non-IBD con-
trols, NC) were requested to participate. Questionnaires included questions on
former and actual smoking behaviour, cessation attempts, nicotine dependence
(Fagerstrom score), and willingness to quit smoking. Patients were questioned on
their awareness of smoking-related risks on several aspects of health, including
detrimental effects on CD (Table 1).
RESULTS: Participation rates were 92% for CD (n 575, 46% male, 44 years,
44% never smoked), 93% for UC (n 238, 57% male, 45 years, 50% never
smoked) and 76% for NC (n 221, 48% male, 48 years, 55% never smoked).
At diagnosis, more CD patients were active smokers compared to UC patients
(40% vs. 17%, p50.001). Previous attempts to stop smoking and nicotine depen-
dence were similar in all groups. Remarkably, smoking cessation rates after
A202 United European Gastroenterology Journal 2(5S)
diagnosis were not higher in CD compared to UC (both 56%, p 0.997). In differentiation. Macrophages constitute one of the central components of the
contrast, more CD than UC patients started smoking after diagnosis (12% vs. inflamed mucosa, and have the ability to modulate epithelial cell function. We
6%, p 0.050). As shown in Table 1, the majority of patients recognized dangers have previously reported1 HIF-1 stabilization in macrophages from the mucosa
of smoking on general health (98-99%), lung cancer (95-97%), myocardial of IBD patients and we aim to analyse here the expression of Notch ligands by
infarction (89-92%), and stroke (78-87%). Although CD patients more fre- macrophages and the role of HIF-1.
quently acknowledged risks of smoking on their disease, only 37% were aware AIMS & METHODS: U937 cells were subjected to hypoxia (3% O2) or nor-
of the link with CD development, 30% of increased surgical rates, and 27% of moxia (21% O2) and protein levels of HIF-1 were analysed by Western blotting
increased postoperative recurrence rates. Of note, within the CD population, and the mRNA expression of Dll4 and Jag1 ligands by real time PCR (n 5). In
awareness was unrelated to actual smoking behaviour. Increased surgery rates some cases, cells were subjected to transient transfection of HIF-1 with miRNA
were acknowledged by 30% of active, 32% of former and 29% of non-smokers or with an empty vector (mock, n 5). Analysis of the Jag1 gene promoter was
(p 0.783). Active smokers not willing to quit smoking, most often denied a performed using a ChIP assay (n 3). Colonic surgical resections from both
potential bad influence of smoking on their disease. Previous surgery, level of damaged and non-damaged mucosa were obtained from IBD patients (n 11).
education and employment did not influence awareness. Finally, UC patients In both cases, macrophages were isolated from the mucosa and the expression of
were more frequently aware of an inverse relationship between smoking and Dll4 and Jag1 ligands was determined by real time PCR. HIF1, CD68 and Jag1
UC development (39% UC, 16% CD, 4% NC, p50.001). immunofluorescence experiments were performed in the mucosa of IBD patients.
RESULTS: In mock U937 cells, hypoxia induced HIF-1 stabilization and a
Smoking increases Certainly I dont I dont I think time-dependent increase in Dll4 and Jag1 mRNA expression, which starts to
the risk of not think so know so Certainly be significantly different from normoxia 5 h later (4.1  0.4 and 18.5  2.1
fold induction vs macrophages in normoxia, respectively). The increase induced
bad general health by hypoxia was significantly decreased when macrophages had been treated with
miHIF-1 (0.94  0.34 and 4.3  2.4 fold induction vs macrophages in normoxia,
CD 0% 0% 2% 13% 85% respectively). ChIP assay showed HIF-1 binding to the proximal promoter
UC 1% 0% 0% 12% 87% region of Jag1 gene in hypoxia through the HREs sequences located between
NC 0% 0% 0% 6% 94% positions -106 and -638. Immunofluorescence experiments revealed that CD68-
lung cancer positive cells were co-localized with HIF-1 and Jag1 in the damaged mucosa of
IBD patients. The mRNA expression of Dll4 and Jag1 was significantly higher in
CD 0% 1% 4% 18% 77% macrophages isolated from damaged mucosa than from non-damaged (1.5  0.2
UC 0% 1% 4% 16% 79% and 3.2  0.7 fold induction vs macrophages from non-damaged mucosa,
NC 0% 0% 3% 12% 85% respectively).
myocardial infarction CONCLUSION: HIF-1 mediates the increase in the expression of Dll4 and
Jag1 induced by hypoxia in macrophages. Jag1 expression co-localizes with
CD 0% 1% 10% 28% 61% HIF1 in macrophages of the mucosa of CD patients and it is higher in macro-
UC 0% 1% 9% 31% 59% phages from damaged than from non-damaged mucosa.
NC 0% 0% 8% 25% 67% REFERENCES
stroke 1. Ortiz-Masia`, D. et al. Hypoxic macrophages impair autophagy in epithelial
cells through Wnt1: relevance in IBD. Mucosal Immunol 2013 Dec 4.
CD 0% 2% 17% 30% 51% Disclosure of Interest: None declared
UC 0% 2% 20% 29% 49%
NC 0% 0% 12% 27% 61%
P0265 THE MACROPHAGE PHENOTYPE DIFFERENTIALLY
CD
MODULATES NOTCH SIGNALING PATHWAY IN EPITHELIAL
CD 4% 14% 45% 19% 18% CELLS: RELEVANCE IN DISEASE CROHNS
UC 2% 19% 61% 10% 8% D. Ortiz-Masia1,*, J. Cosin-Roger1, S. Calatayud1, C. Hernandez2,
NC 0% 5% 71% 14% 10% D. Barrachina1
1
CD surgery PHARMACOLOGY, CIBEREHD-UNIVERSIDAD DE VALENCIA,
2
CD 1% 10% 59% 20% 10% PHARMACOLOGY, FISABIO, VALENCIA, Spain
Contact E-mail Address: mdorma@uv.es
UC 1% 10% 72% 12% 5%
NC 0% 4% 77% 11% 8% INTRODUCTION: Crohns disease (CD) is associated with impaired epithelial
postoperative CD recurrence barrier function. Restoration of mucosal integrity involves proliferation and
differentiation of intestinal epithelial cells and Notch signaling has been shown
CD 2% 9% 62% 18% 9% to be central in the regulation of these processes. Macrophages are present in the
UC 0% 12% 74% 10% 4% microenvironment surrounding the crypts in the intestine and may modulate the
NC 0% 3% 81% 9% 7% behavior of epithelial cells. We have previously reported presence of both M1
UC and M2 macrophage phenotypes in the mucosa of ulcerative colitis patients1. We
aim to determine the role of different macrophage phenotypes on epithelial
CD 4% 12% 67% 13% 4% Notch signaling and the relevance of this pathway in CD.
UC 10% 29% 48% 8% 5% AIMS & METHODS: U937 cells were polarized towards a M1 phenotype with
NC 1% 3% 76% 13% 7% IFN and LPS (24h) or M2 phenotype with IL-4 (72h) and these cells were co-
cultured with HT29 cells for 24h. Next we determined in epithelial cells, the
expression of HES1 by static cytometry and alkaline phosphatase activity.
Damaged mucosa of patients with CD was obtained. Protein levels of HES1
CONCLUSION: Although CD patients were better informed on the detrimental and the expression of CD86 (M1 marker) or CD206 (M2 marker), were quanti-
effects of smoking, the awareness rate was still low. These data may also suggest fied in the mucosa.
more denial for the adverse consequences of smoking in active smokers. More RESULTS: Immunofluorescence experiments show that M1 macrophages co-
efforts need to be done on informing and educating patients regarding the risks cultured with HT29 cells did not significantly modify the expression of HES1
of smoking. (87.4  5.4% vs the basal expression in HT29 cells) but induce a significant
Disclosure of Interest: C. De Bie: None declared, V. Ballet: None declared, G. (P50.05) increase in AP activity in epithelial cells (125.4  3.0% vs the basal
Van Assche Financial support for research from: Abbvie, Ferring, Lecture fee(s) activity in HT29 cells). In contrast, M2-macrophages significantly (P50.05)
from: Abbvie, MSD, Janssen Biologics, Consultancy for: PDL BioPharma, UCB reduced in HT29 cells both, HES1 expression (62.1  11.1% vs the expression
Pharma, Sanofi-Aventis, Abbvie, Ferring, Novartis, Biogen Idec, Janssen in HT29 cells) and AP activity (62.5  4.1% vs the activity in HT29 cells). A
Biologics, NovoNordisk, Zealand Pharma, Takeda, Shire, Novartis, BMS, S. quantitative analysis of the number of CD86-and CD206-positive cells in the
Vermeire Financial support for research from: UCB Pharma, MSD, Abbvie, damaged mucosa of CD patients as well as protein levels of HES1, reveal a
Lecture fee(s) from: Abbvie, MSD, Ferring, UCB Pharma, Janssen Biologics, negative and significant correlation between the ratio of M2/M1 macrophages
Consultancy for: UCB Pharma, AstraZeneca, Ferring, Abbvie, Merck, Shire, and HES1 protein levels (Pearson r -0.6775, P value 0.031, n 10).
Pfizer, M. Ferrante Financial support for research from: Abbvie, Janssen CONCLUSION: M2 macrophages induced a profound reduction in epithelial
Biologics, MSD, Lecture fee(s) from: Abbvie, Janssen Biologics, MSD, Notch signaling and impair enterocyte differentiation while M1 macrophages
Tillotts, Ferring failed to do that. In the damaged mucosa of CD patients, the prevalence of
M2 macrophages, through diminution of both epithelial Notch signaling and
enterocyte differentiation, may impair epithelial regeneration.
P0264 HIF-1 MEDIATES THE HYPOXIC UP-REGULATION OF DLL4 REFERENCES
AND JAG1 IN MACROPHAGES: RELEVANCE IN IBD 1. Cosin-Roger J, et al. M2 macrophages activate WNT signaling pathway in
D. Ortiz-Masia1,*, D.C. Macias-Ceja1, J. Cosin-Roger1, S. Calatayud1, epithelial cells: relevance in ulcerative colitis. PLoS One 2013; 8.
C. Hernandez2, D. Barrachina1 Disclosure of Interest: None declared
1
PHARMACOLOGY, CIBEREHD-UNIVERSIDAD DE VALENCIA,
2
PHARMACOLOGY, FISABIO, VALENCIA, Spain
Contact E-mail Address: mdorma@uv.es
INTRODUCTION: Mucosal healing, which has been established as a target goal
in inflammatory bowel disease, involved the coordinated regulation of several
signaling pathways, including Notch signaling which plays an essential role in
United European Gastroenterology Journal 2(5S)
P0266 A DIMINISHED NOTCH SIGNALLING AND IMPAIRED
ENTEROCYTE DIFFERENTIATION IS OBSERVED IN EPITHELIAL
CELLS FROM DAMAGED MUCOSA OF CROHNS DISEASE
PATIENTS
1,* 1 1 2
D. Ortiz-Masia , J. Cosin-Roger , S. Calatayud , C. Hernandez ,
D. Barrachina1
1
PHARMACOLOGY, CIBEREHD-UNIVERSIDAD DE VALENCIA,
2
PHARMACOLOGY, FISABIO, VALENCIA, Spain
Contact E-mail Address: mdorma@uv.es
INTRODUCTION: Mucosal healing has been established as a key treatment
goal in Crohns disease (CD) that predicts sustained clinical remission and resec-
tion-free survival of patients. This process depends on the proper reconstruction
of the intestinal epithelium that depends on proliferation and differentiation of
progenitor cells, a process that is tightly regulated by activation of the Notch
signalling. We aim to determine the regulation of the Notch pathway and epithe-
lial differentiation in the mucosa of CD patients.
AIMS & METHODS: Colonic surgical resections from both damaged and non-
damaged mucosa were obtained from CD patients (n 11). Human intestinal
crypts were isolated from mucosa by using a non-enzymatic dissociation techni-
que based on short-term EDTA treatment. Protein levels of IAP (marker of
enterocyte differentiation) and HES1 (a specific Notch target gene) were ana-
lyzed by Western blotting and immunohistochemistry (HES1). The expression of
MUC2 (a marker of goblet cell differentiation), CDX2 (a transcriptional activa-
tor of intestine specific genes involved in differentiation) and Math1 (a gene that
is repressed by HES1) was analyzed in epithelial cells by real time PCR. The
quantitative analysis of goblet cells was performed in the mucosa stained with
PAS.
RESULTS: A comparative study (fold induction vs crypts from non-damaged
mucosa) revealed a significant (P50.05) diminution in protein levels of HES1
(0.28  0.07) and IAP (0.20  0.10) and a significant increase in mRNA levels of
MUC2 (11.8  2.3), CDX2 (2.1  0.8) and Math1 (3.4  0.8) in crypts from
damaged mucosa. Immunostaining for HES1 revealed lack of this protein in
epithelial cells of the damaged mucosa. The percentage of goblet cells vs. total
nuclei in the crypt was significantly (P50.05) higher in the damaged (47.8 
4.4%) than in the non-damaged mucosa (29.2  2.4%).
CONCLUSION: The diminished Notch signaling and impaired enterocyte dif-
ferentiation detected in epithelial cells from damaged mucosa of CD patients may
mediate the weakened mucosal healing observed in these patients.
Disclosure of Interest: None declared
P0267 HUMAN INTESTINAL FIBROBLASTS ARE NOVEL TARGET
CELLS FOR ALPHA-MELANOCYTE-STIMULATING HORMONE
POSSIBLE IMPLICATIONS FOR THE TREATMENT OF
STRICTURING CROHNS DISEASE WITH MELANOCORTIN
PEPTIDES AND DERIVATIVES
D. Bettenworth1,*, A. Stegemann2, P.R. Tepasse1, E. Rijcken3, M. Apel2,
M. Bohm2
1
Department of Medinice B, 2Department of Dermatology, 3Department of General
and Visceral Surgery, University Hospital Munster, Munster, Germany
Contact E-mail Address: dominik.bettenworth@ukmuenster.de
INTRODUCTION: Efficient treatment against fibrotic complications like intest-
inal strictures is still an unmet need in patients with Crohns disease. In dermal
fibroblasts, melanocortin peptides such as a-melanocyte-stimulating hormone (a-
MSH) were shown to modulate collagen synthesis. Moreover, in the bleomycin
scleroderma mouse model this peptide had anti-fibrotic effects. Thus, we won-
dered if human intestinal fibroblasts are also target cells for melanocortins in the
context of extracellular matrix synthesis.
AIMS & METHODS: Human intestinal fibroblasts were isolated from macro-
scopically normal colonic specimens of patients undergoing scheduled colonic
surgery (n 5) and were characterized by immunohistochemistry with anti-
desmin, anti-vimentin and anti-alpha-smooth muscle actin antibodies.
Melanocortin receptor (MC) expression was determined by RT-PCR.
Intracellular Ca2 mobilization indicating functional coupling of the detected
MC was assessed by FURA-2AM loading and fluorescence analysis. Collagen
type I expression was determined by RT-PCR and secretion of procollagen type I
C-terminal peptide by ELISA.
RESULTS: Immunocytochemistry with anti-desmin, anti-vimentin and anti-
alpha-smooth muscle actin antibodies confirmed a myofibroblast phenotype of
isolated cells. MC expression profiling proved that these cells exclusively express
MC1. Truncated transcripts for proopiomelanocortin (POMC), the precursor of
a-MSH, were also detected but no functional full-length POMC mRNA. In
accordance, cells lacked POMC protein expression ruling out an autocrine
loop for alpha-MSH. No Ca2 mobilization was detected by FURA-2AM load-
ing, after stimulation with a-MSH and fluorescence analysis. However, a-MSH at
doses between 10-6 and 10-10 M significantly suppressed procollagen type I C-
terminal peptide secretion induced by TGF-b1. This effect was not paralleled by
reduction in corresponding COL(I) mRNAs indicating a posttranscriptional
mechanism of the regulatory effect of a-MSH on collagen synthesis.
CONCLUSION: These findings demonstrate that human intestinal fibroblasts
are novel targets for alpha-MSH. It will be intriguing to assess the effect of other
melanocortins and derivatives in these cells on collagen synthesis as well as the
impact of them in animal models of intestinal fibrosis.
A203
Disclosure of Interest: None declared
P0268 HEARING LOSS IN PATIENTS WITH INFLAMMATORY BOWEL
DISEASE (IBD)
D. Wengrower1,*, C. Shaul2, U. Peleg2, L. Cohen3, M. Gross3, B. Koslowsky1
1
Digestive Disease Institute, 2ENT Dept, Shaare Zedek Medical Center, 3ENT
Dept, Hadassah University Hospital, Jerusalem, Israel
Contact E-mail Address: dovwen@szmc.org.il
INTRODUCTION: IBD has many characteristics of autoimmune diseases.
Sensorineural hearing loss has been reported in many autoimmune diseases.
Little is known about hearing loss in patients with IBD.
AIMS & METHODS: A prospective blinded comparative study was conducted
over a 3 year period. IBD patients and controls underwent a complete otorhi-
nolaryngeal examination and eudiometry test.
RESULTS: Altogether 105 participants (76 patients and 29 controls) took part in
this study. 59(77%) had Crohns disease (CD) and 17(23%) had ulcerative colitis
(UC). Mean age was 36, 51% were males and 40% of the patients were presently
hospitalized due to IBD exacerbation. 16/76(21%) of the IBD patients com-
plained of hearing loss since first IBD diagnosis and 13% had current hearing
disabilities. Audiometric examination revealed that any hearing loss (mild to
severe) was found in 23(30%) of the IBD population, compared to 3 (10%) of
the control group (p50.05). Sensironeural was the hearing deficiency type in
93% of them. Out of 46 patients, whose extraintestinal manifestation (EIM)
status was clearly documented, 43% (n 20) had EIMs. Hearing loss was present
in 5/20 (25%) of these patients, compared to 0/23 who did not have EIMs
(p50.01). IBD phenotype (inflammatory vs. obstructive/fistulary), current hos-
pitalization and disease type (CD vs. UC) was not different between these groups.
CONCLUSION: Sensironeural hearing loss may be another EIM of IBD. It is
found in 30% of IBD patients, and in up to 43% of patients with other EIMs.
Early hearing evaluation should be recommended to IBD patients who have
other EIMs
Disclosure of Interest: None declared
P0269 ANTI-TNF-A INDUCTION REGIMEN MODULATES GUT
MICROBIOTA MOLECULAR COMPOSITION WHILE INDUCING
CLINICAL REMISSIONS: RESULTS FROM A PRELIMINARY
EVALUATION ON CROHNS DISEASE PATIENTS
F. Scaldaferri1,*, L. Lopetuso1, V. Petito1,1, D. Zambrano1, E. Schiavoni1,
R. landi1, M.T. pistone1, D. dambrosio1, O. Ricca1, G. Cammarota1, F. Paroni
Sterbini2, F. franceschi1, E. Gaetani1, M. Sanguinetti2, L. Masucci2,
A. Gasbarrini1,2
1
Internal Medicine Department, Gastroenterology division, 2Institute of
Microbiology, Catholic University of Sacred Heart of Rome, Rome, Italy
Contact E-mail Address: francoscaldaferri@gmail.com
INTRODUCTION: IBD, and in particular Crohns disease, is chronic inflam-
matory condition characterized by an abnormal immune response towards self
microbiota and by an abnormal gut microbiota composition, as determined by
new molecular techniques. Anti-TNF-a is one of the strongest therapeutical
options available, able to induce mucosal healing and restore mucosal immune
homeostasis. Little information exists on the ability of antiTNF-a to modulate
gut microbiota composition.
AIMS & METHODS: Aim of our study was to evaluate gut microbiota compo-
sition in Crohns disease patients before and after 6 weeks after anti-TNF-a
therapy.
Fecal samples were collected in 3 consecutive CD patients, the first day of the
first dose of anti-TNF-a therapy (infliximab) and following 6 weeks: 2 patients
displayed colonic CD and 1 ileo-ciecal CD (2 males of 23 and 33 years, and 1
female of 53 years), no-one took any antibiotic 2 weeks before starting anti-TNF-
a therapy or during the active treatment. Harvey Bradshaw scores at baseline and
after 6 weeks were respectively 4 and 3, 7 and 3 and 4 and 1.
Microbiota composition was assessed by Metagenomic, a technique assessing 16S
rRNA (Roche 454 GS Junior), following DNA isolation from stool samples
stored in 80 C. Data obtained were analyzed by suite Qiime.
RESULTS: Bacteria amplicons were detected in all samples. Prevalent classes of
bacteria were: Bacteroidia (min 18% - max 95%), Firmicutes (min 2% - max
58%%) and Proteobacteria (min 2% - max 22%). Following anti-TNF-a ther-
apy, bacteroidetes reduced in all patients (min from 3% max from 67%).
Firmicutes, on the contrary, increased in levels. In 2 patients also proteobacteria
increased. Species Faecalibacterium was not present in 2 out of 3, but in one
patient, Fecalibacterium increased from 17% before therapy to 23% after
therapy.
CONCLUSION: Anti TNF-a treatment is associated with active modulation of
intestinal microbiota, including decrease in bacteroidetes and increase in firmi-
cutes. Metagenomics seems a promising technique whose real application in clinic
is still under development.
REFERENCES
Arumugam M. 2011; 473.
Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience
of the human gut microbiota. Nature 2012; 489: 220-230.
Lozupone CA, Stombaugh JI, Gordon JI, et al. Diversity, stability and resilience
of the human gut microbiota. Nature 2012; 489: 220-230.
Disclosure of Interest: None declared
A204
P0270 CHANGING TRENDS IN IBD HOSPITAL ADMISSIONS AND
MANAGEMENT IN ENGLAND, 2001-02 TO 2010-11
A. Ahmad1,*, T. Cowling1, A. Laverty1, J.-Y. Kang2, A. Majeed1, R. Pollok2
1
Department of Primary Care and Public Health, Imperial College, 2St Georges
Healthcare NHS Trust, London, United Kingdom
Contact E-mail Address: ahmir.ahmad@nhs.net
INTRODUCTION: Inflammatory bowel disease is a chronic disorder, affecting
240,000 people in the UK. The long-term impact of recent advances in IBD
management on hospital admissions and surgery is uncertain.
AIMS & METHODS: Our aim was to investigate trends in hospital admission,
fatality rates, surgery, endoscopy and cytokine inhibitor infusions for CD and
UC in England between 2001-02 and 2010-11.
We used admissions data from Hospital Episode Statistics, a national adminis-
trative database of all National Health Service hospital admissions and popula-
tion data from the Office for National Statistics, England.
RESULTS: From 2001-02 to 2010-11, age-sex standardised day-case admission
rates increased by 460.4% (p50.001) and 127.0% (p50.001) for CD and UC
respectively. There was no significant change in inpatient admission rates for
CD and UC. Both inpatient and day-case rates of surgery and endoscopy fell
for both CD and UC [inpatient: CD surgery -8.9% (p50.001) CD endoscopy -
14.4% (p50.001) UC surgery -6.8% (p50.001) UC endoscopy -10.5% (p50.01);
day-case: CD surgery -75.3% (p50.001) CD endoscopy -55.9% (p50.001) UC
surgery -66.7% (p50.001) UC endoscopy -17.2% (p50.001)]. Day-case infusions,
including cytokine inhibitor treatment, rose in both CD and UC, by 308.9%
(14.8% to 60.6%, p50.001) and 3475.0% (0.4% to 15.4%, p50.001) respectively.
CONCLUSION: Over the past decade inpatient admission rates for IBD have
remained static, but day-case admission rates have risen whilst the requirement
for surgery and endoscopy has fallen. The reduction in surgical and endoscopic
activity and the switch towards day-case activity may reflect recent advances in
IBD management, notably, the substantial increase in anti-TNF therapy.
Disclosure of Interest: None declared
P0271 EPIDEMIOLOGY AND TEMPORAL TRENDS (2000-2012) OF
INFLAMMATORY BOWEL DISEASE IN ADULT PATIENTS IN A
CENTRAL REGION OF SPAIN
A.J. Lucendo1,*, D. Herv as Cruz2, O. Roncero3, R. Lorente4, A. Bouhmidi5,
T. Angueira1, C. Verdejo4, I. Saluena5, S. Gonzalez-Castillo1, A. Arias6 on behalf
of The Ciudad Real province IBD working group
1
Gastroenterology, Hospital General de Tomelloso, Tomelloso, 2Gastroenterology,
Hospital Virgen de Altagracia, Manzanares, 3Gastroenterology, Hospital General
Mancha Centro, Alcazar de San Juan, 4Gastroenterology, Hospital General
Universitario de Ciudad Real, Ciudad Real, 5Gastroenterology, Hospital Santa
Barbara, Puertollano, 6Research Support Unit, Hospital General Mancha Centro,
Alcazar de San Juan, Spain
INTRODUCTION: A growing incidence of IBD in southern Europe has been
recently reported, with records of pediatric cases confirming these tendencies in
Spain. Data on adult population however, has not been provided for over 10
years and needs to be updated.
AIMS & METHODS: This study has two main objectives: (1) to estimate the
current prevalence of IBD in central Spain, and (2) to examine recent trends in
disease prevalence. A further goal was to characterize changes in disease presen-
tation over time.
A multicenter retrospective registry of all adult patients with a diagnosis of IBD,
including both Crohns disease (CD) and ulcerative colitis (UC), attended in 5
public hospitals covering a population of 514,368 inhabitants was carried out.
RESULTS: In 2012, the prevalence of CD and UC in adults was 137.17/100,000
inhabitants [95% confidence interval (CI): 114 160] and 99.84/100,000 inhabi-
tants (95% CI: 79 119), respectively. The mean incidence rate during 2000-1012
period of CD and UC was 8.9 and 5.6/100,000 inhabitants per year, respectively.
Most of our patients (75.55%) were diagnosed during the last 13 years. CD
affected equally both genders; a trend to progressive increase in the age at diag-
nosis, ileal location and inflammatory behavior was documented for CD patients.
In contrast, UC affected with a higher frequency to male subjects (57.8%,
p 0.015), specifically at an age over 40 years old. Age at UC onset trended to
progressively increase from 2000 to 2012 (p50.001), but the extension on the
disease remained unchanged.
CONCLUSION: A significant increase in the prevalence of IBD, especially for
CD, was documented in our region regarding previous estimation in Spain. CD
incidence reached similar figures to those provided for Northern Europe, increas-
ing the burden of IBD over the health system.
Disclosure of Interest: None declared
P0272 HEPATOBILIARY DISEASES IN A PROSPECTIVE POPULATION
BASED COHORT WITH INFLAMMATORY BOWEL DISEASES
(ICURE)
A. Ronnblom1,*, T. Holmstrom1, H. Tanghoj1, F. Rorsman1, D. Sjoberg1
1
Dpt of Medical Sciences, Uppsala, Sweden
Contact E-mail Address: anders.ronnblom@akademiska.se
INTRODUCTION: The relation between hepatobiliary diseases and IBD has
been the focus for scientific research for many years. There are, however, few
prospective population based cohort studies in this area. Between 2005 and 2009
all newly diagnosed cases of IBD in all age groups in the Uppsala Health Care
Region were registered. The cohort consists of 790 individuals corresponding to
an average incidence of 20.0 new cases of UC/100 000/year and 9.9 new cases of
Crohns disease/100 000/year (REFERENCES
United European Gastroenterology Journal 2(5S)
JCC. 2013 Oct 1;7(9):e351-7. and JCC. 2014 Mar 1;8(3):215-22.)
AIMS & METHODS: During the winter 2013/14 all medical records were scru-
tinized and the results were collected. Liver function tests and investigation of
hepatobiliary diseases were collected. Liver function tests had been checked at
least once in 97.1% of the cohort. The main method for the diagnosis of PSC was
magnetic resonance cholangiopancreaticography (MRCP), or endoscopic retro-
grade cholangiopancreatography (ERCP) when the results were ambiguous.
Parenchyma diseases were investigated with liver biopsy and biochemical tests.
IBD was classified according to the Montreal classification.
RESULTS: Seventeen patients with PSC were diagnosed corresponding to an
overall prevalence of 2.15% (for UC 1.90% and for Crohns disease 2.65%). The
average age of these was 25,0 years. Among the 92 paediatric patients (517 years
old) three patients had autoimmune hepatitis, but none PSC. Three patients have
undergone liver transplantation and one has died of colonic carcinoma. Eleven
patients have demonstrated persistent elevation of ALP but have had a normal
MRCP or refused further investigation.
CONCLUSION: In this prospective population based cohort consisting of 526
patients with UC and 264 with Crohns disease, 17 cases of PSC was found,
among whom so far have been liver transplanted or have died because of
carcinoma. The average age of those affected by PSC is considerably lower than
usually is reported. Forthcoming study of ICURE will reveal if more patients will
be affected by liver disease.
Disclosure of Interest: None declared
P0273 CELIAC DISEASE IN IBD. OBSERVATIONS FROM A
POPULATION BASED COHORT OF IBD (ICURE)
A. Ronnblom1,*, T. Holmstrom1, H. Tanghoj1, A. Wanders1, D. Sjoberg1
1
Dpt of Medical Sciences, Uppsala, Sweden
Contact E-mail Address: anders.ronnblom@akademiska.se
INTRODUCTION: IBD and celiac disease are diseases with worldwide distribu-
tion and an increased incidence of them have been reported from many areas.
There is a shortage of studies investigating the possible concomitant appearance
of these diseases in the same individual and whether those affected by both
diseases demonstrate any particular phenotype. ICURE (IBD Cohort Uppsala
health Region) is a population based cohort of individuals with ulcerative colitis
(n 526, JCC. 2013 Oct 1;7(9):e351-7) Crohns disease (n 264, JCC. 2014 Mar
1;8(3):215-22) and microscopic colitis (n 272). We have previously reported the
occurrence of celiac disease among patients with microscopic colitis (Scand J
Gast 2013;48:825-830) and we now aimed to study the patients with UC and
Crohns disease in the same respect.
AIMS & METHODS: In 790 individuals diagnosed with ulcerative colitis or
Crohns disease between 2005 and 2009, the possible concomitant occurrence
of celiac disease was investigated. Medical notes were scrutinized and pathologi-
cal specimens were re-examined.
RESULTS: Three hundred and ninety-nine of the 790 patients had been exam-
ined for the possibility of celiac disease, corresponding to an investigation of
49.4% of the total cohort. Sixteen patients with celiac disease were found, repre-
senting 2.05% of the cohort. Two patients with IBD and celiac disease developed
collagenous colitis 5 and 7 years later and one PSC after 3 years. A young man
with UC developed collagenous sprue. Compared with the non-celiacs the
patients with both IBD and celiac disease were younger (22.5 vs. 34.5 years,
p 0.0015) and those with colitis more often had an extensive disease (9/3 vs.
163/328, p 0.0026) and 76% were women.
CONCLUSION: Celiac disease is sufficiently common among patients with IBD
to motivate screening for this condition in the regular workup of patients with
ulcerative colitis and Crohns disease. Those affected by both diseases are pre-
dominantly young women with extensive colitis.
Disclosure of Interest: None declared
P0274 WORK DISABILITY AND PRODUCTIVITY LOSS IN PATIENTS
WITH INFLAMMATORY BOWEL DISEASES IN HUNGARY IN THE
ERA OF BIOLOGICS
B.D. Lovasz1,*, A. Balint2, M. Mandel1, P.A. Golovics1, L. Gulacsi3, B. Strbak3,
K. Farkas2, Z. Kurti1, B. Szilagyi1, A. Mohas1, T. Molnar2, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, 21st Department
of Medicine, University of Szeged, Szeged, 3Department of Health Economics,
Corvinus University of Budapest, Budapest, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: The IBD is a chronic and potentially debilitating disease
course can represent a heavy burden for patients, impacting every aspect of the
affected individuals life.
AIMS & METHODS: To assess work disability (WD) rates in an inflammatory
bowel disease (IBD) cohort involving patients with Crohns disease (CD) or
ulcerative colitis (UC) cohort and to identify possible clinical or demographic
factors associated with WD. Data from 443 (M/F: 202/241, CD/UC: 260/183,
mean age: 35.5 (CD) and 40.5 (UC) years, biological drug exposure 31.2% /
11.5%) consecutive patients were included. WD data were collected by question-
naire and the Work Productivity and Activity Impairment (WPAI) instrument.
Disability pension (DP) rates in the general population were retrieved from
public databases.
RESULTS: The overall DP rate in this IBD population was 32.3%, with partial
disability in 24.2%. Of all DP events, 88.8% were directly related to IBD.
Overall, full DP was more prevalent in IBD (RR:1.51, p50.001) and CD
(RR:1.74, p50.001) but not in UC compared to the general population and
also in CD compared to UC (OR: 1.57, p 0.03). RR for full DP was increased
only in young CD patients (RR535 year olds: 9.4; RR36-40 year olds: 9.4 and 5.6,
p50.01 for both). In CD, age group, previous surgery, disease duration, frequent
United European Gastroenterology Journal 2(5S)
relapses, and the presence of arthritis/arthralgia were associated with an
increased risk for DP. Among employed patients, absenteeism and presenteeism
was reported in of 25.9% and 60.3% patients, respectively, leading to a 28% loss
of work productivity and a 32% activity loss, and was associated with disease
activity and age group. Average cost of productivity loss due to disability and
sick leave with human capital approach was 1450 and 430 E/patient/year, respec-
tively (total productivity loss 1880 E/patient/year).
CONCLUSION: Risk of DP was highly increased in young CD patients (six to
nine fold). Previous surgery and presence of arthritis/arthralgia was identified as
risk factor for DP. Work productivity is significantly impaired in IBD and is
associated with high productivity loss.
Disclosure of Interest: None declared
P0275 INCREASED INTESTINAL PERMEABILITY AMONG FIRST-
DEGREE RELATIVES OF CROHNS PATIENTS IS NOT
ASSOCIATED WITH INCREASED MUCOSAL ULCERATIONS ON
SMALL BOWEL VIDEO CAPSULE ENDOSCOPY
C. Teshima1,*, M. El Kalla2, S. Turk3, W. El Matary4, R. Valcheva1,
R. Danchak2, M. Gordon2, P. Ho1, A. Mullins2, D. Wong1, J. Meddings5,
H. Huynh2, L. Dieleman1
1
Medicine, 2Pediatrics, University of Alberta, Edmonton, Canada, 3Medicine, Free
University Amsterdam, Amsterdam, Netherlands, 4Pediatrics, University of
Manitoba, Winnipeg, 5Medicine, University of Calgary, Calgary, Canada
INTRODUCTION: First-degree relatives (FDR) of Crohns disease (CD)
patients have the highest risk for developing CD. CD patients and a substantial
portion of FDR have increased intestinal permeability. It is unclear whether
FDR have abnormal permeability because of early, asymptomatic CD or
whether this occurs without mucosal inflammation. Video capsule endoscopy
(VCE) is the most sensitive means of imaging the small intestine and can identify
mucosal lesions suggestive of subclinical CD. The purpose of our study was to
determine if abnormal small intestinal permeability in healthy FDR is associated
with small bowel mucosal abnormalities detected by VCE.
AIMS & METHODS: 342 CD patients consented to have their FDR between 10-
45 years of age contacted regarding study participation. Eligible FDR underwent
small bowel permeability testing as measured using the lactulose/mannitol (L/M)
test that is based on the fractional urinary excretion of these sugars. FDR with
abnormal permeability (defined as  0.030) were compared to FDR with normal
small permeability (50.025) by VCE to assess for small bowel inflammatory
changes. The primary outcome was the number of mucosal ulcerations seen on
VCE in each permeability group.
RESULTS: 223 FDR consented to participate and completed the intestinal per-
meability test. 40 (17.5%) had abnormally increased permeability. Subsequently,
59 subjects with normal and 29 subjects with abnormal permeability underwent
VCE. On VCE, there was no difference in small bowel mucosal abnormalities
with a mean of 2.27 (range 0-16) ulcers in the normal and 2.52 (range 0-15) ulcers
in the abnormal permeability groups respectively (NS). Surprisingly, 23.5% of
asymptomatic FDR had more than 3 small bowel lesions as shown by VCE,
irrespective of their intestinal permeability. These lesions were significantly asso-
ciated with fecal calprotectin of 4 50 mg/g stool.
CONCLUSION: There is no association between small bowel ulcerations seen
on VCE between asymptomatic FDR of Crohns patients with abnormally
increased intestinal permeability and FDR with normal permeability. Thus, the
increased small bowel permeability in FDR does not seem to be caused by sub-
clinical CD, but is likely an intrinsic gut barrier defect. Surprisingly, over 23% of
these FDR had 3 or more small bowel ulcers, associated with increased fecal
calprotectin levels.
Disclosure of Interest: None declared
P0276 PRE-POUCH ILEITIS: A MORE TREATMENT REFRACTORY
SUB-GROUP OF POUCHITIS
D.C. de Jong1,*, M.A. Samaan1, S. Sahami2, G.van den Brink1, M. Lowenberg1,
C. Ponsioen1, W.A. Bemelman2, G.R. DHaens1
1
Inflammatory Bowel Disease Unit, Academic Medical Centre, Amsterdam,
2
Department of Surgery, Academic Medical Centre, Amsterdam, Netherlands
Contact E-mail Address: markasamaan@gmail.com
INTRODUCTION: Following restorative proctocolectomy (RPC) with ileal
pouch-anal anastomosis (IPAA) for ulcerative colitis, (UC) up to 50% of patients
will develop pouchitis. Moreover, a subgroup will also develop inflammation in
the pre-pouch ileum (pre-pouch ileitis, PI). Endoscopically, PI can mimic Crohns
disease (CD) but evidence suggests that PI may be a distinct disease entity. PI has
been reported more frequently in UC patients with primary sclerosing cholangitis
(PSC) undergoing IPAA. This group is also known to have higher rates of back-
wash ileitis and certain similarities have also been described between this and PI1.
AIMS & METHODS: Our aim was to assess the incidence, predictive factors and
response to treatment in a single centre cohort of pouch patients. We retrospec-
tively collected data on 246 consecutive UC patients who underwent RPC and
IPAA over the last 15 years. Endoscopic and histological records were used to
identify individuals with PI, defined as ulceration seen in the afferent limb at
endoscopy and evidence of active inflammation in biopsy samples.
RESULTS: Seventy-nine (32%) of the 246 patients were found to have had
pouchitis. Twelve patients were found to have concurrent PI, representing 5%
of the total cohort. No patients had PI in the absence of pouchitis. Of those with
PI, 6 patients (50%) had antibiotic-refractory, chronic pouchitis (as previously
defined1): four of whom required steroids/immunomodulators and two required
treatment with anti-TNF agents. One had antibiotic-dependent pouchitis. The
remaining 5 were antibiotic responsive and did not require long-term treatment
for their symptoms. A higher proportion of patients in the PI group had PSC (2
A205
of 12, 17%) compared to the non-PI group (11 of 234, 5%) though this difference
did not reach statistical significance (p 0.07).
Table 1: Showing demographic data for patients with and without pre-pouch
ileitis (PI)
PI (n 12) Non-PI (n 234)
Gender (female:male) 4:8 (33%:66%) 109:125 (47%:53%)
Smoker 1 (8%) 26 (14%, n 185)
Pouchitis 12 (100%) 67 (30%, n 227)
PSC 2 (17%) 11 (5%, n 234)
EIM 1 (8%) 21 (10%, n 219)
CONCLUSION: Compared with pouchitis, PI is a rarer and less well-defined
condition. Its recognition is relevant to clinicians as the inflammation involved is
more extensive and can be more treatment refractory than isolated pouchitis. Our
study demonstrates high rates of antibiotic-refractory, chronic pouchitis among
those with concurrent PI when compared with published pouchitis cohorts2. An
alternative possibility is that PI is a distinct clinical entity with different patho-
physiology to isolated pouchitis. The diagnosis of PI should be considered in all
patients with ulceration of the afferent limb rather than making the assumption
that Crohns disease is the underlying condition.
REFERENCES
1. Shen B, et al. Primary sclerosing cholangitis is associated with endoscopic and
histologic inflammation of the distal afferent limb in patients with ileal pouch-
anal anastomosis. Inflamm Bowel Dis 2011; 17: 1890-900.
2. Madiba TE and Bartolo DC. Pouchitis following restorative proctocolectomy
for ulcerative colitis: incidence and therapeutic outcome. J R Coll Surg Edinb
2001; 46: 334-337.
Disclosure of Interest: D. de Jong: None declared, M. Samaan: None declared, S.
Sahami: None declared, G. van den Brink: None declared, M. Lowenberg: None
declared, C. Ponsioen Financial support for research from: Abbott Laboratories,
Schering-Plough Corp., Falk Pharma, Tramedico, Consultancy for: Abbott
Laboratories, Glaxo Smith Kline, W. Bemelman: None declared, G. DHaens
Financial support for research from: Falk Pharma, MSD, Lecture fee(s) from:
MSD, UCB Inc., Abbott, Ferring Pharmaceuticals Inc., Consultancy for:
Abbott, Jansen Biologics,TEVA, Glaxo Smith Kline, Shire Pharmaceuticals
Inc., Nova Nordisk A/S, Pfizer Inc, MSD, UCB Inc.
P0277 UPTAKE OF INFLUENZA VACCINE IN ULCERATIVE COLITIS-
A LONGITUDINAL, POPULATION BASED STUDY
D. Boltin1,2,*, R. Gingold-Belfer3, N.A. Kimchi2, O. Ben-Bassat1, J. Langiewicz4,
Y. Niv1, S. Birkenfeld4
1
Gastroenterology, Rabin Medical Center, Petah Tikva, 2Gastroenterology, Bat
Yamon Medical Center, Bat Yam, 3Rabin Medical Center, Petah Tikva, 4Clalit
Health Services, Tel Aviv, Israel
Contact E-mail Address: dboltin@gmail.com
INTRODUCTION: The incidence of vaccine-preventable disease is increasing.
Current practice guidelines recommend annual influenza vaccination for all
inflammatory bowel disease (IBD) patients.
AIMS & METHODS: We aimed to determine the annual uptake of influenza
vaccine in UC patients. Using the Business Objects database of Clalit Health
Services in the Tel Aviv district we identified all patients over 18 years old with a
diagnosis of Ulcerative colitis (UC) on 31.12.2005. This cohort was followed until
31.12.2012. Subjects over age 50 without IBD who are also targeted for influenza
vaccination served as controls. The uptake of annual influenza vaccination was
recorded.
RESULTS: 470 UC patients were included (241 (51.3%) males, age 50.418.4
years, disease duration 158.986.5 months), and 2960 controls. During the years
2006, 2007, 2008, 2009, 2010, 2011 and 2012 the uptake of influenza vaccination
was 101 (21.5%), 122 (26.0%), 147 (31.3%), 181 (38.5%), 177 (37.7%), 170
(36.2%) and 178 (37.9%) amongst UC patients, and 993 (33.5%), 1360
(45.9%), 1524 (51.5%), 1611 (54.4%), 1446 (48.9%), 1576 (53.2%) and 1557
(52.6%) amongst controls (p50.0001 for every year). Independent predictors
of vaccination included age (OR, 1.05; 95% CI, 1.03-1.06; p50.001) and cardi-
ovascular risk (OR, 1.81; 95% CI, 1.31-2.49; p50.01).
CONCLUSION: Although uptake influenza vaccination is consistently lower in
UC compared to controls, an upward trend was observed over the study period.
Public health initiatives should target this high-risk population to promote
immunization.
REFERENCES
1. Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based
Consensus on the prevention, diagnosis and management of opportunistic infec-
tions in inflammatory bowel disease. J Crohns Colitis 2009; 3: 4791.
2. Longuet R, Willot S, Ginie`s J, et al. Immunization status in children with
inflammatory bowel disease. Eur J Pediatr 2013.
3. Wilckens V, Kannengiesser K, Hoxhold K, et al. The immunization status of
patients with IBD is alarmingly poor before the introduction of specific guide-
lines. Scand J Gastroenterol 2011; 46: 855861.
4. Benchimol EI, Hawken S, Kwong JC, et al. Safety and utilization of influenza
immunization in children with inflammatory bowel disease. Pediatrics 2013; 131:
e1811-e1820.
5. Fields SW, Baiocco PJ and Korelitz BI. Influenza Vaccinations: Should They
Really be Encouraged for IBD Patients Being Treated with
Immunosuppressives? Inflammatory Bowel Diseases 2009; 15: 649651.
Disclosure of Interest: None declared
A206
P0278 UK IBD TWIN AND MULTIPLEX REGISTRY: CONCORDANCE
AND ENVIRONMENTAL RISK FACTORS OF TWINS WITH IBD
H. Gordon1,*, T. Orchard2, A. Steel1, M. Harbord1
1
Gastroenterology, Chelsea and Westminster Hospital, 2Gastroenterology, St
Marys Hospital, London, United Kingdom
INTRODUCTION: Twins offer insight into the relative importance of genetic
and environmental factors in disease development. Twin studies to date show
concordance in monozygotic twins with CD and UC to be 20-55% and 6.3-17%
respectively. Dizygotic concordance rates are 0-3.6% (CD) and 0-6.3% (UC) (1).
The UK IBD Twin and Mutliplex Registry is a research database established in
October 2013; this study reviews disease patterns and environmental risk factors
of twin pairs recruited.
AIMS & METHODS: Data subjects were recruited via clinician referral, IBD
charities and retracing members of a database dormant since 1996. Adult twin
pairs discordant and concordant for IBD were recruited. Data subjects com-
pleted a questionnaire regarding demographics, disease history and environmen-
tal exposure. Medical records were reviewed when available.
RESULTS: Demographics, Concordance and Zygosity: 100 twin pairs were
recruited. Mean age 57 years 5 months, range 21-83 years. 31 monozygotic:69
dizygotic. Ratio CD:UC 48:52. Concordance of twin pairs classified by zygos-
ity and disease type is as follows:
Crohns Disease Ulcerative Colitis
Monozygotic 53.3% 25%
Dizygotic 10% 19.4%
Early Environment: Higher rates of exclusive breastfeeding were reported in
concordant compared with discordant pairs (27.3% n 22 pairs vs 16.7%
n 78 pairs). Self reports of perceived childhood illness did not show any differ-
ence between IBD and healthy twins of discordant pairs (16.7%, 13/78 vs 19.2%,
15/78). However, the IBD twin more often recalled frequent gastrointestinal
infection prior to IBD onset in comparison with their healthy twin (10.3%, 8/
78 vs 3.8%, 3/78).
Diet: IBD twins from discordant pairs reported higher rates of consuming "ready
made" meals at least weekly before disease incidence (12.8%, 10/78 vs 5.1%, 4/
78).
Smoking: On review of discordant twin pairs (n 72), there was no significant
difference in numbers of current, ex and non smokers between subjects with UC
(n 41), CD (n 32) and their healthy twin at time of symptom onset.
Medication and Stress: On review of all IBD sufferers, 7.1% (8/112) and 13.4%
(15/112) used NSAIDS and antibiotics within 3 months preceding onset. 48.2%
(54/112) reported significant stress within the year preceding onset.
Time of onset in concordant pairs: The mean lag between diagnosis of concor-
dant pairs was 7 years 5 months.
CONCLUSION: Concordance of twin pairs with CD is in keeping with previous
studies. However UC concordance is greater than expected; in particular 19.4%
dizygotic twin pairs with UC are concordant. This is 4 fold expected rates of non-
twin sibling concordance(2), suggesting early environment to be important in
pathogenesis. This study supports an associaton between diet, stress and gastro-
intestinal infection with IBD onset. The lack of associatoin with smoking at
incidence may reflect sample size.
REFERENCES
1. Brant S. Update on the heritability of inflammatory bowel disease: The impor-
tance of Twin Studies. Inflamm Bowel Dis 2012.
2. Bodger, et al. Concordance for IBD among twins compared to ordinary sib-
lings a Nowegian population based study. J Crohns Colitis 2010.
Disclosure of Interest: None declared
P0279 TEMPORAL TRENDS IN NON-STRICTURING, NON-
PENETRATING BEHAVIOUR AT DIAGNOSIS OF CROHNS
DISEASE IN OREBRO, SWEDEN: A POPULATION-BASED
RETROSPECTIVE STUDY UPDATED FOR 1988-2010
Y. Zhulina1, R. Udumyan2, I. Henriksson3, C. Tysk1,3, S. Montgomery2,
J. Halfvarson1,3,*
1
School of Health and Medical Sciences, Orebro University, 2Clinical
Epidemiology and Biostatistics Unit, Orebro University Hospital, 3Dep of Internal
Medicine, Div of Gastroenterology, Orebro University Hospital, Orebro, Sweden
Contact E-mail Address: jonas.halfvarson@orebroll.se
n
INTRODUCTION: The incidence of Crohns disease is continuing to rise in
w
several countries and in others it appears to have already levelled off. We updated
h d ra
our previous population based study,1 by re-extraction of all information on
patients diagnosed with Crohns disease between 1963 and 1987, and included
i t
patients diagnosed with Crohns disease up to 2010.
W
AIMS & METHODS: Our aim was to assess temporal trends in incidence, pre-
valence and disease phenotype at diagnosis. Patients of all ages with a potential
diagnosis of Crohns disease were identified retrospectively by evaluation of
medical notes of all current and previous patients at the Colitis clinic, Orebro
University Hospital amended by computerised search in the inpatient, outpati-
ents, primary care and histopatological records. The medical notes were reviewed
and patients were included if they lived within the catchment area at any time
during their disease course, were diagnosed between 1963-2010 and fulfilled the
Lennard-Jones criteria for Crohns disease. Disease phenotype was defined
according to the Montreal classification.
United European Gastroenterology Journal 2(5S)
RESULTS: The mean incidence for the period 1988-2010 was 7.6/105 (95% CI:
6.7-8.4/105). A comparison with the earlier period 1963-1987 showed increased
age and sex standardised incidence rates of Crohns disease, with an incidence
a n
rate ratio of 1.32 (1.11-1.57). The median (range) age at diagnosis increased from
w
28 (379) years to 37 (587) years (p 0.0002). Similarly, the point prevalence
r
d
increased from 178/105 (157-199) on 31 December 1987 to 267/105 (244 291) on
i t h
31 December 2010. Non-stricturing, non-penetrating disease at diagnosis
W
increased from 12.5% in 1963-1965 to 82.3% in 2005-2010.
CONCLUSION: The incidence of Crohns disease during the last two decades
increased. A striking increase in non-stricturing, non-penetrating disease at diag-
nosis was observed, suggesting earlier diagnosis or phenotypic change. The
observed point prevalence in 2010 is among the highest reported.
REFERENCES
1. Lindberg E and Jarnerot G. The incidence of Crohns disease is not decreasing
in Sweden. Scand J Gastroenterol 1991; 26: 495-500.
Disclosure of Interest: None declared
P0280 INTERLEUKIN 6 GEN POLYMORPHISM IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASES
D. Cibor1,*, D. Owczarek1, M. Glowacki1, K. Jablonski2, A. Jurczyszyn3,
A. Ciesla1, T. Mach1
1
Gastroenterology, Hepatology & Infectious Diseases, 2Medical Education,
3
Hematology, JAGIELLONIAN UNIVERSITY MEDICAL COLLEGE,
Krakow, Poland
Contact E-mail Address: dorota.cibor@gmail.com
INTRODUCTION: Interleukin 6 (Il-6) plays an important role in the develop-
ment of inflammatory process in IBD patients. The 174 G/C IL-6 promoter
polymorphism affects IL-6 transcription. The GG genotype seems to induce
higher IL-6 levels while the C allele (GC or CC) seems to be associated with
decreased transcription and secretion of IL-6.
AIMS & METHODS: Our study aimed to evaluate the effect of single nucleotide
polymorphism of IL-6 (174 G/C) on the disease course in patients with UC and
CD.
Material and methods: 105 patients (aged 18-75 years) with diagnosed IBD: 50
with CD and 55 with UC were involved in the study. The controls consisted of
124 healthy individuals. In all patients were evaluated following parameters:
disease duration, disease location, presence of complications, present pharma-
cotherapy, past surgical procedures, BMI, cigarette smoking. In all subjects
morphology, biochemical parameters, CRP, fibrinogen, IL-6 level and IL-6 poly-
morphism were assessed.
RESULTS: No statistically significant differences in IL-6 polymorphism were
observed between patients with UC, CD and controls. Patients with GG geno-
type were significantly younger at the disease onset. In IBD patients with GG
genotype higher mean IL-6 level was noticed as compared to other genotypes
(4.685 /- 5.9 vs 2.715 /- 5.1 in GC and 3.186 /- 3.6 in CC). In both UC and
CD patients with GG and GC genotype a positive correlation between IL-6 and
fibrinogen level as well CRP was found. In IBD patients with CC genotype no
correlation between IL-6 and fibrinogen was found (p 0.48).
CONCLUSION: The risk of developing IBD is not connected with IL-6 poly-
morphism. However, IL-6 variation might have an influence on the course of the
disease in IBD patients.
Disclosure of Interest: None declared
P0281 THE TPMT AND ABCB1 POLYMORPHISMS IN IBD PATIENTS
IN CRETE: IMPACT ON DISEASE AND RESPONSE TO TREATMENT
C. Coucoutsi1, A. Voumvouraki1, O. Sfakianaki1, G. Emmanuel1, E. Digenakis1,
I. Koutroubakis1, E. Kouroumalis1,*
1
Gastroenterology, University of Crete Medical School, Heraklion Crete,
Heraklion, Greece
Contact E-mail Address: kouroum@med.uoc.gr
INTRODUCTION: It is well known that polymorphisms of the TPMT gene
(coding for thiopourine methyl-transferase), influence response to treatment
with azathioprine. Polymorphisms of the ABCB1 gene (coding for p-glycoprotein
170) has been associated with IBD and resistance to treatment but results are
conflicting.
AIMS & METHODS: The aim of this study was to determine the frequencies of
TPMT and ABCB1 gene polymorphisms in IBD patients from Crete, a popula-
tion genetically homogeneous, and how these polymorphisms might influence
response to treatment and disease behaviour. A total of 222 IBD patients, records
were reviewed for intake of azathioprine, possible adverse reactions, response to
treatment and need for colectomy. All patients were genotyped for TPMT gene
polymorphisms, that have been related to intolerance to azathioprine (G238C,
G460A and A719C) as well as ABCB1 gene polymorphisms (G2677T/A and
C3435T), using a PCR-RFLP method. The same polymorphisms were also deter-
mined in 119 age and sex healthy controls.
RESULTS: Allele frequencies of TPMT gene in our study population were found
to be in concordance with those reported in other Caucasian populations. 76 IBD
patients were identified receiving azathioprine, of whom 16 were discontinued (10
CD, 6 UC) due to adverse reaction. 2 of them were found to carry the G460A and
A719G alleles (TPMT 3A genotype) (12.5%). For the ABCB1 gene, G2677T/A
allele frequencies were found to be similar to those reported in the literature. There
was no association of G2677T/A or C3435T with clinical phenotype, or resistance
to treatment. However, 77.3% of 22/222 patients who did not respond to therapy
and required surgery, were found to carry both the C3434T and the G2677T
mutation
CONCLUSION: Our study was conducted in a genetically homogenous popula-
tion in the island of Crete. No correlation of any single SNP was found with
United European Gastroenterology Journal 2(5S)
either clinical activity or response to treatment. However, most patients who
carried both the G2677T and C3435T mutations were refractory to treatment,
a finding which implies that resistance to treatment in IBD patients is a more
complex issue, which requires the presence of a genetic locus rather than a single
SNP.
Disclosure of Interest: None declared
P0282 FC RECEPTOR TYPE IIIA POLYMORPHISMS AND THEIR
CORRELATION WITH CLINICAL OUTCOME IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE DURING A LONG TERM
FOLLOW UP
G. Bodini1,*, V. savarino1, P. dulbecco1, I. baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: A total of 20-30% of patients with active Crohns disease
(CD) do not respond to anti-TNF- treatments and up to 40% of patients in
chronic therapy experience a loss of response. Furthermore about 50% of
patients with ulcerative colitis (UC) experience a loss of response to anti-
TNF therapy after one year. The cause of this limited efficacy is unclear, but
past studies hypothesized that the individual variation of drug metabolism may
play an important role. Thus, given the limited data available, the role of Fc
IIIa receptor (i.e. one of the four receptors involved in the catabolic pathway of
anti-TNF- drugs) polymorphisms should be further explored.
AIMS & METHODS: The aim of this prospective, long-term follow up study
was to evaluate the correlation between Fc IIIa receptor polymorphisms and
clinical outcome in IBD patients undergoing biologic therapy.
We enrolled consecutive IBD patients who achieved clinical remission by anti-
TNF- therapy. Blood samples were collected at the beginning of biological
therapy. The assessment of IBD activity was based on the Harvey-Bradshaw
Index score (HBI, remission 55, mild disease 5-7, moderate disease 8-16,
severe disease 416) for CD patients and on the Mayo score (Mayo52 remission,
mild disease 2-5, moderate/severe disease 6-12) for UC patients. Biochemical
evaluation and clinical score were assessed every 8 weeks. For the genotyping
analysis we used a Light Snips (Tib-Molbiol, Genova, Italy) and the Real-Time
PCR Technique developed by Light Cycler 480 Instrument (Roche, Mannheim,
Germany).
RESULTS: We prospectively included 39 patients (12UC/27 CD, 16F/23M) with
a median follow-up of 66.8 weeks (10-112). A total of 25 (64.1%) (10UC/15CD)
patients kept in remission during the whole follow up period, while 14 (35.9%)
(2UC/12CD) experienced disease relapse. As shown in the Table, four out of 14
(28.6%) (1UC/3CD) patients who experienced disease relapse, had FcIIIa-158
V/V receptor polymorphism, while the remaining 10 (71.4%) (9CD/1UC) had
FcIIIa-158 F/V or F/F receptor polymorphisms. Out of 25 patients who kept in
remission, 3 (12%) (1CD/2UC) had FcIIIa-158 V/V receptor polymorphism,
whereas the remaining 22 (88%) (14CD/8UC) showed FcIIIa-158 F/V or F/F
receptor polymorphisms. Patients in remission tended to have more often
FcIIIa-158 V/V receptor polymorphism compared to patients who relapsed,
but statistical significance was not reached.
Patients in Remission Relapsers
(n 25) (n 14) p value
Polymorphism V/V 3 (12%) 4 (28.6%) 0.2251
Polymorphism V/F F/F 22 (88%) 10 (71.4%)
CONCLUSION: The evaluation of Fc IIIa-158 V/V receptor polymorphism
does not seem useful in identifying patients who are more likely to lose anti TNF-
 response during long term period. However, further larger studies are necessary
to investigate the role of Fc IIIa receptor polymorphisms.
Disclosure of Interest: None declared
P0283 GENOME-WIDE STUDY OF ANTI-TNF RESPONSE IN
INFLAMMATORY BOWEL DISEASES
M. Hubenthal1,*, A. Franke1, V. Andersen2,3 on behalf of The Danish anti-TNF
study group
1
Christian-Albrechts-University of Kiel, Kiel, Germany, 2South Danish University,
Odense, 3South Jutland Hospital, Aabenraa, Denmark
Contact E-mail Address: vandersen@health.sdu.dk
INTRODUCTION: Biomarkers predictive of treatment response will help select
the optimal treatment for the individual patients. Genome-wide association stu-
dies (GWAS) on anti-TNF response in patients with Crohns Disease (CD) and
ulcerative colitis (UC) are limited.
AIMS & METHODS: We performed a GWAS using ImmunoChip on a clini-
cally-based cohort of anti-TNF treated patients with CD and UC. Data on the
first treatment of anti-TNF was sampled retrospective from 18 medical depart-
ments in Denmark by young medical doctors from the patient records. Efficacy
was evaluated using a simple 3-step scale (full/partial/non-responds) based on the
information in the patient records. Efficacy reflected the maximum response
within 26 weeks after anti-TNF treatment initiation. In total, 130061 autosomal
single nucleotide polymorphisms (SNPs) pass quality control QC) (62341 failed
QC) in 592 unrelated individuals ( 34 failing QC). SNPs were assessed for full
versus non-responders (partial responders were omitted).
RESULTS: In total, 364 cases had CD (270 full, 41 partial, and 53 non-respon-
ders) and 197 cases had UC (124 full, 23 partial, and 50 non-responders) and 31
cases had undetermined disease and/or response. Loci previously published to be
A207
risk factors for CD or UC could be shown to be significantly associated with
differences in anti-TNF response in CD (full vs. non-response) and UC (full vs.
non-response), respectively.
CONCLUSION: This is the first GWAS of anti-TNF treatment response in IBD.
Power for detecting associated markers was limited. Collaboration between
owners of anti-TNF treated cohorts e.g. in the regi of the International
Inflammatory Bowel Disease Genetic Consortium (IIBDGC) may increase the
power for identifying SNPs associated with treatment response.
Disclosure of Interest: M. Hubenthal: None declared, A. Franke: None declared,
V. Andersen Consultancy for: MSD & Janssen
P0284 RARE VARIANTS IN XIAP IN MALE PEDIATRIC-ONSET
CROHNS DISEASE
Y. Zeissig1,2,*, B. Petersen3, S. Milutinovic4, J. Hartwig1, G. Mayr3, E. Bosse1,
K. Peuker1, M. Kohl2, M. Laass5, S. Billmann-Born3, C. Rocken6, M. Schrappe2,
P. Rosenstiel3, J.C. Reed4, S. Schreiber1, A. Franke3, S. Zeissig1
1
Internal Medicine I, 2Department of Pediatrics, 3Institute of Clinical Molecular
Biology, Kiel University, Kiel, Germany, 4Sanford-Burnham Medical Research
Institute, La Jolla, United States, 5Childrens Hospital, Medical Faculty Carl
Gustav Carus, Technische Universitat Dresden, Dresden, 6Institute of Pathology,
Kiel University, Kiel, Germany
Contact E-mail Address: szeissig@1med.uni-kiel.de
INTRODUCTION: The genetic basis of inflammatory bowel disease (IBD) is
incompletely understood and it has been suggested that rare genetic variants
contribute to the heritability of IBD.
AIMS & METHODS: Here, we aimed to study rare variants involved in the
pathogenesis of IBD. We performed exome sequencing and detailed immunolo-
gical profiling in a patient with early onset Crohns disease (CD). The coding
region of the gene encoding X-linked inhibitor of apoptosis protein (XIAP) was
sequenced in samples of 275 paediatric IBD patients and 1047 adult-onset CD
patients. XIAP genotyping was performed in samples of 2680 IBD patients and
2864 healthy controls. Functional effects of the identified variants were investi-
gated in primary peripheral blood mononuclear cells (PBMCs) and cultured cell
lines.
RESULTS: A novel, de novo, nonsense mutation in the gene encoding XIAP, a
gene previously linked to primary immunodeficiency, was identified in a male
patient with early-onset CD. Sanger sequencing of XIAP in large cohorts of
paediatric IBD and adult-onset CD revealed several additional XIAP variants.
XIAP variants were detected in four percent of male patients with paediatric-
onset CD and were confined to this subset of IBD patients without detection of
XIAP variants in either UC or adult-onset CD. CD in patients harbouring XIAP
variants was characterized by small and large intestinal involvement, perianal
disease, and stricturing behaviour. Functional studies in primary PBMCs and
cultured cell lines revealed that the majority of identified XIAP variants were
associated with selective defects in NOD1 and NOD2 signalling. NOD1/2 defects
occurred as a consequence of impaired association of mutant XIAP with RIPK2
and/or altered XIAP-dependent ubiquitylation of RIPK2 thus uncoupling
NOD1/2 from its downstream mediator NF-B.
CONCLUSION: Our studies reveal the frequent occurrence of XIAP variants in
male, pediatric onset CD. Moreover, our data provide a mechanistic basis to the
previously unexplained observation of functional NOD2 defects in the absence of
genetic variants in NOD2. Finally, given the known association of XIAP muta-
tions with primary immunodeficiency and the observed defect in NOD1/2 signal-
ing, our data lend further support to the concept of primary immunodeficiency in
a subset of CD patients.
Disclosure of Interest: None declared
P0285 MALNUTRITION SCREENING IN INFLAMMATORY BOWEL
DISEASE PATIENTS
A.A. Csontos1,*, A. Molnar2, I. Kovacs3, D. Kocsis4, M. Juhasz4, L. Herszenyi4,
P. Miheller4
1
2nd Departement, 2School of PhD. Studies of Semmelweis University,
Pathological Sciences, Health science research, Semmelweis University,
3
Hungarian Dietetic Association, 4Semmelweis University, 2nd Department of
Medicine, Budapest, Hungary
Contact E-mail Address: csontosagnesanna@gmail.com
INTRODUCTION: According to current guidelines, all IBD patients should be
screened regularly for malnutrition with a validated tool (focusing on BMI,
weight loss and food intake). In a previous screening study conducted in hospi-
talized patients (n 1252) malnutrition was as observed up to 20% using the
body mass index (BMI) calculation, while it was high as 40% according to the
validated malnutrition universal screening tool (MUST). We hypothesized that
even MUST is not the sufficient method to evaluate the risk of malnutrition of an
IBD patient.
AIMS & METHODS: 173 consecutive IBD (126 with Crohns disease CD and
47 with ulcerative colitis UC) patients were enrolled into the study. Body
composition was measured by InBody 720 body analyser device, using the bioe-
lectrical impedance method. BMI and MUST were also calculated and compared
to main results of BIA (skeletal muscle mass SMM, body fat mass BFM fat
free mass-FFM).
RESULTS: Rate of malnutrition in IBD patients was detected in 16%, 32% and
44% in patients using BMI, MUST and BIA, respectively. Almost half of the CD
patients have a high risk of malnutrition based on the BIA parameters (48%),
while it was lower using the MUST criteria (34%) or the simple BMI calculation
(17%).
We compared patients body composition regarding their ranking on MUST
scale. We found that UC patients SMM and FFM altered significantly in the
A208
MUST cathegories (SMM p 0.032, FMM p 0.034 S, BFM p 0.083 NS),
while we found no significant changes among CD patients. (SMM p 0.823,
FMM p 0.815, BFM p 0.660 NS).
Although the differences werent significant, highest risk of malnutrition was
detected in stenosing CD patients (57%, 43% and 29% with BIA, MUST and
BMI, respectively). High portion of CD and UC patients was underweighted
(48% vs. 34%). Fat tissue deficiency was more pronounced in CD than in UC
(52% vs. 23%), even in patients with stenosing disease phenotype (57%).
CONCLUSION: BMI calculation is not the appropriate method to estimate the
risk of malnutrition in IBD patients. MUST score calculation is able to detect a
higher portion of endangered subjects. Although the availability is not as wide as
it should be, the BIA method is the most accurate test to evaluate the risk of
malnutrition. According to our findings it is a useful tool to plan the dietary
therapy of the patients, and it can be a recommended method especially in UC
patient care.
Disclosure of Interest: None declared
P0286 CORRELATION BETWEEN THE CLINICAL, ENDOSCOPIC AND
HISTOLOGICAL ACTIVITIES OF ULCERATIVE COLITIS
A. Milassin1,*, K. Farkas1, Z. Szepes1, M. Szu cs2, T. Nyari2, F. Nagy1,
00
A. Balint1, R. Bor1, T. Wittmann1, T. Molnar1
1
First Department of Medicine, 2Department of Medical Physics and Informatics,
University of Szeged, Szeged, Hungary
Contact E-mail Address: milagn422@gmail.com
INTRODUCTION: The assessment of ulcerative colitis (UC) activity is based on
a combination of symptoms, clinical examination and endoscopic finding. The
most important goals of the recent therapies of UC are to induce and maintain
clinical remission and to achieve mucosal healing. Mucosal healing is defined as
Mayo endoscopy subscore of 0 or 1 in the majority of the studies. Interestingly,
rate of endoscopic remission has been shown to be higher than that of clinical
remission in some trials.
AIMS & METHODS: The aim of our study was to evaluate the correlation
between clinical and endoscopic disease activities of UC defined by activity
scores. Clinical activities were defined by two activity indices: the
Rachmilewitz Activity Index (CAI) and the partial Mayo score. Every patient
underwent colonoscopy performed by 3 experienced gastroenterologists and
endoscopists. They graded the findings both according to the endoscopic part
of the Rachmilewitz Activity Index (EI) and the Mayo endoscopic subscore.
Mucosal healing was defined as Mayo endoscopic subscore and EI of 0.
Histological activity was scored by Riley score.
RESULTS: 100 UC patients were enrolled in the study (49 males, 51 females;
mean age at diagnosis: 32.5 years). They were diagnosed on the basis of standard
clinical, endoscopic and histologic criteria. Clinical and endoscopic activities
showed strong correlations using both scoring systems (p 0.0029 and
p 0.0001). Endoscopic disease activity also correlated with the histological
activity (p0.001). Significant correlation was shown between the clinical activity
and mucosal healing (p 0.0012 and p0.001). No association was showed with
the extension of the disease and clinical or endoscopic activity.
CONCLUSION: Assessment of mucosal healing is very important for guiding
therapy and for evaluation of remission in patients with UC. Our result showed
that the correlation between the clinical, endoscopic and histological activities is
very good in UC. Mucosal healing highly associated with clinical remission.
Disclosure of Interest: None declared
P0287 DIAGNOSTIC DELAY IN PEDIATRIC CROHNS DISEASE
PATIENTS IS LONGER THAN IN PEDIATRIC ULCERATIVE
COLITIS PATIENTS
A. Schoepfer1,*, E. Safroneeva2, N. Fournier1, G. Rogler3, J. Ezri1, A. Nydegger1,
S. Vavricka4, C. Braegger3 on behalf of Swiss IBD Cohort Study Group
1
University Hospital Lausanne / CHUV, Lausanne, 2University of Bern, Bern,
3
University Hospital of Zurich, 4University Hospital Zurich, Zurich, Switzerland
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: We have recently shown that the median diagnostic delay
(time from first IBD symptoms until IBD diagnosis is established) was 9 months
in adult Crohns disease (CD) patients and 4 months in adult ulcerative colitis
(UC) patients in Switzerland. Of note, 25% of CD patients had a diagnostic
delay 424 months. We also showed that the length of diagnostic delay in CD
patients represents a risk factor for complicated disease course and intestinal
surgery. There is a lack of data regarding diagnostic delay in pediatric IBD
patients.
AIMS & METHODS: We aimed to assess the diagnostic delay in pediatric CD
and UC patients and to identify risk factors for long diagnostic delay. Data from
the Swiss IBD cohort study were analyzed. Patients were recruited from univer-
sity centers (80%), regional hospitals (19%), and private practices (1%). Data on
diagnostic delay was provided by parents and physician questionnaires.
Diagnostic delay was further divided into the time interval from first symptoms
to the first consultation with the physician (patient-related interval) and the
interval from first physician consultation until IBD diagnosis was established
(physician-related interval). Long diagnostic delay was defined as delay lying
avove the 75th percentile. Non-normal data are presented as median, interquartile
range [IQR] and range.
RESULTS: A total of 100 pediatric CD (37% females) patients and 75 pediatric
UC patients (56% females) were included. Age at disease onset was 12 [10-14]
years in CD and 11 [7-13] years in UC patients. Diagnostic delay in CD was 4 [2-
8] (range 0-82) months with the interval form first symptoms to physician visit of
1 [0-3] (range 0-24) months and from physician visit to diagnosis of 3 [1-9] (range
0-82) months. In UC patients the median diagnostic delay was 2 [1-7] (range 0-52)
United European Gastroenterology Journal 2(5S)
months with an interval from first symptom onset to physician visit of 0 [0-3]
(range 0-36 months) and from physician visit to diagnosis of 2 [1-4] (range 0-20)
months. Diagnostic delay in CD patients was significantly longer than in UC
patients (median 4 vs. 2 months, p 0.011). Long diagnostic delay was defined as
period of 48 months in CD and 47 months in UC patients. Neither gender, age
at diagnosis, disease location, positive IBD family history, nor provenience (rural
vs. non-rural) were associated with long diagnostic delay.
CONCLUSION: the median diagnostic delay in pediatric CD and UC patients in
Switzerland is 4 and 2 months, respectively. However, one fourth of pediatric CD
patients needs 48 monhts and one fourth of pediatric UC patients needs 47
months from first symptom onset to IBD diagnosis.
Disclosure of Interest: None declared
P0288 BEHAVIOR OF P-GLYCOPROTEIN 170 (P-GP) FUNCTIONAL
ACTIVITY IN PERIPHERAL BLOOD LYMPHOCYTES (PBL) OF
IBD PATIENTS DURING TREATMENT WITH ANTI-TNFS
A.M. Sambuelli1,*, C. Cortada2, A. Gil1, S. Negreira1, S. Huernos1,
S. Goncalves1, B. Maricel1, T. Pablo1
1
Medicine (IBD Section), HOSPITAL UDAONDO, 2Centro de Diagnostico
Molecular (CDM), Ciudad de Buenos Aires, Argentina
Contact E-mail Address: asambu@fibertel.com.ar
INTRODUCTION: Pgp, encoded by the MDR1 gene is a transmembrane, ATP-
dependent, efflux pump, expressed in cells with barrier function and PBL, remov-
ing drugs, toxins, xenobiotics. IBD share drugs Pgp influenced with other dis-
eases (as steroids, 6-MP in leukemia cells). Pgp overexpression was implicated in
highly active resistant RA (Tsujimura, Ann Rheum Dis 2008) induced by IL2 and
TNF, influencing steroid efflux from lymphocytes, reporting that a single inflix-
imab (IFX) infusion overcame refractoriness with elimination of Pgp high expres-
sing CD4lymph and recovery of dexametasone in PBL with Ppg marked
decrease. Pgp measure in PBL could be an early marker of AntiTNFs efficacy
and Pgp activity could modify the efflux of concurrent Pgp substrates drugs.
AIMS & METHODS: We aimed to study Pgp activity in PBL of IBD pts. treated
with antiTNFs, investigating a potential role in IBD management. Pgp function-
ality was evaluated in PBL of IBD and healthy controls (HC: n30), studied in 5
groups of IBD pts. (n123 recruited) with at least 10 CD/10 UC each: - Before and
after 20 days of AntiTNF (IFX or ADA) in steroid refractory (group 1) or
thiopurine refractory (group 2), - Before and after 3 mo of 6-MP in steroid
refractory (group 3), - In Thiopurine sensitive (group 4) and Steroid sensitive
(group 5). Response criteria: at 45 days of AntiTNFs or 3 mo. of 6-MP (CDAI: a
70 points drop, Mayo score 3 points30% drop) categorized in: remission
(CDAI150, Mayo Sc.2) and partial response. Rhodamine123 (fluorescent
Pgp substrate) efflux was studied by flow cytometry, expressed by the behaviour
of 2 markers defined by % of cells with different fluoresc. levels: M1 (high
fluoresc./low Pgp pump activity), M2 (low fluoresc./Pgp high activity, used for
the results).
RESULTS: Basal Pgp values (meanSD) in total PBL (M2) were: Group 1: 41.4
18.5, Group 2: 32.1 13.6, Group 3: 44.119.8, Group 4: 36.116.9, Group 5:
37.516.4 and HC 39.012.3. Major finding was a significant decrease of Pgp
after AntiTNFs in IBD in most of responder pts. ( -difference- in refractory vs
remission p: 0.030018, and 0.0023 for groups 1 and 2, and vs. partial response
p 0.014 in group 2, Mann Whitney). Initial Pgp values of pts. with available
Pgp post AntiTNFs measures according response were: Group 1 (n 20)
38.017.7, 44.68.4, 38.621.0, Group 2 (n 23) 35.916.0, 34.89.9, 23.17.1
for remission, partial response and refractory. Post AntiTNFs: 26.216.0,
29.012.1, 47.019.3 (Group 1) and 21.011.6, 22.311.5, 36.011.7 (Group
2). Pts. with 6-MP monotherapy (n23) did not show signif. changes in Pgp. A
signif. decrease of Pgp in CD3 lymph. (only group 2 p50.003) after AntiTNFs
was observed in remission vs refractory pts. In B lymph. lower values post
AntiTNFs (group 1) were shown in responders as a trend. Values of post-treat.
IBD were lower than HC (p50.04).
CONCLUSION: 1) We found that AntiTNFs decreased Pgp activity in PBL of
IBD pts., significantly associated with treatment response; 2) AntiTNFs could
modify the transport of concurrent Pgp substrates. MDR1 polymorphism typing
is ongoing. Longer follow-up and larger size sample are needed to verify the value
of Pgp activity measurement in IBD management.
Disclosure of Interest: A. Sambuelli Financial support for research from: Invest.
iniciate study Abbvie, C. Cortada: None declared, A. Gil: None declared, S.
Negreira: None declared, S. Huernos: None declared, S. Goncalves: None
declared, B. Maricel: None declared, T. Pablo: None declared
P0289 PREDICTIVE FACTORS FOR CHRONIC INFLAMMATORY
BOWEL DISEASES IN PATIENTS PRESENTING WITH NEW
ONSET DIARRHEA
A.-M. Singeap1,*, A. Trifan1, I. Girleanu1, O.C. Stoica2, C. Stanciu2
1
INSTITUTE OF GASTROENTEROLOGY AND HEPATOLOGY IASI, GR T
POPA UNIVERSITY OF MEDICINE AND PHARMACY, 2INSTITUTE OF
GASTROENTEROLOGY AND HEPATOLOGY IASI, Iasi, Romania
Contact E-mail Address: anamaria.singeap@yahoo.com
INTRODUCTION: The diagnosis of chronic inflammatory bowel diseases (IBD)
requires chronic changes over time (colonoscopic inflammatory changes lasting
at least 6 months and chronic histological inflammation). The onset of chronic
IBD may mimic acute diarrhea (defined as having sudden onset and lasting less
than four weeks); on the other hand, acute diarrhea may be mistaken with a new
case of chronic IBD. Our aim was to find clinical or biological predictive factors
for the diagnosis of chronic IBD.
AIMS & METHODS: A prospective study was conducted on all cases of new
onset diarrhea which presented in our Gastroenterology Unit during 2012. Their
United European Gastroenterology Journal 2(5S)
initial evaluation included clinical exam, complete biological picture and colono-
scopy. All cases of new onset diarrhea with uncertain etiology were followed and
the final diagnosis was established at least 6 months after the onset, by repeating
colonoscopy with biopsy. The final diagnosis was correlated with clinical and
biological parameters evaluated at the first presentation.
RESULTS: A total of 120 patients with new onset diarrhea presented to our unit
in 2012. After the initial work-up, 82 patients had a positive diagnosis (infectious
colitis, colorectal cancer, radiation colitis, ischemic colitis). The remaining 38
patients, including both patients with inflammatory changes at colonoscopy
and patients with normal colonoscopy were reevaluated by colonoscopy and
biopsies after 6 months. For 11 patients, results were conclusive for chronic
IBD, 5 patients had collagenous or lymphocytic colitis, and 22 patients were
diagnosed with acute self-limiting colitis or irritable bowel syndrome (IBS).
Among the parameters we analysed, anemia and hypoalbuminemia in the
onset of the symptomatology were significantly correlated with the subsequent
diagnosis of chronic IBD; elevated levels of inflammatory parameters like C-
reactive protein and erythrocyte sedimentation were present in similar propor-
tions in the different types of final diagnosis except IBS; other biological para-
meters were not contributive; non-significant correlation was found with respect
to age, weight loss and clinical history or associated symptoms.
CONCLUSION: Anemia and hypoalbuminemia are predictive factors for
chronic inflammatory bowel diseases in patients presenting with new onset diar-
rhea; a more extensive initial work-up applied in these patients could bring an
early diagnosis for IBD.
Disclosure of Interest: None declared
P0290 INCIDENCE AND RISK FACTORS OF C. DIFFICILE INFECTION
IN ULCERATIVE COLITIS
O.C. Stoica1, A. Trifan1,*, I. Girleanu1, A.-M. Singeap1, C. Cojocariu1,
C. Stanciu2
1
University of Medicine and Pharmacy "Gr. T. Popa", 2Gastroenterology, Institute
of Gastroenterology and Hepatology, Iasi, Romania
Contact E-mail Address: stoica_oanacristina@yahoo.com
INTRODUCTION: Recent epidemiologic studies have shown that patients with
inflammatory bowel disease (IBD), in particular those with ulcerative colitis
(UC) are at increased susceptibility for Clostridium difficile infection (CDI) com-
pared with the general population.
AIMS & METHODS: The objectives of this study were to assess the incidence
and risk factors for CDI in UC patients in a tertiary center from North-Eastern
Romania.
Data of all UC patients admitted at the Institute of Gastroenterology and
Hepathology, Iasi, Romania, between January 2012 and October 2013 were
analyzed. In patients with concomitant CDI, risk factors for CDI were identified.
RESULTS: A total of 70 UC patients were included in this prospective study,
amongst which eight (11.5%) were identified as having a concomitant CDI. On
univariate analysis, age 4 65 years (OR 1.53, CI 0.93-16.27; p 0.048), male
gender (OR 1.38, CI 0.30-14.91; p 0.032), hemoglobin 59 g/dL
(OR 1.93, CI 0.19-18.52; p 0.043), severe UC disease (OR 1.22,
CI 0.14-10.5; p 0.037), and serum albumin 53 g/dL (OR 1.86, CI 1.12-
10.14; p 0.012) were associated with CDI. However, on multivariate analysis,
only severe disease and serum albumin retained statistical significance.
CONCLUSION: CDI was detected in one of eight patients admitted with a UC
flare; severe UC disease and low serum albumin were independent risk factors for
CDI.
Disclosure of Interest: None declared
P0291 ASSESSMENT OF WALL INFLAMMATION AND FIBROSIS IN
CROHNS DISEASE AND ITS CORRELATION WITH BOWEL
SONOGRAPHY AND MRI-ENTEROGRAPHY
A. Rispo1,*, P.P. Mainenti2, G.D. De Palma3, D. Musto1, L. Bucci4,
F.P. DArmiento5, A. Testa1, M. Rea1, F. Sasso1, N. Caporaso1, F. Castiglione1
1
Gastroenterology, 2Radiology, 3General Surgery, 4Colorectal Surgery,
5 1
Pathology, AOU Policlinico Federico II of Naples, Naples, Italy
INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel dis-
order which is relapsing and remitting in nature and is characterised by trans-
mural inflammation. About the therapeutical management of CD, it is believed
to be particularly important to differentiate between active inflammation and
fibrotic lesions in CD patients. Bowel sonography (BS) and MRI-enterography
(MRI) are procedures widely used for diagnosing CD and its complications.
AIMS & METHODS: to define the features of the CD strictures, also correlating
BS and MRI with histopathology.
We performed an observational prospective study including all CD patients
undergoing surgery for strictures. Pre-operative assessment was performed by
BS and MRI. BS investigated for: bowel wall thickness (BWT), bowel wall
stratification, power-Doppler vascular pattern of the bowel wall, mesentery
hypertrophy and enlarged lymphnodes. MRI study included: BWT, T1-weighted
gadolinium-based contrast uptake, enhancement pattern, mural and lymph node/
cerebrospinal fluid (CSF) signal intensity ratios on T2-weighted fat-saturated
images, mesenteric signal intensity on T2-weighted fat-saturated images.
Histopathological inflammation was graded by the acute inflammatory score
(AIS); the semi-quantitative degree of fibrosis was performed according to the
literature. Statistical analysis was performed using chi-square, MannWhitney U
test and Cohens k measure.
RESULTS: The study included 20 CD patients. The indications to surgery were:
obstructive symptoms in 13 patients, penetrating complications in 7 patients. All
but 3 strictures (87%) showed acute inflammation coexisting with fibrosis while
only 3 strictures were predominantly fibrotic On BS, the presence of a layered
A209
bowel wall stratification was the only variable associated with the presence of
fibrosis (k 0.72; p 5 0.03). About MRI, AIS correlated with mural thickness
and mural/CSF signal intensity ratio on T2 sequences (p 0.04, p 0.02) but not
with mural enhancement on T1 images (p 0.62).
CONCLUSION: The majority of strictures in CD patients treated by surgery are
consistent with a mixed type inflammation (acute inflammation plus fibrosis).
The presence of stratified BS pattern shows a significantly higher degree of
fibrosis while the evidence of high mural signal intensity on T2-weighted fat-
saturated images on MRI reflects histological features of acute inflammation.
Even if the ideal definition of the type of the strictures in CD still remains
significantly out of reach, the combined use of BS and MRI can offer useful
information in a sub-group of patients needing surgery for complicating CD.
Disclosure of Interest: None declared
P0292 NEUTROPHIL VOLUME DISTRIBUTION WIDTH AS A NEW
MARKER IN MONITORING INFLAMMATORY BOWEL DISEASE
ACTIVITY
Y. Aydemir1, A. Yuce1,*, A. Pnar2, G. Hizal1, B. Berberoglu Ates1,
H. Hzarcoglu Gulsen1, H. Demir1, I.N. Saltik Temizel1, F. Akbiyik2, H. Ozen1
1
Pediatric gastroenterology, 2Department of Biochemistry, Hacettepe university
school of medicine, Ankara, Turkey
Contact E-mail Address: dryusufaydemir@yahoo.com
INTRODUCTION: Inflammatory bowel diseases (IBD) are immune-mediated
disorders resulting in chronic, relapsing inflammation of the gastrointestinal
tract. A prominent feature of inflammation in IBD is the involvement of effector
cells such as neutrophils, eosinophils and mast cells. Neutrophil volume distribu-
tion width (NVDW) generated by VCS technology is a new marker which reflects
neutrophil activation.
AIMS & METHODS: We sought to investigate the value of NVDW parameter
in monitoring disease activation in IBD patients. Neutrophil VCS parameters
were measured in IBD patients admitted to our outpatient clinic. Age and sex
matched healthy subjects were taken as the control group. Patients with acute or
chronic infection and accompanying inflammatory disease were excluded.
Pediatric Crohn Disease Activity Index (PCDAI) and Pediatric Ulcerative
Colitis Activity Index (PUCAI) were used to define disease activation.
Complete blood count, albumin, eritrocyte sedimentation rate, C-reactive protein
ve fecal calprotectin were studied routinely at each visit.
RESULTS: A total of 34 pediatric patients with IBD and 29 controls were
enrolled in the study. NVDW was significantly higher in patients with IBD
compared to healthy controls (p50.001). An increased NVDW level was
observed in IBD patients with activation (22.422.13) compared to those in
remission (19.221.63) (p50.001). There was no statistically significant differ-
ence between IBD patients in remission and healthy controls (p 0.115). A sig-
nificantly increased NVDW was observed in CD patients with activation
compared to CD patients in remission (22.872.19 vs 19.681.85, p 0.002).
NVDW was significantly higher UC patients with activation compared to UC
patients in remission (22.072.08 vs 18.530.93, p50.001). NVDW was corre-
lated with WBC count (r:0.712), platelet count (r:0.347), ESR (r:0.471), CRP
(r:0.699), fecal calprotectin (r:0.812), PUCAI (r:0.852) ve PCDAI (r:0.670). The
best cut-off of NVDW for prediction of disease activation in CD and UC in this
series was 20.39 with a sensitivity of % 90.9 and a specificity of %75 (AUC:0.852
CI 0.698-1.000 p 0.002) and 19.74 with a sensitivity of % 92.9 and a specificity
of % 90.9 (AUC:0.961, CI:0.889-1.000, p50.001) respectively.
CONCLUSION: As a quantitative, objective, and sensitive parameter, NVDW
has a potential to be an additional predictor for disease activation in IBD.
Disclosure of Interest: None declared
P0293 IBS-LIKE SYMPTOMS ARE COMMON IN PATIENTS WITH
ULCERATIVE COLITIS IN DEEP REMISSION BUT THEY DO NOT
SEEM TO BE CAUSED BY LOW GRADE INFLAMMATORY
ACTIVITY
B. Jonefjall1,*, L. Ohman1,2, M. Simren1,3, H. Strid1
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine,
Sahlgrenska Acadamy, University of Gothenburg, 2Department of Microbiology
and Immunology, Sahlgrenska Acadamy, University of Gothenburg, Institute of
Biomedicine, 3University of Gothenburg Centre for Person-Centred Care (GPCC),
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: borje.jonefjall@vgregion.se
INTRODUCTION: Gastrointestinal (GI) symptoms compatible with Irritable
Bowel Syndrome (IBS) are common in patients with ulcerative colitis (UC). It
has been suggested that these symptoms are a reflection of occult inflammation
rather than coexisting IBS.
AIMS & METHODS: The aim was to investigate possible factors correlating
with IBS-like symptoms in UC patients in deep remission by assessing inflam-
matory markers, other GI symptoms, psychological symptoms and quality of life
(QOL). In total, 297 patients with UC were included at a regular outpatient clinic
visit. The patients completed self-administrated questionnaires to assess diagnos-
tic criteria for IBS (Rome III), severity of GI symptoms (Gastrointestinal
Symptom Rating Scale (GSRS)), QOL (IBDQ), psychological symptoms
(Hospital Anxiety and Depression scale (HAD)), stress (QPS Nordic) and non-
GI somatic symptoms (PHQ-12). Fecal calprotectin was used as inflammatory
marker. Patients with a normal rigid sigmoidoscopy and calprotectin 4200 g/g
were further investigated with flexible sigmoidoscopy. Deep remission was
defined as a total Mayo-score 2 (endoscopic findings, rectal bleeding and phy-
sician global assesment subscores 0), with no relapse during the three-month
period prior to visit. Comparisons where made between patients in deep remis-
sion with (UCRIBS) and without (UCR-IBS) IBS-like symptoms and patients
A210
with active disease (UCA). Comparisons between the three groups were per-
formed with Kruskal-Wallis test and thereafter post-hoc tests with Mann
Whitney U test and Bonferroni correction, with p-value 50.017 considered
significant.
RESULTS: Among the patients, 46% (n 138) met the criteria for deep remis-
sion and 18% (n 25) of these patients experienced IBS-like symptoms. There
was no difference in fecal calprotectin levels between the UCRIBS and the
UCR-IBS patients. The UCRIBS patients reported significantly more severe
GI symptoms in general, lower QOL scores, higher levels of anxiety, stress and
non-GI somatic symptoms than the UCR-IBS patients (see table). The level of
somatic and psychological symptoms did not differ between the UCRIBS
patients and the UC patients with active disease (see table).
Median (IQR) UCR UCR- UCR UCR
Level of sign IBS IBS UCA IBS IBS
p50.017 (n 25) (n 113) (n 159) vs UCR-IBSvs UCA UCR-IBS
Calprotectin (g/g) 18 (7-30) 32 (13-64) 280 (80-715) p 0.044 p50.001 p50.001
GSRS Total 2.5 (2.1-3.1) 1.5 (1.2-1.9) 2.5 (1.8-3.1) p50.001 p 0.701p50.001
Anxiety (HAD) 5.0 (3.5-8.0) 2.0 (1.0-5.0) 4.5 (2.0-8.0) p 0.001 p 0.291p50.001
Depression (HAD) 2.0 (1.0-7.5) 1.0 (0.0-3.0) 3.0 (1.0-6.0) p 0.048 p 0.941p50.001
Stress (QPS Nordic) 2.0 (1.0-3.0) 1.0 (0.0-2.0) 2.0 (1.0-3.0) p 0.003 p 0.281p 0.001
Non-GI Sympt (PHQ)6.0 (3.5-8.5) 3.0 (1.0-5.0) 4.0 (2.0-7.0) p50.001 p 0.132p50.001
QOL (IBDQ) 183 (163-198)205 (192-213)167 (144-195)p50.001 p 0.142p50.001
CONCLUSION: IBS-like symptoms in UC patients in deep remission are
common. Psychological factors rather than low grade inflammatory activity
seem to be of importance for symptom generation. Interestingly, UC patients
in deep remission with IBS-like symptoms experience GI symptoms, reduced
psychological well-being and QOL compatible with UC patients with active
disease.
Disclosure of Interest: None declared
P0294 THE SEVERITY OF ABDOMINAL PAIN AT ONSET OF
ULCERATIVE COLITIS IS ASSOCIATED WITH IBS-LIKE
SYMPTOMS DURING CLINICAL REMISSION
B. Jonefjall1,*, H. Strid1, L. Ohman1,2, J. Svedlund3, A. Bergstedt3, M. Simren1,4
1
Department of Internal Medicine and Clinical Nutrition, Institute of Medicine,
Sahlgrenska Acadamy, University of Gothenburg, 2Department of Microbiology
and Immunology, Institute of Biomedicine, Sahlgrenska Acadamy, University of
Gothenburg, 3Department of Psychiatry, Institute of Neuroscience and Physiology,
Sahlgrenska Acadamy, University of Gothenburg, 4University of Gothenburg
Centre for Person-Centred Care (GPCC), Sahlgrenska Academy, University of
Gothenburg, Gothenburg, Sweden
INTRODUCTION: Symptoms compatible with Irritable Bowel Syndrome (IBS)
are common in patients with ulcerative colitis (UC) in clinical remission. It has
been suggested that these symptoms might arise due to postinflammatory
changes comparable with postinfectious IBS. Factors that increase the risk for
developing IBS-like symptoms in patients with new onset of ulcerative colitis are
not known.
AIMS & METHODS: The aim was to study factors in patients with new onset of
UC that predicts development of IBS-like symptoms during clinical remission. In
total, 98 patients with new onset of UC were followed prospectively during three
years with yearly follow up visits. The patients completed self-administrated
questionnaires at each visit to assess diagnostic criteria for IBS (Rome II), sever-
ity of gastrointestinal (GI) symptoms (GI Symptom Rating Scale (GSRS)) and
psychological symptoms (Hospital Anxiety and Depression scale (HAD)). Fecal
calprotectin, ESR and CRP were used as inflammatory markers. The Mayo score
was used to evaluate clinical disease activity. Remission was defined as a total
Mayo score 2 and an endoscopic subscore 1, with no relapse during the three-
month period prior to visit. Data from the first visit at the onset of UC were
compared between the group of patients that fulfilled the criteria for IBS while in
remission (UCRIBS) during follow-up and the group that did not (UCR).
RESULTS: Among the UC patients, 87 met the criteria for clinical remission,
and 25 (29%) of these reported IBS-like symptoms in remission, on at least at one
of the three follow-up visits. The UCRIBS patients suffered from more severe
GI symptoms including abdominal pain (see table) during their primary flare
than the UCR patients. The patients that experienced mild to severe abdominal
pain had an increased risk for developing IBS-like symptoms during follow-up
(OR 3.1 (95% CI 1.1-8.4) p 0.03), this occurred in 39% (n 17) of these
patients compared to 20% (n 8) of the patients that reported none or minor
abdominal pain. Female gender (p 0.10), being unmarried/single (p 0.05) and
higher depression scores (HAD p 0.09) tended to be more common among
UCRIBS patients. There was no difference in clinical disease activity
(Mayoscore p 0.42), inflammatory markers (Calprotectin p 0.29, CRP
p 0.36, ESR p 0.58) or disease extension (p 0.57) between the two groups.
United European Gastroenterology Journal 2(5S)
Table to abstract P0294
GSRS - Median (IQR) UCRIBS UCR p - value
Total 3.5 (2.2-4.0) 2.7 (2.1-3.3) 50.05
Diarrhea 5.0 (3.3-6.3) 5.3 (3.8-6.7) 0.56
Constipation 2.3 (1.7-2.8) 2.0 (1.7-2.7) 0.30
Abdominal Pain 2.7 (1.8-2.8) 2.0 (1.7-3.0) 50.05
Indigestion 3.8 (2.8-4.6) 3.3 (2.4-4.1) 0.09
Reflux 1.0 (1.0-2.0) 1.0 (1.0-1.5) 0.07
UCA vs CONCLUSION: Patients with ulcerative colitis that develop IBS-like symptoms
during follow-up experience more severe GI symptoms, including abdominal
pain, at disease onset, despite no difference in inflammatory disease activity.
This might indicate a more sensitive GI tract in this category of patients.
Disclosure of Interest: None declared
P0295 NEUTROPHIL GELATINASE-ASSOCIATED LIPOCALIN AS A
POTENTIAL BIOMARKER FOR AXIAL INVOLVEMENT IN
INFLAMMATORY BOWEL DISEASE PATIENTS
C. Gonen1,*, D. Kurtulus2, K. Kochan1, A. Yesil1
1
Gastroenterology, Istanbul Haydarpasa Numune Training and Research Hospital,
2
Physical Therapy and Rehabilitation, Umraniye Training and Research Hospital,
Istanbul, Turkey
Contact E-mail Address: drcgnn@yahoo.com
INTRODUCTION: Axial arthropathy associated with inflammatory bowel dis-
eases (IBD) includes isolated sacroiliitis, inflammatory back pain and ankylosing
spondylitis. There is no reliable laboratory test that can be used as a diagnostic
tool in the management or diagnosis of axial arthropathy in IBD. Neutrophil
gelatinase associated lipocalin (NGAL) is a recently identified molecule, which
has tissue destructive effects by protecting matrix metalloproteinase-9 from auto-
degradation. This represents an important mechanism by which NGAL may
contribute to the degradation and remodelling of the extracellular matrix, leading
to rheumatologic manifestations of IBD. Previously, we showed that serum
NGAL levels in IBD patients were significantly higher than healthy controls.
AIMS & METHODS: To investigate serum NGAL levels in IBD patients with
or without axial arthropathy. A total of 83 patients (64 with IBD, 19 with IBD
and axial arthropathy), and 40 age- and sex-matched healthy controls (HC) were
included in this study. Patients with peripheral joint involvement were excluded.
Serum NGAL levels were measured using ELISA.
RESULTS: The patients were aged between 16 and 74 years, and their mean age
was 39.1  11.5 years. Age, gender, and disease-year distributions were not
statistically significantly different among the groups. Serum NGAL levels were
elevated significantly in IBD patients with axial artropathy [median 234 U/L,
range (122-312) ng/ml] compared to IBD patients without axial involvement [168
U/L (57-310 ng/ml] (p:0.001) and HC group [122 (45-234) ng/ml] (p:0.004).
NGAL levels of the IBD group were significantly higher than those of the control
group (p:0.001). There was no significant difference between the IBD group and
IBD with axial involvement group in Hgb, WBC, CRP, and ESR values.
CONCLUSION: Serum NGAL levels were found to be elevated in IBD patients
with axial involvement when compared to IBD patients without involvement,
suggesting a partial pathophysiologic role in this particular extraintestinal man-
ifestation. NGAL seems to be a promising biomarker for the diagnosis and
management of axial arthropathy in IBD.
REFERENCES
1. Yesil A, Gonen C, Senates E, et al. Relationship between neutrophil gelati-
nase-associated lipocalin (NGAL) levels and inflammatory bowel disease type
and activity. Dig Dis Sci 2013; 58: 2587-2593.
2. Gupta K, Shukla M, Cowland JB, et al. Neutrophil gelatinase-associated
lipocalin is expressed in osteoarthritis and forms a complex with matrix metallo-
proteinase 9. Arthritis Rheum 2007; 56: 3326-3335.
3. Mattey DL, Packham JC, Nixon NB, et al. Association of cytokine and matrix
metalloproteinase profiles with disease activity and function in ankylosing spon-
dylitis. Arthritis Res Ther 2012; 14: R127.
Disclosure of Interest: None declared
P0296 ANORECTAL STRICTURE IN CROHNS DISEASE: NATURAL
FATE OR CHALLENGING TARGET TO TREAT?
C. Brochard1,*, L. Siproudhis1, T. Wallenhorst1, P.N. DHalluin1, J.F. Bretagne1,
G. Bouguen1
1
Service des maladies de lappareil digestif, Rennes, France
Contact E-mail Address: charlene.brochard@chu-rennes.fr
INTRODUCTION: The natural history of non-fistulising perianal Crohns dis-
ease (PCD) remains unknown.
AIMS & METHODS: This study aimed to assess the long-term outcome of
anorectal strictures. Between January 2005 and October 2013, a tertiary referral
centre prospectively recorded each clinic of patients with PCD with detailed data
about the phenotype and disease activity of luminal and anal CD, medical treat-
ment and surgery. At each visit, CD and PCD were assessed using the Harvey-
Bradshaw Score, the Cardiff-Hughes classification and with the Perianal Disease
Activity Index. Follow-up was determined by the duration between the diagnosis
of anorectal stricture and the last visit. Cumulative incidence of stricture healing
(disappearance of the anal stricture) was estimated using a Kaplan-Meier method
United European Gastroenterology Journal 2(5S) A211
and factor associated with an unfavourable course (persistent stricture S2, per- were evaluated for Extra Intestinal Tuberculosis. Patients were followed up and a
sistent stoma or proctectomy) with non-parametric test. repeat colonoscopy was performed at 3 months and at of 6 months of treatment;
RESULTS: A total of 102 patients (M/F: 37/65) were included. The duration of diagnosis was revised if the patient did not demonstrate mucosal healing when
CD at diagnosis was 8.9 years. After a median follow-up period of 2.8 years, 52 compared to the previous colonoscopy. Patients who completed follow up were
of the 88 followed patients (59%) achieved anorectal stricture healing. Two included in final analysis.
patients (2%) developed anal adenocarcinoma. Female gender (HR 2.05 [1.1- RESULTS: Sixty patients were included in the study of which fifty-five patients
4.03], p 0.0221), disease duration of CD of less than 10 years (HR 1.94 [1.01- completed follow up and were included in the analysis. A final diagnosis of CD
3.63], p 0.0271), and anal fistula at stricture diagnosis (HR 2.36 [1.21-5.05], was made in 37 patients (67%), ITB in 18 patients (33%). Differentiating features
p 0.0106) were significantly associated with anorectal stricture healing in a of ITB and Crohns are summarised in table -1. Quantiferon TB Gold in Tube
multivariate analysis model. Twenty-eight patients (32%) had an unfavourable test was positive in 94.4% of ITB patients versus 19.3% of Crohns disease
course at the end of follow-up. Gender and introduction or optimisation of patients (P- 50.001). The Sensitivity, Specificity, Positive predictive value,
TNF antagonist treatment decreased the risk of unfavourable course in multi- Negative predictive value for Quantiferon TB Gold in tube test was 94.44%,
variate analysis. Conversely, the Luminal B2 phenotype at CD diagnosis was the 83.78%, 73.91% and 96.88% respectively.
only factor associated with unfavourable course.
CONCLUSION: Anorectal stricture does not imply a non-reversible and com- Variables CD (n 37) TB (n 18) P value
plicated condition related to severe perianal Crohns disease. However, both
diagnosis of cancer and sepsis drainage remain challenging in this situation. Mean Age (in years) 32.5 45 0.1
Disclosure of Interest: None declared
Male/ Female 20/17 8/10 0.7
Mean Duration of illness (Months) 13.6 8 0.026
P0297 REDUCING UNNECESSARY COLONOSCOPY A COST Bleeding PR 7 (18.9%) 0 (0) 0.04
MINIMIZATION ANALYSIS OF NEW DIAGNOSTIC STRATEGIES
Fever 4 (10.8%) 8 (44.4%) 0.004
FOR EXCLUDING ORGANIC BOWEL DISEASE IN PRIMARY CARE
PATIENTS TB QuantiferonGold in Tube 50.001
C. Helsper1,*, L. Kok1, S.G. Elias1, H.E. Koffijberg1, K.G. Moons1, N.J. de Wit1 Positive 6 17
1 Negative 31 1
Julius Center for Health Sciences and Primary Care, UNIVERSITY MEDICAL
CENTER UTRECHT, Utrecht, Netherlands Granuloma Characteristics
Contact E-mail Address: c.helsper@gmail.com Caseation 0 (0) 5 (28%)
INTRODUCTION: In general practice, complaints of the lower digestive tract Large 5(13%) 12 (66.6%)
are frequently presented. Of those affected, only an estimated 7% suffers from Confluent 7 (19%) 13(72.2%)
organic bowel disease (OBD), such as inflammatory bowel disease, diverticulitis More than 5 granulomas/hpf 8 (21%) 10 (55.5)
and cancer. [1] These patients should be referred for colonoscopy without delay.
Unfortunately, OBD is found in only one third of referred patients, indicating a Band of epitheloid Histiocytes 71(19%) 8 (44.4%)
considerable number of unnecessary referrals in primary care.[2] Our research Lymphoid cuff 19 (51%) 11 (61%)
group developed several diagnostic strategies to optimize colonoscopy referral Pericryptal 21(56.7%) 3 (16.7%)
policy. Microgranulomas 30 (81.1%) 3 (16.7%)
AIMS & METHODS: We aim to assess the benefits and costs of the diagnostic
strategies developed to reduce unnecessary colonoscopy referrals in primary care. Focally enhanced colitis 15 (40.5%) 2 (11.1%)
The diagnostic strategies combine patient history and physical examination with Histology abnormal in 23 (60.5%) 1(5%)
two point of care tests (POCT); calprotectine and/or iFOBT. We evaluated the endoscopically normal sites
benefits and costs of three diagnostic strategies, each at three cut-off points.
Strategies are: 1. iFOBT added to history and physical examination (iFOBT),
2. calprotectine added (Calpro), and 3. both POCT added (CiF). The three CONCLUSION: Longer duration of illness, bleeding per rectum, pericryptal
different cut-off points are based on OBD risk for referral. Benefits are prevented granulomas, microgranulomas, focally enhanced Colitis, histological changes
costs and prevented unnecessary referrals for colonoscopy. Costs are additional in antrum and histological abnormality in endoscopically normal sites favored
costs and missed diagnoses. Crohns disease. Presence of fever, large granulomas, caseating granulomas, con-
RESULTS: A reduction of 0.5% (iFOBT), 5.4% (Calpro) and 5.9% (CiF) in the fluent granulomas, favored ITB. Quantiferon TB Gold in Tube test had good
number of colonoscopies cover the additional testing costs. The largest cost- sensitivity but poor specificity in differentiating ITB from Crohns disease.
savings are achieved by iFOBT and CiF. At the 2.5% cut-off, these strategies REFERENCES
provide a modest cost reduction (1.3 and 0.2mln Euros, respectively) with 84 Kim BJ, Choi YS, Jang BI, et al. Prospective evaluation of the clinical utility of
(2%) and 0 (0%) patients incorrectly not referred for colonoscopy annually in the interferon-c. Assay in the differential diagnosis of intestinal tuberculosis and
Netherlands. At a referral threshold of 5% OBD probability, a cost reduction of Crohns disease. Inflamm Bowel Dis 2011; 17: 13081313.
E5.8 (iFOBT), E2.3 million (Calpro) and E4.7(CiF), Euros would be achieved at Disclosure of Interest: None declared
an annual cost of 720 (4%), 720 (4%) and 306 (3%) incorrectly averted referrals
in the Netherlands, respectively. Cost reduction for all strategies even increased
at 7.5% OBD risk, but this threshold yielded much higher incorrectly referred P0299 REPRODUCIBILITY OF SEROLOGIC ANTIBODY ACTIVITY AT
patients for all three strategies, above 1000 patients annually in the Netherlands. DIAGNOSIS AND AFTER TREATMENT IN PEDIATRIC
CONCLUSION: Implementation of the diagnostic strategies as developed in the ULCERATIVE COLITIS AND CROHNS DISEASE
CEDAR study are likely to reduce the colonoscopy related costs at a burden of C. Olbjrn1,*, G. Perminow2, M.C. Smastuen3, B. Nakstad1, M.H. Vatn4
incorrectly averted referrals for colonoscopy. Implementation of the CiF and 1
Department of Pediatrics and Adolescent Medicine, Akershus University Hospital,
iFOBT strategies at the lowest threshold value for referral, is likely to be safe Lrenskog, 2Department of Pediatrics, Oslo University Hospital, Ulleval,
and modestly cost-saving. The CiF and iFOBT strategy at the 5% OBD prob- 3
Department of Biostatistics, University of Oslo, 4Epigen, Faculty Division
ability threshold, might also be a valuable alternative in current practice given the Akershus University Hospital, Oslo University Hospital, Oslo, Norway
substantial costs savings and relative safety. The most appropriate threshold and Contact E-mail Address: chrisolb@gmail.com
the resulting cost savings needs to be determined for the health care setting in
which it will be used. INTRODUCTION: Serologic nuclear and anti microbial antibodies have been
REFERENCES recognized as predictive markers of disease course and complications in ulcera-
[1]. Muris J, et al. One-year prognosis of abdominal complaints in general prac- tive colitis (UC) and Crohns disease (CD). The stability of serologic titers over
tice: a prospective study of patients in whom no organic cause is found. Br J Gen time of these markers has been questioned.
Pract 1996; 46: 715719. AIMS & METHODS: The aim of the present study was to compare antibody
[2]. Morini S, et al. Diagnostic yield of open access colonoscopy according to titers before and after treatment in newly diagnosed treatment naive pediatric
appropriateness. Gastrointest Endosc 2001; 54: 175179. patients with inflammatory bowel disease (IBD). Patients aged 518 years,
Disclosure of Interest: None declared (N 57) diagnosed with IBD were included between 2005-2007 and followed
prospectively. Blood specimens were analyzed for antibodies (Prometheus labs,
San Diego) at diagnosis, and repeatedly after 1-2 years of treatment.
P0298 DIFFERENTIATING CROHNS DISEASE FROM INTESTINAL RESULTS: Among the 19 UC patients 68% were ANCA-positive versus 32% of
TUBERCULOSIS IN A TUBERCULOSIS ENDEMIC AREA the 38 CD patients (p 0.02). In CD and UC patients respectively, the median
C. Panackel1,*, P.K.R.1, R. Thomas1, B. Sebastian1, R.M. Thomas2, S. Mathai1 titers in EU/ml at baseline against I2, 249 and 257, Anti-Omp C, 3.1 and 3.6,
1
Department of Gastroenterology and Hepatology, 2Pathology, Medical trust ASCA IgA, 8.4 and 3.1, ASCA IgG, 11.9 and 3.1 and CBir, 27 and 16, were not
Hospital, Kochi, kerala, India, Kochi, India significantly different at follow- up. The titers against ASCA IgA and IgG were
Contact E-mail Address: charlespanackel@hotmail.com significantly higher in the CD patients versus UC patients both at diagnosis and
at follow-up (p 0.01 and p50.01, respectively) with post-treatment ASCA IgA
INTRODUCTION: Crohns disease (CD) and Ileocolonic Tuberculosis (ITB) 7.5 and ASCA IgG 12.8 in CD versus 3.1 and 6 in UC respectively (p50.01 and
mimic each other in clinical, endoscopic and histologic features. In an ITB ende- 0.03). There were no statistically significant differences for gender, or between the
mic country like India differentiating one from the other remains a challenge. different treatments of CD patients, in whom 18 of 38 patients had received
AIMS & METHODS: The aim of our study was to revalidate the existing clin- infliximab.
ical, laboratory and histological parameters that aid in differentiating Ileocolonic CONCLUSION: UC patients were significantly more frequently ANCA posi-
Tuberculosis from Crohns disease. tive, whereas the CD patients had significantly higher titers against ASCA IgA
Methods: We prospectively included patients with Ileocolonic ulcers. Patients and IgG both at diagnosis and at follow-up. The present study demonstrates a
were diagnosed as either ITB or CD based on established criteria. All patients general reproducibility of the presence and titers of serologic antibodies from the
A212
time of diagnosis until 1-2 years of follow- up for IBD, indicating that serologic
markers measured at diagnosis may be applied as prognostic markers even after
years of treatment.
Disclosure of Interest: None declared
P0300 ULTRASOUND BASED REAL TIME ELASTOGRAPHY
RELIABLY IDENTIFIES FIBROTIC GUT TISSUE IN PATIENTS
WITH STRICTURING CROHNS DISEASE (GUT-RTE)
D.C. Baumgart1,*, H.-P. Muller1, U. Grittner2, D. Metzke1, A. Fischer1,
O. Guckelberger3, A. Pascher3, I. Sack4, M. Vieth5, B. Rudolph6
1
Department of Medicine, Division of Gastroenterology and Hepatology,
2
Department of Biostatistics and Clinical Epidemiology, 3Department of Surgery,
4
Department of Experimental Radiology, Charite Medical Center - Medical School
of the Humboldt-University of Berlin, Berlin, 5Department of Pathology,
University of Bayreuth, Bayreuth, 6Department of Pathology, Charite Medical
Center - Medical School of the Humboldt-University of Berlin, Berlin, Germany
Contact E-mail Address: daniel.baumgart@charite.de
INTRODUCTION: Crohns disease (CD) is a relapsing inflammatory disease.
Many patients experience intestinal strictures that require surgery if non amen-
able to medical therapy. Moreover, there is an unmet need to objectively assess
new treatment endpoints such as disease modification, structural damage and
restitution. Real time ultrasound elasticity imaging has not been systematically
developed yet to evaluate the viscoelastic properties of the human gut in vivo.
AIMS & METHODS: In this prospective, controlled and partially blinded study
unaffected and affected gut segments of 10 CD patients (male 6, median
age 49, median Harvey Bradshaw index 6) were examined pre-, intra- and
postoperatively with ultrasound including real time elastography (RTE) to assess
strain. Following surgical resection strain of full gut wall segments was analyzed
by direct tensiometry. Histopathological scoring of fibrosis with two indepen-
dent, specific stains, molecular quantification of collagen content as well as mor-
phometrics were performed. Data were aggregated at patient level and non-
aggregated at segment level prior to statistical analysis including a non-linear
model where appropriate.
RESULTS: RTE strain was significantly different between unaffected and
affected segments (mean  SD 169.0  27.9 vs. 43.0  25.9; p50.001).
Moreover, mean RTE strain per patient was completely different in unaffected
(all 4 132) compared with affected (all 5 87) segments. An RTE strain cut point
of 110 reliably distinguished segments. Tensiometry strain in segments with an
RTE strain of 4110 was significantly greater than in those with 5 110 (mean 
SD 77.1  21.4 vs. 12.9  9.5; p50.001). These findings were further corrobo-
rated by morphometrics, collagen content and fibrosis score.
CONCLUSION: RTE allows bedside assessment of gut tissue mechanical prop-
erties in CD.
REFERENCES
Baumgart DC et al. Lancet 2012; 380: 1590-605.
Disclosure of Interest: D. Baumgart Other: The ultrasound unit was provided free
of charge for the duration of the study., H.-P. Muller: None declared, U.
Grittner: None declared, D. Metzke: None declared, A. Fischer: None declared,
O. Guckelberger: None declared, A. Pascher: None declared, I. Sack: None
declared, M. Vieth: None declared, B. Rudolph: None declared
P0301 CORRELATION BETWEEN MAGNETIC RESONANCE
ENTEROGRAPHY, CAPSULE ENDOSCOPY, FECAL
CALPROTECTIN AND CRP IN PATIENTS IN CLINICAL REMISSION
WITH KNOWN SMALL BOWEL CROHNS DISEASE PRELIMINARY
RESULTS FROM THE PROSPECTIVE ISRAELI IBD RESEARCH
NETWORK (IIRN) STUDY
D. Yablecovitch1,*, S. Ben-Horin1, M. Amitai2, A. Lahat1, S. Neuman1,
B. Avidan1, O. Har-Noy1, N. Levhar1, R. Eliakim1
1
Departmet of Gastroenterology, 2Departmet of Radiology, Chaim Sheba Medical
Center, Tel Aviv University, Tel Hashomer, Tel Aviv, Israel
Contact E-mail Address: doronyab@gmail.com
INTRODUCTION: The correlation between clinical activity and intestinal
inflammation in Crohns Disease (CD) is modest. Biomarkers and imaging tech-
niques are objective tools able to assess the biological activity.
AIMS & METHODS: Our aim was to objectively evaluate disease activity in
patients in clinical remission (CR) with small bowel CD (SBCD) by using capsule
endoscopy (CE), magnetic resonance enterography (MRE) and correlate the
findings with laboratory parameters of inflammation.
Thirty-five consecutive patients with known SBCD in CR were prospectively
recruited and underwent MRE, followed by Agile patency capsule (PC), and if
patency was proven, a video capsule. The Lewis score was calculated for each
tertile. C-reactive protein (CRP) and fecal calprotectin (FC) were evaluated for
their association with clinical activity, MRE and CE findings.
RESULTS: Eight of 35 cases with abnormal passage of PC were excluded, all of
which were predicted by MRE (NPV 100%). All video capsules reached the
cecum, including 9 additional cases predicted to be retained by MRE which
proved to be false positives (53%) by the PC. CE detected active disease in the
proximal-mid SB in 44% of the patients and in the distal SB in 48%. MRE
detected proximal-mid SB disease in only 18% and distal disease in 67% of
patients. Most (81%) of patients with SB lesions detected by CE had elevated
FC (cutoff, 30mg/g) while CRP (cutoff, 5mg/l) was increased in 19% of these
patients. FC modestly correlated with Lewis score (r 0.4). There was no corre-
lation between CRP and Lewis score. Similarly, 78% of patients with active
disease on MRE had increased FC, while CRP was elevated in 22% of the
patients.
United European Gastroenterology Journal 2(5S)
CONCLUSION: 1. A PC prior to the CE procedure diminished the likelihood of
CE retention, and was superior to MRE in prediction of capsule retention. 2.
Despite CR active inflammation was detected in 4 50% of patients by CE. 3.
Proximal SB disease was better detected by CE than MRE. 4. FC associated
better than CRP with disease activity found by CE or MRE. 5. When used
properly, CE is a safe procedure in patients with SBCD.
# with the support of a grant from the Helmsley charitable trust.
Disclosure of Interest: None declared
P0302 SYSTEMATIC ANALYSIS OF FACTORS ASSOCIATED WITH
PROGRESSION AND REGRESSION OF ULCERATIVE COLITIS IN
THE SWISS IBD COHORT STUDY
E. Safroneeva 1,*, S. Vavricka2, N. Fournier3, F. Seibold4, C. Mottet3,
A. Straumann5, G. Rogler2, A. Schoepfer3 on behalf of Swiss IBD Cohort Study
Group
1
University Hospital Bern, Bern, 2University Hospital Zurich, Zurich, 3University
Hospital Lausanne / CHUV, Lausanne, 4Tiefenaustpital Bern, Bern, 5University
Hospital Basel, Basel, Switzerland
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: There is a lack of studies having systematically assessed in a
large cohort of patients with ulcerative colitis (UC) the disease location over time
as well as risk factors associated with progression or regression of disease extent.
AIMS & METHODS: We aimed to assess disease location over time and to
evaluate associated risk factors. Data from the Swiss IBD cohort study were
analyzed. Patients were recruited from university centers (68%), regional hospi-
tals (14%), and private practices (18%). Disease locations over time were ana-
lyzed and risk factor analysis for a change in disease location was performed
using logistic regression modeling. Non parametric data are illustrated as median
and interquartile range [IQR].
RESULTS: A total of 1,016 UC patients (45.6% females, median age at diag-
nosis 31 [23.3-40.5] years) were included. At diagnosis, UC patients presented
with the following disease locations: 199 (19.6%) proctitis, 338 (33.3%) left sided
colitis, 381 (37.5%) extensive colitis/pancolitis, and 98 (9.6%) unknown. During
a median of 9 [5-16] years disease duration, a disease progression was documen-
ted in 145/1016 (14.3%) of patients, a regression in 176/1016 (17.3%) of patients,
whereas 624/1016 (61.4%) of patients had a stable disease location (7% of
patients with unknown evolution of disease location over time). Logistic regres-
sion modeling identified the following factors associated with disease progression
in UC patients presenting with proctitis or left-sided UC at diagnosis: treatment
with systemic steroids (OR 2.077, 95%4CI 1.359-3.174, p 0.001), treatment
with immunomodulators (azathioprine, 6-MP, methotrexate) (OR 1.647,
95%4CI 1.119-2.424, p 0.011), treatment with TNF-antagonist(s) (OR
1.668, 95%4CI 1.077-2.581, p 0.022), and treatment with calcineurin-inhibi-
tors (OR 3.159, 95%4CI 1.679-5.943, p 5 0.001). Neither gender, age at UC
diagnosis, body mass index, presence of extraintestinal manifestations, smoking
status at diagnosis, positive UC family history, nor 5-ASA treatment were asso-
ciated with disease progression. No specific factors were found to be associated
with regression in UC patients with extensive colitis/pancolitis or left-sided colitis
at diagnosis.
CONCLUSION: Over a median of 9 years disease duration about two-thirds of
UC patients maintained the initial disease location whereas one-third either had a
progression or a regression of the initial disease location. Treatment with sys-
temic steroids, immunomodulators, TNF-antagonists, or calcineurin-inhibitors
was significantly associated with disease progression.
Disclosure of Interest: None declared
P0303 PSORIASIS PHENOTYPE IN INFLAMMATORY BOWEL
DISEASE: A CASE-CONTROL PROSPECTIVE STUDY
E. Lolli1,*, R. Saraceno2, A. Ventura2, G. Condino1, S. Onali1, P. Scarozza1,
A. Capanna1, C. Petruzziello1, E. Calabrese1, S. Chimenti2, F. Pallone1,
L. Biancone1
1
Gastroenterology Unit, University of Rome Tor Vergata, 2Dermatology Unit,
University of Rome Tor Vergata, Rome, Italy
Contact E-mail Address: elisabetta.lolli@uniroma2.it
INTRODUCTION: Psoriasis has been associated with Inflammatory Bowel
Disease (IBD). However, whether IBD is associated with specific phenotypes
of psoriasis is unknown.
AIMS & METHODS: In a case-control prospective study, we aimed to assess
psoriasis phenotype in IBD patients (pts), when using a non-IBD patients popu-
lation as controls (non-IBD C). From January 2011 to November 2013, derma-
tological assessment was performed in 251 IBD pts under follow up.
Dermatological assessment was focused in detecting the presence of psoriasis
(present/absent) and in defining its characteristics (localization, phenotype),
including severity (mild/moderate/severe). In order to define psoriasis phenotype
in IBD, each IBD pt with psoriasis was matched for gender, ethnicity and age
(5 years) with one non-IBD pt with psoriasis, referring to the same centre. Data
were expressed as median (range) and differences between groups assessed by the
T test or the chi-squared test, as appropriate.
RESULTS: Dermatological assessment was performed in 251 IBD pts (115 F,
age 46 yrs, range 16-85; IBD duration 9 yrs, range 1-46): 93 UC (42 M, age 50,
range 22-85; UC duration 7 yrs, range 1-41; UC extent: proctitis 33, left 13,
extensive 42, ileal pouch 3, ileostomy 1, ileo-rectal anastomosis 1) and 158 CD
(91 M, age 43, range 16-80; CD duration 10 yrs, range 1-46; CD colitis 13, ileo-
colitis 32, ileitis 51, neo-terminal ileum 56, ileostomy 2, distal ileum jejunum 4).
Non-IBD C included 62 pts (35 M, age 47, range 18-75). Among the 251 IBD pts,
psoriasis was detected in 62 (25%; 36 CD, 26 UC). In the IBD group, the median
age and IBD duration were comparable in pts with or without psoriasis (years:
United European Gastroenterology Journal 2(5S)
age 50 range 23-72 vs 47 range 16-85; IBD duration 9.5, range 1-46 vs 9, range 1-
41; p ns for both). Mild plaque type psoriasis was detected in a higher propor-
tion of IBD pts (52/62; 84%) than non-IBD C (33/62; 53%; p50.001). Scalp
psoriasis and sebopsoriasis were the more common psoriasis phenotype in IBD
(21/62; 84%), followed by palmo-plantar psoriasis (9/62; 14%) and by inverse
psoriasis (8/62; 13%). Psoriatic arthritis was detected in 10/62 (16%) non-IBD-C
and in 6/62(10%) IBD patients (p n.s.). Among the 62 IBD pts with psoriasis,
psoriasis developed after anti-TNFs in 6 (10%), including palmo-plantar (n 4),
sebopsoriasis (n 1), inverse psoriasis (n 1).
CONCLUSION: Results from a cohort of IBD patients matched with non-IBD
control patients suggest that specific phenotypes of psoriasis may be associated
with IBD.
Disclosure of Interest: None declared
P0304 CONTRAST ENHANCED ULTRASOUND AS A POINT-OF-CARE
TECHNIQUE IN COMPLICATED CROHNS DISEASE PATIENTS
E. Calabrese1,*, F. Zorzi1, E. Stasi1, E. Lolli1, S. Onali1, P. Scarozza1,
G. Condino1, C. Petruzziello1, L. Biancone1, F. Pallone1
1
Department of Systems Medicine, Gastroenterology Unit, University of Rome Tor
Vergata, Rome, Italy
Contact E-mail Address: emma.calabrese@uniroma2.it
INTRODUCTION: Crohns disease (CD) is associated with penetrating compli-
cations such as phlegmons and intra-abdominal abscesses. As the management of
the patients is influenced by the presence of such complications, a readily avail-
able tool for the diagnosis of extramural complications in CD is needed.
Preliminary findings suggest that the assessment of vascularity within intra-
abdominal masses may distinguish between phlegmons and abscesses.
AIMS & METHODS: Aim of our study was to evaluate the use of contrast
enhanced ultrasound (CEUS) to distinguish between phlegmons and intra-
abdominal abscesses in CD patients as a point-of-care technique. From
November 2011, consecutive patients with complicated CD were enrolled.
Indications of patient assessments by CEUS were symptoms, signs and biochem-
ical exams indicating penetrating behavior (abdominal pain, mass, fever, elevated
CRP and leukocytosis). A total of 22 CD pts (14 M; median age 27 yrs, range 18-
75; disease duration: median 54 mos, range 1-564; CD site: ileal in 13 pts, ileo-
colonic in 9 pts; CD behavior: penetrating in 20 pts, stricturing in 2 pts; previous
ileocolonic resection in 9 pts) were included. Clinical evaluation by an IBD expert
and other cross sectional imaging techniques (MR and CT) were considered as
the standard.
RESULTS: CEUS detected abscesses in 9 and phlegmons in 12 pts. One patient
had an unspecified lesion that was diagnosed as metastasis by PET. Six out of 9
abscesses were confirmed by CT-Enteroclysis and these pts underwent surgery
during the follow up. The remaining 3 pts with abscesses were treated with
antibiotics and are still in follow up (17.5 mos). In the phlegmon group, 4 out
of 12 patients were evaluated by CT or MRI that confirmed CEUS findings in 3
cases but in one patient a deep abscess was identified and surgery was scheduled.
Eight out of 12 pts were clinically followed up (median: 16 mos). Two of these
patients developed an abscess after one week from CEUS despite medical treat-
ment. Overall CEUS correctly identified 19 out of 22 lesions (86%) on the basis
of cross sectional imaging modalities and clinical follow up used as final
diagnosis.
CONCLUSION: CEUS is a non-invasive, radiation-free and point-of-care tech-
nique able to differentiate phlegmons from abscesses driving a prompt clinical
management in complicated CD patients.
Disclosure of Interest: None declared
P0305 ACCURACY OF SMALL INTESTINE CONTRAST
ULTRASONOGRAPHY COMPARED TO MAGNETIC RESONANCE
ENTEROGRAPHY IN CHARACTERIZING LESIONS IN PATIENTS
WITH CROHNS DISEASE
E. Calabrese1,*, E. Stasi1, F. Zorzi1, E. Lolli1, G. Condino1, S. Onali1,
C. Petruzziello1, M.C. Fantini1, P. Cerro1, P. Scarozza1, L. Biancone1,
F. Pallone1
1
Department of Systems Medicine, Gastroenterology Unit, University of Rome Tor
Vergata, Rome, Italy
Contact E-mail Address: emma.calabrese@uniroma2.it
INTRODUCTION: Small intestine contrast ultrasonography (SICUS) can detect
intestinal damage in patients with Crohns disease (CD).
AIMS & METHODS: We evaluated the diagnostic accuracy of SICUS in deter-
mining the site, extent, and complications of CD, compared with magnetic reso-
nance (MR)-enterography as the standard. We performed a retrospective
analysis of 59 patients with CD [(M 34; median age: 46, CD site: ileal 36
(61%), ileocolonic 18 (30%), jejuno-ileal, 3 (5%), colonic 1 (2%); behaviour:
non-stricturing non-penetrating 10 (17%), structuring 31 (53%), penetrating 18
(30%); previous surgery 25 (42%)] evaluated by SICUS and MR-enterography 3
months apart, between January 2011 and March 2014. We evaluated disease site
(based on bowel wall thickness), extent of lesions, presence of complications
(stenosis, prestenotic dilation, abscess, or fistulas) using MR-Enterography as
the standard. Sensitivity, specificity, and diagnostic accuracy were calculated.
We determined the correlations in maximum wall thickness and disease extent
in the small bowel between results from SICUS and MR-Enterography.
RESULTS: SICUS identified the site of small bowel CD with 96% sensitivity,
71% specificity, and 93% diagnostic accuracy; it identified the site of colon CD
with 73% sensitivity, 93% specificity, and 88% diagnostic accuracy. Results from
SICUS and MR-enterography correlated in determination of bowel wall thick-
ness (rho 0.51) and disease extent (rho 0.75; P5.0001 for both). SICUS
detected ileal stenosis with 90% sensitivity, 94% specificity, and 91.5%
A213
diagnostic accuracy, and pre-stenotic dilation with 66% sensitivity, 83% specifi-
city, and 73% diagnostic accuracy. SICUS detected abscesses with 75% sensitiv-
ity, 100% specificity, 98% diagnostic accuracy, and fistulas with 82% sensitivity,
81% specificity, and 81% diagnostic accuracy.
CONCLUSION: SICUS identified lesions and complications in CD patients
with high levels of sensitivity, specificity, and accuracy compared to MR-enter-
ography. SICUS might be used as an imaging tool as part of a focused diagnostic
and follow up examination of patients with CD.
Disclosure of Interest: None declared
P0306 ASSOCIATION BETWEEN HIGH ADALIMUMAB DRUG LEVEL
AND MUCOSAL HEALING IN PATIENTS WITH CROHNS DISEASE
E. Zittan1,2,*, B. Kabakchiev2,3, J. Stempak2,3, G. Nguyen1,2, K. Croitoru1,2,
G.Van Assche1,2, A. Steinhart1,2, M. Silverberg1,2
1
University of Toronto, 2Zane Cohen Center Mount Sinai, 3lunenfeld-tanenbaum
research institute, Mount Sinai Hospital, Toronto, Canada
Contact E-mail Address: EZittan@mtsinai.on.ca
INTRODUCTION: The current approach to managing loss of response to anti-TNF
agents is based on clinical symptoms and empirically increasing the dose or shortening
the treatment interval as opposed to tailoring the drug concentrations in individual
patients. The primary objective of this study was to evaluate adalimumab drug levels
(ADL) and antibodies to adalimumab (ATA) in relation to disease activity.
AIMS & METHODS: A cohort of 61 patients with Crohns disease (CD) treated
with adalimumab between 2005-2013 were recruited to the study. Demographic
and clinical information was obtained from chart reviews and patient interview.
Disease activity was determined by Harvey-Bradshaw Index (HBI), ileocolono-
scopy reports, and CRP levels. Clinical remission was defined by HBI4.
Mucosal healing was defined by the disappearance of all ulceration in all ileoco-
lonic segments. ADL and ATA were tested using a liquid phase assay. ATA  1
U/mL were considered low titer.
RESULTS: 61 CD patients were included in the analysis. 39 of the patients were
previously on infliximab. 37 were on doses of adalimumab greater than 40mg
every other week. 18 of the patients were on concomitant immunosuppressant
therapy (methotrexate or azathioprine). 40 of the patients were in clinical remis-
sion. 11 (18%) subjects exhibited elevated ATA titers (41 U/mL). 14 had any
detectable ATA (4 0 U/mL). ADL levels were significantly higher in patients
with low ATA compared to those with elevated ATA titers (p 0.001). ADL
levels were not associated with CRP levels or with clinical remission (p 0.07 and
p 0.93, respectively. However, high median ADL drug level (5.8 mg/mL) was
associated with complete mucosal healing (p 0.017).
CONCLUSION: Adalimumab levels are not significantly associated with clinical
remission or CRP levels in Crohns disease patients. However, high adalimumab
drug levels were associated with complete mucosal healing. Further evaluation with
larger, prospective studies is required to further assess the important of drug level
monitoring in this setting, however, this study suggests that achieving adequate
adalimumab levels may be important toward realizing the goal of mucosal healing.
Our results also demonstrate the importance of using endoscopic assessment rather
than clinical or laboratory assessments to assess therapy response.
Disclosure of Interest: None declared
P0307 USEFULNESS OF A FAECAL CALPROTECTIN RAPID
SEMIQUANTITATIVE TEST IN PREDICTING RELAPSE IN
PATIENTS WITH ULCERATIVE COLITIS IN REMISSION
E. Domenech1,2,*, E. Garcia-Planella3, M. Manyosa1,4, M. Chaparro5,
M. Barreiro-De-Acosta6, B. Beltran7, E. Ricart1,8, V. Garcia-Sanchez9,
M. Esteve1,10, M. Piqueras11, F. Bermejo12, A. Lopez-Sanroman13,
C. Taxonera14, J. Llao15, J. P5,16, E. Cabre1,4 on Behalf of the precucal Study
of Geteccu
1
Ciberehd, Barcelona, 2Gastroenterology, Hospital Universitari Germans Trias I
Pujol, Badalona, 3Hospital Santa Creu I Sant Pau, Barcelona, 4Hospital
Universitari Germans Trias I Pujol, Badalona, 5Hospital La Princesa, Madrid,
6
Chu Santiago, Santiago De Compostela, 7Hospital La Fe, Vale`ncia, 8Hospital
Clinic, Barcelona, 9Hospital Reina Sofa, Cordoba, 10Hospital MuTua De
Terrassa, 11Consorci Sanitari De Terrassa, Terrassa, 12Gastroenterology, Hospital
De Fuenlabrada, 13Hospital Ramon y Cajal, 14Hospital Clinico San Carlos,
Madrid, 15Xarxa Hospitalaria Althaia, Manresa, 16Ciberehd, Madrid, Spain
Contact E-mail Address: eugenidomenech@gmail.com
INTRODUCTION: Faecal calprotectin (CALf) is fairly correlated with clinical
and endoscopic activity in ulcerative colitis (UC), and it has also been demon-
strated to be a good predictor of relapse. However, the routine use of CALf
measurement is constrained by the need for the patient to carry stool samples,
as well as handling and processing them in the laboratory. The availability of
hand held, single-use devices for CALf measurement that could be performed by
the patient himself, might spread the use of CALf in clinical practice.
AIMS & METHODS: Aim: To evaluate the usefulness of a rapid semi-quanti-
tative test of CALf in predicting relapse in patients with UC in remission.
Patients and Methods: A prospective, multicentre study that included patients
with left-sided or extensive UC in clinical remission for 6 months on mainte-
nance treatment with mesalazine. At baseline and every 3 months, patients were
evaluated clinically and semi-quantitative CALf was measured using a monoclo-
nal immunochromatography rapid test (PreventID CaldetectTM,
Immunodiagnostic AG, Germany) without manipulation of stools or laboratory
analysis, until relapse or 12 months of follow-up.
RESULTS: At least one determination of CALf with clinical follow-up was
available in 192 out 206 patients initially included in the study. 55% with exten-
sive UC, 62% required corticosteroids in the past, and 88% were non-smokers.
From a total of 695 measurements of CALf, 81 (12%) were above the upper
A214
threshold of normality of the test (460 g/g) and 57 (8%) had limiting values
(15-60 g/g). During follow-up, 32 relapses (17% of patients) occurred. Having a
CALf 460 g/g was significantly associated with relapse at follow-up (35% vs.
12%, p50.0001), with a PPV of 35% and a NPV of 88%. 644 CALf determina-
tions with a three-month follow-up were available; undetectable CALf was sig-
nificantly associated with absence of recurrence, with a PPV of 100% and a NPV
of 93% (0% vs. 6%, p 0.002).
CONCLUSION: Rapid semi-quantitative measurement of CALf, with no need
for laboratory analysis and faecal samples handling, may be useful for monitor-
ing patients with UC in remission.
Disclosure of Interest: None declared
P0308 MICRORNA-320 AS A BIOMARKER TO MONITOR THE COURSE
OF DISEASE ACTIVITY IN EXPERIMENTAL COLITIS AS WELL AS
IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE
F. Pott1,2,*, C. Cichon3, M. Bruckner1, A. Schmidt3, D. Foll2, D. Bettenworth1
1
Department of Medicine B, 2Department of Pediatric Rheumatology and
Immunology, 3Infectiology, Centre for Molecular Biology of Inflammation,
University of Munster, Munster, Germany
Contact E-mail Address: AnnaFriederike. Pott@ukmuenster.de
INTRODUCTION: The pathogenesis of inflammatory bowel disease (IBD) is
still incompletely understood and patient-tailored therapy is an unmet need.
Thus, biomarkers are needed to follow the course of disease; however, sensitive
non-invasive markers to monitor the disease activity are still missing. Previously,
we could demonstrate a significant increase of microRNA-320 (miR-320) expres-
sion in murine DSS-induced colitis. Aim of this study was to evaluate the poten-
tial of miR-320 to monitor the course of inflammation in immunological and
bacterial driven experimental colitis as well as in IBD patients.
AIMS & METHODS: MiR-320 expression was assessed by qRT-PCR in murine
colonic tissue after induction of T cell transfer colitis as well as Salmonella and
Citrobacter (C.) rodentium-induced colitis. Additionally, miR-320 level was mea-
sured in human blood and stool samples from patients with Crohns disease (CD;
n 8) or Ulcerative colitis (UC, n 4) in remission or during acute flare and in
healthy controls (n 11). Disease activity was assessed by Crohns disease activ-
ity index (CDAI; active disease: CDAI4220; inactive disease: CDAI5150) in
CD patients and the clinical activity index (CAI; active disease: CAI44; inactive
disease: CAI53) in UC patients.
RESULTS: MiR-320 level in tissue samples from the transfercolitis was signifi-
cantly increased in animals with severe colitis (410% loss of body weight) as
compared to controls (0.180.01 (colitis) vs. 0.110.03 (control);P 0.05)
whereas there was no significant increase of miR-320 in samples from C. roden-
tium-induced colitis (0.60.3 (control) vs. 1.10.7 (colitis);P 0.2) and
Salmonella-induced colitis (0.60.4 (control) vs. 0.060.02 (colitis);P 0.3).
MiR-320 expression in blood of CD patients was significantly increased in
acute flare (mean CDAI 2317.2) as compared to remission (mean
CDAI 9733.9) and healthy controls (x-fold increase:435.4152.7 (flare) vs.
70.128.7 (remission);P 0.05; vs. 24.68.8 (control);P50.001). Moreover,
miR-320 level of controls was significantly lower as compared to CD patients
in remission (P 0.01). Furthermore, miR-320 expression in blood as well as
stool from CD patients revealed a strong correlation with the CDAI (r2 0.78
(blood);r2 0.81 (stool)). In UC patients, miR-320 expression in blood obtained
during acute flare (mean CAI 6) or quiescent disease (mean CAI 1.5) also
revealed a significant increase of miR-320 expression as compared to healthy
controls (182.15111.4 vs. 24.68.8;P 0.03). As opposed to CD, miR-320
level in blood from UC patients was not significantly increased in acute flare
as compared to quiescent disease. However, miR-320 expression in stool from
UC patients was significantly enhanced in acute flare as compared to quiescent
disease (225.3535.4 (flare) vs. 68.540.6 (remission);P 0.02) showing a strong
correlation with the CAI (r2 0.68).
CONCLUSION: Our preliminary results indicate that miR-320 expression is
increased in classical IBD models but not significantly altered in bacterial-
induced colitis. Furthermore, miR-320 expression in human blood and stool
samples follows the course of disease activity in IBD patients. Future studies
are needed to elucidate the potential of miR-320 to predict relapse and disabling
courses of disease.
Disclosure of Interest: None declared
P0309 THE APPROPRIATENESS OF TESTING AND INTERPRETATION
OF ANTI-TNF DRUG AND ANTIBODY CONCENTRATIONS: WHEN
SHOULD THEY BE ORDERED, AND WHAT TO DO WITH THE
RESULTS?
G.Y. Melmed1,2, P.M. Irving1,*, G.G. Kaplan1, B. Bressler1, J. Jones1,
P.L. Kozuch1, M.P. Sparrow1, F.S. Velayos1, L. Baidoo1, A.S. Cheifetz1,
S.M. Devlin1, L.E. Raffals1, N. Vande Casteele3, D.R. Mould4, M.C. Dubinsky2,
J.-F. Colombel5, W.J. Sandborn3, C.A. Siegel1 on behalf of BRIDGe (Building
Research in IBD Globally)
1
The BRIDGe Group, Hanover, 2Cedars-Sinai, Los Angeles, 3University of
California, San Diego, 4ProjectionsResearch Inc, Phoenixville, 5Mt Sinai Hospital,
New York, United States
Contact E-mail Address: melmedg@cshs.org
INTRODUCTION: The availability of drug concentration and antibody testing
for anti-TNF therapy promises optimized drug dosing and informed decision-
making for patients with inflammatory bowel disease (IBD) treated with these
agents. However, there is no consensus on when to test and how to interpret the
results for various clinical scenarios. We applied the RAND/UCLA
Appropriateness Method toward establishing the appropriateness of when
these tests should be obtained, and how to act upon their results.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: A comprehensive literature review was conducted on the
topic of drug concentration and anti-drug antibodies in patients with IBD for all
approved anti-TNF therapies. This review was presented to an expert panel
including clinician and pharmacokinetic experts who have published on the
topic, and the Building Research in Inflammatory Bowel Disease Globally
group, a globally diverse panel of 13 gastroenterologists clinically experienced
in IBD treatment and therapeutic drug monitoring. A total of 35 scenarios
assessed the appropriateness of obtaining these tests, and 143 additional scenar-
ios addressed the appropriateness of various clinical strategies in response to test
results. Panelists used a modified Delphi method to rate each scenario through a
web-based survey, and then met in-person to discuss and anonymously re-rate
appropriateness on a 1-9 scale (1-3 inappropriate, 4-6 uncertain, 7-9 appropriate).
Disagreement was assessed using a validated index.
RESULTS: Assessment of anti-TNF drug and antibody concentrations was
rated appropriate at the end of induction therapy in primary nonresponders, in
secondary nonresponders, at least once during the first year of therapy, in
patients experiencing immune-related side effects, and when restarting a drug
following a drug holiday (before 2nd infusion). Routine assessment in responders
at the end of induction was rated uncertain. Panelists rated the appropriateness
of various clinical management options including changing therapy within-class,
switching out of class, adjusting drug dose/interval, adding/adjusting concomi-
tant immunomodulators, and doing nothing for each of 6 permutations of
high/low drug concentration and high/low/undetectable antibody concentra-
tions. These ratings were highly dependent on the specific clinical scenario for
which the test was obtained. For example, switching out of class when drug and
high antibody concentrations were detected was appropriate at the end of
induction in nonresponders, uncertain at the end of induction in responders,
and inappropriate during maintenance in responders.
CONCLUSION: The appropriate timing and how to respond to anti-TNF drug
and antibody testing for IBD was determined through a modified Delphi panel
based on expert interpretation of the literature. The time to test and clinical
action on the results is dependent on the specific clinical scenario. These recom-
mendations can help guide clinicians to best optimize anti-TNF therapy.
Disclosure of Interest: G. Melmed Financial support for research from:
Prometheus Labs, Consultancy for: Abbvie, Jannsen, UCB, P. Irving Financial
support for research from: Therediag, Consultancy for: Abbvie, MSD, G.
Kaplan Financial support for research from: Merck, Abbvie, and Shire,
Lecture fee(s) from: Jansen, Merck, Schering-Plough, Abbvie, and UCB
Pharma, Consultancy for: Jansen, Abbvie, Merck, Schering-Plough, Shire, and
UCB Pharma, B. Bressler: None declared, J. Jones: None declared, P. Kozuch:
None declared, M. Sparrow Lecture fee(s) from: jannsen, abbvie, Consultancy
for: jannsen, F. Velayos: None declared, L. Baidoo: None declared, A. Cheifetz
Lecture fee(s) from: jannsen, abbvie, S. Devlin Financial support for research
from: Merck, Lecture fee(s) from: Abbvie, Janssen, Merck, Consultancy for:
Abbvie, Janssen, Merck, L. Raffals: None declared, N. Vande Casteele Lecture
fee(s) from: Abbvie, Consultancy for: Janssen Biologics BV, D. Mould
Consultancy for: Abbvie, Jannsen, Prometheus Lab, M. Dubinsky Financial
support for research from: Janssen, Prometheus Labs, Consultancy for:
Abbvie, Jannsen, Prometheus Labs, UCB, J.-F. Colombel Financial support
for research from: Abbvie, Jannsen, UCB, Consultancy for: Jansen, Merck,
Schering-Plough, Abbvie, and UCB Pharma, W. Sandborn Financial support
for research from: Janssen, Prometheus Labs, Consultancy for: Abbvie,
Jannsen, Merck, Prometheus Labs, UCB, C. Siegel Financial support for
research from: Abbvie, Jannsen, UCB, Consultancy for: Abbvie, Jannsen,
Prometheus Labs, UCB
P0310 IBD RECURRENCE AFTER STOPPING ANTI-TNF-ALPHA
THERAPY: A PROSPECTIVE RANDOMIZED CONTROLLED
STUDY COMPARING MESALAMINE AND AZATHIOPRINE AD
INTERIM RESULTS
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: The advent of tumor necrosis factor (TNF) antagonists has
dramatically changed the management of patients with inflammatory bowel dis-
eases (IBD). However, despite more than a decade of clinical experience, there is
still debate about the optimal exit strategies from biologic therapies. Indeed, an
important issue concerns how to manage patients with long-standing remission
after stopping anti-TNF- drugs. Data on different maintenance strategies are
lacking.
AIMS & METHODS: We aimed to assess the efficacy of mesalamine (MESA)
vs. azathioprine (AZA) as maintenance therapy in IBD patients who withdrew
biological therapy after obtaining deep remission (i.e. clinical remission, biomar-
ker remission and mucosal healing). Consecutive IBD patients who achieved
deep remission due to anti-TNF- therapies withdrew them and were prospec-
tively randomized to two different maintenance treatments: MESA 2.4 gr/die in
ulcerative colitis (UC) and 3 gr/die in Crohns Disease (CD) patients or AZA 2.5
mg/kg/die. Then, patients were followed up every two months or before in case of
relapse, by means of routine biochemistry, clinical examination and endoscopy at
1-year or before in case of relapse. The Harvey-Bradshaw Index (HBI; remission
55) and Mayo score (remission 53) was used to evaluate clinical activity for CD
and UC, respectively, whereas endoscopy activity was assessed by means of
Mayo endoscopic score (endoscopic remission 52) or CD endoscopic index
(CDEIS; endoscopic remission 53).
RESULTS: We prospectively enrolled 16 patients with IBD [6UC/10CD; 8F/8M;
median age 44 (25-57)] who were followed-up for a median period of 48 (20-78)
weeks after achieving deep remission due to anti-TNF- therapy. Ten patients
[2UC/8CD; 5F/5M; median age 37.5 (25-53)] were randomized to MESA 2.4 gr/
die or 3gr/die and 6 patients [1UC/5CD; 3F/3M; median age 41.2 (21-47)] to
United European Gastroenterology Journal 2(5S)
AZA 2.5 mg/kg/die. All AZA-treated patients (100%) kept in remission during
the entire follow up period [median period of 55.5 weeks (20-76)], whereas 3/10
(30%) MESA-treated patients [1UC/2CD; 0F/3M; median age 42 (29-52)] experi-
enced clinical relapse after a median period of 14 weeks (8-26). The latter three
patients were shifted to AZA and clinical remission was restored.
CONCLUSION: Our preliminary data showed that AZA is more effective than
MESA in maintaining clinical remission in IBD patients who stopped biological
therapy after obtaining deep remission. Moreover, we observed that disease
recurrence due to mesalamine failure occurs a few weeks after biologic with-
drawal and can be successfully treated with AZA.
Disclosure of Interest: None declared
P0311 MRI AND CLINICAL ASSESSMENTS FOR PERIANAL CROHNS
DISEASE: GAIN AND LIMITS
A. GARROS1, L. SIPROUDHIS1, B. TCHOUNDJEU1, T. ROHOU2,
C. BROCHARD1, T. WALLENHORST1, G. BOUGUEN1,3,*
1
Service des Maladies de lAppareil Digestif, 2Service de radiologie et imagerie
medicale, CHU Pontchaillou, 3INSERM U991, Universite de Rennes 1, Rennes,
France
INTRODUCTION: Assessment of perianal Crohns disease (PCD) remains chal-
lenging. ECCO guidelines recommended Magnetic resonance imaging (MRI) as a
gold standard but both accuracy and advantage of MRI remain scarce as com-
pared to systematic clinical assessment. The aim of the study was to define
diagnosis values of both assessments.
AIMS & METHODS: Between January 2006 and April 2012, consecutive
patients with PCD assessed by MRI and clinical exam were prospectively
recorded. At each visit, perianal activity (Perianal Disease Activity Index) and
perianal phenotype (Cardiff-Hughes classification) were notified. MRI analyses
were independently reviewed and interpreted according to Cardiff-Hughes and
Van Assche classifications.
RESULTS: Overall, 122 combined evaluations were assessed in 70 different
patients. MRI failed to show superficial ulcerations in 20 of 21 patients as well
as severe ulcerations in 13 of 15 patients. MRI constantly failed to diagnose anal
stenosis (n 21). According to fistulizing lesions, the global agreement between
clinic and MRI was 60% to assess complex fistula. Clinical assessment under-
estimated 52% of multiple or ramified fistula tracts. Clinical exam (including
induration) failed to diagnose half abscesses described on MRI.
Table. Overall value of clinical or MRI assessment for each items
Youden
Items test G-S Se Sp Index** Pos LR Neg LR C
Ulceration MRI Clinic 0.08 0.94 0.02 1.33 0.98 0.68
Stenosis 0 1 0 - 1 0.83
Fistula Cardiff* Clinic MRI 0.94 0.15 0.09 1.12 0.40 0.58
Induration 0.4 0.86 0.26 2.86 0.70 0.28
Abscess 0.14 1 0.14 - 0.86 0.70
CONCLUSION: ECCO guidelines for assessment of PCD should be applied
with some caution because of the low sensitivity of MRI for the diagnosis of
non-fistulizing PCD. Concomitant clinical and MRI assessments should be
recommended.
Disclosure of Interest: None declared
P0312 STEM CELL THERAPY IN EXPERIMENTAL ULCERATIVE
COLITIS: LOCAL VERSUS SYSTEMIC APPROACH
A. Sultan1,*, M. Maher1, S. Elgamal1, A. Elhawary2, Y. Zakaria1
1
Gastroenterology & Hepatology Unit, 2Pathology, Faculty of Medicine Mansoura
University, Mansoura, Egypt
Contact E-mail Address: ahmed_hasan_sultan@hotmail.com
INTRODUCTION: Ulcerative colitis (UC) is a chronic inflammatory bowel
disease of unknown etiology(1), affecting patients quality of life, and increases
cancer colon. Its incidence and prevalence are growing all over the world (2). Its
conventional therapy commonly fails to give satisfactory results and may cause
serious side effects(3). So, new treatment is needed. In UC, both damaged intest-
inal tissue and the immune system need to be repaired. Only stem cells (SCs) can
do this(4). Among adult SCs, adipose derived SCs can be easily obtained with less
heterogeneity in their immunophenotype and multilineage differentiation ability
than do bone marrow derived MSCs(5). Several papers had reported the efficacy
of systemically infused MSCs in treating experimental UC, but some trapped in
liver and lung, decreasing their effect in local injury site (colon) and increasing
required dose(4). Meanwhile, some papers reported the use of MSCs on experi-
mental external wounds and reported some efficacy(6).
AIMS & METHODS: Evaluate effectiveness of stem cell therapy through local
enema & intravenous approaches. Induction of UC in sprague dawley (SD) rats
by 5% dextran sulphate sodium (DSS). Isolation of MSCs from adipose tissue
was done under sterile conditions. Cells were characterized using cell surface
markers by fluorescence-activated cell sorting analyses. First group was control
healthy group. Second group received 5% DSS for 7 days with no therapy. Third
group received local 1x106 ADMSCs enema. Fourth group received systemic iv
1x106 ADMSCs. Disease activity index (DAI) was assessed daily. On day 7 colon
was examined macroscopically & microscopically.
RESULTS: All groups received DSS had DAI higher than healthy control group
with statistically significant difference (p 50.05). Both groups receiving stem cells
A215
showed less DAI, macroscopic & microscopic score than control diseased group
(p 50.05). Local enema group and systemic iv groups had no statistically sig-
nificant difference in DAI, macroscopic nor microscopic scores.
CONCLUSION: Stem cell therapy via enema is a potential future therapy with
expected low side effects than systemic route for treating UC.
REFERENCES
1- Ko IK, Kim BG, Awadallah A, et al. Targeting improves MSC treatment of
inflammatory bowel disease. Am Soc Gene Cell Ther 2010.
2- Lanzoni G, Roda G, Belluzzi A, et al. Inflammatory bowel disease: moving
toward a stem cell-based therapy. World J Gastroenterol 2008; 14: 4616-4626.
3- Toruner M, Loftus EV Jr, Harmsen WS, et al. Risk factors for opportunistic
infections in patients with inflammatory bowel disease. Gastroenterology 2008;
134: 929936.
4- Singh Udai P, Singh Narendra P, Singh Balwan, et al. Stem cells as potential
therapeutic targets for inflammatory bowel disease. Front Biosci (Schol Ed) 2011;
2: 993908.
5- De Ugarte DA, Morizono K, Elbarbary AS, et al. Comparison of multi-line-
age cells from human adipose tissue and bone marrow. Cells Tissues Organs
2004; 174: 101109.
6- Jackson Wesley M, Nesti Leon J and Tuan Rockey S. Concise review: Clinical
translation of wound healing therapies based on mesenchymal stem cells. Stem
Cells Transl Med 2012; 1: 4450.
Disclosure of Interest: None declared
P0313 SUSTAINED CLINICAL BENEFIT AND IMPROVED QUALITY OF
LIFE FROM MAINTENANCE INFLIXIMAB TREATMENT IN
INFLAMMATORY BOWEL DISEASE
A. Hossain1,*, M. Lordal1, A. Olsson1, A. Storlahls1, R. Befrits1
1
Gastroenterology and Hepatology, Karolinska university Hospital, Stockholm,
Sweden
Contact E-mail Address: akter.hossain@karolinska.se
INTRODUCTION: Infliximab is effective in inducing remission in inflammatory
bowel disease and many patients are treated for several years with sustained
clinical remission.
AIMS & METHODS: To evaluate the long-term outcome of maintenance inflix-
imab (IFX) treatment in inflammatory bowel disease (IBD), regarding inflam-
matory activity, concomitant medication, quality of life (QoL) and whether
reduced intestinal surgery could be observed after initiation of treatment.
Patients with Crohns disease or ulcerative colitis, responding to IFX treatment
during one year and thereafter on continuous maintenance treatment, were eli-
gible. Two hundred patients with Crohns disease (CD; n: 164), or ulcerative
colitis (UC; n: 36), were involved. Median age at diagnoses was 22 (3-64)
years. Five mg /kg body weight IFX was usually administered every eight
week. Inflammatory activity was assessed by Harvey Bradshaw index (HBI) in
Crohns disease. Concomitant medications were followed during the study
period, and Short Health Scale (SHS), a validated short questionnaire, was
used for measuring QoL. Hb, LPK, Albumin, CRP and calprotectin were mon-
itored. Side effects and reasons for discontinuation were recorded. In this retro-
spective study the observation period ended in March 2014. Parameters and
treatment duration were estimated by last observation carried forward.
RESULTS: Median disease duration at start of treatment was 5.0 (0.2 - 44) years.
Median duration of IFX treatment was 3.4 (1.0-13.9) years. Table 1: Parameters
of inflammatory activity before and after start of IFX treatment
HBI CRP Alb WBC Calprotectin
(n:164) (n: 196) (n:199) (n:198) (n:50)
Before 8.04 29.23 34.98 8.70 3135 (1872-6200)
After 2.76 8.45 37.28 7.54 158 (30-1503)
P-value 50.0001 50.0001 50.0001 50.0291 50.0012
SHS (n:60) was significantly improved in all QoL dimensions. Steroid treatment
and immunosuppression at start of IFX treatment were 51% and 62%, respec-
tively. Corresponding figures at latest infusion were 10% and 43%. No oppor-
tunistic infection has been diagnosed. Ten infusion related moderate to severe
side effects were observed, leading to treatment discontinuation. Loss of response
occurred in 42 patients. Of those, 20 needed intestinal surgery. Twelve changed
anti-TNF therapy, one patient received alternative biological treatment and 9
continued without biological treatment. Surgery before initiation of IFX therapy
was necessary in 27% compared to 11% after treatment. Sixteen patients in
remission decided to stop treatment and 13 of those are still in remission with
only 4 on immunosuppression. One patient died several years after stopping
treatment from lung cancer and the remaining 2 were restarted on anti-TNF.
Twenty-four patients moved, while on therapy. Three patients were lost to follow
up and two stopped treatment because of malignancies.
CONCLUSION: Almost three-quarters of the patients demonstrated clinical
benefit from IFX treatment. Use of steroids was dramatically reduced with less
influence on the use of immunosuppression. SHS showed significant improve-
ment of QoL. During the studied time period, surgery was less frequent after
initiation IFX treatment.
Disclosure of Interest: None declared
A216
P0314 MEAN PLATELET VOLUME AND NEUTROPHIL-TO-
LYMPHOCYTE RATIO AS NEW BIOMARKERS OF SUSTAINED
RESPONSE TO INFLIXIMAB THERAPY IN CROHNS DISEASE
PATIENTS
A. Sobolewska1,*, M. Wlodarczyk1, K. Stec-Michalska1, J. Fichna2,
M. Wis niewska-Jarosinska1
1 IFX (mg/ml)
Department of Gastroenterology, 2Department of Biochemistry, Medical
Univeristy of Lodz, Lodz, Poland
Contact E-mail Address: dr.mwlodarczyk@gmail.com
INTRODUCTION: The loss of response to infliximab (IFX) in Crohns disease
(CD) patients is currently an important clinical problem. Therefore, searching for
predictors of maintenance or loss of response to anti-tumor necrosis factor-
(anti-TNF-) agents has become the aim of current studies in the field.
Recently, the neutrophil-lymphocyte ratio (NLR) and mean platelet volume
(MPV) have been proposed as new biomarkers of subclinical inflammatory pro-
cess. Here we hypothesized that NLR or MPV may be used as cost-effective
biomarkers of subclinical inflammation during 52-week IFX therapy in CD
patients responding to induction treatment.
AIMS & METHODS: The study aimed at establishing whether NLR or MPV at
baseline and pre-infusion at week 14 are good predictors of sustained response
after week 14 in CD patients undergoing 52-week IFX therapy. 30 adult patients
with CD (11 women and 19 men; mean ageSD 32.08.6 years), who underwent
a 52-week course of treatment with IFX and achieved response to induction
treatment evaluated at week 14 were enrolled to the study. The control group
consisted of 12 healthy subjects. The association between NLR or MPV, baseline
disease parameters and maintained clinical response or remission during IFX
therapy was assessed.
RESULTS: Fifteen of CD patients (50%) have not reached full one year main-
tenance IFX treatment without loss of response. The analysis showed a statisti-
cally significant higher NLR (4.622.43 vs. 1.490.76; p5.001) and lower MPV
(10.250.99 vs. 11.291.08 fL; p .003) in CD patients compared to controls.
Higher NLR at baseline (5.852.71 vs. 3.391.28; p .003) and at week 14
(4.792.61 vs. 2.581.23; p .006) were observed in CD patients with loss of
response to IFX maintenance treatment than in those with sustained response.
NLR lower than 4.068 at baseline predicts sustained response with 80% sensi-
tivity and 87% specificity. NLR lower than 3.667 at week 14 predicts sustained
response with 67% sensitivity and 80% specificity. MPV at week 14 in CD
patients with loss of response was significantly higher (11.311.16 fL vs.
10.190.52 fL; p .001) than in CD patients with sustained response. In patients
with sustained response to maintenance IFX treatment higher MPV between
baseline and week 14 was calculated (0.780.34 fL vs. 0.230.39 fL; p5.001).
MPV higher than 10.3 fL at week 14 predicts sustained response with 67%
sensitivity and 80% specificity. MPV between baseline and week 14 higher
than 0.4 fL predicts sustained response with 87% sensitivity and 93% specificity.
CONCLUSION: In CD patients with loss of response to IFX therapy higher
NLR and lower MPV were observed. It can be suggested that NLR and MPV
may serve as good predictors of sustained response to IFX maintenance treat-
ment in CD patients as well as may allow selection of the most appropriate
therapy based on the individual approach. Further studies are warranted to
confirm our observations and to establish the cut-off points in a larger cohort.
Disclosure of Interest: None declared
P0315 ANTI-DRUG ANTIBODIES INHIBIT NEUTRALIZATION OF TNF-
ALPHA IN INFLIXIMAB TREATED PATIENTS WITH
INFLAMMATORY BOWEL DISEASE (IBD)
A. Eser1,*, H. Vogelsang1, S. Reinisch1,2, G. Novacek1, C. Dejaco1, L. Kazemi-
Shirazi1, C. Primas1, C. Lichtenberger1, S. Brehovsky1, X. Liu3, A. Jain3,
S. Singh3, W. Reinisch1,2
1
Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria,
2
Department of Internal Medicine, McMaster University, Hamilton, Canada,
3
Prometheus Therapeutics & diagnostics, Prometheus Therapeutics & diagnostics,
San Diego, United States
Contact E-mail Address: walter.reinisch@meduniwien.ac.at
INTRODUCTION: Infliximab (IFX) trough levels (TL) as well as c-max levels
have been positively associated with its efficacy and negatively with IFX immu-
nogenicity in patients with IBD. Clearance of IFX is increased in the presence of
anti-drug antibodies (ADA). However, to what extent ADAs impact the binding
and neutralization of soluble TNF-alpha in vivo remains largely unknown. In this
study we assessed the relationship between IFX-, ADA- and TNF-alpha levels at
a mid-infusion visit and at trough in patients with IBD on maintenance therapy.
AIMS & METHODS: Serum samples from 90 consecutive patients with IBD
(Crohns disease: n 66, ulcerative colitis: n 24) on IFX maintenance therapy
were obtained at mid-infusion visits and at trough. IFX and ADA were measured
by a homogeneous mobility shift assay from Prometheus, which allows detection
of ADA in the presence of IFX. Serum TNF- was measured by a Collaborative
Enzyme Enhanced immuno-Reactive (CEER) Assay.
RESULTS: Patients had received a median number of 11 IFX infusions (range 3
- 71) with a median dose of 5.5 mg/kg (4.1- 10.9 mg/kg) before study entry.
ADAs were detected in 18 pts at mid-infusion and in 21 pts at trough. In
ADA positive pts median serum concentration of IFX was significantly lower
than in ADA negative pts both at mid-infusion and at trough. Inversely, signifi-
cantly higher serum concentrations of TNF- were detectable in ADA positive
pts at both visits (see Table). At trough the TNF-/IFX ratio was significantly
higher in ADA positive patients than in those without ADA (p50.0001). No
difference was seen in TNF- levels when segregated by IFX serum levels alone.
United European Gastroenterology Journal 2(5S)
Mid-infusion Trough
ADA neg. ADA pos. ADA neg. ADA pos.
n 69 n 21 p-value n 69 n 21 p-value
13.59 0.75 50.0001 6.36 0.42 50.0001
median (range) (3.2-35.2) (0.08-16.37) (range) (range)
TNF- (pg/ml) 5.5 (range) 10.2 0.04 7.5 25.6 50.0001
median (range) (range) (range) (range)
Interestingly, 3/10 (30%) ADA negative pts at mid-infusion with an IFX con-
centration below 8 mg/ml turned ADA positive at trough versus 1/36(3%) pts
with an IFX concentration 8 mg/ml.
CONCLUSION: ADA detected in patients with IBD on IFX maintenance ther-
apy impairs neutralization of soluble TNF- and is associated with lower serum
concentrations of IFX and higher levels of TNF- both at mid-infusion and at
trough. Our finding favours a strategy of a pre-emptive dose optimization in
ADA positive patients due to insufficient control of inflammation.
Disclosure of Interest: A. Eser Lecture fee(s) from: MSD, Abbvie, Consultancy
for: MSD, H. Vogelsang: None declared, S. Reinisch: None declared, G.
Novacek: None declared, C. Dejaco: None declared, L. Kazemi-Shirazi: None
declared, C. Primas: None declared, C. Lichtenberger: None declared, S.
Brehovsky: None declared, X. Liu: None declared, A. Jain: None declared, S.
Singh: None declared, W. Reinisch Lecture fee(s) from: MSD, Abbvie,
Consultancy for: MSD, Abbvie, Prometheus Labs
P0316 INFORMATION NECESSARY TO PREDICT INDIVIDUAL
INFLIXIMAB (IFX) PHARMACOKINETICS (PK) IN PATIENTS
WITH IBD
A. Eser1,*, H. Vogelsang1, G. Novacek1, S. Reinisch1, C. Primas1,
C. Lichtenberger1, S. Brehovsky1, D. Mould2, W. Reinisch1
1
Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria,
2
Projections Research Inc., Projections Research Inc., Phoenixville, United States
Contact E-mail Address: walter.reinisch@meduniwien.ac.at
INTRODUCTION: The increasing interest in monitoring serum IFX concentra-
tions for purposes of therapeutic dose adjustment (TDA) has led to the avail-
ability of various assays whose validity remains to be determined. Only
population-based approaches to determine individual IFX PK are used so far.
AIMS & METHODS: Objectives: 1) Evaluate the performance of 3 different
IFX assays and 2) Determine how many samples are needed in order to estimate
individual PK accurately and precisely.
Serum samples were collected after the 3rdIFX infusion for measurement of IFX
and anti-drug antibodies (ADA) in 117 patients with IBD (87 CD, 30 UC).
The mean IFX dose was 5.84 mg/kg for patients with a mean weight of 68.37 kg
(ADA positive n 19, ADA negative n 98). For each patient, at least 2 samples
from within the same infusion interval were available. 41 patients had 42 IFX
concentrations. IFX serum concentrations were measured with ELISA assays
provided by Theradiag (France) (TD) and Immundiagnostik (ID, Bensheim,
Germany). IFX and ADA were also determined by a homogeneous mobility
shift assay from Prometheus. Assay performance was evaluated by running a
population PK model using Nonmem (version 7.2 Icon Dublin Ireland).
Estimated clearance, between subject variability (BSV) and residual error were
compared with literature values. Bayesian updating and forecasting was con-
ducted using individual patient data and forecasting with different subsets of
information for each subject. Initially, only subject demographics (age, weight,
gender, albumin, ADA status and planned dose) were used. Forecast concentra-
tions based only on this information were compared with the first observed
concentration value. Subsequent evaluations included progressively more PK
observations. Agreement between observed and forecast concentrations was eval-
uated graphically and via root mean square error (RMSE) and concordance.
RESULTS: Ability of assays to estimate clearance was variable with Prometheus
and ID performing better than TD, but all provided reasonable estimates. The
number of observations needed to accurately and precisely estimate individual
PK was similar for all 3 assays. If no serum concentrations are available the
precision of the prediction of subsequent IFX concentrations is poor
(RMSE 0.46, concordance 0.43) which is reflective of high BSV in IFX
PK. With more serum IFX concentration per patient, precision of forecast con-
centrations increased. With 3 observations (RMSE 0.15, concordance 0.86),
PK estimates were markedly improved. With 4 observations the predicted con-
centration was within the assay error (RMSE and concordance). Two vs. one
observation within a dose interval does not substantially impact precision, but
does impact time required to collect enough observations to obtain precise esti-
mates of future IFX PK.
CONCLUSION: Assay quality is important for precisely estimated IFX clear-
ance in IBD patients. TDA according to patient demographics and patient fac-
tors is imprecise. At best 3 to 4 measurements of IFX would be taken early on.
Based on this information it becomes feasible to dose to a target concentration
and to determine the dose necessary. It further provides tools to prospectively
determine which concentrations are leading to most favourable responses.
Disclosure of Interest: A. Eser Lecture fee(s) from: MSD, Abbvie, Consultancy
for: MSD, H. Vogelsang: None declared, G. Novacek: None declared, S.
Reinisch: None declared, C. Primas: None declared, C. Lichtenberger: None
declared, S. Brehovsky: None declared, D. Mould: None declared, W.
Reinisch: None declared
United European Gastroenterology Journal 2(5S)
P0317 PROSPECTIVE, RANDOMIZED CLINICAL TRIAL COMPARING
THE EFFICACY OF TWO VACCINES AGAINST HEPATITIS B VIRUS
(HBV) IN INFLAMMATORY BOWEL DISEASE (IBD) PATIENTS
M. Chaparro1,2, J. Gordillo3, E. Dome`nech2,4, M. Esteve2,5, M. Barreiro de-
Acosta6, A. Villoria7, E. Iglesias-Flores8, E. Alvarado3, J. Naves2,9, O. Ben tez2,5,
L. Nieto6, X. Calvet2,7, V. Garc a-Sanchez8, J.R. Villagrasa10, A.C. Mar n1,2,
M. Ramas1,2, I. Moreno11, J. Mate1,2, J.P. Gisbert1,2,*
1
Gastroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
3
Gastroenterology Unit, Hospital Santa Creu i Sant Pau, Barcelona,
4
Gastroenterology Unit, Hospital Universitario Germans Trias i Pujol, Badalona,
5
Gastroenterology Unit, Hospital Universitario Mutua de Terrassa, Terrassa,
6
Gastroenterology Unit, Complejo Hospitalario Universitario de Santiago,
Santiago de Compostela, 7Gastroenterology Unit, Hospital de Sabadell, Sabadell,
8
Gastroenterology Unit, Hospital Universitario Reina Sofa, Cordoba,
9
Gastroenterology Unit, Hospital Universitario Germans Trias i Pujol, Barcelona,
10
Preventive Medicine Unit, Hospital de La Princesa, 11Fundacion de Investigacion
Biomedica, Hospital de La Princesa and IP, Madrid, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: Around 50% of IBD patients do not respond to the HBV
vaccine. To increase the success rate, different vaccination protocols have been
proposed although no study has been able to establish the optimal strategy for
IBD patients.
AIMS & METHODS: Aims: To compare the success rate between two HBV
vaccines in IBD patients: traditional (Engerix) and a new vaccine with adjuvant
(Fendrix). Secondary aim was to identify predictor factors of response to the
vaccine.
Methods: IBD patients with negative HBV serology and without previous vacci-
nation against HBV were randomized to receive Fendrix or double doses of
Engerix at months 0, 1, 2 and 6. Anti-HBs concentration was measured 2
months after the 3rd and 4th doses (EUDRA CT number:2010-023947-14).
RESULTS: 170 patients had been included: 55% male, 52% with Crohns dis-
ease, 30% under immunosuppressants and 37% under anti-TNF treatment. 54%
of patients received Engerix and 46% Fendrix; the main characteristics of
patients (age, gender, type of IBD and treatment) were similar between the 2
groups. Overall, 44% of patients had response (anti-HBs3 100 IU/l) after the first
3 doses (161 patients have already received 3 doses), and 71% after the comple-
tion of the vaccination (134 have completed the vaccination). The response rate
after the 4 doses was 67% with Engerix vs. 76% with Fendrix (p 0.2); con-
sidering anti-HBs310 IU/l (the standard threshold), the response rate was higher
with Fendrix than with Engerix (87 vs. 73.6%, p 0.04). In patients under
immunosuppressants or anti-TNF drugs, the response (anti-HBs3100 IU/l) after
the 4 doses was 55% with Engerix vs. 69% with Fendrix (p 0.12). In the
multivariate analysis, older age (odds ratio [OR] 0.9, p50.0001) and immuno-
suppressants or anti-TNF concomitant treatment (OR 0.04, p50.0001), but
not the type of vaccine (OR 1.9, p 0.1), were associated with the response
rate to the vaccination. 7.7% of patients flared up during the study period, and
13% suffered adverse events (only 41% related with the vaccine, and all of them
mild). The frequencies of flaring up and adverse events were similar between the 2
groups.
CONCLUSION: A statistically significant different response rate to Fendrix
(single dose) or Engerix (double dose) has not been demonstrated in IBD
patients yet (although the trial is still ongoing). A 4-dose schedule increases the
response rate around 30% compared with a 3-dose regimen. The older age and
the immunosuppressive and anti-TNF treatment decrease the success rate of the
vaccine. Both vaccines seem to be safe in IBD patients.
Disclosure of Interest: M. Chaparro Other: Dra. M Chaparro has served as a
speaker and has received research funding from MSD and Abbvie, J. Gordillo:
None declared, E. Dome`nech: None declared, M. Esteve: None declared, M.
Barreiro de-Acosta: None declared, A. Villoria: None declared, E. Iglesias-
Flores: None declared, E. Alvarado: None declared, J. Naves: None declared,
O. Ben tez: None declared, L. Nieto: None declared, X. Calvet: None declared,
V. Garc a-Sanchez: None declared, J. R. Villagrasa: None declared, A. Mar n:
None declared, M. Ramas: None declared, I. Moreno: None declared, J. Mate:
None declared, J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker, a
consultant and advisory member for, and has received research funding from
MSD and Abbvie.
P0318 EFFICACY OF A SECOND ANTI-TNF IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE WHOSE PREVIOUS ANTI-
TNF TREATMENT HAS FAILED: A META-ANALYSIS
J.P. Gisbert 1,2,* 1,2 1,2
, A.C. Mar n , A.G. McNicholl , M. Chaparro 1,2
1
Gasttroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: One-third of patients with Crohns disease (CD) or ulcera-
tive colitis (UC) receiving anti-TNF therapy do not respond to treatment (pri-
mary failure), and a relevant proportion experience a loss of response (secondary
failure) or intolerance.
AIMS & METHODS: To investigate the efficacy of a second anti-TNF agent
after failure or intolerance to a first drug.
METHODS: Inclusion criteria: Studies evaluating the efficacy of infliximab
(IFX), adalimumab (ADA), and certolizumab pegol (CZP) as the second anti-
TNF drug in CD or UC. Search strategy: Bibliographical searches in PubMed.
Data synthesis: Percentage of response/remission; the meta-analysis was per-
formed using the inverse variance method.
RESULTS: We included 42 studies (35 CD, 6 UC, 1 pouchitis). The CD studies
comprised 30 switching IFX!ADA, 4 IFX!CZP, and 1 ADA!IFX. Overall,
A217
the second anti-TNF in CD induced remission in 43% (95%CI 38-48%;
I2 75%; 27 studies; 2,345 patients) and a response in 65% (95%CI 57-73%;
I2 92%; 26 studies; 1,922 patients) of patients. The remission rate was higher
when the reason to withdraw the first anti-TNF was intolerance (61%;
95%CI 40-82%; I2 89%) than after secondary (45%; 95%CI 34-57%;
I2 79%) or primary failure (30%; 95%CI 22-37%; I2 8%); response rates
were, respectively, 72%, 66%, and 60%. Six UC studies were identified, all of
them switching IFX!ADA, and only 4 of them reporting remission rates (151
patients), with figures ranging from 0% to 50%
CONCLUSION: The efficacy of a second anti-TNF in CD patients largely
depends on the cause for switching. The remission rate was higher when the
reason to withdraw the first anti-TNF was intolerance (61%), compared with
secondary failure (45%) and primary failure (30%).
Disclosure of Interest: J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker,
a consultant and advisory member for, and has received research funding from
MSD and Abbvie., A. Mar n: None declared, A. McNicholl: None declared, M.
Chaparro Other: Dra. M Chaparro has served as a speaker and has received
research funding from MSD and Abbvie
P0319 THE ONE-YEAR EFFICACY OF INFLIXIMAB DOES NOT
DEPEND ON THE TIMING OF BIOLOGICAL THERAPY IN
ULCERATIVE COLITIS
A. Balint1,*, T. Nyari2, Z. Szepes1, F. Nagy1, P. Miheller3, G. Horvath4,
P.L. Lakatos5, K. Palatka6, K. Farkas1, R. Bor1, T. Wittmann1, T. Molnar1
1
First Department of Medicine, 2Department of Medical Physics and Informatics,
University of Szeged, Szeged, 32nd Department of Medicine, Semmelweis
University, Budapest, 4Department of Gastroenterology, Semmelweis Health
Center, Miskolc, 51st Department of Medicine, Semmelweis University, Budapest,
6
2nd Department of Medicine, University of Debrecen, Debrecen, Hungary
Contact E-mail Address: molnar.tamas@med.u-szeged.hu
INTRODUCTION: Infliximab is an effective therapeutic option in patients with
refractory ulcerative colitis (UC). The optimal timing of infliximab therapy is still
one of the outstanding questions in the therapy of UC.
AIMS & METHODS: The aim of our study was to assess whether there is an
association between the one-year remission rates and the elapsed time between
the diagnosis and the start of infliximab therapy. 116 UC patients treated with
infliximab were enrolled in this retrospective study. The time elapsed between the
diagnosis and the first biological therapy was assessed in every patient, who was
then categorized to groups according to the elapsed time (45 years and 55
years; 0-2 years, 2-5 years, 5-10 years etc).
RESULTS: The mean elapsed time between the diagnosis and the start of bio-
logical therapy was 7 years (0-38 years). 50.4% of patients started infliximab
therapy within 5 years after diagnosis. After induction with infliximab 65.6%
of the enrolled patients achieved remission and 34.4% achieved response. After
one-year treatment period, the remission and response rates remained 67.7% and
21.8%. 10.6% of patients showed loss of efficacy at one year infliximab therapy.
Complete mucosal healing was detected in 31.2% and deep remission in 13.9% of
the patients at week 52. Response rates to infliximab therapy at one year were
significantly lower compared to rates at week 14 (p 0.029). The rate of remis-
sion and loss of efficacy did not depend on the elapsed time between the diagnosis
and the start of biological therapy. However, response rates were higher in longer
elapsed time (p 0.036).
CONCLUSION: Infliximab is effective for drug-refractory UC to induce and
maintain clinical remission. Our results did not reveal an association between the
remission rates and the elapsed time between the diagnosis and the first biological
therapy in UC.
Disclosure of Interest: None declared
P0320 HEAD-TO-HEAD COMPARISON OF 5 FECAL MARKERS TO
PREDICT RESPONSE TO INDUCTION AND MAINTENANCE
THERAPY WITH INFLIXIMAB IN ULCERATIVE COLITIS
PATIENTS; A PROSPECTIVE STUDY
A.C. Frin1,*, S. Nancey2, J. Filippi1, G. Boschetti2, B. Flourie2, J. Drai3,
P. Ferrari4, X. Hebuterne1
1
Gastro enterology, CHU Archet 2, Nice cedex 3, 2Gastro enterology,
3
Biochemistry, CHU Lyon sud, Hospices civils de Lyon, Pierre Benite, Lyon,
4
Biochemistry, CHU Pasteur, Nice cedex 3, France
INTRODUCTION: The role of faecal markers in monitoring anti TNF alpha
therapies has been insufficiently explored. This study aimed to determine the
usefulness of five faecal proteins in the prediction of clinical response to
Infliximab (IFX) in Ulcerative Colitis (UC): calprotectin (fCal), Lactoferrin
(fLac), M2PK (fM2PK), neopterin (fNeo), and zonulin (fZo).
AIMS & METHODS: Thirty-one consecutive patients with an active UC, requir-
ing IFX [5 mg/kg at week 0 (W0), 2, 6 and every 8 W] were prospectively studied.
At W0, W2, W6 and W14, clinical activity was recorded and a stool sample
collected. Clinical response to induction therapy was defined at W14 as a reduc-
tion of at least 3 points and 30% of the Mayo score. In 25 patients, endoscopies
were performed at W0 and W12; an endoscopic Mayo subscore of 0 or 1 defined
endoscopic remission. Clinical response to maintenance therapy was evaluated at
W52 and optimization or discontinuation of IFX were considered as a failure.
RESULTS: At W0 the median partial Mayo Score, the endoscopic Mayo and the
UCEIS scores were 7/9 (2-9), 3/3 (2-3) and 8/11 (6-11) respectively. At W14, 19
patients (61%) were clinical responders and 13 (52%) experienced an endoscopic
response. The median levels of fCal drop dramatically from W0 to W14 in
responders [from 4260 mg/g (96-25051) to 128 mg/g (11-3782); p 0.0001]. In
contrast, it did not differ significantly in non-responders [from 9077 mg/g (215-
50000) to 2781 mg/g (203-14149); p 0.287]. Same trends were observed for fLac
A218
and fM2PK levels. At W2, fLac and fM2PK predicted accurately clinical
response to IFX induction (area under the curve (AUC) 0.82, 0.84 and 0.88
respectively): cuts-offs of 800 mg/g for fCal, 20000 ng/g for fLac and 50 UI/mL
for fM2PK determined by ROC curves allowed to discriminate clinical respon-
ders from non responders to induction therapy, with good sensitivities (Se) (82%,
81% and 88%, respectively), and specificities (Sp) (69%, 70% and 80%, respec-
tively). FLac measured at W2 were the more valuable marker to predict endo-
scopic remission at W12 [(AUC 0.80, Se and Sp 72% with a cut-off of 32891
ng/g). At W14, the three previous markers were also reliable to predict clinical
response at W52 (AUC 0.82, 0.86 and 0.75 respectively) with best cut-offs of
146 mg/g for fCal, 3457 ng/g for fLac and 2.25 UI/mL for fM2-PK. FCal, fLac
and fM2PK were well correlated with both the endoscopic Mayo subscore and
the UCEIS. FNeo and fZo did not show any relevant result.
CONCLUSION: FCal, flac and fM2-PK predicted with a good accuracy the
clinical response to induction and maintenance IFX therapy in UC. The mea-
surement of one of these markers at W0 and at the end of induction might
distinguish responders from non responders to IFX maintenance therapy
within one year.
Disclosure of Interest: None declared
P0321 ALTERATIONS OF FECAL MICROBIOTA AND METABOLIC
LANDSCAPE IN RESPONSE TO ORAL OR INTRAVENOUS IRON
REPLACEMENT THERAPY IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASES
T. Lee1, A. Schmidt2,*, I. Lagkouvardos2, T. Clavel2, A. Walter3, M. Lucio3,
K. Smirnov3, P. Schmitt-Kopplin3, R. Fedorak1, D. Haller2
1
University of Alberta, Edmonton, Canada, 2Technical University of Munich,
Freising, 3Helmholtzzentrum Munchen, Munchen, Germany
Contact E-mail Address: annemarie.schmidt@tum.de
INTRODUCTION: Iron deficiency is a common complication in patients with
inflammatory bowel diseases (IBD) and oral iron replacement therapy is sug-
gested to exacerbate IBD symptoms. We hypothesized that oral iron may impact
the composition of the gut microbiota and thereby affect the disease status.
AIMS & METHODS: An open-labelled clinical trial including patients with
Crohns disease (CD; N 29) or ulcerative colitis (UC; N 19) as well as control
patients with iron deficiency (iron saturation 5 16% and ferritin 5 100)
(N 20) was performed to compare the effects of oral (PO; ferrous sulfate) vs.
intravenous (IV; iron sucrose) iron replacement therapy over a period of three
months. The health status was assed via quality of life (EQ 5D and SIBDQ) and
disease activity (HBI and PMS) questionnaires. Stool and sigmoid mucosal biop-
sies were collected before and after treatment. Gut bacterial diversity and com-
position were assessed by high-throughput sequencing of 16S rRNA genes (V4
region). Fecal metabolites were analyzed by ESI-FT-ICR-MS.
RESULTS: PO and IV treatments were comparable regarding amelioration of
iron deficiency, with superior but not significant levels of ferritin and iron satura-
tion in the IV group. Worsening or improvement of disease activity and quality
of life were independent of iron treatments (no difference between PO and IV).
Fecal bacterial diversity was significantly different between control, UC and CD
patients before and after iron treatment. Samples from IBD patients were char-
acterized by marked inter-individual differences as well as lower phylotype rich-
ness and proportions of unknown Clostridiales. We identified the presence of 18
CD-specific molecular species (OTUs), many of which matched sequences of
facultative anaerobic bacteria. Major shifts in bacterial diversity occurred in
approximately half of the participants after treatment, independently of disease.
In those samples where bacterial profiles shifted, changes in diversity were sig-
nificantly higher in IBD patients. However, no consistent changes in the occur-
rence of specific OTUs relative to iron treatment could be identified, suggesting
individual-specific responses to treatment. Metabolite analysis using OSC-PLC
classification showed a clear separation of both UC and CD from control
patients before the iron treatment. After therapy, metabolite profiles were only
different in UC patients indicating a possible convergence of CD patients with
control subjects in response to the iron treatment. Separation into IV- and PO-
specific metabolite profiles appeared in the control and CD group but not in the
UC group.
CONCLUSION: Shifts in bacterial diversity associated with iron treatment are
independent of the route of administration and are more pronounced in IBD
patients. Efficiency and clinical outcome of both iron therapies are comparable in
both IBD patient cohorts.
Disclosure of Interest: None declared
P0322 DIFFUSION-WEIGHTED MAGNETIC RESONANCE IMAGING
PARAMETERS AS PREDICTORS OF REMISSION IN CROHNS
DISEASE PATIENTS TREATED WITH ANTI-TNF THERAPY
A. Buisson1,2,*, C. Hordonneau3, J. Scanzi1, F. Goutorbe1, M. Goutte1,
B. Pereira4, G. Bommelaer1,2
1
Gastroenterology department, CHU Estaing Clermont-ferrand, 2Microbes,
Intestine, Inflammation and susceptibility of the host UMR 1071, Inserm/
Universite dAuvergne; USC-INRA 2018, 3Radiology department, CHU Estaing
Clermont-ferrand, 4Biostatistics unit, DRCI, CHU Clermont-ferrand, Clermont-
ferrand, France
INTRODUCTION: Anti-TNF agents are the most effective therapy in Crohns
disease (CD). However, almost one-third of the patients experience primary fail-
ure to anti-TNF therapy. Diffusion-Weighted Magnetic Resonance Entero-
Colonography (DW-MREC) has shown good accuracy to detect and assess
inflammatory activity in CD1,2.
AIMS & METHODS: We aimed to study the DW-MREC parameters as pre-
dictors of advanced remission (clinical remission defined as CDAI 5150 AND
United European Gastroenterology Journal 2(5S)
CRP 55 mg/L), surgery, clinical remission (CDAI 5150) or clinical response
(CDAI70) after induction regimen of anti-TNF (week 12).
Overall, 28 consecutive CD patients were prospectively included during 1 year.
All the patients underwent a DW-MREC1,2 within 4 weeks before starting anti-
TNF. Adalimumab (ADA) was administered as 160mg at W0, 80mg at W2 and
40mg e.o.w. Infliximab (IFX) was administered as 5mg/kg at W0, W2 and W6.
The collected MRI parameters were: Clermont score1,2, apparent diffusion coef-
ficient (ADC), Magnetic Resonance Index of Activity (MaRIA), presence of
stenosis, fistula, abscess, sclerolipomatosis or mesenteric lymph nodes.
RESULTS: Median age and disease duration at inclusion were 37 years (17-71)
and 34 months (0-456) respectively. Overall, 14 (50%) were smokers, 7 (25%)
underwent previous intestinal resection and 7 (25%) had ano-perineal lesions. 13
patients (46.4%) had ileal CD (L1), 3 (10.7%) colonic CD (L2), 12 (42.8%)
ileocolonic CD (L3). CD phenotypes were non-stricturing non-fistulizing (B1),
stricturing (B2) and fistulizing (B3) in 9 (32.1%),12 (42.9%), and 7 (25.0%)
patients, respectively. While 13 patients were treated with IFX (44.4%), 15
were treated with ADA (55.6%). Among them, 10 (35.7%) patients received
concomitant thiopurines. At inclusion, median CDAI was 225 (170-393) and
median C-reactive protein value was 17.1 mg/L (2.9-148). 13 patients (46.4%)
experienced advanced remission at W12.
Mean ADC seemed lower (1.912 vs 2.162, p 0.07) and mean MaRIA seemed
higher (47.0 vs 41.9, p 0.13) in the patients treated with anti-TNF therapy
which experienced advanced remission at W12.
Presence of mesenteric lymph nodes was predictive of no need for surgery at W12
in the patients treated with anti-TNF therapy (p 0.01). Sclerolipomatosis
seemed also predictive of no requirement for surgery at W12 in the patients
treated with anti-TNF therapy (p 0.13). Presence of mesenteric lymph nodes
was predictive of response to anti-TNF therapy at W12 (p 0.05).
CONCLUSION: MRI parameters reflecting inflammatory activity (presence of
mesenteric lymph nodes, sclerolipomatosis, low ADC) seemed predictors of
advanced remission or response to anti-TNF agents in CD. Despite the lack
of power due to small sample size, the intermediary results of our study show that
DW-MREC could be a useful and promising tool to predict effectiveness of anti-
TNF therapy in CD.
REFERENCES
Buisson A et al. Aliment Pharmacol Ther 2013; 37: 537-545.
Buisson A, Hordonneau C, et al. Am J Gastroenterol 2014; 109: 89-98.
Disclosure of Interest: A. Buisson Lecture fee(s) from: Abbvie, MSD, C.
Hordonneau: None declared, J. Scanzi: None declared, F. Goutorbe: None
declared, M. Goutte: None declared, B. Pereira: None declared, G.
Bommelaer: None declared
P0323 PREDICTIVE FACTORS OF EARLY INFLIXIMAB INFUSION
REACTIONS IN INFLAMMATORY BOWEL DISEASE
C. Duron1, A. Buisson1,2,*, M. Goutte1, B. Pereira3, G. Bommelaer1
1
Gastroenterology department, CHU Estaing Clermont-ferrand, 2 Microbes,
Intestine, Inflammation and susceptibility of the host UMR 1071, Inserm/
Universite dAuvergne; USC-INRA 2018, 3Biostatistics unit, DRCI, CHU
Clermont-ferrand, Clermont-ferrand, France
INTRODUCTION: Anti-TNF agents including infliximab (IFX), a chimeric
antibody, are the most effective therapies in inflammatory bowel diseases
(IBD). Early IFX Infusion Reaction (EIIR) is rare, but is a serious complication
in IBD patients, and could lead to drug withdrawal and consequently impact the
therapeutic strategy. The role of premedication remains uncertain.
AIMS & METHODS: We aimed to establish predictors of EIIR in IBD patients
and to assess the impact of premedication.
Patients, disease and infusions characteristics, collected for all IFX infusions
performed in our IBD Unit, were retrieved from electronic charts from 2008 to
2013. The EIIR were defined as events related to IFX infusions occurring within
two hours of the infusion. Univariate and multivariate analysis were performed
taking into account the inter-patients and intra-patients variability and interac-
tion test.
RESULTS: Among the 80 included IBD patients, 51 (63.8%) had Crohns dis-
ease (CD). The mean age and disease duration were 38.8 years (14.1) and 7.4
years (7.0) respectively.
Overall, 23 IBD patients (28.8%) experienced EIIR. Age, prior history of intest-
inal resection, atopy or allergy, familial history of IBD, type of IBD, disease
location, disease extent or disease duration were not predictive of EIIR. In uni-
variate analysis, non-stricturing non fistulising CD was predictive of EIIR
(26.4% vs 52.2%, p 0.03). This result was confirmed by multivariate analysis.
Of 1107 infusions, we observed 38 EIIR (3.4%). In univariate analysis, the first
four infusions (26.4% vs 52.6%, p 0.002) and the resumption of IFX after drug
holiday (17.2% vs 29.0%, p 0.001) were predictive of EIIR. Multivariate ana-
lysis confirmed that the resumption of IFX after drug holiday was a major risk
factor of EIIR (OR 24, p50.001) but not the first four infusions. Surprisingly,
a premedication (anti-histaminic or hydrocortisone) seemed to be a risk factor
for EIIR in univariate and multivariate analysis while concomitant therapies did
not prevent EIIR. As resumption of IFX after drug holiday was a major risk
factor for EIIR, interaction test was performed and showed that the increased
risk induced by the premedication was related to resumption of IFX after drug
holiday.
The patients who experienced EIIR and those who did not experience EIIR have
had to discontinue IFX therapy in 69.6% (16/23) and 50.9% (29/57) of cases,
respectively (NS).
CONCLUSION: EIIR is a major event in the history of IBD patients treated by
IFX as it leads to drug discontinuation and thus limits considerably the available
therapeutic armamentarium. The resumption of IFX after drug holiday is the
major risk of EIIR and could be predicted in part by the measurement of anti-
drug antibodies. Non stricturing non penetrating CD could be also a risk factor.
United European Gastroenterology Journal 2(5S)
The efficacy of premedication remains questionable and could be limited to the
high risk patients.
Disclosure of Interest: C. Duron: None declared, A. Buisson Lecture fee(s) from:
Abbvie, MSD, M. Goutte: None declared, B. Pereira: None declared, G.
Bommelaer: None declared
P0324 COMPARISON BETWEEN INFLIXIMAB AND ADALIMUMAB
FOR THE TREATMENT OF PERIANAL FISTULISING CROHNS
DISEASE
A. Tursi1, W. Elisei2, M. Picchio3, R. Faggiani4, C. Zampaletta4, G. Pelecca4,
G. Brandimarte5,*
1
Gastroenterology Service, ASL BAT, Andria, 2Division of Gastroenterology, ASL
Roma H, Albano Laziale (Roma), 3Division of Surgery, "P. colombo" Hospital,
ASL Roma H, Velletri (Roma), 4Division of Gastroenterology, "Belcolle"
Hospital, Viterbo, 5Division of Internal Medicine and Gastroenterology, "Cristo
Re" Hospital, Rome, Italy
INTRODUCTION: Infliximab (IFX) and Adalimumab (ADA) have improved
the management of perianal Crohns disease (CD). However, comparative studies
have not been reported previously.
AIMS & METHODS: Our aim was to compare the outcomes of CD patients
with perianal fistulising disease treated with IFX or ADA.
A retrospective medical record review of CD patients, who received IFX or ADA
for perianal fistulising disease, was conducted. Fistulas were assessed using
Magnetic Resonance Imaging (MRI), and seton placement was performed
when appropriate. A 36-month follow-up was performed.
RESULTS: Twenty CD patients (9 males and 11 females; median age 31.5 years,
range 18-39) were treated (9 with IFX and 11 with ADA). Seton placement was
performed in 18 patients (8 in IFX and 10 in ADA group).
The baseline Harvey-Bradshaw index (HBI) and perianal disease activity index
(PDAI) significantly decreased after 6 weeks and remained at similar levels for
the entire follow-up in both groups.
The complete response rate of fistulas was 75% of patients at 36 months (78% in
IFX and 73% in ADA group), with no significant difference between the two
study groups.
Setons were withdrawn from twelve patients (5 in IFX and 7 in ADA group),
who experienced complete response and showed no radiological evidence of dis-
ease at 12-month follow-up.
Two patients with complex fistulas failed to obtain fistula closure under anti-
TNF (one in each groups). Changing the anti-TNF was useless and both
patients underwent to permanent colostomy.
CONCLUSION: Efficacy of IFX and ADA was similar in treating perianal
fistulising CD patients.
Disclosure of Interest: None declared
P0325 EFFICACY AND SAFETY OF GRANULOCYTE, MONOCYTE/
MACROPHAGE ADSORPTIVE APHERESIS IN STEROID-
DEPENDENT ACTIVE UC WITH INSUFFICIENT RESPONSE OR
INTOLERANCE TO IMMUNOSUPPRESSANTS AND/OR
BIOLOGICAL THERAPIES (THE ART TRIAL): SAFETY RESULTS AT
12 WEEKS
A. Dignass1,*, B. Bonaz2, A. Akbar3, R. Gruber4 on behalf of The ART trial
working group
1
Agaplesion Markus Krankenhaus, Frankfurt am Main, Germany, 2CHU
Grenoble, Grenoble, France, 3St. Marks Hospital, London, United Kingdom,
4
Otsuka Pharmaceutical Europe Ltd., Frankfurt, Germany
Contact E-mail Address: axel.dignass@fdk.info
INTRODUCTION: Current medical treatment options for patients with steroid-
dependent, active ulcerative colitis (UC) with insufficient response or intolerance
to immunosuppressants (IS) and/or biologicals are limited and not evidence-
based. In addition, the recognised related safety profiles are considerable. The
clinical use of Granulocyte, Monocyte/Macrophage Adsorptive (GMA) apher-
esis with Adacolumn has previously demonstrated a safe and efficacious use in
this subgroup of UC patients.
AIMS & METHODS: This study was an uncontrolled, open-label, multicenter
trial conducted in the UK, France and Germany (ART, NCT01481142).
Consecutive eligible patients (18-75 years, steroid-dependent active UC with a
Rachmilewitz (CAI) index 6 and an Endoscopic Activity Index (EAI) 4, and
insufficient response or intolerance to IS and/or biologicals) were included.
Patients received at least 5 weekly GMA apheresis. Evaluation visits were
planned at Week 12, 24 and 48. The primary endpoint was the remission rate
(CAI 4) at Week 12 in the Intention-to-treat (ITT) population. We report safety
results observed along with the earlier communicated 12 weeks interim efficacy
results of 55.9% response and 39.3% remission.
RESULTS: The safety population comprised 85 subjects having received at least
one apheresis treatment. 14 out of 85 patients (16.5%) discontinued up to Week
12. 61/85 patients (71.8%) experienced any AE; in 54 patients (63.5%) these were
of mild or moderate intensity, all transient, mainly consisting of headaches and
problems related to venous access difficulties. Six (7.1%) patients experienced
serious adverse events (SAEs), all unrelated to the study treatment. SAEs or AEs
that led to discontinuation or withdrawal from the study were either related to
the indication being studied (ulcerative colitis), or to poor venous access/ vascular
access. There were no clinically significant changes in vital signs. There were few
shifts from baseline to week 12 among clinically significant values in safety-
relevant laboratory parameters.
CONCLUSION: GMA apheresis with Adacolumn has shown benefit in more
than 50% of patients with moderate to severe, active, steroid-dependent UC and
insufficient response or intolerance to IS and/or biological agents. No new safety
A219
signals were observed, confirming the safety profile of GMA apheresis even in a
difficult-to-treat UC patients group.
REFERENCES
Habermalz B and Sauerland S. Clinical effectiveness of selective granulocyte,
monocyte adsorptive apheresis with the Adacolumn device in ulcerative colitis.
Dig Dis Sci 2010; 55: 14211428.
Disclosure of Interest: A. Dignass Financial support for research from: ART trial:
Investigator, Lecture fee(s) from: Otsuka, Consultancy for: Otsuka, B. Bonaz
Financial support for research from: ART trial: Investigator, Lecture fee(s) from:
Otsuka, Consultancy for: Otsuka, A. Akbar Financial support for research from:
ART trial: Investigator, Lecture fee(s) from: Otsuka, Consultancy for: Otsuka,
R. Gruber Other: Employee of Otsuka Pharmaceutical Europe Ltd.
P0326 MID-AND LONG-TERM OUTCOMES AND REMISSION
MAINTENANCE RATE BY PROLONGED TREATMENT WITH
TACROLIMUS FOR REFRACTORY ULCERATIVE COLITIS
A. Ito1,*, K. Shiratori1, O. Teppei1, M. Tanishima1, K. Tomoko1, I. Bunnei1
1
Departoment of Medicine, Institute of Gastroenterology, Tokyo Womens Medical
Unvercity, Tokyo, Japan
Contact E-mail Address: itoayumi@ige.twmu.ac.jp
INTRODUCTION: Efficacy of tacrolimus (TAC) as remission induction therapy
for refractory ulcerative colitis (UC) has been reported. However, hitherto mid-
and long-term outcomes and remission maintenance rates following a prolonged
treatment with TAC have not been evaluated.
AIMS & METHODS: In this study, we were interested to evaluate the clinical
remission maintenance rate for TAC in patients with UC. For this study, we
included 29 patients (15 male and 14 female) who had received a TAC-based
induction therapy between April 2009 and December 2013 (mean observation
period 728  311 days). In 10 patients, TAC was administered for 90 days
including the period of remission induction, followed by switch to an immuno-
modulator (azathioprine) to maintain remission (group 1). In 19 patients, TAC
was continued beyond the period of remission induction to maintain remission
(group 2). The patients in groups 1 and 2 were matched with respect to gender,
disease duration, pre-TAC haemoglobin (Hb), C-reactive protein (CRP), clinical
activity index (CAI, according to Lichtiger), and endoscopic index (EI) at one
month after TAC administration. The total dose of prednisolone administered up
to the time when clinical remission was achieved, duration of hospital stay, and
the time to recurrence between the two groups were factored into analyses.
Remission was defined as a CAI score of 4 or less at week 4 or later after
TAC administration. Likewise, recurrence was defined as a case in whom the
blood trough level was increased (10 ng/dl or above) by means of intense intra-
venous regimen of prednisolone, switch to a biological preparation, repeat or
dose-escalating TAC administration required to induce remission.
RESULTS: There was no significant difference in gender, disease duration, pre-
TAC Hb, CRP, CAI, total dose of prednisolone administered until remission,
duration of hospital stay, and the time to recurrence between the two groups. The
mean TAC administration period in group 2 was 235  122 days vs 86  13 days
for group 1. Further, the EI scores at one month after TAC administration were
5.8  1.6 and 7.8  2.1 for group 1 and group 2, respectively; the difference was
significant (P 5 0.012). Regarding the treatment safety, finger tremor was
observed in 2 patients in group 1 and 5 patients in group 2, renal dysfunction
was observed in none of the group 1 patients, but in 3 of group 2 patients.
CONCLUSION: In this study, although no significant difference was found in
the time to recurrence, the EI score at one month after TAC treatment was
significantly higher in group 2 compared with group 1. This finding suggests
that a maintenance dose of TAC is likely to maintain remission even in patients
with delayed mucosal healing. However, longer TAC therapy may carry higher
risk of adverse side effects.
Disclosure of Interest: None declared
P0327 STRESS AND NONSTEROIDAL-ANTIINFLAMMATORY DRUGS
(NSAID)-INDUCED EXACERBATION OF EXPERIMENTAL COLITIS
IS ATTENUATED BY ANTIBIOTIC RIFAXIMIN AND PROBIOTIC
SACCHAROMYCES BOULARDII
B. Brzozowski 1,*, M. Zwolinska-Wcislo 1, E. Karczewska 2, A. Ptak-Belowska3,
K. Urbanczyk 4, G. Krzysiek-Maczka3, M. Strzalka3, T. Brzozowski 3
1
Gastroenterology, Hepatology and Infectious Diseases Clinic, 2Department of
Microbiology, Faculty of Pharmacy, 3Department of Physiology, 4Department of
Pathomorphology, Jagiellonian University Medical College, Cracow, Poland
INTRODUCTION: Clinical and experimental studies have indicated that stress
plays an important role in the initiation and perpetuation of inflammatory bowel
disease (IBD), however, the mechanism of stress-induced alterations in the sever-
ity of the inflammatory process of colonic mucosa remains unclear. Colonic
microbiota is important component of IBD pathogenesis but its influence on
the colonic mucosal barrier under stress conditions as well as the efficacy of
treatment with antibiotics or probiotics on experimental colitis have not been
fully explained.
AIMS & METHODS: We studied the effect of cold stress on healing of experi-
mental colitis induced in rats by intrarectal administration of 2,4,6- trinitroben-
zenosulfonic acid (TNBS) and we assessed the involvement of colonic microflora
in healing of TNBS colitis in rats exposed to stress and stress combined with
aspirin (ASA) treatment. The efficacy of antimicrobial therapy by antibiotic
rifaximin or probiotic Saccharomyces boulardii on stress-induced impairment of
the healing of experimental colitis in the absence or presence of ASA treatment
was investigated. Animals with TNBS-induced colitis and exposed to cold stress
for 20 min every second day were treated i.g. daily with 1) vehicle (saline), 2)
Saccharomyces boulardii (108CFU/rat), 3) rifaximin (100 mg/kg), 4) ASA (20mg/
A220
kg) alone or 5) ASA (20 mg/kg) combined with Saccharomyces boulardii (108CF/
rat) or rifaximin (100 mg/kg). At day 10 upon colitis induction, the colonic blood
flow (CBF) was determined by H2-gas clearance technique, the blood was with-
drawn for measurement of plasma MPO, IL-1 and TNF- levels and the expres-
sion of proinflammatory markers IL-1, TNF-, iNOS, COX-2 and HIF- were
analyzed in colonic mucosa of stressed rats.
RESULTS: Exposure to stress significantly increased the area of TNBS damage
and the concomitant administration of ASA further augmented the area of these
lesions. This delay in mucosal healing caused by cold stress was accompanied by
a significant fall in the CBF, the significant rise in tissue weight, a 4-fold increase
in MPO activity and the mucosal overexpression of IL-1, TNF-, iNOS, COX-2
and HIF1. In stressed animals, the significant increase of E. coli counts in feces
and the spleen were observed and this effect was significantly attenuated by both
rifaximin and Saccharomyces boulardii. Treatment with rifaximin and to lesser
extent with probiotic Saccharomyces boulardii significantly decreased the area of
colonic lesions while increasing CBF and significantly reducing the plasma IL-1
and TNF- levels and the colonic expression of proinflammatory markers.
CONCLUSION: 1/ Stress exacerbates experimental colitis due to increase of
intestinal pathogenic E. coli and this pathogenic bacteria translocation to the
extra-intestinal organs such as spleen, and 2/ Modifying of the intestinal micro-
biota through probiotics or selected antibiotics could be of clinical importance in
the limitation of the consequences of environmental factors such as stress and
adverse effects of NSAID therapy in patients with lower GI-tract disorders.
Disclosure of Interest: None declared
P0328 TNF-ALPHA AS INDUCTION AND MAINTENANCE THERAPY
FOR CROHNS DISEASE: A PROSPECTIVE OBSERVATIONAL
STUDY IN GERMANY
B. Bokemeyer1,2,*, U. Helwig3, N. Teich4, C. Schmidt5, T. Krummenerl6, A.-
K. Rupf7, H. Hartmann8, M. Blaker9, A. Krummenerl10, M. Duffelmeyer11,
R. Hinrichs12, P. Hartmann2, S. Nikolaus1, D. Huppe8, S. Schreiber1
1
Clinic of General Medicine I, University Hospital Schleswig-Holstein, Campus
Kiel, Kiel, 2Gastroenterology Practice Minden, Minden, 3Gastroenterology
Practice Oldenburg, Oldenburg, 4Gastroenterology Practice Leipzig, Leipzig,
5
Gastroenterology Clinic IV, University Hospital Jena, Jena, 6Gastroenterology
Practice, Munster, 7Medical Department, Clinic of Friedrichshafen,
Friedrichshafen, 8Gastroenterology Practice Herne, Herne, 9Gastroenterology
Practice Eppendorfer Baum, Hamburg, 10Department of Internal Medicine I,
Martha-Maria Hospital Halle Dolau, Halle (Saale), 11IOMTech GmbH, Berlin,
12
Competence Network IBD, Kiel, Germany
Contact E-mail Address: bernd.bokemeyer@t-online.de
INTRODUCTION: The nationwide BioCrohn Registry (Biological Registry with
Crohns Disease Patients in Germany) of the German Competence-Network IBD
is a five-year prospective registry of about 1,500 patients with Crohns disease
(CD) in Germany. This is a sub-study of the BioCrohn Registry reporting the
anti TNF-alpha antibody (TNF) steroid-free remission rates of induction and
maintenance therapy in 391 anti-TNF-na ve CD-patients with adalimumab
(ADA) or infliximab (IFX) up to 12-months follow-up.
AIMS & METHODS: Within the framework of this non-interventional prospec-
tive online documentation, data in respect to the course of disease, psychosocial
burden of disease, health economics and the genetic profile were examined. End
of 2012 the recruitment was stopped having 1,525 CD-patients included by 59
different gastroenterology practices and hospitals with IBD experience. All
patients have a 5 year follow-up period. The databank for baseline and 12-
months data has been closed in 03/2013 and after databank cleansing now we
have the finalized data including the 6- and 12-months visits.
RESULTS: 391 TNF-naive CD-patients (ADA: n 264; IFX: n 127) have
been analysed (average age: 36 years; female: 52%; smokers 34%; disease dura-
tion: 9.3 years; bowel resection: 33%; prior immunosuppressive therapy: 75%).
Baseline characteristics were similar in the two groups. The IBD-therapy fol-
lowed an accelerated step-up management. Immunosuppressants were used in
19% at 6 and in 21% after 12 months. Accordingly to the TNF therapy, the use
of systemic glucocorticoids dropped over time (baseline until 6 and 12 months)
from 22.0% to 6.3% and 8.3%, respectively (p50.001). The remission rate
(PGA) at 6 months was 70.9% and 72.1% after 12 months. In spite of the
TNF-induced clinical remission (4 70%) the psychosocial impairments with
anxiety/depression (EQ-5D) showed only minor improvement and remained on
a relatively high level (baseline: 37%, 6 months: 31%, 12 months: 28%). In the
induction therapy with TNF we found a steroid-free remission (HBI5 5) in
67.1% at 6 months and in 68.9% at 12 months in the maintenance therapy.
Evaluating the efficacy of ADA vs. IFX we did not find any difference in ster-
oid-free remission rates as an induction therapy at month 6 (ADA: 68.2%; IFX:
64.6%; p n.s.) or as a maintenance therapy at month 12 (ADA: 68.1%; IFX:
70.6%; p n.s.). In the per protocol TNF-group with regular visits at 6 and 12
months (n 264) 91.7% of these patients were still on TNF after 12 months.
Additionally 5.7% of the ADA-patients switched to IFX and 9.2% of the IFX-
patients switched to ADA. This means that 76.8% of the patients starting with
TNF were on the same TNF therapy after 12 months.
CONCLUSION: In this real life setting anti-TNF therapy could induce steroid-
free remission in about 70% with the relatively early escalation of therapy in
IBD-experienced centres. In comparison there is no difference in steroid-free
remission rates between ADA vs. IFX.
Disclosure of Interest: B. Bokemeyer Financial support for research from:
Abbvie, Ferring; UCB, Lecture fee(s) from: Abbvie, MSD, Ferring, Falk,
Takeda, Consultancy for: Abbvie, MSD, Ferring, Takeda, U. Helwig: None
declared, N. Teich: None declared, C. Schmidt: None declared, T.
Krummenerl: None declared, A.-K. Rupf: None declared, H. Hartmann: None
declared, M. Blaker: None declared, A. Krummenerl: None declared, M.
Duffelmeyer: None declared, R. Hinrichs: None declared, P. Hartmann: None
United European Gastroenterology Journal 2(5S)
declared, S. Nikolaus: None declared, D. Huppe: None declared, S. Schreiber:
None declared
P0329 PREDICTORS OF HOSPITALIZATION IN PATIENTS WITH
MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
FROM ULTRA 1 AND ULTRA 2
B. Feagan1,*, W.J. Sandborn2, W. Reinisch3, S. Ghosh4, A.M. Robinson5,
A. Lazar6, Q. Zhou5, M. Skup5, R.B. Thakkar5
1
Robarts Research Institute and University of Western Ontario, London, Canada,
2
UCSD, La Jolla, United States, 3McMaster University, Hamilton, 4University of
Calgary, Calgary, Canada, 5AbbVie Inc, North Chicago, United States, 6AbbVie
Deutschland GmbH & Co. KG, Ludwigshafen, Germany
INTRODUCTION: Patients with moderately to severely active ulcerative colitis
(UC) are frequently hospitalized due to disease deterioration. The factors asso-
ciated with hospitalization risk in patients treated with non-biologic therapy for
UC are analyzed in patients randomized to placebo (PBO) in ULTRA 11 and
ULTRA 22.
AIMS & METHODS: ULTRA 1 had an 8 to 12 week double-blind (DB) phase
followed by an open-label (OL) all adalimumab (ADA) phase to week 52.
ULTRA 2 was a 52-week DB trial in which patients with inadequate response
could receive OL ADA 40 mg beginning at week 12. Patients with loss of
response or intolerance to prior anti-TNF use could enrol in ULTRA 2.
Logistic regression was used to determine predictors of all-cause and UC-related
hospitalization in PBO randomized patients from ULTRA 1 and ULTRA 2.
Baseline variables assessed were age, sex, disease duration, pancolitis, prior
anti-TNF use, CRP, albumin, Mayo score, aminosalicylate use, immunomodu-
lator use, corticosteroid use, alcohol use, smoking status, and weight. Model 1
also included baseline endoscopy subscore (2 vs 3) and Model 2 also included
stool frequency (SFS, 0-1 vs 2-3), rectal bleeding (RBS, 0-1 vs 2-3), and PGA (0-2
vs 3) subscores. Patients were censored 70 days after moving to OL ADA.
RESULTS: Selected odds ratios for the association of baseline variables with
hospitalization for PBO randomized patients from ULTRA 1 and 2 are shown in
the table. In both regression models, male sex was a significant predictor for
lower risk of all-cause and UC-related hospitalization, whereas lower baseline
albumin and higher baseline CRP concentration were significant predictors for
higher risk of all-cause and UC-related hospitalization. Alcohol use was asso-
ciated with UC-related hospitalization in both models. Disease activity at base-
line, as measured by Mayo score or individual subscores, disease duration, prior
anti-TNF use, pancolitis, or use of aminosalicylates, immunomodulators, or
corticosteroids were not associated with hospitalization risk in either model.
Table. Logistic regression odds ratios for hospitalization in PBO-randomized
patients from ULTRA 1 and 2
Model 1 Model 2
All-cause UC-related All-cause UC-related
Sex (male) 0.37** 0.41* 0.35** 0.38*
Baseline CRP (mg/L) 1.01* 1.02** 1.01* 1.02**
Albumin (540 g/L) 2.39* 2.82** 2.50* 3.00**
Current alcohol use 1.82 2.11* 1.82 2.12*
CONCLUSION: In this analysis, factors associated with hospitalization in
patients receiving non-biologic therapy for UC were sex, increased inflammation
(as measured by CRP) and low baseline albumin. These factors may be useful
when evaluating future therapeutic interventions in patients with UC failing
conventional therapy.
REFERENCES
1. Reinisch, et al. Gut 2011; 60: 780.
2. Sandborn, et al. Gastroenterol 2012; 142: 257.
Disclosure of Interest: B. Feagan Financial support for research from:
Millennium Pharmaceuticals, Merck, Tillotts Pharma AG, AbbVie, Novartis,
Centocor, Elan/Biogen, UCB Pharma, Bristol-Myers Squibb, Genentech,
ActoGenix, Wyeth, Lecture fee(s) from: AbbVie, UCB, and Janssen,
Consultancy for: Millennium, Merck, Centocor, Elan/Biogen, Janssen-Ortho,
Teva Pharmaceuticals, Bristol-Myers Squibb, Celgene, UCB Pharma, AbbVie,
Astra Zeneca, Serono, Genentech, Tillotts Pharma AG, Unity Pharmaceuticals,
Albireo Pharma, Given Imaging, Salix Pharmaceuticals, Novonordisk, GSK,
Actogenix, Prometheus Therapeutics and Diagnostics, Athersys, Axcan,
Gilead, Pfizer, Shire, Wyeth, Zealand Pharma, Zyngenia, GiCare Pharma Inc,
Sigmoid Pharma, W. Sandborn Financial support for research from: AbbVie,
Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen, Millennium,
Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire Pharmaceuticals,
and UCB Pharma., Lecture fee(s) from: AbbVie, Bristol-Myers Squibb, and
Janssen, Consultancy for: AbbVie, ActoGeniX NV, AGI Therapeutics, Inc.,
Alba Therapeutics Corporation, Albireo, Alfa Wasserman, Amgen, AM-
Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic Healthcare Limited,
Aptalis, BioBalance Corporation, Boehringer-Ingelheim Inc, Bristol-Myers
Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL, Cerimon
Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies, Coronado
Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai Medical
Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly, Enteromedics,
Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion Therapeutics, Inc.,
Funxional Therapeutics Limited, Genzyme Corporation, Genentech, Gilead
Sciences, Given Imaging, GlaxoSmithKline, Human Genome Sciences,
Ironwood Pharmaceuticals, Janssen, KaloBios Pharmaceuticals, Inc., Lexicon
United European Gastroenterology Journal 2(5S)
Pharmaceuticals, Lycera Corporation, Meda Pharmaceuticals, Merck Research
Laboratories, MerckSerono, Merck & Co., Millennium, Nisshin Kyorin
Pharmaceuticals Co., Ltd., Novo Nordisk A/S, NPS Pharmaceuticals, Optimer
Pharmaceuticals, Orexigen Therapeutics, Inc., PDL Biopharma, Pfizer, Procter
and Gamble, Prometheus Laboratories, ProtAb Limited, Purgenesis
Technologies, Inc., Receptos, Relypsa, Inc., Salient Pharmaceuticals, Salix
Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, Sigmoid Pharma
Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. A. Pharma
(UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts Pharma
AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Biogenics
Limited (VBL), Warner Chilcott UK Limited, W. Reinisch Consultancy for:
AbbVie, Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers
Squibb, Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan,
Ferring, Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin
Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma
Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer,
Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough,
Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult,
Zyngenia, Austria and 4SC, S. Ghosh Financial support for research from:
AbbVie, Consultancy for: AbbVie, Shire, Pfizer, Bristol-Myers Squibb, Janssen
and Merck & Co, Other: advisory committee or review panel for AbbVie and
Merck & Co., A. Robinson Shareholder of: AbbVie, Other: Employee: AbbVie,
A. Lazar Shareholder of: AbbVie, Other: Employee: AbbVie, Q. Zhou
Shareholder of: AbbVie, Other: Employee: AbbVie, M. Skup Shareholder of:
AbbVie, Other: Employee: AbbVie, R. Thakkar Shareholder of: AbbVie,
Other: Employee: AbbVie
P0330 DEEP REMISSION IMPROVES CLINICAL OUTCOMES AFTER
INFLIXIMAB DISCONTINUATION IN INFLAMMATORY BOWEL
DISEASES
C. Felice1,*, D. Pugliese1, M. Marzo1, G. Andrisani1, O.M. Nardone1, A. Papa1,
I. De Vitis1, G.L. Rapaccini1, L. Guidi1, A. Armuzzi1
1
IBD Unit, Internal Medicine and Gastroenterology, Complesso Integrato
Columbus, Catholic University, Rome, Italy
Contact E-mail Address: carla.felice@virgilio.it
INTRODUCTION: Recent studies underlined the importance to treat inflam-
matory bowel diseases (IBD) looking beyond symptoms and considering also
tangible indicators of disease remission, such as mucosal healing and normal-
ization of biomarkers. A clear definition of deep remission has not been validated
yet. However, the achievement of clinical remission associated to mucosal healing
has been demonstrated to improve clinical outcomes during biological treat-
ments. Some studies also showed that high C-reactive protein (CRP) levels at
the time of infliximab (IFX) discontinuation may represent a risk factor for
clinical relapse. No data are available so far about clinical outcomes of IBD
patients who discontinue IFX being in deep remission defined as the combination
of clinical remission, mucosal healing and normal CRP.
AIMS & METHODS: This single-centre study included IBD patients who dis-
continued maintenance treatment with IFX because of sustained steroid-free
clinical remission (HBI4 for Crohns disease -CD- and partial Mayo score2
for ulcerative colitis UC-, with no intake of systemic steroids during the last 12
months before discontinuation). Deep remission was defined as sustained steroid-
free clinical remission associated to normal CRP (5 mg/l) and mucosal healing
(defined as absence of ulcers in CD, or endoscopic Mayo score of 0-1 in UC).
Primary endpoint was the comparison of clinical relapse between two groups of
patients who were in deep remission (group 1) or not (group 2) at the time of IFX
discontinuation. Secondary endpoints were endoscopic recurrence, hospitaliza-
tions, surgeries and retreatment with anti-TNF between the two groups.
RESULTS: Sixty-one patients (40 CD, 21 UC) were included in the study (group
1 n 34, group 2 n 27). Median follow-up after IFX discontinuation was 36
months (IQR 23-60). No significant differences were found among baseline char-
acteristics. The rate of clinical relapse resulted significantly different between
groups: 14/34 (41%) in group 1 relapsed in comparison with 21/27 (78%) in
group 2 (p 0.009). Mucosal healing was the only other variable associated to
a lower incidence of clinical relapse (p 0.03). Median values of CRP at the time
of IFX discontinuation were not associated to a different clinical outcome. Time
to clinical relapse was significantly shorter in group 2: patients not in deep
remission at the time of IFX discontinuation relapsed after a median of 12
months (IQR 8,25-19.5) in comparison with 36 months (IQR 23-57) of group 1
(p50.001). No differences were found considering rates of endoscopic recur-
rence, hospitalization, surgery and need for anti-TNF retreatment. However,
patients in group 2 required hospitalization and retreatment with anti-TNF
significantly earlier in comparison with group 1 (p 0.02 and p 0.03,
respectively).
CONCLUSION: IBD patients who discontinue IFX because of sustained ster-
oid-free clinical remission may relapse over time. However, the presence of deep
remission (clinical remission associated to mucosal healing and normal CRP) at
the time of IFX discontinuation seems to guarantee better clinical outcomes.
Disclosure of Interest: C. Felice: None declared, D. Pugliese: None declared, M.
Marzo: None declared, G. Andrisani: None declared, O. Nardone: None
declared, A. Papa: None declared, I. De Vitis: None declared, G. L.
Rapaccini: None declared, L. Guidi Other: MSD, AbbVie, A. Armuzzi
Financial support for research from: MSD, Lecture fee(s) from: MSD,
AbbVie, Chiesi, Ferring, Nycomed, Otsuka, Consultancy for: AbbVie, MSD,
Other: MSD, AbbVie, Ferring, Nycomed
A221
P0331 PHARMACOLOGY OF ETROLIZUMAB IN A PHASE 2 STUDY IN
MODERATELY TO SEVERELY ACTIVE ULCERATIVE COLITIS
C. Looney1, F. Fuh1, M.T. Tang1, X. Wei1, M.E. Keir1, G.W. Tew1, J. Eastham-
Anderson1, L. Diehl1, A. Salas2, G. De Hertogh3, S. Francom1, H. Gilbert1,
D. Luca1, J.G. Egan1, S. Vermeire3, J.C. Mansfield4, C. Lamb4, B. Feagan5,
J. Panes2, D. Baumgart6, S. Schreiber7, I. Dotan8, W. Sandborn9, P. Rutgeerts3,
T.T. Lu1,*, S. OByrne1, M. Williams1
1
Genentech, Inc., South San Francisco, United States, 2Hospital Clinic de
Barcelona, Barcelona, Spain, 3University of Leuven, Leuven, Belgium, 4University
of Newcastle, Newcastle upon Tyne, United Kingdom, 5University of Western
Ontario, London, Canada, 6Humboldt-University of Berlin, Berlin, 7Christian
Albrechts University, Kiel, Germany, 8Tel Aviv University, Tel Aviv, Israel,
9
University of California San Diego, La Jolla, United States
Contact E-mail Address: bishop.caroline@gene.com
INTRODUCTION: Etrolizumab, a humanized antibody to the integrin 7,
blocks 47:MAdCAM-1 and E7:E-cadherin interactions, and has been
shown in a Phase 2 study to be effective at inducing clinical remission in patients
with moderate-to-severely active ulcerative colitis (UC).1 Maximal occupancy of
7 receptors was observed on lymphocyte subsets in peripheral blood and colonic
tissue in both dose cohorts (monthly subcutaneous doses of 100mg [low] or
300mgloading dose [high]), with a corresponding increase in B and T intestinal
homing lymphocytes in peripheral blood.2 Here we present the pharmacody-
namic (PD) effects of etrolizumab in colonic tissue and the serum pharmacoki-
netics (PK) from the Phase 2 study.
AIMS & METHODS: Changes from baseline were assessed in colonic tissue gene
expression at weeks 6 and 10 (qPCR, n 96) and in E cells at week 10 (immu-
nohistochemistry [IHC], n 55 & 73 in epithelium and lamina propria, respec-
tively). Serum drug levels were measured at multiple time points following
etrolizumab administration.
RESULTS: Etrolizumab displayed linear kinetics, with 4.4 fold exposure
separation between the two dose cohorts. The average serum concentration of
etrolizumab at week 10 was 8.5mg/mL and 37.8mg/mL for the low and high dose
cohorts, respectively. There were no differences in 7 gene expression in colonic
tissue between the etrolizumab and placebo treated groups. E cells were
decreased in the intestinal crypt epithelium, but not in the lamina propria, in
etrolizumab-treated patients compared with placebo. Reduction in multiple mar-
kers associated with proinflammatory infiltration and active disease was
observed in etrolizumab-treated patients who achieved clinical remission com-
pared to those who did not, including decreases in expression of proinflamma-
tory cytokines, lymphocyte subset markers (CD3, CD19), MAdCAM-1, and
epithelial cell-associated E cells. Although maximal occupancy of 7 receptors
was observed in both low and high dose groups, there were no apparent differ-
ences in PD effects between the two etrolizumab-treated cohorts. Furthermore,
within the etrolizumab-treated cohorts, there were no observed drug exposure/
clinical remission relationships.
CONCLUSION: In this Phase 2 study, we confirmed etrolizumab target engage-
ment and subsequent biological effects, both in peripheral blood and at the site of
disease pathobiology. PD effects were consistent with decreased inflammation in
the colonic mucosa, particularly in patients who attained clinical remission.
These findings contribute to the understanding of the mechanism of action of
etrolizumab: blockade of leukocyte homing to, and decreased inflammation in,
the colon.
REFERENCES
Vermeire S, et al. DDW, oral presentation, 18 May 2013.
Williams M, et al. UEGW, poster presentation, 15 October 2013.
Disclosure of Interest: C. Looney Other: Genentech, employee, F. Fuh Other:
Genentech, employee, M. Tang Other: Genentech, employee, X. Wei Other:
Genentech, employee, M. Keir Other: Genentech, employee, G. Tew Other:
Genentech, employee, J. Eastham-Anderson Other: Genentech, employee, L.
Diehl Other: Genentech, employee, A. Salas Financial support for research
from: Palau Pharma, Roche Pharma AG, Boehringer Ingelheim, Lecture fee(s)
from: Pfizer, G. De Hertogh Consultancy for: Genentech, Inc, Centocor, Inc.,
Shire Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc, Galapagos NV, S.
Francom Other: Genentech, employee, H. Gilbert Other: Genentech, employee,
D. Luca Other: Genentech, employee, J. Egan Other: Genentech/Roche,
employee, S. Vermeire Financial support for research from: Merck, Abbvie,
UCB, Consultancy for: Pfizer, Abbvie, Merck, Takeda, UCB, Shire, Ferring,
J. Mansfield Financial support for research from: Genentech, Inc.,
Consultancy for: Genentech, Inc., Tillotts Pharmaceuticals, C. Lamb Financial
support for research from: Genentech, Immundiagnostik, Roche Diagnostics
UK, B. Feagan Consultancy for: Abbott/AbbVie, ActoGenix, Amgen, Astra
Zeneca, Avaxia Biologics, Axcan, Baxter Healthcare Corp, Boehringer-
Ingelheim, Bristol-Myers Squibb, Celgene, Elan/Biogen, EnGene, Ferring,
Roche/Genentech, GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood
Pharma, Janssen Biotech, Kyowa Hakko Kirin Co, Lexicon, Lilly, Merck,
Millennium Pharma, J. Panes Consultancy for: Abbvie, BMS, Genentech,
MSD, Roche, Tygenics, Boehringer Ingelheim, Pfizer, Nutrition Science
Partners, Topivert, Novo Nordisk, D. Baumgart Financial support for research
from: Abbott, Shire, Hitachi, Lecture fee(s) from: medac, Shire, Ferring
Pharmaceuticals, MSD, Falk Foundation, Consultancy for: Abbott, MSD,
Roche, Genentech, Pfizer, S. Schreiber Financial support for research from:
AstraZeneca Pharmaceuticals, UCB Pharma, Shire Pharmaceuticals Group,
Lecture fee(s) from: Falk Foundation, Consultancy for: Abbott, AstraZeneca
Pharmaceuticals, Bayer AG, Berlex Laboratories, Bristol-Myers Squibb,
Centocor, Chemocentryx, Ferring Pharmaceuticals, Otsuka Pharma.,
Progenika Biopharma, Genentech, Schering-Plough, Shire Pharmaceuticals
Group, UCB Pharma, Novartis Pharmaceuticals, Pfizer Inc, NovoNordisk, hos-
pira, Takeda, I. Dotan Lecture fee(s) from: Abbott Laboratories, Falk Pharma,
Ferring Pharmaceuticals, J. C. healthcare, Consultancy for: Centocor, Inc.,
A222
Genentech, Atlantic Healthcare Ltd, Pfizer, Bioline Rx, W. Sandborn
Consultancy for: ActoGeniX NV, Amgen, AM-Pharma BV, Boehringer-
Ingelheim Inc, Bristol Meyers Squibb, Celgene, Cosmo Technologies,
Coronado Biosciences, Eisai Medical Research Inc., Elan Pharmaceuticals, Eli
Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences, Glaxo Smith Kline,
Ironwood Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Millennium
Pharmaceuticals, Nisshin Kyorin Pharmaceuticals Co., Ltd, Novo Nordisk A/
S, Orexigen Therapeutics, Inc., Pfizer, Prometheus Laboratories, Receptos, P.
Rutgeerts Financial support for research from: UCB Pharma, Abbott, J&J,
Merck & Co, Lecture fee(s) from: Abbott, Merck & Co, Consultancy for:
UCB Pharma, Merck, Bristol-Myers Squibb, Genentech Inc., Abbott,
Centocor - J&J, Millenium/ Takeda, Neovacs, Actogenics, Robarts, Amgen,
Pfizer, Falk Pharma, Tillotts, T. Lu Other: Genentech, employee, S. OByrne
Other: Genentech, employee, M. Williams Other: Gilead Sciences, employee
P0332 CLINICAL OUTCOME OF PERIANAL CROHNS DIESEASE AND
IMPACT OF TREATMENT STRATEGIES OVER THE TIME
C. Reenaers1,*, A. Natalis1, E. Louis2
1
CHU Sart Tilman, Liege, Belgium, Liege, Belgium, 2Hepato-Gastroenterology,
CHU Sart Tilman, Liege, Belgium, Liege, Belgium
Contact E-mail Address: catherinereenaers@hotmail.com
INTRODUCTION: Perianal Crohns disease (pCD) is associated with complica-
tions leading to recurrent surgery and tissue damage. Immunosuppressive drugs
(IS) including anti-TNF have changed the management of pCD.
AIMS & METHODS: Our aim was to describe the management and the natural
history of a cohort of patients with active pCD and to identify predictive factors
of poor evolution.
Methods: A retrospective study of pCD patients registred in the database of the
university hospital of Lie`ge, Belgium. Perianal lesions included abscess, fistulae,
anal fissure, anal strictures. pCD treatments included antibiotics, surgical drai-
nage (with or without seton), stoma. Medical treatments including IS and anti-
TNF were recorded at pCD diagnosis and over follow-up. pCD relapse was
defined as antibiotherapy for recurrent abscess, the need for surgical drainage
or stoma. The subroups of patients followed before (old cohort) and after (young
cohort) the year 2000 were compared in a subanalysis.
RESULTS: 181 patients with pCD were included. Mean follow-up was 7.9 years
Mean time between CD and pCD diagnosis was 6.3 years. Lesions at pCD
diagnosis were abscess in 93/181 (51%), fistula in 91/181 (50%; 77/93 of complex
fistulae), anal fissure in 28/181 (15%), anal stricture in 18/181 (10%). At diag-
nosis abscess drainage was performed in 31/181 (17%), drainage seton in 44/
181 (24%), stoma in 18/181 (10%). 132/181 (74%) and 83/181 (47%) had IS and
anti-TNF respectively at pCD diagnosis. Relapse rate was 51% within a mean
time of 33 months. During follow-up 15% required a stoma. Predictive factors of
relapse were perianal abscess (p50.0001, HR 4.4), fistula (p50.0001,
HR 4.5) or surgical drainage at diagnosis (p50.0001, HR 4.5), young age
at pCD diagnosis (28 versus 31 yo, p 0.02), short time between CD and pCD
diagnosis (5.7 versus 7 years, p 0.01), IS (p 0.04, HR 1.8) and anti-TNF
(p 0.01, HR 1.5) at pCD diagnosis. Anti-TNF during follow-up, time to
introduce them and duration of anti-TNF treatment were not predictive of
relapse. The young and old cohort had the same characteristics at pCD diagnosis
except a higher use of IS (87% vs 48%, p50.0001) and anti-TNF (3% vs 68%,
p50.0001) in the young cohort. Clinical outcome including the time to relapse,
type of relapse, need for surgery and stoma was similar in both cohorts.
CONCLUSION: In our cohort of pCD patients half of them had a perianal
relapse over the time requiring surgery in more than 2/3 of them. At pCD
diagnosis perianal abscess, fistula, surgical drainage, young age, treatment with
IS or anti-TNF were associated with a higher risk of relapse. Although higher
prescription of anti-TNF and IS in the last years new treatment strategies have
not impacted the outcome of pCD.
Disclosure of Interest: None declared
P0333 BIOMARKER ANALYSES FROM A PHASE 2 STUDY
EVALUATING THE ANTI-INTERLEUKIN-13 ANTIBODY
TRALOKINUMAB IN PATIENTS WITH ULCERATIVE COLITIS
C. Balendran1,*, J. Kilhamn1, S. Pierrou1, E. Rehnstrom1, N. Henderson1,
K. Randall2, G. Hughes2, M. Knutsson1, F. Erlandsson1, M.B. Hansen1,
S. Danese3
1
AstraZeneca, Molndal, Sweden, 2AstraZeneca, Alderley Park, United Kingdom,
3
Istituto Clinico Humanitas, Milan, Italy
INTRODUCTION: Interleukin-13 (IL-13) is a central cytokine effector in the T-
helper 2 immune response that has been proposed to be a key driver of ulcerative
colitis (UC) pathogenesis. Tralokinumab (CAT-354) is a human immunoglobulin
G4 antibody that inhibits binding of IL-13 both to IL-13 receptor (IL-13R) alpha
1 and IL-13R alpha 2.
AIMS & METHODS: The aim of these analyses was to gain insight into the
mechanistic action of tralokinumab in a phase 2 study in patients with UC.
Overall, 111 patients with moderate-to-severe UC were randomised in a 1:1
ratio to receive tralokinumab 300 mg or placebo subcutaneously every 2 weeks
during a 12-week treatment phase. Serum samples were obtained at baseline and
at 2-week intervals throughout the treatment phase. Biopsies were taken during
colonoscopy at baseline and after 8 weeks of treatment from mucosal areas
judged by the endoscopist to represent inflamed and normal colonic mucosa.
IL-13 levels were assessed in serum and biopsy homogenates at baseline and
following treatment. Changes from baseline to week 8 in colonic mRNA expres-
sion were assessed by in situ hybridisation for the tight junction protein claudin-2
and by quantitative PCR for selected IL-13-regulated genes. Data were analysed
by treatment and treatment response, with clinical response defined as a decrease
United European Gastroenterology Journal 2(5S)
in total Mayo score of  3 points and  30%, and a decrease in rectal bleeding
subscore of  1 point or an absolute subscore of 0 or 1.
RESULTS: A time-dependent increase in total IL-13 serum levels was observed
with tralokinumab but not with placebo. Free IL-13 was detectable in homoge-
nates of inflamed colonic mucosa; however, there was no consistent trend regard-
ing changes from baseline after 8 weeks treatment with tralokinumab. At
baseline, in situ claudin-2 mRNA expression was higher in inflamed versus
normal colonic mucosa. Claudin-2 mRNA expression decreased from baseline
in clinical responders. There were numerical increases from baseline in colonic
mucosal mRNA levels for IL-6, IL-8 and S100 calcium binding protein A8 (a
subunit of calprotectin) in clinical responders in the tralokinumab group com-
pared with clinical responders in the placebo group. A numerical decrease from
baseline in mRNA for tumour necrosis factor receptor superfamily member 12A
was seen in the tralokinumab group compared with placebo. However, gene
expression changes were small and would not remain significant after correcting
for multiple statistical comparisons.
CONCLUSION: Claudin-2 may be a useful prognostic biomarker for UC. Total
IL-13 in serum increased with tralokinumab treatment, supporting systemic
target engagement. In colonic mucosa, small expression changes in IL-13-regu-
lated genes were associated with tralokinumab treatment, though measurement
of free IL-13 could not confirm target engagement by tralokinumab in colonic
mucosa.
Disclosure of Interest: C. Balendran Other: Employee of AstraZeneca, Molndal,
Sweden, J. Kilhamn Other: Employee of AstraZeneca, Molndal, Sweden, S.
Pierrou Other: Employee of AstraZeneca, Molndal, Sweden, E. Rehnstrom
Other: Employee of AstraZeneca, Molndal, Sweden, N. Henderson Other:
Employee of AstraZeneca, Molndal, Sweden, K. Randall Other: Employee of
AstraZeneca, Alderley Park, United Kingdom, G. Hughes Other: Employee of
AstraZeneca, Alderley Park, United Kingdom, M. Knutsson Other: Employee of
AstraZeneca, Molndal, Sweden, F. Erlandsson Other: Employee of AstraZeneca,
Molndal, Sweden, M. Hansen Other: Employee of AstraZeneca, Molndal,
Sweden, S. Danese Lecture fee(s) from: Schering-Plough, Abbott Laboratories,
Merck & Co, UCB Pharma, Ferring, Cellerix, Celtrion, Millenium, Takeda,
Nycomed, Pharmacosmos, Actelion, Alpha Wasserman, Genentech,
Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals,
TiGenix, Vifor and Johnson & Johnson, Consultancy for: Schering-Plough,
Abbott Laboratories, Merck & Co, UCB Pharma, Ferring, Cellerix, Celtrion,
Millenium, Takeda, Nycomed, Pharmacosmos, Actelion, Alpha Wasserman,
Genentech, Grunenthal, Pfizer, AstraZeneca, Novo Nordisk, Cosmo
Pharmaceuticals, TiGenix, Vifor and Johnson & Johnson, Other: Advisory
board member for Schering-Plough, Abbott Laboratories, Merck & Co, UCB
Pharma, Ferring, Cellerix, Celtrion, Millenium, Takeda, Nycomed,
Pharmacosmos, Actelion, Alpha Wasserman, Genentech, Grunenthal, Pfizer,
AstraZeneca, Novo Nordisk, Cosmo Pharmaceuticals, TiGenix, Vifor and
Johnson & Johnson
P0334 THREE-YEAR STEROID FREE REMISSION AND SAFETY OF
AZATHIOPRINE TREATMENT IN INFLAMMATORY BOWEL
DISEASE PATIENTS
C. Cassieri1,*, R. Pica1, E. V. Avallone1, M. Zippi1, C. Corrado1, P. Vernia1,
P. Paoluzi1, E.S. Corazziari1
1
Internal Medicine and Medical Specialties, Sapienza "University", Rome, Italy
Contact E-mail Address: claudio.cassieri@libero.it
INTRODUCTION: Purine analogue azathioprine (AZA) is widely used for
induction and maintenance of remission in steroid dependent patients with
inflammatory bowel disease (IBD).
AIMS & METHODS: We investigated its efficacy and safety in maintaining
steroid-free remission in steroid dependent IBD patients three years after the
institution of treatment. Data from consecutive IBD outpatients referred in
our Institution, between 1985-2012, were reviewed and all patients treated with
AZA were included in this retrospective study. AZA was administered at the
recommended dose of 22.5 mg/kg. Blood chemistry was analysed before admin-
istration of the drug, every 10-15 days for the first 3 months and then every 1-2
months following the institution of treatment.
RESULTS: Out of 2472 consecutive IBD outpatients visited in the index period,
AZA was prescribed to 360 patients, 189 (52.5%) were affected by Crohns
disease (CD) and 171 (47.5%) by ulcerative colitis (UC). Seventy-eight patients
with a follow-up 536 months were excluded from the study. Two hundred and
eighty-two patients were evaluated, 152 (53.9%) with CD and 130 (46.1%) with
UC. One hundred and fifty-four (54.6%) were male and 128 (45.4%) female
(average age of 33.7513.82 SD years, range 14-76 y.). Three years after the
institution of treatment, 170 (60.3%) patients still were in steroid-free remission
(101 CD vs 69 UC, 66.4% and 53.1%, respectively, p 0.0279), 62 (22%) had a
relapse requiring retreatment with steroids (38 UC vs 24 CD, 29.2% and 15.8%,
respectively, p 0.0091), 50 (17.7%) discontinued the treatment due to side
effects (27 CD vs 23 UC, 17.8% and 17.7%, respectively). Loss of response
from 1st to 3rd year of follow-up was low, about 12%.
CONCLUSION: Three years after the onset of treatment 60% of patients did
not require further steroid courses. After the first year loss of response was low in
two subsequent years. In the present series the maintenance of steroid-free remis-
sion was significantly higher in CD than in UC patients. The occurrence of side
effects leading to the withdrawal of AZA treatment has been low.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0335 EFFICACY OF AN MMP9-SPECIFIC MONOCLONAL ANTIBODY
IN A DSS-INDUCED COLITIS MODEL OF ULCERATIVE COLITIS
D. Marshall1, R. Spangler1, C. OSullivan1, J. Adamkewicz1, V. Smith1,*
1 1
Gilead Sciences, Inc., Foster City, United States
INTRODUCTION: Ulcerative colitis (UC) remains a high unmet medical need
with no current curative therapies; the majority of patients with UC require life-
long treatment to prevent disease progression. UC is characterized by disease-
specific upregulation of matrix metalloproteinase 9 (MMP9). MMP9 can exert
pathogenic effects both by degrading extracellular matrix (ECM) proteins and
participating in tissue destruction and by activating or releasing growth factors
and cytokines from the ECM or cell surface. Previous attempts to target MMPs
with broad-spectrum or semi-selective inhibitors in oncology and inflammatory
diseases have been unsuccessful, partly due to their lack of specificity.
AIMS & METHODS: Here we used immunohistochemistry to confirm MMP9
induction at colitic foci in both human and DSS-exposed mice and evaluated
efficacy of a therapeutically-dosed MMP9-specific monoclonal antibody
(AB0046) in a DSS-induced colitis model of UC.
RESULTS: MMP9 immunoreactivity was limited in the healthy colon, but was
strongly induced and had a similar pattern of expression at active disease sites in
human UC and mouse DSS-colitis tissue. In disease, MMP9 was expressed in
abscessed and necrotic crypts and regions of cryptitis containing neutrophilic
infiltrates as well as by macrophages within the lamina propria. Extracellular
MMP9 staining colocalized with regions of destruction in the epithelial crypt
basement membrane. Inhibiting MMP9 in established DSS-induced colitis with
AB0046 resulted in a significant protection (50%) against body weight loss and
endoscopically assessed disease, and a 45% reduction in the incidence of diar-
rhea. Colons from AB0046-treated animals exhibited less crypt destruction, less
inflammatory cell infiltration, and a reduction in MMP9 expression. In concor-
dance with the IHC analysis, AB0046 treatment resulted in a decrease in histo-
pathologic disease scores. Interestingly, AB0046 treatment resulted in reduction
of serum markers of inflammation including IL-6, CXCL2, KC/GRO, MPO,
LIF, MCP-1/2/5, MIP-3, and TIMP-1.
CONCLUSION: MMP9 is highly expressed in human UC and in mouse DSS-
exposed colons. The ability of MMP9 to degrade basement membrane and to
activate or release pro-inflammatory factors from the ECM make this protein a
compelling therapeutic target in colitis. Treatment of established DSS-induced
colitis with an MMP9-specific monoclonal antibody resulted in improvement in
clinical measures of disease, histopathology, as well as in systemic markers of
inflammation. These data suggest that an MMP9 specific monoclonal antibody is
a promising therapeutic strategy for treatment of UC. Gilead Sciences has devel-
oped a humanized MMP9-specific monoclonal antibody that is currently in a
Phase 1b clinical trial in UC.
Disclosure of Interest: D. Marshall Other: Is an employee of Gilead Sciences, Inc.,
R. Spangler Other: Is an employee of Gilead Sciences, Inc., C. OSullivan Other:
Is an employee of Gilead Sciences, Inc., J. Adamkewicz Other: Is an employee of
Gilead Sciences, Inc., V. Smith Other: Is an employee of Gilead Sciences, Inc.
P0336 INFLIXIMAB ONE HOUR INFUSIONS A GOOD CHOICE FOR
IBD PATIENTS?
D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
INTRODUCTION: The use of anti-TNF agents as maintenance therapy in IBD
patients is well documented. However, administration of Infliximab (IFX)
implies long hours at the hospital, with significant costs and inconvenience. A
shorter infusion protocol would minimize such drawbacks, maintaining the same
safety and efficacy.
AIMS & METHODS: To evaluate the safety and efficacy profile of one hour
IFX infusion.
Between November 2012 and December 2013, the occurrence of acute adverse
reactions to IFX was prospectively documented. Patients under maintenance
therapy, with at least 4 infusions with no history of reactions, received one
hour infusions. This was followed by 1-hour surveillance in the next 5 infusions,
and 30 minutes from then on.
RESULTS: From a total of 95 patients under IFX therapy (Average age: 38.8 
14.2 years old; Female - 58%; Crohns Disease 66, Ulcerative Colitis 25,
Unclassified IBD 4), about 68% (65/95) started receiving one hour infusions
(average of 6 per patient, total of 390 infusions), while 31.6% (30/95) were kept
under the usual two hour protocol, with two hour infusions followed by one or
two hours of surveillance.
In the one hour infusion group, 38.4% were under combined therapy with immu-
nosuppressive agents and 23% received hydrocortisone and/or clemastine as
prophylactic medication. There was no adverse reaction noted in this group. In
92.3% of the patients, the therapeutic regimen remained the same, but in the
remaining 7.7%, an increase in dosage or interval shortening was needed. One
patient had to change to Adalimumab (ADA) due to poor response to IFX.
In the 2-hour infusion group, 56.7% were under combined therapy with immu-
nosuppressants and 43.3% received prophylactic medication. A total of 5 reac-
tions were described (2.46%), 2 of which were severe (0.98%), leading to IFX
definitive suspension. Initial regimen was maintained in 93.3% (28/30) of these
patients, while 6.7% (2/30) had to increase IFX dosage or shorter intervals
between infusions.
CONCLUSION: During maintenance therapy, 1 hour infusions are safe and
effective, minimizing costs associated with IFX therapy, and allowing shorter
hospital stays and better quality of life to IBD patients.
Disclosure of Interest: None declared
A223
P0337 BODY MASS INDEX VARIATION IN INFLIXIMAB-TREATED IBD
PATIENTS
D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
INTRODUCTION: A significant number of patients with IBD present with
nutritional deficiencies and malnutrition is relatively common. There are several
ways of describing response to Infliximab (IFX). However, nutritional status is
rarely used as a tool to evaluate the efficacy of this anti-TNF agent.
AIMS & METHODS: To establish a relation between BMI changes and clinical
response in patients treated with IFX.
Patients with IBD treated with IFX for at least a year were included. Their BMI
was measured before starting IFX, after remission induction therapy, and then
after 1 and 3 years of maintenance therapy. Response to IFX was evaluated
through clinical and laboratorial data.
RESULTS: A total of 62 patients were included (average age 37.3  13.8 years
old; 71% females; Crohns Disease 45, Ulcerative Colitis 19). Their initial
average BMI was 21.43.07 (10 patients with BMI518.5 16.1%; 8 patients
with BMI425 12.9%). After induction, no significant change was noted in
BMI, but one year later, a meaningful increase was noted (21.4 to 22.7;
p 0.049). After three years of therapy, this tendency was more evident (21.4
to 22.8; p 0.026), as only 2 patients still had BMI518,5, whilst 16 had weight
excess (26%).
There was a significant increase in BMI in patients who responded to therapy, in
contrast to those who maintained clinical activity. The average BMI actually
decreased in the latter group (1,81 vs. -0,96; p 0.012). This increase was
noted particularly in patients who had initial BMI518.5 (p 0.032), as well as
in male patients and with small bowel involvement. Factors such as age, disease
duration, smoking or other medication did not show significant association with
BMI.
CONCLUSION: Nutritional deficits are common clinical issues in IBD patients.
Therapy with Infliximab is clearly associated with improved nutritional status in
patients who are responders, unlike those who mantained disease activity. This
association is more clearly noted in the group with lower initial BMI.
Disclosure of Interest: None declared
P0338 MONITORING VITAL SIGNS DURING INFLIXIMAB INFUSION
IS IT REALLY USEFUL?
D. Branquinho1,*, P. Freire1, S. Mendes1, M. Ferreira1, F. Portela1, C. Sofia1
1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
Contact E-mail Address: diogofbranquinho@yahoo.com
INTRODUCTION: Monitoring vital signs is part of the surveillance protocol
during Infliximab infusions in most IBD reference centers. Despite being innoc-
uous, it is a time consuming task, representing another burden to already strained
healthcare professionals. In this era of increasing medical care costs, and with the
growing number of IBD patients treated with biological agents, it becomes essen-
tial to analyze if this practice is able to predict or identify adverse reactions to
Infliximab.
AIMS & METHODS: To evalute the usefulness of monitoring vital signs during
Infliximab infusions.
From January 2013 to December 2013, each patients pulse (HR), systolic blood
pressure (SBP), temperature (Temp) and pulse oximetry (SpO2) were registered
during Infliximab infusions. Acute adverse reactions were also recorded.
RESULTS: A total of 593 Infliximab infusions were administered to 95 patients
(average of 6.2  1.3 infusions per patient; median age: 38.8  14.2 years old;
59% females; Crohns Disease 66, Ulcerative Colitis 29). The overall inci-
dence of acute infusion reaction was 2.2% (13 of 593 infusions), affecting 6
patients (6.3%). Two of them were serious, with bronchospasm and angioedema.
Comparing baseline vital signs between groups with and without acute reactions,
no relevant differences were noted (HR: 78 vs. 81/min, p 0.23; SBP: 106 vs. 109
mmHg, p 0.12; Temp: 35.9 vs. 36.1 C, p 0.68; SpO2: 98% vs. 99%, p 0.42).
Vital signs measured immediately before and during acute reactions were also
compared. No significant change was noted in most cases, except during the two
serious reactions, in which there was an increase in heart rate (67 to 110 beats/
min and 86 to 112/min) and a fall in one of the patients SpO2 (97 to 85%),
maintaining stable blood pressure and temperature.
CONCLUSION: Scheduled monitoring of vital signs during Infliximab infusions
was unable to predict acute reactions or to identify patients with increased risk of
such reactions, though it can help to assess its severity. Such conclusions do not
suggest a more distant surveillance, but emphasize that clinical symptoms should
be the main focus.
Disclosure of Interest: None declared
A224
P0339 HISTOLOGICAL AND ENDOSCOPIC REMISSION INDUCED BY
INFLIXIMAB IN MODERATE TO SEVERELY ACTIVE ULCERATIVE
COLITIS PATIENTS HERICA STUDY
F. Magro1,*, S. Lopes2, J. Lopes2, E. Rodrigues-Pinto2, F. Portela3, M. Silva3,
J. Cotter4, M. Joao Moreira4, P. Lago5, C. Lopes5, C. Caetano5, P. Peixe6,
C. Chagas6, L. Carvalho6, S. Lopes3, B. Rosa4, A. Albuquerque7, C. Camila-
Dias8, J. Afonso9, K. Geboes10, F. Carneiro7 on behalf of Working group
1
Gastroenterology, 2Centro Hospitalar Sao Joao, Porto, 3Centro Hospitalar de
Coimbra, Coimbra, 4Centro Hospitalar do Alto Ave, Guimaraes, 5Centro
Hospitalar do Porto, Porto, 6Centro Hospitalar de Lisboa Ocidental, Lisboa,
7
Centro Hospitalar de Sao Joao, 8CINTESIS - Center for research in health
technologies and information systems, 9Department of Pharmacology and
Therapeutics, Porto, Portugal, 10University Hospital KU, Leuven, Belgium
Contact E-mail Address: fm@med.up.pt
INTRODUCTION: Correlation between histological activity, endoscopic find-
ings, levels of calprotectin and lactoferrin in ulcerative colitis (UC) are not well
established. Infliximab can induce remission. Residual microscopic active inflam-
mation may predict relapse. Non-invasive methods such as calprotectin may be
appropriate for this purpose.
AIMS & METHODS: The primary aim was to evaluate the histological remis-
sion induced by infliximab at week 8 (Geboes 53.0); secondary aims were to
evaluate the association between histological remission, mucosal healing, faecal
calprotectin and faecal lactoferrin. 20 patients with moderate to severe UC
(Mayo score 6-12) with inadequate response to corticosteroids or corticosteroid
dependence, all of them anti-TNF na ve, started infliximab in a prospective,
open-label, multi-centre study, with 1 year of follow-up, 4 visits assessments
(baseline, week 8, week 30, and week 52). Topical treatment was not allowed.
In each visit, Mayo score, faecal calprotectin and lactoferrin were evaluated, and
sigmoidoscopy with biopsies was performed. The worst sample was used for
histological score (Geboes index GI) and the patients were considered in
deep remission when in clinical remission (Mayo score 52) and GI 3 and
calprotectin levels 5100mg/L and lactoferrin 7.25mg/L and mucosal healing
at endoscopy (0 or 1).
RESULTS: Out of the 20 patients, 13 had left-sided colitis (E2) and 7 had
pancolitis (E3). At weeks 8, 30 and 52, 15%, 30% and 35% of the patients,
respectively, were on histological remission. At the same intervals, 10%, 20%
and 10% of the patients, respectively, were in deep remission. Sixty-six percent of
those on histological remission at week 8 had persistent remission at week 30 and
52, and 100% of those on histological remission at 30 week persisted thereafter.
Calprotectin 4100mg/L at week 8 predicted histological activity (sensitivity:
76%; specificity: 100%), with a positive predictive value (PPV) of 100% and a
negative predictive value (NPV) of 42%. Lactoferrin levels higher than 7.25 mg/L
at week 8 predicted histological activity (sensitivity: 94%; specificity: 66%), with
a PPV of 94% and a NPV of 66%. The probability of being in histological
remission once achieving mucosal healing (PPV) was 55% (weeks 30 and 52)
and the probability of endoscopic mucosal healing with calprotectin 100mg/L
was 100% and 75%, respectively, at weeks 30 and 52.
CONCLUSION: Infliximab is able to induce and maintain histological remission
in ulcerative colitis patients. High levels of calprotectin and lactoferrin predict
persistent histological activity.
Disclosure of Interest: None declared
P0340 ANTI-TNF HAS A FAVORABLE EFFECT ON INSULIN
SENSITIVITY IN NON-DIABETIC, NON-OBESE PATIENTS WITH
INFLAMMATORY BOWEL DISEASE
F. Kothonas1,*, S.A. Paschou2, A. Myroforidis1, V. Loi2, T. Terzi 2,
O. Karagianni2, A. Poulou1, A. Vryonidou2, K. Goumas1
1
Gastroenterology Department, 2Endocrinology Department, Hellenic Red Cross
Hospital, Athens, Greece
Contact E-mail Address: fotiskothonas@gmail.com
INTRODUCTION: Insulin resistance is very common in autoimmune systemic
diseases and recently it was also found in children and adults with inflammatory
bowel disease (IBD). Inflammation and insulin resistance are closely linked, and
inflammatory cytokines such as tumor necrosis factor alpha (TNFa) may inhibit
insulin signaling and promote insulin resistance. The aim of this study was to
investigate the effect of anti-TNF therapy on glucose and lipid metabolism in
non-diabetic, non-obese patients with IBD.
AIMS & METHODS: We studied 41 patients with IBD (25M/16F, 36.4  11
(19-64) years old, 28 with Crohns disease and 13 with ulcerative colitis), without
known history of diabetes. Eighteen patients (9M/9F, 33.6  8.8 years) were on
anti-TNF therapy for more than 1 year, while the other 23 patients (16M/7F,
38.7  12.5 years) were treated with azathioprine and mesalazine (Aza/Mes).
Nine of the patients from the second group were then treated with anti-TNF
and studied again 6 months after. Fasting glucose, insulin, c-peptide, HbA1c,
lipids, and CRP levels were determined and HOMA-IR index was calculated, in
all patients. Statistical analysis of the data was performed using SPSS 16.00.
RESULTS: Three of the patients were diagnosed with overt diabetes and were
excluded from the analysis. Patients from the two therapy groups were matched
for age (anti-TNF: 33.6  8.8 years vs Aza/Mes: 38.7  12.5 years, p40.05) and
BMI (anti-TNF: 23.3  3.4 vs Aza/Mes: 23.1  1.7, p40.05), and were not
obese. We did not find any statistical differences between the patients from the
two therapy groups in the levels of fasting glucose (anti-TNF: 88  10.7 vs Aza/
Mes: 93.4  14.9 mg/dl, p40.05), insulin (anti-TNF: 10.9  7.9 vs Aza/Mes: 12.1
 6.6 mIU/ml, p40.05), c-peptide (anti-TNF: 1.9  0.9 vs Aza/Mes: 2.2  1.4
ng/ml, p40.05), HbA1c (anti-TNF: 5.2  0.3 vs Aza/Mes: 5.3  0.4%, p40.05),
total cholesterol (anti-TNF: 168.6  32.7 vs Aza/Mes: 162.8  34.3 mg/dl,
p40.05), HDL (anti-TNF: 57.5  15.7 vs Aza/Mes: 53.8  20.3 mg/dl,
United European Gastroenterology Journal 2(5S)
p40.05), LDL (anti-TNF: 95.8  28.7 vs Aza/Mes: 90.7  24.4 mg/dl,
p40.05), triglycerides (anti-TNF: 75.8  37.6 vs Aza/Mes: 90.8  61.3 mg/dl,
p40.05), CRP (anti-TNF: 3  5.4 vs Aza/Mes: 4.9  6.1, p40.05) and in the
HOMA-IR index (anti-TNF: 2.77  2 vs Aza/Mes: 3.1  1.9, p40.05). In
patients who were treated for 6 months with anti-TNF, a statistically significant
decrease in insulin (before: 15.4  5.8 vs after: 10.2  2.7 mIU/ml, p 0.049) and
c-peptide (before: 2.4  1.2 vs after: 1.4  0.4 ng/ml, p 0.038) levels as well as
the HOMA-IR index (before: 4.1  2.1 vs after: 2.3  0.7, p 0.047) was
observed, without any statistically significant changes in weight, BMI, glucose,
HbA1c, lipids and CRP levels (in all comparisons p40.05).
CONCLUSION: These preliminary data indicate that anti-TNF therapy may
have a favorable effect on insulin sensitivity in non-diabetic, non-obese patients
with inflammatory bowel disease.
Disclosure of Interest: None declared
P0341 HUMAN SAFETY, PHARMACOKINETICS AND
PHARMACODYNAMICS OF THE GPR84 ANTAGONIST GLPG1205,
A POTENTIAL NEW APPROACH TO TREAT IBD
F. Vanhoutte1,*, S. Dupont2, T.Van Kaem1, M.-H. Gouy2, L. Gheyle3,
R. Blanque2, R. Brys1, N. Vandeghinste1, W. Haazen3, G.van t Klooster1,
J. Beetens1
1
GALAPAGOS NV, Mechelen, Belgium, 2GALAPAGOS SASU, Romainville,
France, 3SGS Life Science Services, CPU, Antwerp, Belgium
Contact E-mail Address: johan.beetens@glpg.com
INTRODUCTION: Free fatty acids (FFAs) are nutritional components and
metabolic intermediates that play important roles in a wide range of cellular
functions (energy source, membrane structure, signalling). Recently, FFAs
have been reported to activate a family of G protein-coupled receptors, which
are involved in the pathophysiology of a variety of diseases, including metabolic
and inflammatory disorders. GPR84 is activated by medium chain FFA (carbon
length C9-C14). The receptor is primarily expressed on white blood cells (PMN,
monocyte/macrophage) consistent with a reported role for GPR84 in
inflammation.
We identified GLPG1205 as a potent and selective antagonist of GPR84, inhibit-
ing GPR84 activation in HEK cells, as well as GPR84-induced neutrophil migra-
tion. In a mouse IBD model (DSS), GLPG1205 dose-dependently decreased the
disease activity index, to a similar level as sulphasalazine and cyclosporine. The
histological score for colon lesions, neutrophil influx as well as colonic MPO
content was substantially reduced.
AIMS & METHODS: To evaluate the safety, tolerability, pharmacokinetics
(PK) and pharmacodynamics (PD) of GLPG1205 in healthy volunteers, and
identify a dose for subsequent Proof of Concept studies in inflammatory bowel
disease.
GLPG1205 was administered as a liquid suspension, providing maximal dose
flexibility, as single doses (10 up to 800 mg) or multiple doses (50, 100 and 200
mg once daily (QD) for 14 days). Each dose level was evaluated in panels of 8
male healthy volunteers, with 6 receiving GLPG1205 and 2 placebo. In order to
evaluate target engagement, PD was assessed by a competitive radiolabeled bind-
ing assay in whole blood, using a tritiated GPR84 antagonist chemically closely
related to GLPG1205.
RESULTS: In healthy volunteers, GLPG1205 was generally safe and well toler-
ated up to 100 mg QD for 14 days, with no adverse effects on ECG, vital signs or
laboratory parameters. The most relevant adverse event was headache. The PK
of the compound showed a good oral bioavailability with a long half-life (4 one
day) and a dose-proportional increase in exposure. Steady state was reached after
8 to 10 days. GLPG1205 showed concentration-dependent target engagement in
whole blood (ex vivo), showing similar potency as in in vitro assays. The single-
dose PK/PD data demonstrated a clear relationship between drug exposure and
PD effect. Complete target occupancy for 24 hours after once daily dosing in
volunteers was observed at doses of 100 and 200 mg QD.
CONCLUSION: GLPG1205, a potent and selective inhibitor of GPR84, is safe
and generally well tolerated in healthy volunteers. It shows a favorable PK/PD
profile, clearly demonstrating the ability of the compound to antagonize GPR84,
a target which might be implicated in several neutrophil- and macrophage-driven
inflammatory conditions. At 100 mg once-daily, full 24-hour inhibition was
obtained. This dose will be studied in Proof of Concept studies to evaluate the
efficacy and safety of GLPG1205 in patients with Crohns disease and ulcerative
colitis.
Disclosure of Interest: F. Vanhoutte Other: employee, S. Dupont Other:
employee, T. Van Kaem Other: employee, M.-H. Gouy Other: employee, L.
Gheyle: None declared, R. Blanque Other: employee, R. Brys Other: employee,
N. Vandeghinste Other: employee, W. Haazen: None declared, G. van t
Klooster Other: employee, J. Beetens Other: employee
P0342 EFFECTS OF A FODMAP- RESTRICTED DIET ON IRRITABLE
BOWEL SYMPTOMS IN PATIENTS WITH INFLAMMATORY
BOWEL DISEASE
F.van Megen1,*, G.E. Kahrs1, J.G. Hatlebakk1
1
1Department of Clinical Nutrition and Section of Gastroenterology, Department
of Medicine, Clinical Institute 1, BERGEN, Norway
Contact E-mail Address: frida_van_megen@hotmail.com
INTRODUCTION: The FODMAP (fermentable oligo- di- and monosacchar-
ides, and polyols) -restricted diet has previously been proven effective to improve
symptoms in patients with irritable bowel syndrome (IBS). FODMAPs are small
osmotic active and poorly absorbed short-chain carbohydrates, and include fruc-
tose (found in fruit), lactose (found in milk products), fructans (found in grain
and vegetables), galacto-oligosaccharides (found in legumes) and polyols (found
United European Gastroenterology Journal 2(5S)
in sweetened products). FODMAPs are rapidly fermented by bacteria in the
colon and can cause bloating, increased gas production, abdominal pain and
altered bowel movements. FODMAPs do not cause IBS, but a FODMAP-
restricted diet may improve the symptoms. Patients with inflammatory bowel
disease (IBD) often suffer from persistent symptoms even though the inflamma-
tory activity is in remission. This study aimed to investigate the FODMAP-
restricted diet in patients with IBD in remission with persistent symptoms con-
sistent with IBS.
AIMS & METHODS: A 6 week intervention was undertaken in 12 IBD-patients
(10 ulcerative colitis and 2 Crohns disease, 3M/9W, age 23-57 years) in remission
with CRP55mg/L and faecal calprotectin 5100mg/kg, and fulfilling the
ROME-III criteria for IBS. FODMAP intake was determined by 4 days pro-
spective dietary registrations at 0 and 6 weeks. Instructions and follow-up were
given by a clinical dietician. IBS-symptoms and quality of life (QoL) were
assessed with questionnaires (IBS-SSS and SF-36). Compliance was assessed by
VAS-scales. Colonic fermentation was measured by breath tests with sampling
for 180min after intake of 10g lactulose. Statistics: T-tests and ANOVA
(p50.05).
RESULTS: FODMAP intake was significantly reduced from median 6.3g/d to
1.5g/d (p 0.0005). IBS symptoms were significantly reduced from median IBS-
SSS score 265.0 to 67.6 (p50.0001), and resolved in 58% of patients (remission
classified as score 575). Symptoms were reduced in the first 3 weeks and
remained stable from 3 to 6 weeks. Mental-related QoL significantly improved
from median score 43.8 to 53.3 (p 0.039). There was a positive trend for phy-
sical-related QoL with mean score 41.0 vs. 47.1 (p 0.05). QoL improved over
the whole 6 weeks of the intervention. The scores for the SF-36 health domains
bodily pain (53.3) and vitality (52.1) improved most, with p-values 0.004 Ltd, Pfizer; Bioline Rx, W. Sandborn Consultancy for: ActoGeniX NV, Amgen,
and 0.017, respectively. Gas production did not change (AUC 3488 vs. 3390 ppm
x min, p 0.8). Mean compliance with the diet was 93%, and 73% continued the
diet one month after the intervention.
CONCLUSION: The FODMAP-restricted diet resolved or improved IBS symp-
toms and QoL, and should be considered an effective treatment for patients
experiencing symptoms in spite of remission from IBD.
Disclosure of Interest: None declared
P0343 INCREASED EXPRESSION OF T-CELL-ASSOCIATED GENES IN
BASELINE BIOPSIES FROM TNF ANTAGONIST NAIVE PATIENTS
WITH MODERATELY TO SEVERELY ACTIVE ULCERATIVE
COLITIS WHO UNDERGO REMISSION IN RESPONSE TO
ETROLIZUMAB IN A PHASE II TRIAL
G.W. Tew1, J. Hackney2, D. Gibbons3, C. Lamb4, D. Luca1, J. Egen1,
S. Vermeire5, J. Mansfield4, B. Feagan6, J. Panes7, D. Baumgart8, S. Schreiber9,
I. Dotan10, W. Sandborn11, J. Kirby4, P. Irving3, G. De Hertogh5,
G.Van Assche5, P. Rutgeerts5, S. OByrne1,*, A. Hayday3, M. Keir1
1
Genentech Research and Early Development, South San Francisco, 2Genentech
Research and Early Development, San Francisco, CA, United States, 3Kings
College London, London, 4University of Newcastle, Newcastle upon Tyne, United
Kingdom, 5University of Leuven, Leuven, Belgium, 6University of Western Ontario,
Ontario, Canada, 7Hospital Clinic Barcelona, Barcelona, Spain, 8Humboldt-
University of Berlin, Berlin, 9Christian Albrechts University, Kiel, Germany, 10Tel
Aviv University, Tel Aviv, Israel, 11University of California, San Diego, United
States
Contact E-mail Address: keir.mary@gene.com
INTRODUCTION: Etrolizumab is a humanized antibody to the integrin 7
subunit that blocks 47 and E7 binding to MAdCAM-1 and E-cadherin,
respectively. In a recent phase II randomized double-blind placebo-controlled
trial (EUCALYPTUS), induction therapy with etrolizumab showed clinically
meaningful efficacy compared to placebo at week 10 in patients with moderate
to severely active ulcerative colitis.
AIMS & METHODS: RNA sequencing of inflamed colonic biopsies from TNF
antagonist na ve etrolizumab-treated patients who took part in EUCALYPTUS
was used as a hypothesis-free approach to identify gene expression patterns
associated with clinical remission in response to etrolizumab. Gene set enrich-
ment analysis of pre-defined immune cell gene sets was performed. Following
this, differentially expressed genes of interest were evaluated in sorted CD4 or
CD8 E7-positive and -negative T cells from colonic biopsies of non-
EUCALYPTUS UC patients and control subjects.
RESULTS: TNF antagonist na ve patients that underwent remission in response
to etrolizumab had higher baseline expression of T cell-associated genes in muco-
sal biopsies, while high baseline expression of neutrophil-associated genes was
associated with etrolizumab non-response. Patients with higher than median gene
expression levels of the T cell associated genes ITGAE (E integrin), granzyme A
and TMEM200A were enriched for remission in response to etrolizumab. As
increased E gene expression was associated with remission, sort purified
E7-positive T cells from biopsies of UC patients were used to test for increased
expression of other remission-associated T cell genes. Gene expression of gran-
zyme A in CD4 and CD8 T cells (p50.01) and TMEM200A in CD8 T cells
(p50.05), along with other effector molecules such as granzyme B and perforin
in CD4 T cells (p50.05), were found to be increased in E7-positive T cells
relative to E7-negative T cells from UC patients but not healthy subjects.
Finally, gene expression of the effector molecules granzyme A and B were
decreased following etrolizumab treatment in patients achieving remission.
CONCLUSION: Enrichment of T cell associated genes, including E and gran-
zyme A, was observed in baseline colonic biopsies from TNF antagonist na ve
patients that achieved clinical remission in response to etrolizumab. These can-
didate biomarkers may identify patients whose disease pathobiology is predomi-
nantly T cell-mediated and may benefit from etrolizumab treatment.
Disclosure of Interest: G. Tew Other: Genentech, employee, J. Hackney Other:
Genentech, employee, D. Gibbons Financial support for research from:
A225
Genentech, Cerimon Pharmaceuticals, C. Lamb Financial support for research
from: Genentech, Immundiagnostik, Roche Diagnostics UK, D. Luca Other:
Genentech, employee, J. Egen Shareholder of: Genentech/Roche, Other:
Genentech/Roche, S. Vermeire Financial support for research from: Merck,
Abbvie, UCB, Consultancy for: Pfizer, Abbvie, Merck, Takeda, UCB, Shire,
Ferring, J. Mansfield Financial support for research from: Genentech Inc.,
Consultancy for: Genentech Inc.; Tillotts Pharmaceuticals, B. Feagan
Consultancy for: Abbott/AbbVie, ActoGenix, Amgen, Astra Zeneca, Avaxia
Biologics, Axcan, Baxter Healthcare Corp, Boehringer-Ingelheim, Bristol-
Myers Squibb, Celgene, Elan/Biogen, EnGene, Ferring, Roche/Genentech,
GiCare Pharma, Gilead, Given Imaging, GSK, Ironwood Pharma, Janssen
Biotech, Kyowa Kakko Kirin Co, Lexicon, Lilly, Merck, Millennium Pharma,
J. Panes Consultancy for: Abbvie, BMS, Genentech, MSD, Roche, Tygenics,
Boehringer Ingelheim, Pfizer, Nutrition Science Partners, Topivert, Novo
Nordisk, D. Baumgart Financial support for research from: Abbott, Shire,
Hitachi; Speaking and Teaching: medac, Shire, Ferring Pharmaceuticals, MSD,
Falk Foundation, Consultancy for: Abbott, MSD, Roche, Genentech, Pfizer, S.
Schreiber Financial support for research from: AstraZeneca Pharmaceuticals,
UCB Pharma, Shire Pharmaceuticals Group, Lecture fee(s) from: Falk
Foundation, Consultancy for: Abbott, AstraZeneca Pharmaceuticals, Bayer
AG, Berlex Laboratories, Bristol-Myers Squibb, Centocor, Chemocentryx,
Ferring Pharmaceuticals, Otsuka Pharma., Progenika Biopharma, Genentech,
Schering-Plough, Shire Pharmaceuticals Group, UCB Pharma, Novartis
Pharmaceuticals, Pfizer Inc, NovoNordisk, Hospira, Takeda, I. Dotan Lecture
fee(s) from: Ferring Pharmaceuticals Inc, Abbott Laboratories, J. C. healthcare,
Falk Pharma, Consultancy for: Centocor, Inc., Genentech, Atlantic Healthcare
AM-Pharma BV, Boehringer-Ingelheim Inc, Bristol Meyers Squibb, Celgene,
Cosmo Technologies, Coronado Biosciences, Eisai Medical Research Inc., Elan
Pharmaceuticals, Eli Lilly, Ferring Pharmaceuticals, Genentech, Gilead Sciences,
Glaxo Smith Kline, Ironwood Pharmaceuticals, Janssen, Lexicon
Pharmaceuticals, Millennium Pharmaceuticals, Nisshin Kyorin
Pharmaceuticals Co., Ltd, Novo Nordisk A/S, Orexigen Therapeutics, Inc.,
Pfizer, Prometheus Laboratories, Receptos, J. Kirby: None declared, P. Irving:
None declared, G. De Hertogh Consultancy for: Genentech, Inc, Centocor, Inc.,
Shire Pharmaceuticals, Inc., Novartis Pharmaceuticals, Inc, Galapagos NV, G.
Van Assche Financial support for research from: Abbvie, MSD, Lecture fee(s)
from: Abbvie, Janssen, Aptalis, Ferring, Warner Chillcott, Consultancy for:
Abbvie, Takeda, MSD, Janssen, BMS, Robarts Clinical Trials, P. Rutgeerts
Financial support for research from: UCB Pharma, Abbott, J&J, Merck & Co,
Lecture fee(s) from: Abbott, Merck & Co, Consultancy for: UCB Pharma,
Merck, Bristol-Myers Squibb, Genentech Inc., Abbott, Centocor - J&J,
Millenium/ Takeda, Neovacs, Actogenics, Robarts, Amgen, Pfizer, Falk
Pharma, Tillotts, S. OByrne Other: Genentech, employee, A. Hayday
Financial support for research from: Genentech, ImmunoQure, Lecture fee(s)
from: MedImmune., Consultancy for: HS-Lifesciences, ImmunoQure, M. Keir
Other: Genentech, employee
P0344 QAX576, AN ANTIINTERLEUKIN (IL)-13 MONOCLONAL
ANTIBODY, FOR THE TREATMENT OF PATIENTS WITH
FISTULISING CROHNS DISEASE (CD): RESULTS OF A PROOF-OF-
CONCEPT STUDY
G. Rogler1,*, A. Stallmach2, S. Fichtner-Feigl3, S. Schreiber4, A. Sturm5,
E. Ramsden6, P. Moulin6, D. Lee6, A. Christ6
1
Division of Gastroenterology and Hepatology, University Hospital, Zurich,
Switzerland, 2Department of Internal Medicine IV, Jena University Hospital, Jena,
3
Department of Surgery, University Medical Center Regensburg, Regensburg,
4
Department of Internal Medicine I, University Hospital Schleswig-Holstein, Kiel,
5
Charite Campus Virchow Klinikum, Medical Department, Berlin, Germany,
6
Novartis Institutes for BioMedical Research, Basel, Switzerland
INTRODUCTION: Recent studies have identified IL-13 as a key cytokine driv-
ing the tissue remodelling that accompanies fistula formation in CD. This study
assessed the effect of QAX576, an antiIL-13 monoclonal antibody on fistula
healing in patients with fistulising CD.
AIMS & METHODS: In this 52 weeks (6 weeks treatment, 46 weeks observa-
tion), multi-centre, parallel group, double-blind, active controlled study, 23
patients (18 years) were planned to be included. Enrolment was stopped after
10 patients due to slow recruitment. Eligible patients (CD  6 months,  1
perianal fistula,  1 ineffective fistula treatment but no previous anti-TNF 
treatment failure) were randomized to receive intravenously either QAX576 10
mg/kg (at baseline, Weeks 3 and 6; placebo at Week 2; n 6) or infliximab (IFX)
5 mg/kg (at baseline, Weeks 2 and 6; placebo at Week 3; n 4). The primary
variable was the number of patients (responders) achieving complete closure of
all perianal fistulas for  4 weeks (compared to historical placebo rate of 13%).
Secondary variables included clinical assessments of the fistulas and MRI-based
activity scores of the fistula tracts.
RESULTS: Nine patients were included in the pharmacodynamic analysis set
(QAX576 6; IFX 3 [one patient excluded due to protocol deviation]). The
primary endpoint was achieved by two patients (33.3%; 90% CI: 0.114, 0.656)
in the QAX576 group. One patient stopped treatment due to abscess formation
(Week 3), one due to lack of efficacy (Week 14). In the QAX576 group, patients
had 1-4 secreting fistulas at baseline. Both responders had complete closure with
absence of any secretion within 3 weeks, although the MRI activity score
remained stable or even increased in these two patients. Fistula secretion
remained stable in three patients and fluctuated in one. All patients in the IFX
group were responders.
Immunohistochemistry of fistula tissue at baseline confirmed epithelial expres-
sion of IL-13R2 (but not IL-13R1) and de-differentiation of distorted,
entrapped crypts; SNAIL expression as marker of invasiveness was not found.
A226
Overall, 35 AEs were reported in four patients (66.7%) in the QAX576 group; 24
AEs were reported in four patients (100%) in the IFX group. Majority of AEs
were mild or moderate in severity. No death was reported in this study. One SAE
(procedural pain) was reported in the IFX group.
CONCLUSION: In this study, QAX576 was well tolerated. As expected IFX was
a powerful agent to induce fistula closure. Blockade of IL-13 may be effective,
too, as compared to historical placebo rates, although the very low patient
number does not allow a formal assessment.
Disclosure of Interest: G. Rogler Financial support for research from: Abbot,
Abbvie, Ardeypharm, Essex/MSD, FALK, Flamentera, Novartis, Roche,
Tillots, UCB, Zeller, Lecture fee(s) from: Astra Zeneca, Abbott, Abbvie,
FALK, MSD, Phadia, Tillots, UCB, Vifor, Consultancy for: Abbot, Abbvie,
Boehringer, Calypso, FALK, Genentech, Essex/MSD, MSD, Novartis, Pfizer,
Roche, UCB, Takeda, Tillots, Vifor, A. Stallmach Financial support for research
from: Abbvie, Pentax, Lecture fee(s) from: Abbott, Boehringer Ingelheim, Dr.
Falk Pharma, MSD, Recordati Pharma, Schering Plough, Shield Holding, Shire,
UCB, Vifor, Consultancy for: 4SC, Abbvie, Astellas, Boehringer Ingelheim,
MSD, S. Fichtner-Feigl: None declared, S. Schreiber Lecture fee(s) from:
MSD, Other: Paid advisor for MSD, A. Sturm: None declared, E. Ramsden
Other: Employed by Novartis, P. Moulin Shareholder of: Novartis, Other:
Novartis employee, D. Lee Shareholder of: Novartis, Other: Novartis employee,
A. Christ Shareholder of: Novartis, Roche, Other: Novartis employee
P0345 THE INFLUENCE OF ANTI-ADALIMUMAB ANTIBODIES ON
ADALIMUMAB TROUGH LEVELS, TNF-A LEVELS AND CLINICAL
OUTCOME
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: There is increasing evidence on the role of low trough levels
and the development of anti-TNF- antibodies for the occurrence of lack/loss of
response to Infliximab (IFX) therapy in patients with Crohns Disease (CD).
Therefore, several recent papers and guidelines suggested the need for dosing
IFX concentrations and anti-IFX antibodies in order to treat better CD patients.
To date, there are limited data on the role of Adalimumab (ADA) trough levels
and anti-ADA antibodies (AAA) for the management of CD patients.
AIMS & METHODS: We assessed the role of AAA on ADA trough levels,
TNF- concentrations, clinical biomarker (i.e. C-reactive protein) and clinical
outcome. In this prospective observational cohort study, performed at a single
tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66)] infliximab-na ve
patients with CD achieving disease remission and in maintenance treatment with
ADA were included and followed-up. Blood samples were drawn at standardized
time points (i.e. every 6 months or in case of CD relapse) just before ADA
injection. Trough ADA serum concentration and AAA were measured using
an homogenous mobility shift assay (HMSA; Prometheus Lab, San Diego,
United States). Blood samples were considered positive for AAA presence if
AAA were  1.7 U/mL and for ADA trough levels if ADA levels were  5
mg/ml. Disease activity was assessed at the same points by means of routine
biochemistry and the Harvey-Bradshaw Index (HBI, remission 55, mild disease
5-7, moderate disease 8-16, severe disease 416).
RESULTS: We have data from 189 blood samples. AAA were observed in 42/
189 (22.2%) samples, out of whom 16/42 (38.1%) had levels of AAA 1.7 U/mL.
ADA trough levels were found in 183/189 (96.8%) samples, out of whom 168/183
(91.8%) had a value of drug levels 5 mg/ml. Overall, 5/23 (21.7%) patients had
AAA and 22/23 (95.6%) were positive for ADA levels. Blood samples with AAA
had lower ADA trough levels [7.54 (0-26.49) vs. 9.45 (0.14-23.62); p 0.002] and
higher TNF- concentrations [5.9 (4.1-11.5) vs. 3.6 (0-27.2); p 0.0007] than
blood samples without evidence of AAA. Moreover, patients with blood samples
positive for AAA reported HBI values higher compared to patients without
evidence of AAA [10 (3-17) vs. 5 (2-17); p 50.0001]. Finally, no difference was
found in terms of mean PCR values between patients with AAA and those with-
out [8.1 (3-76.4) vs. 5.2 (2.6-56); p 0.39].
CONCLUSION: Development and presence of AAA decreases ADA trough
levels and increases TNF- concentrations in blood samples from CD patients
on maintenance treatment with ADA, thus favoring clinical relapse in them as
demonstrated by the increased values of HBI scores recorded at the time of blood
sampling.
Disclosure of Interest: None declared
P0346 TNF-A LEVELS STRONGLY CORRELATED WITH DISEASE
ACTIVITY BASED ON HBI AND CDEIS IN PATIENTS WITH
CROHNS DISEASE IN MAINTENANCE TREATMENT WITH
ADALIMUMAB
G. Bodini1,*, V. Savarino1, P. Dulbecco1, I. Baldissarro1, E. Savarino1
1
IRCCS San Martino DIMI, genova, Italy
Contact E-mail Address: bodini.giorgia@gmail.com
INTRODUCTION: In the last two decades the therapeutic paradigm of Crohns
disease (CD) has changed dramatically thanks to the use of biological drugs. In
this scenario, we must consider the pivotal role of tumor necrosis factor-alpha
(TNF-), a pro-inflammatory cytokine, in the pathogenesis and relapse of CD.
High levels of TNF- have been associated with the development of intestinal
inflammation in CD and blocking this cytokine with anti-TNF- molecules may
result in mucosal healing. In addition several studies have shown increased TNF-
 levels in the serum and in the intestinal mucosa of patients with CD. However,
little is known about the course of TNF- levels and their relationship with
disease recurrence in CD patients during maintenance treatment with
Adalimumab.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: We assessed TNF- levels in patients with CD who were
in maintenance treatment with ADA and correlated them with clinical and endo-
scopic disease activity. In this prospective observational cohort study, performed
at a single tertiary referral center, 23 [14M/9F; mean age 41 (range 21-66) inflix-
imab-na ve patients with CD in maintenance treatment with ADA were included
and followed-up. Blood samples were drawn at standardized time points (i.e.
every 6 months and in case of CD relapse) just before ADA injection.
Antibodies against ADA (AAA) were measured using an homogenous mobility
shift assay (HMSA; Prometheus Lab, San Diego, United States). Blood samples
were considered positive for AAA presence if 1.7 U/mL. Disease activity was
assessed at the same points by means of the Harvey-Bradshaw Index (HBI,
remission 55). Moreover, endoscopic activity was assessed at baseline and at
the time of relapse by means of CD endoscopic index (CDEIS; endoscopic remis-
sion 59).
RESULTS: We have data from 133 blood samples. AAA were observed in 26/
1339 (19.5%) samples, and 10/26 (38.5%) had a value of AAA 1.7 U/mL.
TNF- levels were present in all samples assessed [mean 4.4, range (0-27.2)].
Patients in clinical remission based on HBI had lower TNF- levels compared
to patients who relapsed [3.7 (0.2-20.2) vs. 5.6 (1.3-27.2); p 0.0002]. Similarly,
patients in endoscopic remission based on CDEIS had lower TNF- levels com-
pared to patients who relapsed [3.1 (0.2-20.2) vs. 4.3 (1.3-27.2); p 0.0034]. Per-
patient median TNF- levels were strongly correlated with median HBI scores
(r2 0.702, p50.0001). Moreover, TNF levels were also correlated with CDEIS
(r2 0.350, p 0.001).
CONCLUSION: TNF- levels strongly correlated with disease activity based on
HBI and CDEIS indices in patients with CD in maintenance treatment with
ADA. Indeed, moderate to severe patients often have high sustained TNF-
levels.
Disclosure of Interest: None declared
P0347 LONG-TERM OUTCOMES OF PATIENTS WITH ULCERATIVE
COLITIS TREATED WITH INFLIXIMAB
F.L. Roy1, L. Siproudhis1, C. Brochard1, V. Desfourneaux2, P.-N. DHalluin1,
M. Pagenault1, J.-F. Bretagne1, G. Bouguen1,3,*
1
Service des Maladies de lAppareil Digestif, 2Service de Chirurgie Viscerale, CHU
Pontchaillou, 3INSERM U991, Universite de Rennes 1, Rennes, France
INTRODUCTION: Data on the long-term efficacy of infliximab for the treat-
ment of ulcerative colitis are scarce. Sustained remission, recurrence and out-
comes after infliximab withdrawal beyond one year as well as predictors of long-
term outcomes are unknown.
AIMS & METHODS: The medical records of all patients with ulcerative colitis
and treated with infliximab in a referral center between 2001 and 2012 were
reviewed through September 2013. The cumulative incidence of surgery, remis-
sion and recurrence with or without infliximab withdrawal were estimated using
the Kaplan-Meier method. Independent predictors of all outcomes were identi-
fied using a Cox proportional hazards model.
RESULTS: A total of 100 patients (63 males) with ulcerative colitis and treated
with at least one infliximab infusion were included. At infliximab initiation, 17%
of patients had severe acute colitis defined by the absence of response following
intravenous steroid and 56% of patients had pancolitis. Concomitant treatment
at infliximab initiation included steroids and immunosuppressants for 62% and
52% of patients, respectively. After a median follow-up of 55.1 months, the
cumulative probabilities of surgery were 27%, 33% and 36% at 1, 3 and 5
years, respectively. A CRP 4 6mg/L at week 6 was associated with colectomy
(HR 3.43, 95% CI, 1.17-10.9; p .023). Clinical remission was obtained in
64% of patients but almost half of the patients relapsed (28/64; 44%). Overall
the cumulative probabilities for sustained clinical remission were 19%, 31% and
38% at 1, 3 and 5 years, respectively. The absence of infliximab withdrawal was
the only factor independently associated with sustained clinical remission
(HR 4.6, 95% IC, 1.66-13.85; p 0.0029). Infliximab was withdrawn in 38 of
the 64 patients in clinical remission. After a median follow up of 54 months
following infliximab withdrawal, 10% (4/38) underwent colectomy, 63.2% (24/
38) patients relapsed, and 36.8% (14/38) remained in clinical remission. The
cumulative probabilities of relapse after IFX withdrawal at 1, 3 and 5 years
were 24%, 61% and 81%, respectively. A young age 5 21 years at UC diagnosis
(HR 12, 95% IC, 2.77-58.24; p 0.001) and platelets rate 4 400000/mm3 at
IFX withdrawal (HR 6.68, 95% IC 1.55-30.82; p 0.011) were associated with
relapse.
CONCLUSION: After a follow-up of almost 5 years, about one-third of patients
experienced sustained clinical remission and one-third of patients underwent
surgery. Most of the patients relapsed after infliximab withdrawal. These results
suggest early optimization of infliximab treatment to avoid dreaded outcomes
and to continue infliximab among responders to sustain remission.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
MONDAY, OCTOBER 20, 2014 9:0017:00
PAEDIATRIC: LOWER GI POSTER EXHIBITION HALL XL_____________________
P0348 CORRELATION OF PROBE-BASED CONFOCAL LASER
ENDOMICROSCOPY FINDINGS IN THE DUODENUM AND
TERMINAL ILEUM OF PEDIATRIC INFLAMMATORY BOWEL
DISEASE PATIENTS, A PILOT STUDY
A.A. Shavrov1,*, A.Y. Kharitonova1, B. Claggett2, D.K. Brown3,
D.A. Morozov4, A.A. Shavrov1, J.J. Liu3
1 MUCO-CUTANEOUS MANIFESTATIONS IN PAEDIATRIC-ONSET
Endoscopy Department, The Scientific Center of Childrens Health Russian
Academy of Medical Sciences, Moscow, Russian Federation, 2Department of
Medicine, Brigham and Womens Hospital Harvard Medical School, Boston,
3
Division of Gastroenterology, University of Arkansas for Medical Sciences, Little
Rock, United States, 4Institute of Pediatric Surgery, The Scientific Center of
Childrens Health Russian Academy of Medical Sciences, Moscow, Russian
Federation
Contact E-mail Address: shavrovnczd@yandex.ru
INTRODUCTION: Studies over the past two decades have convincingly demon-
strated the role of barrier dysfunction in the pathogenesis of inflammatory bowel
disease (IBD). We have previously found that optical biopsy with probe-based
confocal laser endomicroscopy (pCLE) could be used to assess mucosal barrier
function and predict disease relapse in pediatric IBD patients. The purpose of
this pilot study is to evaluate the correlation of pCLE findings between duodenal
and terminal ileum in pediatric IBD patients.
AIMS & METHODS: This is a prospective study of pediatric IBD (Crohns
disease - CD and ulcerative colitis-UC) patients undergoing pCLE during both
EGD and colonoscopy in a tertiary referral center. The barrier function was
assessed with the density of epithelial gaps on pCLE of the duodenum and
terminal ileum. Adequate imaging of the duodenum and terminal ileum were
defined as at least 3 normal, non-diseased areas sampled; a minimum of 3 villi
with the highest number of epithelial gaps were analyzed. The epithelial gap
density was calculated based on the total number of epithelial gaps observed
normalized per 1000 epithelial cells counted on adequately imaged villi.
RESULTS: A total of 13 IBD patients (9 CD, 4 UC) underwent EGD and
colonoscopy with adequate pCLE imaging of the duodenum and terminal
ileum in the study. There were 8 F (62%) and 5 M (38%) with a median age
of 15 yr (range 10 to 20). The median duration of disease at the time of pCLE was
3 yr (range 0 to 9); for therapy, 4 patients (31%) were on anti-TNF agents, 6
(46%) were on 5-ASA and/or immunomodulators, 1 (7%) were on steroids, 2
(15%) were on no therapy. The disease distributions for CD were: ileo-colitis in 7
patients (78%), ileitis in 1 (11%) and colitis 1 patients (11%). For UC: 1 patients
(25%) had pan-colitis, distal colitis in 2 (50%) and proximal colitis in 1 (25%).
The gap density (mean  SE) in the terminal ileum was 5.6  1.7 gaps/1000 cells,
while in the duodenum was 1.7  0.5 gaps/1000 cells. There were modest correla-
tion between the gap density in the terminal ileum and duodenum with a spear-
man correlation coefficient of 0.42 (p 0.15)
CONCLUSION: In this pilot study of pediatric IBD patients, we found pCLE
findings of barrier function as measured by epithelial gap density in the terminal
ileum and duodenum had modest correlation. Future larger studies are war-
ranted to further investigate the correlation of barrier function in the proximal
and distal intestine.
Disclosure of Interest: None declared
P0349 INCIDENCE OF PEDIATRIC INFLAMMATORY BOWEL
DISEASE IN MINHO-PORTUGAL IS INCREASING
C.A. Machado1,*, I. Martinho2, C. Laranjeira3, M. Figueiredo4, C. Carvalho5,
A. Reis6, F. Pereira7, E. Trindade8, H. Antunes9,10
1
School of Health Sciences, University of Minho, Braga, 2Paediatrics Department,
Unidade Local de Saude do Alto Minho, Viana do Castelo, 3Paediatrics
Department, Centro Hospitalar do Alto Ave, Guimaraes, 4Paediatrics Department,
Centro Hospitalar do Medio Ave, Vila Nova de Famalicao, 5Paediatrics
Department, Hospital de Santa Maria Maior, Barcelos, 6Paediatrics, Centro
Hospital do Tamega e Sousa, Amarante, 7Paediatric Gastroenterology
Department, Centro Hospitalar do Porto, 8Paediatrics, Centro Hospitalar de Sao
Joao, Porto, 9Life and Health Sciences Research Institute (ICVS), School of
Health Sciences, ICVS/3Bs - PT Government Associate Laboratory, University of
Minho, Braga/Guimaraes, 10Gastroenterology, Hepatology and Nutrition Unit,
Paediatrics Department, Hospital de Braga, Braga, Portugal
Contact E-mail Address: caamachado@sapo.pt
INTRODUCTION: INTRODUCTION: Inflammatory bowel disease (IBD)
includes Crohns disease (CD), ulcerative colitis (UC) and indeterminate IBD
(IIBD). Although it primarily affects adults, the diagnosis in patients under 18
is about 25% to 30%, being CD the most frequent. Studies report an increase in
the incidence of CD, but a stable incidence of UC. A 2010 study in Minho reports
an incidence of 6.4/100000 (CD:66%; UC:34%).
AIMS & METHODS: Our aim was to characterize patients diagnosed with IBD
from 2002 to 2013, between the ages of 0 to 17 years and 365 days, residents in
Minho (districts of Braga and Viana do Castelo), calculate the incidence and
evaluate the health-related quality of life. We conducted a retrospective study, by
collecting information from the patients personal clinical chart. Also performed
was a cross-sectional study applying the IMPACT-III questionnaire that
assesses the quality of life of pediatric patients with IBD above 9 years old.
RESULTS: 137 subjects were found. The incidence in 2002-2013 was 5.0/100000
children-years (CD:66%, UC:32%, IIBD:2%), increasing from 2.4/100000
(CD:65%, UC:35%) in the first three years to 8.8/100000 (CD:75%, UC:23%,
IIBD:2%) in the last three (p 50.0001). Abdominal pain was the most frequent
symptom in CD and hematochezia in UC. In the IMPACT-III, the average
score was 136.5  19.2 (n 32), with a Cronbachs alpha 0.91. with response (67% and 95%, respectively). Observed remission and response
A227
CONCLUSION: There was a significant increase in the incidence of IBD, mainly
due to CD. The symptoms usually indicate the type of IBD, and again in pedia-
tric cases, abdominal pain is more prevalent than diarrhea in the presentation of
CD. The quality of life seems to be similar to that found in other studies, still
showing good internal consistency of the IMPACT-III.
Disclosure of Interest: None declared
P0350 CUMULATIVE INCIDENCE AND ASSOCIATED FACTORS OF
CROHNS DISEASE: A POPULATION-BASED STUDY
C. Templier1,*, H. Sarter2, D. Turck3, M. Fumery4, G. Savoye5, B. Catteau1,
C. Spyckerelle6, E. Laberenne7, O. Mouterde8, D. Djeddi9, S. Buche1, L. Peyrin-
Biroulet10, E. Delaporte1, C. Gower-Rousseau2 on behalf of Epimad Group
1
Dermatology, 2Epidemiology, 3Paediatric Clinic, UNIVERSITY AND
HOSPITAL LILLE, Lille, 4Gastroenterology, University and Hopsital, Amiens,
5
Gastroenterology, University and Hopsital, Rouen, 6Paediatric Clinic, Catholic
University, Lille, 7Gastroenterology, General Hospital, Seclin, 8Paediatric Clinic,
University and Hopsital, Rouen, 9Paediatric Clinic, University and Hopsital,
Amiens, 10Gastroenterology, University and Hopsital, Nancy, France
Contact E-mail Address: corinne.gower@gmail.com
INTRODUCTION: Muco-cutaneous manifestations (MCM) are common in
adult patients with Crohns disease (CD), but their frequency in paediatric-
onset CD is unknown.
AIMS & METHODS: The aims of our study were in a population-based paedia-
tric-onset CD cohort: i) to determine the cumulative incidence of MCM, includ-
ing aphtous stomatis (AS), erythema nodosum (EN) and pyoderma gangrenosum
(PG); and ii) to identify the socio demographic and clinical factors at CD diag-
nosis associated with a higher risk of developing MCM during the CD course.
Patients and Methods: Clinical data at diagnosis and at maximal follow-up were
recorded in a population-based paediatric-onset CD cohort (n 537, 517 years
at CD diagnosis) diagnosed from 1988 to 2004. Data on MCM were reviewed by
a dermatologist. Risks of developing MCM were estimated by survival analysis
and Cox models.
RESULTS: Median age at CD diagnosis was 14.6 years (Q1 12.2; Q3 16.1)
and 53.6% of patients were males. At CD diagnosis, 87 patients (16.2%) had
MCM including 26 of them (30%) with at least 2 MCM. After a median follow-
up of 11 years (Q1 7; Q3 15), 148 patients (28%) developed a total of 175
MCM, including 110 (63%) AS, 59 (34%) EN, and 6 (3%) PG. Cumulative
incidence of developing MCM was 21% [17.7 -24.6], 25% [21.6-29.0], 27%
[23.5-31.2] and 28% [24.3-32.3] at 1, 5, 10 and 15 years, respectively. In multi-
variate analysis, female gender (HR 2.6 [1.4-4.6]; p 0.002), patients 515 years
at diagnosis (HR 2.2 [1.3-3.8]; p 0.003) and L4 location at diagnosis
(HR 2.2 [1.3-3.6]; p 0.002) were significantly associated with a higher risk
of developing MCM during the CD course.
CONCLUSION: In this population-based paediatric-onset CD cohort, MCM
are frequent both at diagnosis and during CD course, and are associated to
female gender, young age and L4 location at CD diagnosis. These results rein-
force the need of a close collaboration between dermatologists, paediatric gastro-
enterologists and gastroenterologists in paediatric-onset CD in order to optimize
the therapeutic management of these patients.
Disclosure of Interest: C. Templier: None declared, H. Sarter: None declared, D.
Turck: None declared, M. Fumery: None declared, G. Savoye: None declared, B.
Catteau: None declared, C. Spyckerelle: None declared, E. Laberenne: None
declared, O. Mouterde: None declared, D. Djeddi: None declared, S. Buche:
None declared, L. Peyrin-Biroulet: None declared, E. Delaporte: None declared,
C. Gower-Rousseau Lecture fee(s) from: Ferring, MSD
P0351 LONG-TERM EFFICACY OF ADALIMUMAB IN PAEDIATRIC
PATIENTS WITH CROHNS DISEASE
W.A. Faubion1, M. Dubinsky2, F. Ruemmele3,*, J. Escher4, J. Rosh5, A. Lazar6,
S. Eichner7, Y. Li7, N. Reilly7, R.B. Thakkar7
1
Mayo Clinic, Rochester, 2Cedars-Sinai Medical Center, Los Angeles, United
States, 3Universite Sorbonne Paris-Cite, Hospital Necker-Enfants Malades, Paris,
France, 4Erasmus MC-Sophia Childrens Hospital, Rotterdam, Netherlands,
5
Goryeb Childrens Hospital/Atlantic Health, Morristown, United States, 6AbbVie
Deutschland GmbH & Co. KG, Ludwigshafen, Germany, 7AbbVie Inc, North
Chicago, United States
INTRODUCTION: The efficacy of adalimumab (ADA) in children with mod-
erately to severely active Crohns disease enrolled in the IMAgINE 1 trial has
been reported up to week (wk) 521. Long-term efficacy of ADA in patients (pts)
enrolled in the on-going open-label (OL) extension, IMAgINE 2, is presented.
AIMS & METHODS: Pts who completed IMAgINE 1 through wk 52 were
allowed to enroll in IMAgINE 2. Pts entering from blinded therapy received
OL ADA according to body weight (40 kg: 40 mg ADA every other wk
[EOW]; 540 kg, 20 mg ADA EOW). At or after wk 8, pts experiencing flares
(increase in PCDAI 15 points compared to PCDAI at previous visit) could
move to wkly (EW) dosing. Pts entering IMAgINE 2 from OL ADA (40 mg
ADA or 20 mg ADA EW) continued to receive the same dose. Remission
(PCDAI10) and response (PCDAI decrease 15 points from IMAgINE 1 base-
line) over time were assessed in pts who entered IMAgINE 2. Missing data were
handled using non-responder imputation (NRI) and last observation carried
forward (LOCF). Endpoints are also reported as observed. A data cut-off of
Jun 30, 2013 was used for this analysis.
RESULTS: Of the 188 randomized pts in IMAgINE 1, a total of 100 pts enrolled
in IMAgINE 2. As of Jun 30, 2013, a total of 54 pts are ongoing in the study.
Approximately 2/3 of pts entered IMAgINE 2 in remission and almost all entered
A228 United European Gastroenterology Journal 2(5S)
rates remained stable over time during IMAgINE 2 (Table). Mean PCDAI scores 75% for DI, which means high response of treatment efficacy for IFX dose-up.
decreased from 40.1 at IMAgINE 1 baseline to 8.6 at wk 192 of IMAgINE 2 Further study about DI will be needed for the risk factors, for optimal timing of
(Table). Adverse event rates from IMAgINE 1 baseline up to wk 260 have been application in clinical course, and for any possible adverse events in long-term
previously reported and no new safety signals were observed with prolonged follow-up.
ADA use.2 Disclosure of Interest: None declared
Table. Rates of remission and response and observed mean PCDAI scores during
IMAgINE 2
P0353 FOCUSED EDUCATION AND VACCINE ACCESS IN CLINIC
IMPROVE INFLUENZA VACCINATION RATES IN CHILDREN
Week 0 24 48 72 96 120 144 168 192
WITH INFLAMMATORY BOWEL DISEASE
Remission (%) K. Huth1,*, E. Benchimol2, D. Mack2
1
NRI 67.0 59.0 55.0 50.0 54.0 51.0 51.0 42.0 26.0 Pediatrics, University of Ottawa, 2Gastroenterology, Hepatology & Nutrition,
LOCF 67.0 62.2 61.2 57.1 61.2 62.2 63.3 62.2 61.2 Childrens Hospital of Eastern Ontario, Ottawa, Canada
Contact E-mail Address: khuth@cheo.on.ca
Observed 67.0 62.8 66.3 64.1 70.1 73.9 79.7 79.2 81.3
Response (%) INTRODUCTION: Patients with inflammatory bowel disease (IBD) are at
NRI 95.0 88.0 75.0 74.0 72.0 66.0 64.0 48.0 29.0 increased risk of experiencing complications of influenza infection, thus interna-
LOCF 95.0 91.8 85.7 87.8 85.7 85.7 87.8 82.7 81.6 tional guidelines recommend annual influenza vaccination for this population.
The vaccine is available at no cost in primary care physician offices, walk-in
Observed 95.0 93.6 90.4 94.9 93.5 95.7 100 90.6 90.6 clinics and pharmacies in Ontario, Canada, yet vaccine uptake remains low.
Mean PCDAI 10.2 10.3 9.2 8.9 9.4 7.9 6.1 7.5 8.6 AIMS & METHODS: We sought to understand barriers to obtaining influenza
vaccination in a pediatric IBD cohort, and to determine the impact of educa-
tional intervention and vaccine provision in IBD clinic on vaccine uptake. The
The number of pts declined over time due to discontinuations and not all pts had study was completed over two successive influenza seasons. During the 2012-
reached later time points. Results after wk 192 are not shown as few pts had 2013 season (Year 1), we surveyed parents and IBD patients aged 14 years
reached longer study durations. regarding influenza vaccination attitudes and practices. The following year
CONCLUSION: Results of the on-going OL study support clinically meaningful (Year 2), an educational module was developed to address concerns about vac-
efficacy with long-term ADA therapy beyond four years of exposure in children cination identified in Year 1. Parents and patients presenting to IBD clinic in the
with moderately to severely active CD. ten weeks prior to the 2013-2014 influenza season were provided with the educa-
REFERENCES tional module (Phase 1). When the trivalent inactivated influenza vaccine (TIIV)
1. Hyams et al. Gastroenterol 2012; 143: 365-374. became available, patients were offered both the educational module and the
2. Rosh et al. J Crohns Colitis 2014; 8: S243. opportunity for vaccination during their IBD clinic visits (Phase 2). Chi-squared
Disclosure of Interest: W. Faubion Consultancy for: Genentech, Connecticut analysis was used to identify significant differences in vaccination rates in each
Childrens Medical Center - Safety officer on subcontracted award through intervention group. Demographic factors were associated with survey responses
NIH for clinical trial, Other: Board membership (no personal compensation): and vaccination status.
Shire Development, Inc - Pediatric UC Advisory Board, Janssen Services LLC - RESULTS: During Year 1, 180 of 183 parents (98%) completed the survey along
DEVELOP Registry Scientific Advisory Committee, UCB Biosciences Advisory with all 108 adolescents. Median patient age at time of study was 11 years, 63%
board, M. Dubinsky Financial support for research from: Janssen, Consultancy were males, and 67% had Crohns disease. Most patients (74%) were on immu-
for: AbbVie, Janssen, Takeda, Pfizer, Prometheus labs, Santarus, UCB, F. nomodulator or biologic medications. In Year 1, 47% of patients obtained the
Ruemmele Lecture fee(s) from: Shering-Plough, Nestle, MeadJohnson, Ferring, TIIV, and 34% of patients reported obtaining the vaccine annually. Reasons for
MSD, Johnson & Johnson, Centocor, Other: Board membership: non-vaccination included a perceived lack of benefit (29%) and concerns about
SAC:DEVELOP (Johnson & Johnson), invited to MSD France, Nestle adverse events (20%). Most families (91%) reported they would obtain influenza
Nutrition Institute, invited to Nestle Health Science, invited to Danone, invited vaccination if their physician provided evidence of its benefit. Year 2 patients
to MeadJohnson, Biocodex, J. Escher Financial support for research from: (n 228) did not differ significantly in age, IBD subtype, disease severity or
MSD, Lecture fee(s) from: MSD, Consultancy for: Janssen Biologics, Other: medications from Year 1 patients. 95% of patients and parents who reviewed
Board membership: scientific advisory committee of DEVELOP study (Janssen the educational module reported that it was useful. 71% reported that the
Biologics), J. Rosh Financial support for research from: AstraZeneca, AbbVie, module informed their decision to obtain the TIIV, including 19% who had
Janssen, UCB, Lecture fee(s) from: Abbott Nutrition, Prometheus, Consultancy not planned to obtain the TIIV prior to reviewing the module. In Year 2, the
for: AbbVie, Janssen, Soligenex, Other: Board membership: GI Health vaccination rate in Phase 1 patients who received the educational module alone
Foundation, A. Lazar Shareholder of: AbbVie, Other: Employee: AbbVie, S. was 75%, compared to 89% of Phase 2 patients who received both the educa-
Eichner Shareholder of: AbbVie, Other: Employee: AbbVie, Y. Li Shareholder tional module and the option of obtaining the TIIV in IBD clinic (p 0.0043).
of: AbbVie, Other: Employee: AbbVie, N. Reilly Shareholder of: AbbVie, Other: Amongst the patients who took part in both Year 1 and Year 2 (n 129), serial
Employee: AbbVie, R. Thakkar Shareholder of: AbbVie, Other: Employee: determinations of influenza vaccination rates demonstrated an increase from
AbbVie 45% to 82% (P50.0001).
CONCLUSION: Despite widespread access to the TIIV at no cost, traditional
methods of promoting vaccination have yielded low uptake in IBD patients.
P0352 LONG-TERM SUSTAINED RESPONSE AND DURABILITY OF Providing a focused educational module on efficacy and safety addressed barriers
INFLIXIMAB FOR THE PEDIATRIC INFLAMMATORY BOWEL faced by vaccine-hesitant families and improved influenza vaccination rates.
DISEASE IN KOREA Additional vaccine uptake can be achieved by combining educational interven-
H.-J. JANG1,*, J.S. MOON1, J. YOO1, P. CHUN1, J.S. KO1, H.R. YANG2, tion with provision of influenza vaccination during IBD clinic visits.
J.Y. JANG3, J.K. SEO1 Disclosure of Interest: None declared
1
Department of Pediatrics, Seoul National University College of Medicine,
2
Department of Pediatrics, Seoul National University Bundang Hospital,
3
Department of Pediatrics, SMG-SNU Boramae Medical Center, SEOUL, Korea, P0354 ACCUMULATION OF INTRA-ABDOMINAL ADIPOSE TISSUE IN
Republic Of PEDIATRIC CROHNS DISEASE
Contact E-mail Address: bearinspring@hotmail.com, mjschj@snu.ac.kr K. Frivolt1,2,*, H. Hetterich3, T. Schwerd1, M.S. Hajji1, P. Bufler1,
E. Coppenrath3, S. Koletzko1
INTRODUCTION: Inflammatory bowel disease (IBD) is increasing in Korea, 1
Dr. v. Hauner Childrens Hospital, University Munich Medical Center, Munich,
especially in the pediatric population. Along with the classical treatment of 5- Germany, 22nd Department of Pediatrics, Comenius University Medical School,
ASA, steroid, and immunomodulators, biologic agents such as infliximab (IFX), Bratislava, Slovakia, 3Institute of Clinical Radiology, University Munich Medical
adalimumab are used increasingly. However, the safety and efficacy of IFX has Center, Munich, Germany
not been evaluated much for long-term follow-up. Contact E-mail Address: klarato@gmail.com
AIMS & METHODS: This is a single-center retrospective cohort study of 100
pediatric IBD (Crohn disease 90, Ulcerative colitis 10) who used infliximab from INTRODUCTION: Increased visceral adipose tissue (VAT) inflammation is a
2004 to 2014. The total duration of IFX administration, the dose intensification characteristic hallmark of surgical resections from Crohns disease (CD) patients.
(DI), the sustainability and efficacy of DI, and immunomodulator use with or Recent evidence points towards an active immunological role of VAT in CD
without IFX were analyzed. We also analyzed 3 groups to assess the efficacy and pathogenesis in addition of VAT being a defense mechanism for bacterial trans-
durability of IFX into sustained remission, recaptured response, and treatment location during intestinal inflammation. Magnetic resonance imaging (MRI)
failure group. Recaptured response meant the patients who recaptured remission studies showed accumulation of intra-abdominal VAT in adults, especially in
by dose intensification. patients with fistulas and strictures.
RESULTS: The total duration of follow-up for patients was 61.746.6 months. AIMS & METHODS: We aimed to quantify the abdominal adipose tissue com-
The mean duration of IFX administration was 31.028.0 months. Average age partments using MRI (Achieva, Philips Healthcare, Hamburg, Germany) in 29
of IFX initiation was 14.13.3 years. The interval between IFX initiation and pediatric CD patients compared with 14 control children (CC) undergoing MRI
dose intensification was 23.423.3 months. Dose intensification was in 53 examination of abdomen for other reason. Total abdominal (TA) adipose tissue,
patients out of 100 for the study period. Sustained remission was in 44 patients consisting of subcutaneous (SC) and intra-abdominal (IA) adipose tissues were
out of total and recaptured response was in 42, respectively. Treatment failure retrospectively measured by a radiologist blinded to the clinical data in transverse
was 16 out of 100, who discontinued IFX eventually. We checked for sustained slices centered on the umbilicus and expressed as mean  standard deviation in
remission rate annually and the rate was declining over time with 46% at 12-24 cm2. IA/TA and IA/height ratios were assessed and analyzed for association
months, 41% at 24-36 months, and 40% at 36-48 months, respectively. markers. We recorded the mathematically weighted Pediatric Crohns Disease
CONCLUSION: This study shows that almost half of the patients with IFX Activity Index (wPCDAI), disease phenotype, laboratory and anthropometric
maintained sustained remission until 2-year follow-up. And recapture rate was data at the time of MRI. Mann-Whitney test was applied to analyze differences
United European Gastroenterology Journal 2(5S)
between patients and CC. The correlation significance was determined by means
of Spearman correlation analysis. P50.05 was considered statistically significant.
RESULTS: CD patients included 20 males and 9 females (mean age 14.8  3.6
years, range 7.7-18.3) with a mean BMI of 18.3  2.7, range 14.0-23.2. Median
disease duration from diagnosis to MRI was 21 months (range 0-136). Non-
complicated disease behavior (B1) was present in 25/29, 4/29 had stricturing
(B2) and 6/29 perianal disease. CC included 4 males and 10 females (mean age
12.8  4.5 years, range 3.0-18.0), BMI (mean 17.6  3.2, range 13.4-23.6). CD
patients had higher IA adipose tissue (41.720.3 vs. 28.711.6, p50.05) but
similar SC and TA adipose tissues compared to CC (104.4  70.9 vs. 96.54 
50.8 and 146.1  84.7 vs. 125.3  61.5, NS). The IA/TA and IA/height ratios
were significantly higher in CD patients compared to CC, respectively (0.310.10
vs. 0.240.04 and 25.912.7 vs. 18.47.8, p50.05). Patients with disease dura-
tion under 2 years (n 14) had lower IA/TA ratio (0.280.08 vs. 0.350.10,
p50.05) compared to longer disease. The IA/TA ratio correlated with disease
duration (p50.05, r 0.425). No association was found between IA/TA and IA/
height ratios and disease phenotype or therapy.
CONCLUSION: Intra-abdominal adipose tissue is increased and accumulates
with disease duration in pediatric-onset CD.
Disclosure of Interest: None declared
P0355 PHARMACOKINETICS AND SAFETY OF MULTIMATRIX
MESALAZINE IN CHILDREN AND ADOLESCENTS WITH
ULCERATIVE COLITIS
C. Cuffari1, D. Pierce2, B. Korczowski3, K. Fyderek4,*, H.Van Heusen5,
S. Hossack6, P. Martin5
1
The Johns Hopkins University School of Medicine, Division of Pediatric
Gastroenterology and Nutrition, Baltimore, MD, United States, 2Shire,
Basingstoke, United Kingdom, 3Medical College, University of Rzeszow, Rzeszow,
4
University Childrens Hospital of Cracow, Cracow, Poland, 5Shire, Wayne, PA,
United States, 6Covance Clinical Research Unit Limited, Leeds, United Kingdom
Contact E-mail Address: pmartin@shire.com
INTRODUCTION: Oral formulations of mesalazine (5-aminosalicylic acid; 5-
ASA) are recommended first-line therapy for adults with active mild-to-moderate
ulcerative colitis (UC). However, little data are available on the use of mesalazine
in paediatric UC. This phase 1, multicenter, randomized, open-label study
(NCT01130844) evaluated the pharmacokinetic and safety characteristics of 5-
ASA and its associated metabolite, acetyl-5-ASA (Ac-5-ASA), after once-daily
administration of multimatrix mesalazine to children and adolescents with UC.
AIMS & METHODS: Patients aged 5-17 years with a UC diagnosis of 3
months were eligible to enrol. Study participants (stratified by body weight)
were administered 30, 60, or 100 mg/kg/day multimatrix mesalazine once-daily
for 7 days. In order to attain these doses in children, smaller-sized 300 mg and
600 mg multimatrix mesalazine tablets were developed to supplement the existing
approved 1200 mg tablet. Mesalazine was administered to patients at home on
Days 1-4 and on-site on Days 5-7, during which pharmacokinetic blood and
urine samples were collected and safety evaluations performed. Plasma and
urine concentrations of 5-ASA and Ac-5-ASA were determined using a validated
LC/MS/MS assay. Derived pharmacokinetic parameters for assessment included
maximum concentration (Cmax, ss), time of Cmax, ss (tmax), area under the curve
for one dose interval (AUCss), renal clearance (CL5SUB4R5/SUB4), and
percent of dose absorbed.
RESULTS: A total of 52 patients (21 at 30 mg/kg; 22 at 60 mg/kg; and 9 at 100
mg/kg) were treated. Mean (standard deviation) age was 13.3 (3.06) years, and
median (range) time since UC diagnosis was of 1.83 (0.2- 9.6) years. By Day 5,
steady state plasma concentrations for 5-ASA and Ac-5-ASA were attained for
all dose groups. On Day 7, dose-proportional increases in mean AUCss and Cmax,
ss for both 5-ASA and Ac-5-ASA were observed between 30 and 60 mg/kg/day
cohorts. For 30, 60, and 100 mg/kg/day doses, the mean percentages of 5-ASA
absorbed from multimatrix mesalazine were 29.4%, 27.0%, and 22.1%, respec-
tively. The mean CLR ranges for 5-ASA and Ac-5-ASA, respectively, were 5.0-
6.5 L/h and 10.0-16.2 L/h. Treatment-emergent adverse events were reported by
19.2% of all patients; events were similar among different dose and age groups
and no new safety signals were identified.
CONCLUSION: Across all dose groups, children/adolescents with UC receiving
multimatrix mesalazine demonstrated pharmacokinetic profiles for 5-ASA and
Ac-5-ASA similar to those observed in historical adult data. Multimatrix mesa-
lazine was well tolerated across all dose and age groups, and no novel safety
signals were reported.
Disclosure of Interest: C. Cuffari Consultancy for: Shire, Prometheus and Abbott
Nutritionals, D. Pierce Shareholder of: Shire, Other: Former employee of Shire,
B. Korczowski: None declared, K. Fyderek Financial support for research from:
Received a grant from Shire for the study research conducted, H. Van Heusen
Shareholder of: Shire, Other: Employee of Shire, S. Hossack Other: Employee of
Covance, which received funding from Shire for assistance with the pharmaco-
kinetic analysis, P. Martin Shareholder of: Shire, Other: Employee of Shire
P0356 DEVELOPMENT OF THE DAILY ULCERATIVE COLITIS SCALE
FOR CHILDREN AND CAREGIVERS: FINDINGS FROM COGNITIVE
DEBRIEFING INTERVIEWS
E. Flood1, D.G. Silberg2, B. Romero1, K. Beusterien3, M.H. Erder2,*
1
ICON Commercialisation and Outcomes, Bethesda, MD, 2Shire, Wayne, PA,
3
ORS Health, Washington, DC, United States
Contact E-mail Address: herder@shire.com
INTRODUCTION: To test and refine the Daily Ulcerative Colitis Scale
(DUCS), an electronic daily sign and symptom diary with a patient-reported
A229
outcomes (PRO) version for children 8-17 years and an observer-reported out-
comes (ObsRO) version for caregivers of children aged 5-10 years.
AIMS & METHODS: This was a twovisit cognitive debriefing interview study
involving children with mild to moderate ulcerative colitis (UC) aged 8-17 years
and caregivers of children aged 5-10 years. Mild to Moderate UC was
defined based on the Pediatric Ulcerative Colitis Activity Index (PUCAI) score
at the time of the interview. The interviews involved an initial set of open-ended
questions on the signs, symptoms and impacts of UC to confirm findings from a
previous concept elicitation study, followed by cognitive debriefing of the DUCS
along with items to assess global health, and items to examine device usability
and characteristics of the sample. The visit 1 interview was held in person and
lasted approximately 1 hour. Visit 2 took place by telephone 3 days after visit 1
and lasted about 25 minutes and was used to explore feasibility. Sample char-
acteristics were analysed using descriptive statistics (mean, SD, median, range for
continuous variables and N, % for categorical variables). Interview transcripts
were analysed using qualitative analysis software, MAXqda, in which codes were
applied to allow focussed review of responses across the sample. Findings were
used to refine the DUCS to ensure clarity, relevance and comprehensiveness.
RESULTS: The PRO sample consisted of 38 participants (22 females and 16
males), with 2 participants completing interviews for 2 different diary versions for
a total of 40 completed interviews. Age at study enrollment ranged from 8 to 17
years (mean of 12.8; SD 2.4; median of 13). The average PUCAI score, adminis-
tered at visit 1, was 12.3 (SD 14.2), range 0 to 45. The caregivers of 7 children
participated in the cognitive debriefing interviews of the ObsRO version. One
caregiver tested two different versions of the eDiary for a total of 8 completed
ObsRO interviews. The average age of the 7 caregiver participants was 41.5 years
(SD 6.4; median of 42). The caregivers children were an average age of 8.5 years
(SD 1.7; median of 9). Findings from the visit 1 concept elicitation questions were
consistent with those of the initial concept elicitation study. Four rounds of
revisions were made to the PRO and ObsRO DUCS based on patient/caregiver
interview feedback, as well as feedback from the FDA. The FDA suggested
changes such as changing response scales, as well as the addition of questions
to capture certain symptoms overnight. Patient input influenced changes such as
clarification of text and graphics, and the selection of the optimal pain scale. The
eDiarys usability was also assessed. Both child and adult participants found the
device easy to use and navigate.
CONCLUSION: The DUCS eDiaries are content valid instruments capturing
signs and symptoms of pediatric UC and are appropriate for measuring treat-
ment benefit in pediatric UC clinical trials.
Disclosure of Interest: E. Flood Other: Employee of ICON, which was contracted
by Shire to perform the research for the creation of the DUCS, D. Silberg
Shareholder of: Shire, Other: Employee of Shire, B. Romero Other: Employee
of ICON, which was contracted by Shire to perform the research for the creation
of the DUCS, K. Beusterien Other: Performed this work when she worked at
Oxford Outcomes, which provides consulting services to Shire, M. H. Erder
Shareholder of: Shire, Other: Employee of Shire
P0357 AORTIC INTIMA-MEDIA THICKNESS AS AN EARLY MARKER
OF ATHEROSCLEROSIS IN CHILDREN WITH INFLAMMATORY
BOWEL DISEASE
M. Aloi1,*, L. Tromba2, V. Rizzo1, G. DArcangelo1, A. Dilillo1, S. Blasi2,
F. Civitelli1, F. Viola1, A. Redled2, S. Cucchiara1
1
Pediatric Gastroenterology And Liver Unit, 2Department of Surgical Sciences,
SAPIENZA UNIVERSITY OF ROME, Rome, Italy
Contact E-mail Address: marina.aloi@uniroma1.it
INTRODUCTION: Aims of this study were to determine the presence of
endothelial dysfunction by measuring aortic intima-media thickness (aIMT)
and carotid intima-media thickness (cIMT) and to evaluate the role of traditional
risk factors for premature atherosclerosis in children with inflammatory bowel
disease (IBD).
AIMS & METHODS: Thirty-four children with IBD [25 Crohns disease (CD)
and 9 ulcerative colitis (UC); mean age 11.1 years] and 27 healthy subjects
matched for sex and age were enrolled. In all patients, demographic character-
istics and risk factors for atherosclerosis (age, sex, body mass index, blood pres-
sure, dyslipidemia, active and passive smoking, family history for cardiovascular
diseases), CD and UC clinical activity scores and inflammatory markers, were
evaluated. Aortic IMT and cIMT were measured by high resolution B-mode
ultrasound.
RESULTS: Aortic IMT was significantly higher in patients than controls
(p50.001). No significant differences were found for cIMT, although the carotid
thickness was higher in IBD patients than healthy subjects. At a univariate
analysis, inflammatory markers levels and tobacco smoking exposure were sig-
nificantly related to higher aIMT values, while at a multivariate analysis the
inflammatory status was the only independent variable correlated with high
aIMT.
CONCLUSION: Aortic IMT is an earlier marker of preclinical atherosclerosis in
young children with active IBD, than cIMT. The inflammatory status and the
smoking exposure are significantly correlated with the premature endothelial
dysfunction. These data emphasize the importance of controlling the chronic
intestinal inflammation and endorsing smoke-free environments for children
and adolescents with IBD
Disclosure of Interest: None declared
A230 United European Gastroenterology Journal 2(5S)

P0358 GROWTH IMPROVEMENT IN ADALIMUMAB-TREATED P0359 TREATMENT OF CORTICOSTEROID NAIVE PAEDIATRIC AND
PAEDIATRIC PATIENTS WITH CROHNS DISEASE: DATA FROM ADOLESCENT PATIENTS WITH ULCERATIVE COLITIS BY
IMAGINE 1 THERAPEUTIC DEPLETION OF MYELOID LINEAGE
T. Walters1,*, W.A. Faubion2, A. Griffiths1, R. Baldassano3, J. Escher4, LEUCOCYTES AS MONOTHERAPY OR IN COMBINATION WITH
F. Ruemmele5, J.S. Hyams6, A. Lazar7, S. Eichner8, Y. Li8, B. Pappalardo8, LOW DOSE PREDNISOLONE AFTER FAILURE OF FIRST-LINE
R.B. Thakkar8 MEDICATIONS
1
The Hospital for Sick Children, Toronto, Canada, 2Mayo Clinic, Rochester, T. Tanaka1,*, S. Sugiyama1, H. Goishi 1, T. Kajihara1, M. Akagi 1, T. Miura1
3
Childrens Hospital of Philadelphia, Philadelphia, United States, 4Erasmus MC- 1
Department of Gastroenterology, Akitsu Prefectural Hospital, Hiroshima, Japan
Sophia Childrens Hospital, Rotterdam, Netherlands, 5Universite Sorbonne Paris- Contact E-mail Address: tomotaka@c.do-up.com
Cite, Hospital Necker-Enfants Malades, Paris, France, 6Connecticut Childrens
Medical Center, Hartford, United States, 7AbbVie Deutschland GmbH & Co. KG, INTRODUCTION: Given that patients with active ulcerative colitis (UC) have
Ludwigshafen, Germany, 8AbbVie Inc, North Chicago, United States elevated and activated myeloid lineage leucocytes including the CD14CD16
monocyte phenotype known to be a major source of tumour necrosis factor-,
INTRODUCTION: Children with Crohns disease (CD) often have impaired selective depletion of these leucocytes by granulocyte and monocyte adsorption
growth. The IMAgINE 1 trial demonstrated the safety and effectiveness of ada- (GMA) should be an effective intervention in UC patients. This thinking is most
limumab (ADA) on inducing and maintaining remission in children with mod- relevant in paediatric and adolescent patients in whom long-term drug therapy
erately to severely active CD1. The impact of ADA therapy on growth in patients may adversely affect their growth and development.
with delayed growth at trial entry is analyzed. AIMS & METHODS: This study was to evaluate the efficacy of GMA as a
AIMS & METHODS: In IMAGINE 1, patients aged 6-17 years with baseline remission induction therapy in children and adolescents with UC in whom
(BL) PCDAI 430 received open-label induction of ADA at weeks 0/2 according first-line medications had failed. In a single centre setting, a total of 27 consecu-
to body weight (40kg, 160/80mg; 540kg, 80/40mg). At week 4, patients were tive children and adolescents, age 11-19 years, bodyweight 31.5-56.5kg were given
randomized to double-blind higher-dose (HD) ADA (40kg, 40mg every other mesalazine or sulphasalazine as a first-line medication. Twenty patients relapsed
week [EOW]; 540kg, 20mg EOW) or lower-dose (LD) ADA (40kg, 20mg while under first-line medication or did not respond to first-line medication and
EOW; 540kg, 10mg EOW) to week 52. Patients were allowed to escalate to received GMA with the Adacolumn, 2 sessions in the first week, and then weekly,
blinded weekly therapy for flare or non-response, followed by open-label HD up to 11 sessions. Patients who achieved a decrease of 5 in the clinical activity
ADA weekly for continued flare or non-response. Change from BL in height index (CAI) were to continue with GMA, while non-responders were to receive
velocity z-score was measured at weeks 26 and 52 in patients with and without 0.5 to 1.0 mg/kg bodyweight/day prednisolone (PSL) plus additional GMA ses-
growth delay at BL (defined as height velocity z-score  -1.0) in all ADA patients sions. However, PSL was to be tapered immediately after CAI started to fall. At
regardless of treatment group. Subgroup analyses by BL corticosteroid use, dis- entry and week 12, patients UC severity was clinically and endoscopically eval-
ease severity (based on median BL PCDAI of study population (PCDAI 5 40, uated, allowing each patient to serve as her/his own control.
moderate CD; PCDAI  40, severe CD), and prior infliximab (IFX) use were RESULTS: At entry, all 27 patients were corticosteroid na ve and none had
performed. extensive loss of the mucosal tissue at the affected sites. Seven patients achieved
RESULTS: Overall, statistically significant improvement in growth was observed sustained remission with the first-line medications and did not receive GMA.
at weeks 26 and 52 with ADA maintenance therapy in patients with growth delay Eight patients did not respond well to the first 5 GMA sessions and received
(median height velocity z-score at BL -2.9 and median change from BL at weeks PSL plus GMA, and in 2 of these with severe UC, the PSL dose was temporarily
26 and 52; 2.4 and 3.3, respectively, each p50.001), but not in patients with increased to 2mg/kg bodyweight while 12 patients responded to the first 5 GMA
normal growth (BL median 0.2; median change from BL 0 at weeks 26 and sessions and received additional sessions. At entry, the average CAI was
52). No statistically significant differences between LD and HD ADA were 13.02.4, range 8-17, and the average endoscopic index was 8.81.6, range 7-
observed. Growth improvement trended to be larger in patients with BL corti- 11. The corresponding values at week 12 were 2.10.2, range 1-4 (P50.001) and
costeroid use, with severe CD, and in IFX na ve patients (Table). 2.40.2, range 1-4 (P50.001). PSL was tapered to 0mg within 3 months in the 8
Table. Median BL height velocity z-score values and change from BL at weeks 26 PSL treated patients. Therefore, at week 12, all 27 patients had achieved clinical
and 52 in patients with growth delay (height velocity z-score  -1.0 at BL) remission, majority with mucosal healing (complete remission). Except difficul-
ties in achieving blood access causing needle pain in a few cases, no serious GMA
BL Week 26 Week 52 related adverse event was observed, and compliance was good, no refusal to
receive GMA and no withdrawal from the GMA treatment.
LD -3.0 (N 47) 2.5* (N 47) 3.4* (N 30) CONCLUSION: In this study, GMA in paediatric and adolescent corticosteroid
na ve patients with active UC refractory to first-line medication was associated
HD -2.8 (N 42) 2.3* (N 42) 3.3* (N 29) with clinical remission and mucosal healing, while in non-responders to GMA
IFX na ve -3.1 (N 54) 2.7* (N 54) 3.8* (N 41) monotherapy, addition of PSL enhanced the efficacy of GMA and tapering of
IFX experienced -2.3 (N 35) 1.7* (N 35) 1.4* (N 18) the PSL dose immediately after the fall in CAI score was not associated with UC
Corticosteroid use at BL -2.8 (N 38) 2.5* (N 38) 4.3* (N 23) relapse. Therefore, with its favourable safety profile, the majority of young ster-
oid na ve patients with active UC refractory to first-line medication should
No corticosteroid use at BL -2.9 (N 51) 2.3* (N 51) 2.3* (N 36) respond well to GMA and be spared from pharmacological interventions.
Moderate CD -3.2 (N 26) 2.7* (N 26) 3.0* (N 22) Disclosure of Interest: None declared
Severe CD -2.7 (N 63) 2.3* (N 63) 3.8* (N 37)

P0360 PAEDIATRIC IBS IS ASSOCIATED WITH INCREASED SERUM

CONCLUSION: ADA treatment significantly improved growth in children with
moderately to severely active CD and growth delay. The pronounced effect of
ADA on growth in children with concomitant corticosteroid use or severe disease
by PCDAI requires confirmatory studies.
REFERENCES
1. Hyams et al. Gastroenterol 2012; 143: 365-374.
Disclosure of Interest: T. Walters Financial support for research from: AbbVie,
Janssen, Merck, Lecture fee(s) from: AbbVie, Janssen, Merck, W. Faubion
Consultancy for: Genentech, Connecticut Childrens Medical Center - Safety
officer on subcontracted award through NIH for clinical trial, Other: Board
membership (no personal compensation): Shire Development, Inc - Pediatric
UC Advisory Board, Janssen Services LLC - DEVELOP Registry Scientific
Advisory Committee, UCB Biosciences Advisory board, A. Griffiths Financial
support for research from: Johnson and Johnson, Abbvie, Lecture fee(s) from:
AbbVie, Consultancy for: Abbvie, Nutricia, Janssen Canada, MSD, Ferring,
Shire, Other: Educational program support: Abbvie; Janssen Canada, R.
Baldassano Consultancy for: AbbVie, Janssen Ortho Biotech, Takeda, J.
Escher Financial support for research from: MSD, Lecture fee(s) from: MSD,
Consultancy for: Janssen Biologics, Other: Board membership: scientific advi-
sory committee of DEVELOP study (Janssen Biologics), F. Ruemmele Lecture
fee(s) from: Shering-Plough, Nestle, MeadJohnson, Ferring, MSD, Johnson &
Johnson, Centocor, Other: Board membership: SAC:DEVELOP (Johnson &
Johnson), invited to MSD France, Nestle Nutrition Institute, invited to Nestle
Health Science, invited to Danone, invited to MeadJohnson, Biocodex, J. Hyams
Lecture fee(s) from: Janssen Orthobiotech, Consultancy for: Janssen
Orthobiotech, AbbVie, TNI Biotech, EnteraHealth, Pfizer, Soligenix, Takeda,
Other: Expert testimony and payment for development of educational presenta-
tions: Janssen Orthobiotech, A. Lazar Shareholder of: AbbVie, Other: Employee:
AbbVie, S. Eichner Shareholder of: AbbVie, Other: Employee: AbbVie, Y. Li
Shareholder of: AbbVie, Other: Employee: AbbVie, B. Pappalardo Shareholder
of: AbbVie, Other: Employee: AbbVie, R. Thakkar Shareholder of: AbbVie,
Other: Employee: AbbVie
LEVELS OF PROINFLAMMATORY CYTOKINES
L. Ohman1,2,*, S. Isaksson1,2, E. Melen3,4, I. Kull3,4, M. Wickman3,4,
A. Bergstrom3, M. Simren1, O. Olen4,5
1
Dept. Internal Medicine and Clinical Nutrition, 2Dept. Microbiology and
Immunology, Sahlgrenska Academy at University of Gothenburg, Gothenburg,
3
Institute of Environmental Medicine, Karolinska Institutet, 4Sachs Children and
Youth Hospital, Stockholm South General Hospital, 5Dept.of Medicine, Clinical
Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden
Contact E-mail Address: lena.ohman@microbio.gu.se
INTRODUCTION: The pathogenesis of irritable bowel syndrome (IBS) in chil-
dren is not completely understood, but in adults IBS has been associated with
low-grade inflammation. The aim of this study was therefore to evaluate the
serum levels of cytokines to determine whether paediatric IBS is associated
with increased immune activity.
AIMS & METHODS: In the population based birth cohort BAMSE (n 4089)
adolescents were invited to participate in the 16-year follow up, of which 2547
(62%) agreed to undergo blood testing and clinical examination. Serum samples
were obtained from 41 IBS patients (33 (80%) females) and 97 controls with no
gastrointestinal (GI) symptoms (63 (65%) females). IBS patients fullfilled the
Rome III criteria and were symptomatic at the time of blood sampling.
MesoScale Discovery (MSD) multiplex immunoassay analysis was used for the
measurement of the following serum cytokines; IL-2, IL-4, IL-5, IL-6, IL-8, IL-
10, IL-12p70, IL-13, IL-17A, IFN-, IL-1, and TNF. Data shown as median
(pg/ml), range 25-75 percentile.
RESULTS: IBS patients had increased serum levels of IL-6 as compared to
controls with no GI symptoms (0.39 pg/ml (0.3-0.7) vs. 0.30 pg/ml (0.2-0.4);
p 0.006). Also levels of TNF (1.65 pg/ml (1.2-2.0) vs. 1.3 pg/ml (1.0-1.8);
p 0.06) and IL-8 (4.51 pg/ml (3.5-5.6) vs. 3.77 pg/ml (2.9-5.3); p 0.1) tended
to be increased in serum of IBS patients relative to controls. The levels of IL-6,
TNF or IL-8 did not differ between patients with or without constipation or
atopic symptoms (asthma, eczema and/or rhinitis). The levels of IL-1 were
under the detection limit in more than 80% of the samples and were therefore
United European Gastroenterology Journal 2(5S)
not statistically analysed. Remaining serum cytokines, IL-2, IL-4, IL-5, IL-10,
IL-12p70, IL-13, IL-17A and INF- were similarly expressed in IBS patients and
controls.
CONCLUSION: Children with IBS have increased serum levels of proinflam-
matory cytokines, which mimics previously presented data from adults with IBS.
Thus, paediatric IBS, similar to IBS in adults, is associated with increased
immune activity.
Disclosure of Interest: None declared
P0361 3D HIGH-DEFINITION ANORECTAL MANOMETRY
CHILDREN WITH FUNCTIONAL ANORECTAL DISORDERS
M. Banasiuk1,*, A. Banaszkiewicz1, P. Albrecht1
1
Pediatric Gastroenterology and Nutrition, Medical University of Warsaw,
Warsaw, Poland
Contact E-mail Address: mbanasiu@tlen.pl
A231
We have found lower ferritin level (p 0.024), higher sTfR level (p 0.043), and
higher sTfR/log ferritin index (p 0.037) in adolescents subgroup with frequent
episodes of RAP (4 2 times per month). No differences have been found in CRP
levels according assigned RAP criteria and RAP frequency. We have also found
no distinctions in ferritin, sTfR, and CPR levels in accordance of presence/
absence of headache, back pain, dizziness, presyncope/syncope, and chronic
fatigue.
CONCLUSION: RAP in adolescents has comorbidity with broad spectrum of
IN other symptoms (recurrent headache, back pain, dizziness and chronic fatigue).
Because of most of these conditions have psychosomatic pathogenic components,
we suggest that RAP diagnostics and treatment in adolescents should require
estimation and correction their mental health status. We also suggest that ado-
lescents with frequent episodes of RAP should be tested for iron deficiency.
Disclosure of Interest: None declared

INTRODUCTION: 3D high-definition anorectal manometry (3D HDARM) is

the most precise tool to assess function and 3D topographic picture of pressures MONDAY, OCTOBER 20, 2014 9:0017:00
along the anal canal. Until now, it has been used only in adult population. The OTHER LOWER GI DISORDERS I POSTER EXHIBITION HALL
feasibility in paediatric population has not been evaluated so far. XL_____________________
AIMS & METHODS: The aim of the study was 3D manometric evaluation of
anorectal function in children with functional anorectal disorders. P0363 PSYCHOLOGICAL EFFECTS OF COLORECTAL CANCER
Children with functional anorectal disorders diagnosed according to III Rome SCREENING INVITATIONS: A RANDOMIZED TRIAL
Criteria were prospectively enrolled in the study. Manometry procedures were B. Kirken1,*, P. Berstad1,2, T.de Lange1, G. Hoff1,2, T. Bernklev2
performed with ManoScan A300 (Given Imaging Ltd) without premedication. 1
Cancer Registry of Norway, Oslo, 2Telemark Hospital, Skien, Norway
Pressures within the anal canal and 3D picture of sphincters were obtained. If Contact E-mail Address: benedicte.kirkoen@kreftregisteret.no
possible, defecation dynamics and thresholds of sensation were evaluated.
RESULTS: 40 children (24 male; age: 9 weeks-15 years, median: 80 months) were INTRODUCTION: A cancer screening programme with the ability to reduce
studied. All children suffered from functional constipation. 13 out of 40 children mortality might be seen as a health service for many with objective benefit for
presented with fecal incontinence and constipation. Mean resting and squeeze only a few. Screening might cause worries, and has a potential negative influence
sphincter pressures were 78.98 mmHg and 190.27 mmHg, respectively. The on the mental health of the population that could outweigh the benefits. The
length of the anal canal was 0.9-4.3 cm. Dyssynergic defecation type I was the present study therefore aimed to investigate the psychological reactions towards
most common type of abnormal defecation dynamics (9 out of 24 children). invitations to screening for colorectal cancer, as part of an evaluation of a pilot
Sensation of urge was absent in 6 out of 18 children with the maximum for a national screening programme in Norway.
volume of balloon equalled 140 cc. Recto-anal inhibitory reflex was present in AIMS & METHODS: In a prospective, randomized trial participants were
all children. There were no lesions of sphincters according to 3D topographic invited to either flexible sigmoidoscopy (FS) screening, Faecal
picture of the anal canal. Immunochemical test (FIT), or no screening (the control arm). With the invita-
CONCLUSION: 3D HDARM is a feasible method that can be used in paediatric tion, the participants received a Health-related Quality of Life (HRQoL) ques-
population. tionnaire (The ShortForm-12) and an anxiety and depression questionnaire
Disclosure of Interest: M. Banasiuk Financial support for research from: Given (Hospital Anxiety and Depression Scale), which they were asked to complete
Imaging GmbH, A. Banaszkiewicz: None declared, P. Albrecht: None declared and return. Number of invited individuals and questionnaire response rates in
the randomization arms were 3804 and 47% in the FS arm, 6780 and 51% in the
FIT arm, and 6433 and 33% in the control arm, respectively. Among the respon-
P0362 RECURRENT ABDOMINAL PAIN IN ADOLESCENTS: ders, mean ages in the trial arms were 63.5, 62.4 and 62.9 years, and 55%, 56%
COMORBIDITY WITH RECURRENT HEADACHE, BACK PAIN, and 57% were women, respectively.
DIZZINESS, PRESYNCOPE/SYNCOPE, CHRONIC FATIGUE AND RESULTS: A one-way Analysis of Variance revealed no significant difference
ASSOCIATION WITH FERRITIN, SOLUBLE TRANSFERRIN between the three arms in four out of the eight HRQoL dimensions (table 1).
RECEPTOR AND C-REACTIVE PROTEIN LEVELS However, contrast analysis revealed that the FIT arm showed significantly lower
M. Shubina1,*, S. Tereshchenko1, N. Gorbacheva1, I. Olkhovskiy1, M. Stolyar1, physical functioning compared to the control arm. The FS arm showed signifi-
V. Babushkin1 cantly better social functioning and mental health, compared to both the FIT
1
Scientific research institute of medical problems of the North, Krasnoyarsk, arm and the control arm, and better role of emotions compared to the control
Russian Federation arm. Further, there was a significant difference between the three arms in the
Contact E-mail Address: legise@mail.ru anxiety subscale of HADS (table 1). The FS arm had lower anxiety levels com-
pared to the control arm and to the FIT arm. The minimal important difference
INTRODUCTION: Many of common complains in routine adolescents medicine was operationalized as a difference of at least half a s.d. Thus none of the
practice such as recurrent abdominal pain (RAP) and other recurrent pain syn- statistical differences were considered clinically relevant, indicating little effect
dromes, dizziness, presyncope/syncope and chronic fatigue are significantly asso- of being invited for screening on HRQoL and anxiety.
ciated with anxiety disorders and depression. Data about association of these Mean
conditions are limited. Some cases of RAP may be associated with iron deficiency
and inflammatory diseases, but association iron deficiency and inflammatory p FS vs p FIT vs p FS vs
markers with RAP frequency is not studied well. FS FIT Control p* control control FIT
AIMS & METHODS: 459 adolescents aged 12-18 were screened for RAP (criteria
were as follow: (1) More than two episodes of RAP per month in the last 2 months Physical functioning 85.5 84.1 86.3 .02 .37 .01 .10
OR (2) Abdominal pain intensity according 7-items Likert-type pain scale  4).
Criteria for recurrent headache were as follow: (1) Headache episodes in the last Role physical 82.5 80.0 80.6 .11
year 4 10 OR (2) Headache episodes 4 1 per month in the last three months OR Bodily pain 82.4 81.1 81.8 .26
(3) Headache intensity according 7-items Likert-type pain scale  4. Criteria for General health 67.0 67.3 67.9 .63
recurrent back pain and dizziness were as follow: (1) More than two episodes per Vitality 60.3 58.7 59.3 .19
month in the last 2 months OR (2) Intensity according 7-items Likert-type scale 
4. Adolescents were asked about history of presence of symptoms presyncope/ Social functioning 89.5 87.3 87.0 5.01 5.01 .64 5.01
syncope. Chronic fatigue was estimated with original 10-items questionnaire Role emotional 87.6 85.6 84.2 .02 .01 .19 .06
with assessment of as difficulty or inability initiating activity; reduced capacity Mental health 81.5 79.7 80.1 .03 .03 .97 .01
maintaining activity; and difficulty with concentration, memory, and emotional Anxiety 3.4 3.8 3.9 5.01 5.01 .81 5.01
stability. Plasma concentrations of ferritin, soluble transferrin receptor (sTfR) and
C-reactive Protein (CRP) were estimated with ELISA kits.
RESULTS: We have found positive association between RAP and recurrent
headache (p 0.002), recurrent back pain (p 0.002), recurrent dizziness Table 1. *One-way ANOVA of differences between the three arms, p5.05.
(p 0.002), and chronic fatigue (p 0.002). Results are shown in Table 1. Higher scores indicate better HRQoL, and higher levels of anxiety.
Table to abstract P0362 CONCLUSION: Our findings indicate no negative psychological reactions to
receiving an invitation for colorectal cancer screening with either of the two
Comorbidity symptoms RAP absence RAP presence P (two-tailed exact screening modalities FS or FIT. Thus the burden of participating in a screening
positive adolescents (n 384) (n 75) Fisher test) programme seems limited at invitation.
Disclosure of Interest: None declared
Recurrent headache (n 193) 38.8% 58.7% 0.002
Recurrent back pain (n 80) 15.1% 29.3% 0.005
Recurrent dizness (n 42) 6.8% 21.3% 0.003
Presyncope/syncope (n 88) 17.1% 26.7% 0.079
Chronic fatigue (n 28) 3.9% 17.3% 50.001
A232 United European Gastroenterology Journal 2(5S)
CONCLUSION: SSA/Ds compared to APs are more common in women, they
P0364 THE COST-EFFECTIVENESS OF FULL SPECTRUM
have a peak incidence 10 years earlier and tend to occur in patients with lower
ENDOSCOPY (FUSE) COLONOSCOPY FOR COLORECTAL
BMI. Waist-hip-ratio, although not statistically significant, had a trend for lower
CANCER SCREENING
values in patients with SSA/D. The results from both analyses show that SSA/Ds
C. Hassan1,*, I. Gralnek2 are less common in patients with diabetes mellitus and hypertension in compar-
1
ONRM Hospital, Rome, Italy, 2Department of Gastroenterology, Rambam ison to APs.
Health Care Campus, Haifa, Israel Disclosure of Interest: None declared
Contact E-mail Address: cesareh@hotmail.com

INTRODUCTION: As compared with Standard Forward Viewing (SFV) colo- P0366 SESSILE SERRATED ADENOMAS, ARE THERE ANY RISK
noscopy, Full Spectrum Endoscopy (Fuse) colonoscopy increases the adenoma FACTORS?
detection rate and thereby impacts the recommended post-polypectomy surveil- G. Michalopoulos1, S. Vrakas1, S. Charalampopoulos1, V. Ntouli1,
lance intervals per current US and European guidelines [1]. S. Lamprinakos1, K. Makris1, C. Tzathas1,*
AIMS & METHODS: As compared to SFV colonoscopy, we aimed to assess the 1
Gastroenterology, Tzaneion, General Hospital of Piraeus, Piraeus, Greece
cost effectiveness of FUSE colonoscopy in a CRC screening and surveillance Contact E-mail Address: gmicha78@hotmail.com
program. We constructed a Markov model to simulate the occurrence of color-
ectal neoplasia in a cohort of 100,000 subjects ages 50 to 100 years of age. The INTRODUCTION: Evidence is conflicting regarding the risk factors for devel-
cost-effectiveness of FUSE was compared with that of SFV colonoscopy, with opment of Sessile Serrated Adenomas.
each test being assumed to be repeated every 10 years for those 50 to 80 years of AIMS & METHODS: This prospective study was performed in order to identify
age. Sensitivity for adenomatous and hyperplastic polyps 5 mm, 6-9 mm, and differences in the characteristics of patients with Sessile Serrated Adenomas with
high-risk polyps (10 mm; 510 mm with unfavourable histology or multiplicity) and without dysplasia (SSA/D) in comparison to patients with normal colonos-
were derived from the recent RCT tandem Fuse colonoscopy study [1]. Post- copies. Data from127 patients (100 with normal colonoscopies and 27 with SSA/
polypectomy surveillance was modeled according to polyp histology. Medicare Ds) regarding age, sex, smoking habits, BMI, waist-hip ratio and medical history
costs were adopted and used in the analysis. (arterial hypertension, diabetes mellitus, past history of polyps) was collected and
RESULTS: For the modeled cohort, the significantly higher sensitivity of FUSE analyzed by multivariate logistic regression analysis. Four age subgroups: 41-50,
colonoscopy in detecting additional colonic adenomas resulted in an increase in 51-60, 61-70 and 71-80 were analyzed with univariate logistic regression analysis.
CRC prevention from 58% to 74%, corresponding to a gain of 9 days per person Analyses was performed using Stata 9.0
(2,413 life-years for the entire cohort). This 16% increase led to an absolute RESULTS:
reduction in the cost of CRC care from $90 million to $57 million. This $33
million cost savings was only minimally impacted by the higher cost of more SSA/D vs Normal (multivariate) OR P-value 95% C. I.
frequent post-polypectomy colonoscopy surveillance rates, so that FUSE was
associated with a savings of $146 per person. Thus, SFV colonoscopy appeared Age 1.04 0.008 1.01-1.08
to be dominated by the FUSE colonoscopy strategy, with FUSE colonoscopy
being both more effective and less costly. By assuming 68 million of American Current smokers 4.35 0.003 1.63-11.59
subjects between 50 and 80 years of age and an annual incidence of 107,483 CRC Personal medical history of polyps 3.34 0.004 1.48-7.58
cases without screening for a discounted annual CRC care cost of $3.7 billion, the Age OR P-Value 95% CI
additional efficacy of FUSE over SFV would result into the annual prevention of SSA/Ds vs Normal (univariate)
10,318 CRC and the annual saving of $0.3 billion for CRC related costs. 41-50 1.33 0.84 0.07-23.5
CONCLUSION: As compared to SFV colonoscopy, FUSE colonoscopy appears
to be more cost-effective for CRC screening and surveillance. In particular, the 51-60 9.88 0.032 1.21-80.07
higher associated costs of more frequent post-polypectomy colonoscopy surveil- 61-70 8.72 0.047 1.02-74.11
lance were compensated by the significant overall reduction in CRC treatment 71-80 26.18 0.003 3.03-225.9
costs.
REFERENCES
[1] Gralnek IM, Siersema PD, Halpern Z, et al. Standard forward-viewing colo-
noscopy versus full-spectrum endoscopy: an international, multicentre, rando- No statistical significant difference was observed regarding diabetes mellitus,
mised, tandem colonoscopy trial. Lancet Oncol 2014; 15: 353-360. hypertension, BMI and waist-hip-ratio.
Disclosure of Interest: None declared CONCLUSION: Smoking and personal past history of polyps increase the risk
for SSA/Ds in comparison to normal population. Increasing age also increases
the risk for SSA/Ds, especially after the age of 50.
P0365 SESSILE SERRATED VERSUS CONVENTIONAL ADENOMAS. Disclosure of Interest: None declared
DIFFERENT POLYPS IN DIFFERENT POPULATIONS
G. Michalopoulos1, S. Vrakas1, S. Charalampopoulos1, V. Ntouli1,
S. Lamprinakos1, K. Makris1, C. Tzathas1,* P0367 DRUG ALLERGY AND RISK OF LYMPH NODE METASTASIS IN
1
Gastroenterology, Tzaneion, General Hospital of Piraeus, Piraeus, Greece RECTAL CANCER
Contact E-mail Address: gmicha78@hotmail.com C. Gao1,*, J.-T. Li1, L. Fang1, H.-C. Zhao1
1
Department of Gastroenterology, China-Japan Friendship Hospital, Ministry of
INTRODUCTION: There are emerging data indicating that Sessile Serrated Health, Beijing, China
Adenomas may have different epidemiological characteristics than conventional Contact E-mail Address: gaochun@bjmu.edu.cn
adenomas.
AIMS & METHODS: This prospective study was aimed to identify any differ- INTRODUCTION: Previous epidemiologic studies have reported that a history
ences in the characteristics of patients with Sessile Serrated Adenomas with and of allergy is associated with reduced risk of colorectal cancer and other malig-
without dysplasia (SSA/Ds) in comparison to patients with conventional nancies. However, no information is available for the association between allergy
Adenomatous Polyps (APs). 85 patients with APs and SSA/Ds were included and risk of lymph node metastasis.
and data regarding age, sex, smoking, BMI, waist-hip-ratio and medical history AIMS & METHODS: Our study was designed to determine this association in
(arterial hypertension and diabetes mellitus) were collected. A univariate and a rectal cancer.
multivariate regression analysis were performed using z test. Patients who were treated at our hospital in the period from January 2003 to
RESULTS: 156 APs and 53 SSA/Ds of 85 patients (mean age 66.19.8 and June 2011, and with a pathological hospital discharge diagnosis of rectal aden-
63.19.4 years, respectively) with their characteristics and the results from uni- carcinoma, were included. The clinical, laboratory and pathologic parameters
variate and multivariate regression analysis are presented in the following table. were analyzed. Multivariate logistic regression model was used to determine
the association. Moreover, for type of allergic drug, sub-group analysis was
SSA/D vs AP (univariate) OR P-value 95% C. I. performed.
RESULTS: 469 patients were included, including 231 with pathological lymph
Sex (women/men) 2 0.034 1.05-3.84 node metastasis (pLNM) (49.3%) and 238 without pLNM. Univariate analysis
showed, compared with patients without pLNM, patients with pLNM had a
BMI 0.92 0.031 0.85-0.99 younger age (60.612.8 yr vs. 63.612.2 yr, p 0.012), a lower percentage of
Waist-hip-ratio 0.01 0.06 0.0002- 1.30 drug allergy (8.7% vs. 16.0%, p 0.016), an increased CEA (median/interquar-
Diabetes Mellitus 0.09 50.001 0.02-0.33 tile-range 5.40/2.40-13.95 vs. 3.50/2.08-8.67, p 0.009), and a lower serum
Hypertension 0.24 50.001 0.12- 0.47 sodium (1413.1mmol/L vs. 1422.9 mmol/L, p 0.028). Multivariate analysis
showed that drug allergy was associated with a reduced risk of pLNM
SSA/D vs AP (multivariate) OR P-value 95% C. I. (OR 0.553; 95% CI, 0.308-0.994; p 0.048). In addition, our results showed
Diabetes mellitus 0.1 50.001 0.03-0.36 that: (1) for tumor classification, patients with drug allergy had a higher percen-
Hypertension 0.3 0.001 0.14-0.63 tage of group patients with pT1/ pT2; and (2) for type of allergic drug, this
inverse association was found for penicillins, not for other allergic drugs.
CONCLUSION: Drug allergy is associated with a reduced risk of pLNM in
rectal cancer.
There was no statistical significant difference regarding sex, BMI and waist-hip- Disclosure of Interest: None declared
ratio (p40.05) in the multivariate regression analysis. A peak incidence of SSA/
Ds was observed in the ages of 51-60 years compared to a peak incidence in the
ages of 61-70 years of APs (p 0.001). No significant difference between groups
regarding smoking was observed (p40.05).
United European Gastroenterology Journal 2(5S)
P0368 PROGNOSTIC VALUE OF HUMAN PAPILLOMAVIRUS IN ANAL
SQUAMOUS CELL CARCINOMA
P.S. Ravenda1, E. Magni1, E. Botteri1, M. Manzotti1, M. Barberis1,
C. Trovato2,*, V. Dellacqua1, M.C. Leonardi1, M. Sideri1, N. Fazio1,
M.G. Zampino1
1
EUROPEAN INSTITUTE OF ONCOLOGY, Milan, Italy, 2Endoscopy
Division, EUROPEAN INSTITUTE OF ONCOLOGY, Milan, Italy
Contact E-mail Address: cristina.trovato@ieo.it
INTRODUCTION: Anal cancer is an uncommon malignancy but its incidence is
increasing worldwide. Chemoradiation is the standard primary treatment for
patients with loco-regional limited disease. However, once patients develop meta-
static spread, the prognosis is very poor. Human papillomavirus (HPV) is present
in around 80% of anal cancers but its prognostic/predictive value is essentially
unknown.
AIMS & METHODS: We retrospectively evaluated 50 patients with anal squa-
mous cell carcinoma treated at our Institution with chemoradiotherapy for loco-
regional disease. HPV status was evaluated from paraffin-embedded tumor tis-
sues collected at the time of diagnosis by a polymerase chain reaction analysis.
RESULTS: Among 50 patients 42 (84%) were HPV-positive. Thirty-two (64%)
patients were positive to genotype 16, two (4%) to genotype 18 and three (6%) to
both 16 and 18. Lymph nodal involvement and clinical stage at diagnosis were
more advanced for HPV-positive patients. After a median follow-up of 4 years
(range 0.4-13.8) 46 (92%) patients were alive. Overall, 8 patients relapsed: 1 loco-
regional, 1 regional and 6 distant recurrences were observed. Four patients died
from metastatic disease. Five-year disease-free survival (DFS) in HPV-positive
and HPV-negative patients was 92.5% and 50.0%, respectively (p 5 0.01). In
multivariate analysis, HPV-positivity was associated with a statistically signifi-
cant better 5-year DFS. Five-year overall survival in HPV-positive and HPV-
negative patients was 93.3% and 66.7%, respectively (p 0.12).
CONCLUSION: In our study HPV-positive anal cancers had a statistically sig-
nificant improved DFS compared to HPV-negative group.
Disclosure of Interest: None declared
P0369 ASSOCIATION BETWEEN COLORECTAL NEOPLASMS AND
METABOLIC SYNDROME IN A PORTUGUESE POPULATION
1,* 1 1 1 1
D. Trabulo , S. Ribeiro , C. Martins , C. Teixeira , C. Cardoso ,
J. Mangualde1, R. Freire1, E. Gamito1, A.L. Alves1, F. Augusto1, I. Cremers1,
A.P. Oliveira1
1
Gastroenterology, Hospital de Sao Bernardo - Centro Hospitalar de Setubal,
Setubal, Portugal
Contact E-mail Address: danieltrabulo@yahoo.com
INTRODUCTION: There has been a growing recognition of metabolic syn-
drome (MS) as an important risk factor for cardiovascular disease and malig-
nancies. Several investigators from Eastern countries have considered MS as a
possible risk factor for colorectal neoplasms.
AIMS & METHODS: The aim of this study was to evaluate the association of
MS and colorectal cancer and adenomas in a Western country, where the inci-
dence of MS is over 27%.
Methods: Prospective study between March 2013 and March 2014. MS was
diagnosed according to National Cholesterol Education Program-ATP III.
Demographic characteristics, anthropometric measurements, metabolic risk fac-
tors and colonoscopy pathologic findings were assessed in patients with MS
(group 1) who underwent routine colonoscopy at our department. This data
was compared with consecutive patients without metabolic syndrome (group
2), with no differences regarding sex and age. Informed consent was obtained
and the ethics committee approved this study. Statistical analysis was performed
with T-student and 2 tests; p-value0,05 was considered statistically significant.
RESULTS: We evaluated a total of 258 patients, 129 with MS; 50% males;
mean-age 67,1 years (50-87). Among the MS group, 94% had high blood pres-
sure, 91% had increased waist circumference, 60% had diabetes, 55% had low
HDL cholesterol level, 50% had increased triglyceride level and 54% had obesity
(BMI30kg/m2). 51% presented 4 criteria of MS. MS was associated with
increased presence of adenomas (43% vs 25%, p 0.004) and colorectal cancer
(13% vs 5%; p 0.027), compared with patients without MS. MS was also
positively associated with multiple (3) adenomas (35% vs 9%, p 0.024) and
sessile adenomas (69% vs 53%; p 0.05). No differences existed between loca-
tion (p 0.086), grade of dysplasia (p 0.196) or size of adenomas (p 0.841).
Increased waist circumference was an independent risk factor for the presence of
adenomas (85% vs 15%, p 0.05).
CONCLUSION: In our population, MS was associated with colorectal cancer
and adenomas. Central obesity was also associated with an increased risk.
Recommendations for colorectal cancer screening in patients with MS may
need to be different from the average risk population. To our knowledge, no
previous study evaluated this association in Portuguese patients.
Disclosure of Interest: None declared
P0370 THIRD ROUND OF TWO-SAMPLE IMMUNOCHEMICAL FECAL
OCCULT BLOOD TEST SCREENING IN THE NETHERLANDS
E.H. Schreuders1,*, S. Nieuwenburg1, A. Kapidzic1, E.J. Grobbee1, A.J.
van Vuuren1, W. Spijker2, M.J. Bruno1, E.J. Kuipers1, M.C. Spaander1
1
Gastroenterology and Hepatology, Erasmus MC, 2Stichting Bevolkingsonderzoek
Zuid-West Nederland, Rotterdam, Netherlands
Contact E-mail Address: e.schreuders@erasmusmc.nl
INTRODUCTION: Screening for colorectal cancer (CRC) by means of immu-
nochemical fecal occult blood test (abbr. iFOBT or FIT) requires successive
A233
rounds for an optimal preventative effect. The diagnostic yield of advanced
neoplasia may increase with the use of two FITs per round. Therefore, in this
study we assessed the diagnostic yield and participation rate of two-sample FIT
screening during three successive rounds in a population-based screening pilot in
the Netherlands.
AIMS & METHODS: A representative sample of the Dutch population
(n 3197) aged 50-75 years was randomly selected and invited by mail for
three rounds of two-sample FIT screening with a 2-year interval. Participants
received two identical FIT tests per round to sample on two consecutive bowel
movements. Tests were analyzed using the OC Sensor Micro (Eiken Japan) with
a positivity cut-off level of 50ng Hb/ml ( 10 mg Hb/g feces). Participants with at
least one positive test were offered colonoscopy. For each round, we excluded
individuals who met exclusion criteria (history of CRC, IBD, colon imaging  3
years, life expectancy 55 years, inability to give informed consent) died, moved
away or were positive at previous rounds.
RESULTS: The participation rate was 64.4% (95% Confidence Interval (CI)
62.566.4%) at the third round, compared to 62.1% (1647/2652; 95% CI:
60.2-63.9%) in the second and 61.3% (1875/3061; 95% CI: 59.663.1%) in the
first round. One test was positive in 145 (9.8%; 95% CI 8.411.4) individuals and
in 41 (2.8%; 95% CI 2.03.7) both FITs tested positive. Of the 134 (92%)
patients who proceeded to colonoscopy, 5 had CRC and 13 had an advanced
adenoma (defined as an adenoma 10mm, with 25% villous component or
high-grade dysplasia). The positive predictive value (PPV) for advanced neopla-
sia was 13.4% (95% CI 8.6-20.3) for at least one positive test and 18.4% (95% CI
9.0-33.9) when both tests were positive. The two-sample methodology detected
61.1% additional participants with advanced neoplasia (p 0.28) who would
have been missed with a single FIT test per round; 4 (80%) participants who
had CRC and 7 (53.9%) who had an advanced adenoma had only 1 positive test.
Table, 2-sample FIT screening (1positive) in multiple rounds
Eligible
invitees Participation PR DR PPV
Advanced Advanced
neoplasia CRC neoplasia %
n n (%) n (%) n (%) n (%) (95% CI)
Round 1 3061 1876 (61.3) 239 (12.8) 76 (4.1) 12 (0.6) 34% (28.3 40.7)
Round 2 2654 1647 (61.2) 141 (8.6) 26 (1.6) 4 (0.2) 19.0% (13.3 - 26.4)
Round 3 2297 1480 (64.4) 145 (9.8) 18 (0.8) 5 (0.2) 13.4% (8.6 - 20.3)
CONCLUSION: Two-sample FIT screening is associated with a stable and high
participation rate of more than 60% after three rounds. Positivity rates and
detection rates with two-sample FIT screening, are higher compared to historical
data of screening with one-sample FIT per round (van Roon Gut 2012). This
implies that FIT screening with two samples has an added benefit to detect a
maximum number of individuals with advanced neoplasia.
Disclosure of Interest: None declared
P0371 LIFESTYLE, ENVIRONMENT OR GENDER WHAT HAS
BIGGER IMPACT ON THE INCIDENCE OF COLORECTAL
NEOPLASIA?
E. Waldmann1,2,*, G. Heinze3, M. Britto-Arias1,2, D. Sallinger1,2, I. Gessl1,2,
A. Ferlitsch1,2, M. Trauner1,2, M. Ferlitsch1,2
1
Quality Assurance Working Group of the Austrian Society of Gastroenterology
and Hepatology, 2Div. of Gastroenterology and Hepatology, Dept. of Internal
Medicine III, 3Department for Medical Statistics, Division of Clinical Biometrics,
Medical University of Vienna, Austria, Vienna, Austria
Contact E-mail Address: monika.ferlitsch@meduniwien.ac.at
INTRODUCTION: Recommendations for colorectal cancer (CRC) screening
are based on patients age and family history of cancer, although men are at
higher risk for adenomas and CRC and develop the lesions earlier than women.
Several risk factors such as BMI, gamma GT levels, presence of diabetes and
physical activity are known to increase the incidence of adenomas and CRC but
less is known about the impact of those risk factors on prevalence of colorectal
neoplasia in men and women.
AIMS & METHODS: To investigate the impact of risk factors on sex specific
adenoma detection rates (ADR) and advanced adenoma detection rates
(AADR). We included patients who attended preventive health check up exam-
inations and screening colonoscopy at the same time point (within six months) in
Austria between November 2007 and December 2012.
RESULTS: The investigated risk factors had greater impact on male patients
than on female patients. High BMI influenced ADR (p50.0001) and AADR
(p50.0001) in male patients and ADR (p 0.0229), but not AADR (p 0.2720)
in female patients. High gamma GT levels also increased ADR (p50.0001,
OR 1.11, CI 1.05-1.16) and AADR (p 0.0045, OR 1.12, CI 1.04-1.21)
in male, but not in in female patients (p 0.5237, OR 1.02, CI 0.96-1.09 for
ADR and p 0.3804, OR 0.95, CI 0.85-1.07 for AADR). Presence of diabetes
has an impact on ADR (p 0.0049, OR 1.2) and AADR (p50.0001, OR 1.6)
in male, but not in female patients (p 0.276, OR 1.1 and p 0.234, OR 1.3).
Physical activity impacts ADR (p 0.0018, OR 0.8) and AADR (p50.001,
OR 0.6) in male as well as AADR in female patients (p 0.0150, OR 0.7)
but not the ADR in female patients (0.0792, OR 0.8).
CONCLUSION: Our results show that acknowledged risk factors for colorectal
neoplasias seem to affect particularly male patients which raises the need of
implementation of gender specific prevention recommendations for CRC, espe-
cially for men with risk factors.
Disclosure of Interest: None declared
A234
P0372 ANTI-HER2/NEU PEPTIDE WAS LABELED WITH TC-99M TO
DETECT HER2-POSITIVE TUMORS IN COLORECTAL HCT-15
DERIVED XENOGRAFTS
A.-S. Ho1,*, C.-C. Cheng2, C.-C. Chang3, H.-C. Lin1, T.-Y. Luo2, J. Chang4
1
Cheng Hsin General Hospital, Taipei, 2Institute of Nuclear Energy Research,
Taoyuan, 3Taipei Medical University Hospital, 4Taipei Medical University, Taipei,
Taiwan, Province of China
Contact E-mail Address: js.chang@tmu.edu.tw
INTRODUCTION: HER2/neu is reported as an overexpressed target on the cell
surface in variety of solid cancers such as gastric cancer and breast cancer. Here,
we (1) validated that HER2 is a tumor-treated target in colorectal cancer, and (2)
designed an anti-HER2/neu peptide (AHNP)-labeled Tc-99m to detect the
expression of HER2 in HER2-postive HCT-15-induced tumors.
AIMS & METHODS: The aim of this study was to create a HER2-binding
peptide, AHNP, labeled with Tc-99m to detect HER2-positive tumors. First,
the colorectal cancer cells, HCT-15, were used to investigate the binding specifi-
city of AHNP. The AHNP was conjugated with HYNIC and PEG at N and C-
terminus, respectively. The designed AHNP was chelated with Tc-99m through
HYNIC and the isotope-labeled rate was analyzed by iTLC. Then, a
nanoSPECT/CT was used for tumor detection.
RESULTS: We found that HER2 was overexpressed in colorectal HCT-15
tumor cells and the tumors of HCT-15-induced xenograft mice using Western
blots. AHNP labeled with fluorescent FITC was performed to detect the binding
efficacy of AHNP to HCT-15 in vitro using flow cytometry. The results revealed
that AHNP specifically bound to HER2-positive HCT-15 cells compared to
HER2-negative gastric MKN45 tumor cells, indicating that AHNP can be
applied to diagnose HER2-positive tumors. Therefore, we labeled nuclear iso-
tope, Tc-99m, with AHNP coupled with PEG to prolong the half-life of peptide
in animals. The labeled rate of Tc-99m with AHNP through HYNIC chelating
was measured 4 90% using iTLC analysis. However we did not observe appar-
ent difference in nuclear imaging for detecting tumors in HCT-15-induced xeno-
grafts, suggesting that peptide was unstable or rapidly metabolized in animals.
CONCLUSION: Our results showed that HER2 overexpressed in colorectal
HCT-15 cells as a tumor target. HER2 specific binding peptide, AHNP, can be
used to detect HER2-positive tumors as a good candidate tool in vitro, however,
it was rapidly metabolized in animals.
Disclosure of Interest: None declared
P0373 BISULFITE-BASED DNA METHYLATION ASSESSMENT FROM
RECENT AND ARCHIVAL FORMALIN-FIXED, PARAFFIN
EMBEDDED (FFPE) COLORECTAL SAMPLES
A. Kalmar1,2,*, B. Peterfia2, P. Hollosi3,4, B. Wichmann1,2, V.A. Patai1,
A. Scholler1, I. Furi1, Z. Tulassay1,2, B. Molnar1,2
1
2nd Department of Internal Medicine, Semmelweis University, 2Molecular
Medicine Research Unit, Hungarian Academy of Sciences, 31st Department of
Pathology and Experimental Cancer Research, Semmelweis University, 4Tumor
Progression Research Group, Hungarian Academy of Sciences, Budapest, Hungary
Contact E-mail Address: alexandra.kalmar@gmail.com
INTRODUCTION: Surgically removed formalin-fixed, paraffin-embedded
(FFPE) specimens are routinely used for morphological and molecular diagnos-
tics, although application of these samples in molecular biology analyses can be
challenging. Methylation-sensitive high-resolution melting analysis (MS-HRM)
is a cost-effective tool for the assessment of DNA methylation level alterations
during several types of tumor formation including colorectal cancer (CRC).
AIMS & METHODS: We aimed to compare the applicability of recent and
archive FFPE tissue samples for gene-specific MS-HRM using two different com-
mercially available DNA isolation kits. Genomic DNA isolation was performed
from two groups of FFPE blocks; archive samples older than 5 years (n 10; 5
CRC, 5 normal adjacent tissue (NAT)), recent samples younger than 6 months
(n 10; 5 CRC, 5 NAT) using FFPE DNA Isolation Kits from Roche and Qiagen.
The yield and purity of DNA samples were evaluated by spectrophotometry and
by fluorometry. The integrity and applicability of DNA for PCR was examined by
qPCR and a multiplex PCR experiment that contains primers producing four
amplicons with different lengths. DNA samples were bisulfite converted and
gene-specific DNA methylation analyses were performed for MAL, SFRP1 and
SFRP2 genes by using MS-HRM analysis and GS Junior sequencing
RESULTS: Based on OD260 measurements the Qiagen method resulted in a
slightly higher recovery in archive and a significantly higher recovery in fresh
FFPE samples compared to the Roche method. More selective detection of RNA
and DNA by fluorometric dyes revealed that Qiagen samples contain high
amounts of RNA, more than the Roche isolated samples, which was also sup-
ported by the higher OD260/280 and OD260/230 ratios of Qiagen samples. The
two isolation methods did not differ significantly in their DNA yield in case of
archive samples, but Qiagen yielded about two times more DNA in average from
fresh FFPE samples. The DNA integrity and amplificability of fresh FFPE
samples were higher than the archive ones. Despite the equal DNA yield of
Qiagen and Roche samples in the archive sample group, the integrity of Roche
samples was higher, and their qPCR amplification was also significantly more
effective. Identical DNA methylation pattern was detected by MS-HRM for
Qiagen and Roche samples in the fresh FFPE group. However, in case of archive
samples, more reproducible methylation results were obtained from Roche sam-
ples. The differences in the methylation level of selected tumor samples could be
confirmed also by sequencing the PCR products of MS-HRM examinations.
CONCLUSION: Sufficiently reproducible MS-HRM results can be obtained
from recently fixed, fresh FFPE samples, but less reliable results can be expected
for archive ones. In case of archive samples more parallel reactions, and usage of
highly effective primer assays is recommended.
United European Gastroenterology Journal 2(5S)
Disclosure of Interest: None declared
P0374 COMPARISON OF AUTOMATED AND MANUAL DNA
ISOLATION FOR DNA METHYLATION ANALYSIS OF BIOPSY,
FRESH FROZEN AND FFPE COLORECTAL CANCER SAMPLES
A. Kalmar1,2,*, B. Peterfia1,2, B. Wichmann1,2, A. V. Patai1, B.K. Bartak1,
Z.B. Nagy1, I. Furi1, M. Juhasz1, L. Herszenyi1, Z. Tulassay1,2, B. Molnar1,2
1
2nd Department of Internal Medicine, SEMMELWEIS UNIVERSITY,
2
Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest,
Hungary
Contact E-mail Address: alexandra.kalmar@gmail.com
INTRODUCTION: A broad range of biological samples are being analysed with
increasing number in the routine pathology; automated DNA isolation can be a
promising solution to decrease the hands-on time.
AIMS & METHODS: Our aim was to analyse the performance of MagNA Pure
96 nucleic acid isolation system in DNA isolation from fresh frozen, biopsy and
formalin-fixed, paraffin-embedded (FFPE) tissue specimens. Furthermore, we
aimed to test the applicability of the isolated DNA in downstream DNA methy-
lation analyses, and to compare results after automated and manual isolation.
Fresh frozen (n 20; 10 CRC, 10 normal adjacent tissue (NAT)) tissue speci-
mens, biopsies (n 20; CRC 10, healthy colonic tissue 10), FFPE blocks
(n 20; 10 CRC, 10 NAT) were collected. DNA isolation was performed from
the fresh frozen and biopsy samples with QIAamp DNA Mini Kit (Qiagen) and
with automated method with MagNA Pure DNA and Viral NA Small Volume
kit (Roche Applied Science) on the MagNA Pure 96 system Kit in parallel, the
FFPE samples were isolated with manual QIAamp DNA FFPET kit (Qiagen)
and with automated MagNA Pure DNA and Viral NA Small Volume kit (Roche
Applied Science). After DNA quantity and quality measurements, DNA methy-
lation levels for MAL, SFRP1 and SFRP2 were analysed with methylation-spe-
cific high resolution melting analysis (HRM).
RESULTS: Yield of manually isolated samples were found to be equal in fresh
frozen tissue samples and significantly higher compared to the automated
method in the case of biopsy and FFPE samples. OD260/280 ratio was found
to be similar in fresh frozen and biopsy samples, while manual isolation resulted
in higher purity in FFPE samples. OD260/230 ratio was similar in fresh frozen
tissue samples after both isolation methods, the automated method was superior
in biopsy samples and the manual protocol in FFPE samples. DNA integrity was
found to be the highest in fresh frozen samples, and half of the analyzed FFPE
samples showed higher integrity after manual extraction, while the rest of sam-
ples had similar integrity after both methods. In biopsy and fresh frozen samples
DNA methylation estimations were found to be highly similar after two isolation
methods. In the FFPE samples the linearity of the assays lower even in FFPE
samples SFRP1 and SFRP2 assays showed good correlation in the methylation
percent data after the two different isolation methods.
CONCLUSION: Similar DNA methylation results were found after automated
and manual DNA isolation, thus automation can be a suitable alternative in
CRC diagnosis workflow beside manual protocols especially for laboratories
with high sample throughput.
Disclosure of Interest: None declared
P0375 CORRELATION BETWEEN THE LOCATION OF THE INITIAL
AND RECURRENT COLONIC POLYPS
A.T. Oliveira1,*, P. Freire1, S. Campos1, S. Giestas2, S. Mendes1, P. Amaro2,
F. Portela1, C. Sofia1
1
Gastroenterology, 2Centro Hospitalar e Universitario de Coimbra, Coimbra,
Portugal
Contact E-mail Address: torresoliveiraana@gmail.com
INTRODUCTION: The post-polypectomy surveillance colonoscopy is recom-
mended because of the risk of synchronous and recurrent lesions. There are
several factors used to stratify the probability of polyp recurrence. However,
there are no studies correlating the location of the initial polyp and that of the
recurrent one.
AIMS & METHODS: The aim of this study is to verify if the polyp location at
the surveillance colonoscopy is correlated with the location of the previously
excised polyps at the baseline colonoscopy.
We included all patients submitted to two total colonoscopies, with at least one-
year interval and complete excision of the polyps detected in the baseline colono-
scopy. We evaluated 346 patients, of whom 78 were excluded for not having
polyps at the surveillance colonoscopy. We divided the intestine into cecum,
ascending, transverse, descending, sigmoid and rectum and also evaluated the
characteristics of polyps. We used the Kolmogorov-Smirnov test to determine the
normality, Kappa for agreement and Chi-square, t-Test or Mann-Whitney as
necessary.
RESULTS: We found a male predominance (64.9%) and a mean age of 6410
years. The number and size of the polyps at the initial and surveillance colono-
scopy was 31 vs 21 polyps and 119 vs 75mm, respectively. The mean
interval between the two colonoscopies was 3720 months. The overall agree-
ment rate of polyp location between colonoscopies was 44%. Probability of
recurrence in the several segments: cecum 50.0% [OR 6.4-62.4], ascending
57.0% [OR 2.3-7.2], transverse 46.4% [OR 1.9-6.9], descending 34.6% [OR
1.3-4.4], sigmoid 57.6% [OR 2.3-6.9], rectum 40.4% [OR 1.6-5.1], p50.001.
No statistically significant difference was found between the rates of recurrence
at the same location, taking into consideration: polyp morphology (sessile
59.8%; pedunculated 51.6%), size (11mm), polypectomy technique (biopsy for-
ceps 64.3%; snare 54.0%; mucosectomy 70.4%), histology (low-grade dysplasia
54.7%, high-grade dysplasia 41.7%; hyperplastic 64.9%), resection (complete
48.6%; fragmented 58.3%). There was also no difference after stratification in
United European Gastroenterology Journal 2(5S)
advanced adenoma (50.5%), non-advanced adenoma (56.8%) and hyperplastic
(64.9%).
CONCLUSION: There seems to be a significant correlation between the initial
location of polyps and the recurrence site in the surveillance colonoscopy. This
may have future implications in terms of technical execution and accuracy of the
procedure, including alerting for better scrutiny of the segment with previous
polypectomy.
Disclosure of Interest: None declared
P0376 COMPARISON THE EFFICIENCY OF HIGH RESOLUTION
MELTING ANALYSIS AND PYROSEQUENCING IN COLON
CANCER DNA METHYLATION STUDIES
B. Peterfia1,*, P. Hollosi2, B. Wichmann1, Z. Tulassay1, B. Molnar1
1
2nd Deptartment of Internal Medicine, 21st Department of Pathology and
Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Contact E-mail Address: peterfiab@yahoo.co.uk
INTRODUCTION: Identification of differentially methylated regions (DMRs)
in the genome of cancer samples by comparing them with normal samples is a
basic process in the course of epigenetic investigations. Methylation-sensitive
high-resolution melting analysis (MS-HRM) and pyrosequencing of bisulphite
modified DNA are two of the most popular technologies among single locus
DNA methylation studies. Both techniques involve PCR amplification of bisul-
phite converted DNA, although they differ in their cost, hands-on time and in the
output information they provide.
AIMS & METHODS: In order to test MS-HRM and pyrosequencing on colon
cancer samples, fresh frozen tissue specimens were collected (20 CRC, 15 ade-
noma and 20 normal adjacent tissue (NAT)). After DNA isolation and bisulphite
conversion, 12 different CpG rich regions of 9 genes were amplified by PCR
(COL1A2, ENTPD5, PRIMA1, PTGDR, SFRP2, SOCS3, SULF1, SULT1A1
and THBS2). PCR amplification was carried out with primers designed to
amplify both methylated and unmethylated templates. After amplification MS-
HRM was carried out, and PCR amplicons were subsequently pyrosequenced.
RESULTS: In general, MS-HRM provided less accurate estimation, thus it is not
suitable to detect very slight methylation level alterations. However, results of
MS-HRM and pyrosequencing were in harmony with each other in 89% of cases.
The number of hypermethylated tumours found by MS-HRM versus pyrose-
quencing was as follows: COL1A2: 5 vs. 7; PRIMA1: 5 vs. 7; PTGDR: 3 vs. 0;
SFRP2: 13 vs. 13; SOCS3: 10 vs. 12; THBS2: 4 vs. 5, respectively. A promoter of
an alternative variant of THBS2 was found to be hypomethylated in 4 vs. 5
tumour samples. The total number of DMRs found in the 20 CRC samples
investigated was 44 by MS-HRM and 49 by pyrosequencing, which means that
the efficiency of MS-HRM is 82% of the pyrosequencing. In contrast to pyro-
sequencing, MS-HRM was able to detect sample heterogeneity, especially in case
of adenomas and tumour samples. Further experiments with laser captured
microdissected cells from these samples revealed that epithelial cells were hyper-
methylated in tumours, while no DNA methylation level alteration could be
detected in stromal cells.
CONCLUSION: Taken together, MS-HRM is cost-effective and needs less
manual work than pyrosequencing, which makes it a suitable tool for DNA
methylation screening study. The efficiency of MS-HRM is close to that of the
pyrosequencing in DMR detection. Moreover, it gives information about sample
heterogeneity. The major advantage of pyrosequencing is its higher sensitivity
and the single CpG site information it provides.
Disclosure of Interest: None declared
P0377 TARGETED, NEXT GENERATION 454 SEQUENCING OF COLON
CANCER BIOPSIES YIELDS THERAPEUTICAL AND DIAGNOSTIC
DATA
B. Peterfia1,*, B. Wichmann2, A. Kalmar1, A. V. Patai1, Z. Tulassay1, B. Molnar1
1
2nd Deptartment of Internal Medicine, 2Molecular Medicine Research Unit,
Semmelweis University, Budapest, Hungary
Contact E-mail Address: peterfiab@yahoo.co.uk
INTRODUCTION: Mutation analysis of certain genes is an essential procedure
for an individualized therapy. The number of important target genes is gradually
rising, pressing a requirement for continuous expansion of analytic methods.
Fulfilling this goal in a time-efficient manner is a big challenge for diagnostic
laboratories, using conventional sequencing procedures.
AIMS & METHODS: Creating a mutation sequencing panel helped us to reach
the aim to investigate the potential of Next Generation Sequencing (NGS) in
colon cancer genotyping. A multiplex PCR panel was designed to amplify muta-
tion hot spots of 12 selected genes. Those genes were selected that are frequently
mutated in colon cancer or that are investigated in routine oncodiagnostics
(APC, BRAF, CTNNB1, EGFR, FBXW7, KRAS, MSH6, NRAS, PIK3CA,
SMAD2, SMAD4, TP53). Amplicons were sequenced by a GS Junior
Instrument (Roche) using ligated and barcoded adaptors. Eight samples could
be sequenced in one single run. Altogether, control cell lines with known muta-
tion profiles and 60 DNA samples were investigated by the panel (8 normal colon
mucose; 33 adenomas and 17 adenocarcinomas).
RESULTS: In control cell lines (HT29 and Caco-2), 4 mutations were antici-
pated to be found by our panel; and three of them were successfully detected.
Only one adenine insertion, which was located in an adenine homopolymer
region, was not detected. We found one mutated normal of eight investigated
samples (12.5%). This rate was much higher in adenomas and carcinomas (78%
and 76%, respectively), indicating high sensitivity. The average number of muta-
tions found in mutated samples was 1 in low grade adenomas; 1.8 in high grade
adenomas; 1.9 in carcinomas and 2.3 in serrated adenomas. The only mutation
found in normal samples was a germ line APC mutation. This typical gatekeeper
A235
suppressor gene was mutated in adenomas more frequently than in carcinomas
(36% vs. 24%), in contrast with other caretaker or proto-oncogenes. The most
frequently mutated genes were APC, TP53 and KRAS with 36%, 18% and 26%
frequencies in adenomas and 24%, 47% and 45% frequencies in carcinomas,
respectively. Interestingly, there was no sample found having APC and TP53
mutations together.
CONCLUSION: Our NGS based screening panel can be a useful and affordable
tool to study the mutation profile of colon cancer. Additionally, not only can it
detect sporadic, but many of frequent germ line mutations as well. Its application
in diagnostic practice to predict therapeutic response is worth to consider.
Disclosure of Interest: None declared
P0378 REPORTED DELAY IN THE DIAGNOSIS OF COLORECTAL
CANCER: ANALYSIS OF GP REPORTS OF AVOIDABLE DELAY
FROM THE RCGP NATIONAL AUDIT OF CANCER
C.M. Dobson1, E. Titova2, G. Rubin1,*
1
School of Medicine, Pharmacy & Health, Durham University, Durham,
2
Lincolnshire Partnership NHS Foundation Trust, UK, Lincolnshire, United
Kingdom
Contact E-mail Address: c.m.dobson@durham.ac.uk
INTRODUCTION: The UK has significantly poorer cancer survival rates than
comparable countries(1) and diagnostic delay is perceived to be a significant
contributory factor to this (2). In 2009/10 The RCGP undertook a National
Audit of Cancer Diagnosis in Primary Care, obtaining data on 18,889 cancer
patients, from 1120 practices (3). GPs also provided free text comments on any
perceived avoidable delays within the patients diagnostic pathway.
AIMS & METHODS: The aim of this study was to analyse the principal causes
of delay, as reported by GPs.
The audit contained data on 2737 patients with colorectal cancer and avoidable
delay was reported for 36%. Free text reports of the nature of the delay were
available for 753 (28%) patients. These were transformed into quantitative data,
utilising an extended version of The Model of Pathways to Treatment (4) as an
analytical framework. Comments were independently categorised by CD and
GR, with disagreements in categorisation reconciled through discussion. A pro-
portion (10%) of cases were also coded by ET, as a data quality measure. In
order to validate GP perceptions of diagnostic delay we compared categorised
primary care and referral intervals for patients with and without perceived delay,
using a chi-squared test.
RESULTS: GP reports of avoidable diagnostic delay were significantly asso-
ciated with longer primary care and referral intervals (p 50.0001). The com-
monest reasons for delay were GP (mis)appraisal (29%), referral delays (e.g.
routine rather than urgent) (13%) and investigation delays (28%). For colorectal
cancer patients, help seeking delay was also a prominent factor (8%). Because
these causes of delay were reported by GPs there was a potential reporting bias,
with delays occurring prior to first consultation or in secondary care possibly
being under-reported.
CONCLUSION: The causes of diagnostic delay for patients with colorectal
cancer are complex. GP appraisal and type of referral appeared to be substantial
contributors to cases of avoidable diagnostic delay. Interventions aimed at redu-
cing the time to diagnosis should consider the specific causes of delay for color-
ectal cancer patients.
REFERENCES
1. Coleman MP, Forman D, Bryant H, et al. Cancer survival in Australia,
Canada, Denmark, Norway, Sweden, and the UK, 1995-2007 (the
International Cancer Benchmarking Partnership): an analysis of population-
based cancer registry data. Lancet 2011; 377: 127138.
2. Trring ML, Frydenberg M, Hansen RP, et al. Time to diagnosis and mor-
tality in colorectal cancer: a cohort study in primary care. Br J Cancer 2011; 104:
934940.
3. Rubin G, McPhail S and Elliott K. Royal college of general practitioners:
national audit of cancer diagnosis in primary care, 2011.
4. Walter F, Webster A, Scott S, et al. The Andersen Model of Total Patient
Delay: a systematic review of its application in cancer diagnosis. J Health Serv
Res Policy 2012; 17: 110118.
Disclosure of Interest: None declared
P0379 CONFOCAL LASER ENDOMICROSCOPY FOR THE DETECTION
OF EARLY MUCOSAL CHANGES IN RECTAL STUMPS OF
PATIENTS WITH FAMILIAR ADENOMATOUS POLYPOSIS
C. Bucci1,2,*, V. DAngelo1, G.B. Rossi1, V. Passananti3, M. De Bellis1,
A. Tempesta1
1
Istituto Nazionale Tumori, Fondazione G. Pascale, Naples, 2University of Salerno,
Salerno, 3University Federico II, Naples, Italy
INTRODUCTION: Familial adenomatous polyposis (FAP) is an inherited,
autosomal-dominant disease caused by a germline mutation of the adenomatous
polyposis coli gene (APC). This condition inevitably leads to colorectal cancer.
Prophylactic colectomy, or proctocolectomy with ileal pouch-anal anastomosis
(IPAA) is recommended. Since any remaining rectal mucosa might still be at risk
for malignancy, endoscopic surveillance of both the residual rectal stump and the
ileal pouch is mandatory. Confocal laser endomicroscopy (CLE) is a novel tech-
nique that performs virtual histology of gastrointestinal mucosa with high accu-
racy, detecting in vivo early mucosal changes.
AIMS & METHODS: Aims: To assess the appropriateness of CLE for in vivo
diagnosis of abnormal mucosal changes in rectal stumps of patients with FAP.
Methods: Both white light endoscopy (WLE) and CLE were utilized in the exam-
ination of rectal stumps in 12 patients who had undergone proctocolectomy with
IPAA. During WLE normal mucosa and polyps were classified according to both
A236
Paris and Kudo classifications. CLE images were scored according to the
MIAMI classification. Targeted biopsies were taken from normal mucosa and
polyps were removed with biopsy forceps or polypectomy snares. CLE and his-
tological findings of both background mucosa and polyps were compared.
RESULTS: WLE revealed that all but one patient had diminutive polyps (table
1) and the background mucosa always appeared normal. CLE confirmed that
background mucosa was normal in all cases, whereas the diminutive polyps were
classified adenomas in 9/11 patients and hyperplastic in 2/11 cases. After patho-
logical examination, biopsies of the background mucosa always revealed normal
colonic mucosa, while the diminutive polyps resulted to be 6/11 adenomas with
low grade dysplasia (LGD), 3/11 adenomas with high grade dysplasia and 2/11
LGD adenomas with serrated features.
United European Gastroenterology Journal 2(5S)
invasive growth. Despite a relative large proportion of patients with adjuvant
treatment, MMs were prognostic for disease recurrence.
Disclosure of Interest: None declared
P0381 PLASMA MICRORNAS AS SCREENING BIOMARKERS FOR
COLORECTAL ADENOMAS
A.M. Verma1,2, M. Patel1,2,*, M. I. Aslam1,2, P. Wurm2, J. Jameson2,
J.H. Pringle1, B. Singh2
1
Cancer Studies and Molecular Medicine, University of Leicester, 2University
Hospitals Leicester, Leicester, United Kingdom
Contact E-mail Address: ajaymarkverma@gmail.com

White INTRODUCTION: The identification and resection of colorectal adenomas

Polyp light Paris/Kudo MIAMI during screening colonoscopy is the cornerstone of colorectal cancer prevention
Patient size (mm) Endoscopy Classification Classification Histology within bowel cancer screening programmes (BCSP).
Biennial faecal occult blood testing (FOBt) of patients aged 60-75 is the screening
1 3 adenoma Is-IIIL adenoma Low grade adenoma tool within the United Kingdom BCSP with a positive test identifying patients
2 4 adenoma Is-IIIL adenoma Low grade adenoma requiring colonoscopy. At screening colonoscopy, the yield for adenomas is
3 4 adenoma Is-IIIL adenoma High grade adenoma 46.5% and for adenocarcinomas in 6%. 1 Whilst effective, FOBt lacks high
4 6 adenoma Is-IIIL adenoma High grade adenoma sensitivity, specificity and accuracy. As a result, half of screening colonoscopies
5 4 adenoma Is-IIIL adenoma Low grade adenoma are normal or reveal other gastrointestinal disorders such as haemorrhoids and
diverticular disease (that have lead to false positive FOBt results). This is a
6 7 adenoma IIa-IIIL adenoma Low grade adenoma with
serrated features concern as colonoscopy is an invasive test which can cause patient harm.
Another concern is the uptake of FOBt within screened populations is less
7 5 adenoma Is-IIIL adenoma Low grade adenoma with
serrated features than 60%. 1
A biomarker screening test based on blood sampling may increase uptake
8 3 adenoma Is-II hyperplastic High grade adenoma
especially for individuals not keen to undertake faecal testing. If a biomarker
9 5 hyperplastic Is-IIIL adenoma Low grade adenoma
had a high sensitivity, specificity and accuracy, the proportion of patients under-
10 3 hyperplastic Is-II adenoma Low grade adenoma going screening colonoscopy and having a non adenoma/ adenocarcinoma diag-
11 3 hyperplastic Is-II hyperplastic Low grade adenoma nosis would fall.
AIMS & METHODS: We plan to investigate microRNAs (miRs short (18-24
nucleotides) evolutionary conserved non-coding RNA molecules) as potential
Table 1. Summary of findings in operated FAP patients undergoing surveillance biomarkers. 220 FOBt positive patients undergoing BCSP colonoscopy were
with WLE and CLE recruited and samples of whole blood were taken (100 patients with adenomas,
CONCLUSION: CLE showed good correlation with pathology in diagnosing 90 controls normal or non adenoma/ adenocarcinoma diagnosis). RNA was
diminutive polyps of rectal stumps in patients with FAP. Possibly, CLE could be extracted from plasma and converted to complementary DNA. Pooled groups of
useful for tailoring the surveillance in these patients. However, further studies are patients with adenomas and controls were analysed using array cards. MiRs 19a,
needed to confirm this hypothesis. 98, 146b, 186, 331-5p, 452 and 625 were identified as candidate biomarkers. All
Disclosure of Interest: None declared cases were analysed for these candidates using quantative polymerase chain
reaction.
RESULTS: All 7 candidate MiRs showed significant differences in expression in
P0380 MICROMETASTASES IN THE SENTINEL NODE OF PATIENTS patients with colorectal adenomas when compared to controls.
WITH STAGE I AND II COLON CANCER MiRs 19a, 331-5p, 452 p 50.05, miRs 98, 146b p 50.01, miRs 186, 625
D.A. M. Sloothaak1,2,*, R.van der Linde3, M.S. Reimers4, C.J. van de Velde4, p 50.001.
W.A. Bemelman1, D. Lips3, J.C. van der Linden5, H. Doornewaard6, P.J. Tanis7, When ROC curve analysis was performed area under the curve was higher in
E.S. van der Zaag2, K. Bosscha3, C.J. Buskens7 patients with diverticular disease/ haemorrhoids than those without (0.866 vs
1
Surgery, Academic Medical Center, Amsterdam, 2Surgery, Gelre Hospital, 0.788).
Apeldoorn, 3Surgery, Jeroen Bosch Hospital, s Hertogenbosch, 4Surgery, Leiden CONCLUSION: This study suggest plasma miRs are potential screening bio-
University Medical Center, Leiden, 5Pathology, Jeroen Bosch Hospital, s markers for patients with colorectal adenomas and also may help to identify
Hertogenbosch, 6Pathology, Gelre Hospital, Apeldoorn, 7Surgery, Academic patients with adenomas in the cohort of patients with background diverticular
Medical Centre, Amsterdam, Netherlands disease/ haemorrhoids. Further study and analysis is needed to validate these
Contact E-mail Address: d.a.sloothaak@amc.nl exciting findings.
REFERENCES
INTRODUCTION: According to the guidelines for TNM staging of colorectal 1. Lee TJW, Rutter MD, Blanks RG, et al. Colonoscopy quality measures:
cancer, occult nodal tumour cells are categorised as micrometastasis (MMs) and experience from the NHS Bowel Cancer Screening Programme. Gut 2012; 61:
isolated tumour cells (ITCs). A recent meta-analysis demonstrated that MMs, 1050-1057.
but not ITCs, are prognostic for disease recurrence in patients with stage I/II Disclosure of Interest: None declared
colon cancer.
AIMS & METHODS: The objective of this retrospective multicentre study was to
analyse the incidence of MMs in the sentinel node of patients with stage I/II colon P0383 ACUTE TREATMENT OF MALIGNANT COLORECTAL
cancer, to analyse the correlation between MMs, tumour differentiation and vaso- OCCLUSION: SELF-EXPANDABLE METALLIC STENTS AS
invasive growth, and to analyse the prognostic value of MMs for disease recur- BRIDGE-TO-SURGERY OR PALLIATIVE TREATMENT VERSUS
rence. Patients with elective surgery for stage I/II colon cancer were identified from EMERGENCY SURGERY
databases about ex vivo sentinel lymph node mapping and ultrastaging, from three D. Fernandes1,*, S. Domingues1, B.M. Goncalves1, J.-B. Soares1, P. Bastos1,
Dutch hospitals (2005-2012 Gelre Hospital (GH), 2011-2013 Leiden University A. Ferreira1, R. Goncalves1, A. Mesquita Rodrigues2, L. Lopes3, C. Rolanda1
Medical Center (LUMC) and 2010-2012 Jeroen Bosch Hospital (JBH)). 1
Gastroenterology, 2Surgery, Hospital de Braga, Braga, 3Gastroenterology,
Immunohistochemical staining was performed with antibody against pan-cytoker- Unidade Local de Saude do Alto Minho, Viana do Castelo, Portugal
atin (LUMC, JBH) or cytokeratin-18 (GH) and findings were classified according Contact E-mail Address: daliafernandes09@gmail.com
to the 6th AJCC staging manual. Univariable analysis was applied for the correla-
tion between MMs, tumour differentiation and vaso-invasive growth. Two year INTRODUCTION: Colorectal cancer presents as acute bowel occlusion in 10-
disease-free-survival (2yDFS) of patients with MMs, ITCs and patients without 40% of the patients. There are two main therapeutic approaches for decompres-
occult nodal tumour cells was compared with a Kaplan-Meier analysis. sion: emergency surgery and the endoluminal placement of self-expandable
RESULTS: A total of 214 patients were pooled in a multicentre database (GH metallic stents (SEMS). Due to high mortality and morbidity rates associated
n 128; LUMC n 19; JBH n 67). MMs were found in twelve patients (5.6%), to emergency surgery, SEMS placement as bridge-to-surgery or as palliation is
ITCs in 39 patients (18.2%) and occult tumour cells were absent in 163 patients being increasingly used with controversial results.
(76.2%). Between these three groups, there were no significant differences in AIMS & METHODS: This study aimed to clarify the risk/benefit of the men-
baseline characteristics or type of surgery. Tumour differentiation and vaso- tioned approaches. We conducted a retrospective longitudinal multicenter study,
invasive growth were comparable as well. Four patients with MMs received including 189 patients with acute malignant colorectal occlusion, diagnosed
adjuvant therapy (33.3%) which was significantly more than patients with between January 2005 and March 2013. Demographic, clinical characteristics
ITCs (n 1; 2.6%) or patients without occult tumour cells (n 7; of the patients, tumor features and procedure details were analyzed.
4.3%)(p 0.004). After a median follow up of 20 months (IQR 20-47) recurrence RESULTS: Globally (85 patients 35 bridge-to-surgery and 50 palliative)
of cancer was diagnosed in 12 patients (5.1%). Three recurrences were diagnosed SEMSs technical success was 94.4%. Palliative SEMS had a limited clinical
in patients with MMs; one locoregional recurrence despite adjuvant treatment, success (60.0%) and were associated to 40.0% of complications. SEMS occlusion
and two distant metastases in patients who did not receive adjuvant treatment. (18.8%) was the more frequent, followed by migration (9.4%) and bowel per-
Survival analysis showed a significantly reduced 2yDFS in patients with MMs foration (7.1%). Elective surgery after stenting was associated to a higher fre-
compared to patients with ITCs or patients without occult tumour cells quency of primary anastomosis (93.8% vs 76.4%; p 0.038), and a lower of
(p 0.013). colostomy (25.7% vs 54.9%; p 0.004) and overall mortality (31.3% vs 56.7%;
CONCLUSION: In this study, the incidence of MMs in patients with stage I/II p 0.020). However, no significant differences were identified concerning to
colon cancer was 5.6%, and was not correlated to tumour differentiation or vaso- postoperative complications. In palliative treatment, there was no difference in
complications rate and overall mortality between SEMS and decompressive
United European Gastroenterology Journal 2(5S)
colostomy. In this SEMS subgroup, we found a higher rate of reinterventions
(40.4% vs 5.0%; p 0.004) and a longer hospital stay (14,9 vs 7,3 days;
p 0.004).
CONCLUSION: SEMS placement as bridge-to-surgery should be considered in
acute treatment of colorectal malignant occlusion, since it has advantages regard-
ing to primary anastomosis, colostomy rate and overall mortality. However, the
longer the SEMS stayed in place the higher the risk for complications. Therefore
in palliative SEMS, despite the possible psychological effect of not having a
colostomy, it does not seem to present significant advantages comparing to the
decompressive colostomy.
Disclosure of Interest: None declared
P0384 THE EVALUATION OF NEW COLORECTAL CANCER
TREATMENTS ON CHEMICALLY INDUCED COLON CANCER
MODEL
H. Kuznietsova1,*, H. Svitina2, O. Lynchak1, O. Babuta1, V. Kyryk3,
I. Skrypkina4, M. Kuchma2, Y. Shablii2, O. Dzhus1, E. Denis1, L. Garmanchuk1,
G. Lobintseva2, V. Shablii2, V. Rybalchenko1
1
Institute of biology, Taras Shevchenko National University of Kyiv, 2Institute of
Cell Therapy, 3State institute of genetics and regenerative medicine Academy of
Medicine of Ukraine, 4Institute of molecular biology and genetics of National
Academy of Science of Ukraine, Kyiv, Ukraine
Contact E-mail Address: biophyz@gmail.com
INTRODUCTION: Today new approaches for colorectal cancer treatment
appear through traditional chemotherapy failure. The specificity of potential
therapeutics, impact on malignant cells and/or their restraint within the tumor
nodes, as well as the mininization of therapy and carcinogenesis side effects, are
at the top of interests. Proteine kinase inhibitors are the most specific anticancer
agents due to malignant cell peculiarities, whereas stem cells are the most specific
anticancer drug vehicles due to tumor node metabolism. But the effects of the
first and the last often are evaluated on xenograft models characterized by the
immune deficient status of the host. So it is impossible to assess the state of the
organism experiencing cancer adequately.
AIMS & METHODS: The investigation of the effects of new protein kinase
inhibitors pyrrol derivates (PD) 5-amyno-4-(1,3-benzothyazol-2-yl)-1-(3-methox-
yphenyl)-1,2-dihydro-3H- pyrrol-3-one and 1-(4-Cl-benzyl)-3-Cl-4-(CF3- fenyla-
mino)-1H-pyrrol-2,5-dione compared with therapeutic 5-fluorouracil (5FU) and
the effect of allogenic trophoblast stem cells (TSC) on the tumor formation and
growth and on the state of apparently healthy colon mucosa was undertaken.
The 1,2-dimethylhydrazine (DMH) induced rat colon cancer model, which has
histopathological and biochemical features similar to human colorectal cancer,
was used. Carcinogenesis was initiated by 20 weekly injections of DMH (20 mg/
kg) (up to tumor formation equal R1-2N0-1M0 stage of human colorectal cancer)
and followed by PD daily or 5FU weekly treatments for 7 weeks, or with TSC
intravenous transplantation at 22nd week with no treatment for further 5 weeks.
At 27th week of experiment the animals were euthanized, the colorectal tumors
were counted and measured, the samples of colon walls with and without tumors
were processed and examined under the light microscopy.
RESULTS: PD reduces the tumor number (Nt) and total tumor lesions area (St)
at 27th week by preventing of new tumor formation and by regress of existing
ones, as well as 5FU does (Nt and St at 27th week are less than these ones at 20th
week). PD also diminishes the DMH-induced inflammation of the apparently
healthy colon mucosa, whereas 5FU escalates this process. The data obtained
suggest cell death predominantly by necrosis was caused by 5FU and by apop-
tosis one caused by PD. TSC transplanted at 22nd week at high dose (1.5*106
cells/kg) stops tumor growth compared to nontreated rats, as well as reduces
mucosa inflammation, but does not cause regression of existing tumors (Nt and
St at 27th week are the same at 22nd week). TSC transplanted at the same time at
low dose (0.5*106 cells/kg) attenuates the inflammation features but doesnt
affect tumor growth. We suppose TSC signals dominate the cancer stem cells
ones and therefore contribute to normalization of cancer stem cells microenvir-
onment and thus prevent further carcinogenesis.
CONCLUSION: Targeted therapy is suitable for non-metastatic stage of color-
ectal cancer, whereas the administration of stem cells could stop further carcino-
genesis only but couldnt reduce the existing tumor nodes.
Disclosure of Interest: None declared
P0385 THE INDICATION FOR ADDITIONAL SURGICAL COLECTOMY
WITH NODAL DISSECTION IN T1 COLORECTAL CARCINOMAS
H. Miyachi1,*, S.-E. Kudo1, K. Ichimasa1, Y. Kouyama1, T. Hisayuki1,
H. Oikawa1, Y. Mori1, M. Misawa1, T. Kudo1, K. Kodama1, T. Hayashi1,
K. Wakamura1, A. Katagiri 1, M. Kaga1, E. Hidaka1, F. Ishida1, S. Hamatani1
1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
HOSPITAL, Yokohama, Japan
INTRODUCTION: With the introduction of screening programs for colorectal
cancer and the recent advancement in EMR and ESD technology, a lot of T1
colorectal carcinomas are resected endoscopically with negative margins, and the
percentage of early carcinomas amenable to endoscopic resection has increased.
But, around 10% of the patients of T1 colorectal carcinoma have lymph node
metastasis (LNM). Then, additional surgical colectomy with nodal dissection
should be considered after endoscopic treatment. Therefore, it is critical to deter-
mine the criteria for curative endoscopic resection.
AIMS & METHODS: The aim is to clarify clinicopathological risk factors for
LNM of T1 colorectal carcinomas and to establish the indication for additional
surgical colectomy with nodal dissection.
A total of 19882 colorectal neoplasms excluding advanced cancers have been
resected endoscopically or surgically at our unit from April 2001 to October
A237
2013. Of these, 907 T1 carcinomas were included. Initial or additional surgical
colectomy with nodal dissection was performed in 568 cases, and of which LNM
was found in 55 cases (9.7%). We analyzed the clinicopathological risk factors as
follows: age, gender, size, location, morphology, vessel permeation, tumor bud-
ding, poorly-differentiated or mucinous carcinoma (POR/MUC) component,
desmoplastic reaction (DR) on the superficial layer, degree of SM invasion,
and state of muscularis mucosae (MM grade). MM grade was evaluated into
two conditions using the desmin immunostaining: MM grade 1 (complete or
almost maintenance) and MM grade 2 (fragmentation or disappearance).
Finally, based on significant factors, we stratified these T1 cancers into 3
groups at ultralow, low and high risk of LNM.
RESULTS: The existence of vessel permeation, tumor budding, POR/MUC
component, MM grade 2 or the gender of female was significant. In contrast
with MM grade 2, no lesions corresponding to MM grade 1 had LNM. Among
T1 carcinomas with MM grade 2, male patients without vessel permeation,
tumor budding or POR/MUC component showed low incidence (1/93: 1.1%)
of LNM, while 54 (12.7%) of 433 patients with at least one factor had LNM.
CONCLUSION: The indication for additional surgical colectomy after endo-
scopic resection has been more clarified and simplified: MM grade 1 was sug-
gested to be an anti-risk factor for nodal metastasis (Ultralow-risk group). T1
carcinomas with MM grade 2 and without female gender, vessel permeation,
tumor budding or POR/MUC component may be acceptable for only monitor-
ing (Low-risk group). For T1 carcinomas with MM grade 2 and with at least one
factor, additional surgical colectomy with lymph node dissection should be
recommended (High-risk group).
Disclosure of Interest: None declared
P0386 DOES THE TYPE OF COLECTOMY MODIFY THE RISK OF
DESMOID TUMOR DEVELOPMENT IN FAMILIAL
ADENOMATOUS POLYPOSIS PATIENTS?
Z. Wang1, T. Walter2, O. Guillaud2, A. Pasquier3, E. Cotte3, O. Vinet2,
G. Poncet4, T. Ponchon5, J.-C. Saurin5,*
1
Hospices Civils de Lyon, Lyon, France, 2Gastroenterology, 3surgery, Hospices
Civils de Lyon, 4surgery, 5Gastroenterology, E. Herriot Hospital, Hospices Civils
de Lyon, Lyon, France
Contact E-mail Address: jean-christophe.saurin@chu-lyon.fr
INTRODUCTION: Desmoid tumors represent one major complication of the
disease in patients with familial adenomatous polyposis (FAP). Our aim was i) to
study factors associated with the development of desmoid tumors in a large
cohort of FAP patients and ii) to review the different treatment proposed with
corresponding results.
AIMS & METHODS: We reviewed retrospectively 190 cases of patients with
FAP, with complete medical records, followed at our institution between 1965
and 2013. There were 10 patients with biallelic MUTYH mutation (mean age
56,5 years) and 180 patients with either identified APC gene mutation, either a
personal and family history suggesting APC-related polyposis (mean age 44,1
years, 22-85).
Treatment of desmoid tumor was proposed in those patients with progressive
disease at radiological evaluation on a 4 to 6 month observational period. The
response was evaluated retrospectively from the reports, according to RECIST
criteria.
RESULTS: The median follow-up since the diagnosis of FAP was of 25 years.
No patients (0/10) with MUTYH mutation ever developed desmoid tumor. In
contrast, 31/180 (17.2%) patients with a mutation/phenotype of APC related
polyposis (11 H, 20 F) developed 58 DT, at a mean age of 44,1 yrs (range 22-
78 yrs). The localization of DT was: mesenteric 25, abdominal wall 25, extra-
abdominal 3 (breast 2, gluteal muscle 1). From these 180 patients, a colectomy
with ileo-rectal anastomosis had been performed in 104 (12 with DT, 11%) and
proctocolectomy in 76 (19 with DT, 25%, p 0.027). There was no other factor
associated with the development of DT, including the modality of surgery (lapar-
otomy versus laparoscopy). As regards the treatment of DT: no treatment was
proposed in 3 patients (mean FU 7,17 years); 12 patients (with 28 DT) had 29
medical therapeutic sessions with a mean duration of 12,8 months (range 3-24
months). Following RECIST criteria, a response was observed in 3 tumors
(10.3%), a stabilisation in 17 cases (58.7%) and a progressive disease in 9
cases (31%). Medical treatment was: celecoxib (6 sessions), sulindac (9), tamox-
ifen (4), imatinib (8), sorafenib (1), bevacizumab (2). Surgical treatment of the
DT was attempted for 32 tumors from 16 patients: 12 mesenteric (5 recurrences,
41.6%) et 21 extra mesenteric (6 recurrences, 28.5%).
CONCLUSION: This study suggests that the type of colorectal surgery
(colectomy versus proctocolectomy) is a major determinant of the risk of devel-
opping desmoid tumors in APC type FAP patients. If confirmed, this may impact
profoundly our surgical choices in these patients. On the other hand, we confirm
the low efficacy of available medical treatments for desmoid tumors of FAP
patients, and the high prevalence of post-surgical recurrences.
Disclosure of Interest: None declared
P0387 RADIATION PROCTOCOLITIS RESPONSE TO ARGON PLASMA
COAGULATION
J.S. Mcgrath1,*, D. Pace2, J. Mercer1, M. Borgaonkar1
1
Medicine, 2Memorial University, St. Johns, Canada
Contact E-mail Address: jmcgrath@mun.ca
INTRODUCTION: A mainstay in the treatment of prostate and some gyneco-
logical cancers is the use of external beam radiation therapy. Radiation proctitis
is a well-recognized complication of pelvic radiation and Argon Plasma
Coagulation (APC) is a very effective means of treatment. The literature support-
ing the use of APC is small.
A238
AIMS & METHODS: The current study is a prospective analysis of patients with
radiation proctitis referred from the Newfoundland and Labrador Bliss Murphy
Cancer Centre. There were 81 patients referred to one gastroenterologist and 55
were treated with APC (Jan. 2010 to Dec. 2013). We studied the complete resolu-
tion of symptoms which was defined as the absence of rectal bleeding. A partial
resolution was defined as a reduction in rectal bleeding.
RESULTS: This prospective cohort study was performed on all adults who
underwent colonoscopy for radiation proctitis. In total, 81 patients were seen,
90.1% men and mean age 68.4 (range: 48-87 years). The average time between
the last dose of radiation and the development of symptoms of proctocolitis was
21.8 months (range: 0-132 months). Complete resolution of symptoms was
reported in 75.9% of cases, partial resolution in 22.2% and only one patient
(1.85%) showed no improvement. The mean sessions of treatment with APC
was 1.86, (range 1-4). Furthermore, 61.5% of those with incomplete response
had other potential sources of rectal bleeding identified such as hemorrhoids or
an anal fissure. The rate of complications was 3.6% with 2 patients developing a
rectal ulcer. Colonic adenomas were detected in 60.5% of individuals and color-
ectal cancer is 6.2%. Hemoglobin values before and after APC were available in
ten patients and the mean increase was 9.6 g/L (range: -3 to 25 g/L).
CONCLUSION: APC is a safe and effective therapeutic modality for the treat-
ment of radiation-induced proctitis. Pelvic radiation exposure can be associated
with the development of symptoms of radiation proctitis. It is also associated
with the development of adenomas and colorectal cancer. This is the largest
reported case series to date regarding the utilization and efficacy of APC.
Disclosure of Interest: None declared
P0388 INHIBITION OF HUMAN AND MOUSE INTESTINAL AFFERENT
MECHANOSENSITIVITY BY ACTIVATION OF GUANYLATE
CYCLASE C
A. Broadhead1,*, C. McGuire1, D. Reed1, M. Peiris1, C. Knowles1, C. Kurtz2,
A. Silos-Santiago2, D. Bulmer1, L.A. Blackshaw1
1
Queen Mary University of London, London, United Kingdom, 2Ironwood
Pharmaceuticals Inc., Cambridge, United States
Contact E-mail Address: a.broadhead@qmul.ac.uk
INTRODUCTION: The guanylate cyclase C (GCC) agonist linaclotide reduces
abdominal pain in constipation-predominant IBS (IBS-C). Its mechanism of
action is via production and release of cyclic guanosine monophosphate
(cGMP) by intestinal epithelial cells, which subsequently acts on high-threshold
colonic afferent endings to reduce generation of pain signals in response to
mechanical stimuli[1].
AIMS & METHODS: To determine 1. if inhibition of afferents by GCC agonism
and by cGMP is seen also in a tubular preparation of mouse colon; 2. if this
translates to inhibition of responses to the same stimulus in human appendix.
Electrophysiological responses were recorded from human extrinsic nerve bun-
dles innervating tubular preparations of appendix[2]. A similar preparation was
used in mice to record responses of lumbar splanchnic afferents innervating the
distal colon.
RESULTS: Distension of mouse colon caused reproducible, stimulus-dependent
excitation of splanchnic afferents up to 60mmHg. Administration of cGMP
(500uM) or GCC agonist (linaclotide 1uM) significantly reduced the response
to medium-level (40mmHg; N 7, p 0.01) and high-level distension (60mmHg;
N 7, p 0.02). No effect was seen on response to low-level distension
(20mmHg; N 7, p 0.9). In recordings of human appendix afferent responses
to ramp distension (0-60mmHg), we attempted to release endogenous cGMP by
activating GCC maximally with intraluminal enterotoxin ST (100nM). This had
a similar pattern of effect as activation of GCC on mice on responses to disten-
sion, inhibiting only at high levels of distension (25% reduction, N 5,
p 0.008).
CONCLUSION: GCC agonists inhibit mechanosensory responses to distension
in intact in vitro preparations of both human and mice large intestine, but only at
high intensities that correspond to those that would evoke pain in vivo. This
provides important validation of the mechanism of action of linaclotide in reliev-
ing pain in IBS-C via peripheral inhibition of nociceptors in human intestine.
REFERENCES
1. Castro J et al. Gastroenterology 2013; 145: 1334-1346.
2. Peiris M et al. Gut 2011; 60: 204-208.
Support: Ironwood Pharmaceuticals Inc., Forest Laboratories.
Disclosure of Interest: A. Broadhead Financial support for research from:
Ironwood Pharmaceuticals Inc., Bowel and Cancer Research, C. McGuire:
None declared, D. Reed: None declared, M. Peiris: None declared, C.
Knowles: None declared, C. Kurtz Financial support for research from:
Ironwood Pharmaceuticals Inc., Shareholder of: Ironwood Pharmaceuticals
Inc., A. Silos-Santiago Financial support for research from: Ironwood
Pharmaceuticals Inc., Shareholder of: Ironwood Pharmaceuticals Inc., D.
Bulmer Financial support for research from: Pfizer, Shareholder of: GSK, L.
A. Blackshaw Financial support for research from: Ironwood Pharmaceuticals
Inc., Grunenthal, Lecture fee(s) from: Almirall
P0389 PATHOPHYSIOLOGICAL CHARACTERIZATION OF
SYMPTOM-BASED CLUSTERS OF PATIENTS WITH IRRITABLE
BOWEL SYNDROME FOLLOWING A COMBINED NUTRIENT AND
LACTULOSE CHALLENGE TEST
B.L. Neve1,*, R. Brazeilles1, M. Derrien1, J. Tap2, D. Guyonnet1, H. Tornblom3,
L. Ohman3, M. Simren3
1
Life Science, Danone Research, Palaiseau, 2INRA, Jouy en Josas, France,
3
Department of Internal Medicine & Clinical Nutrition, Institute of Medicine,
United European Gastroenterology Journal 2(5S)
Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: boris.le-neve@danone.com
INTRODUCTION: We recently demonstrated that a combined nutrient and
lactulose challenge test allows symptom-based clustering of patients with irritable
bowel syndrome (IBS) unrelated to exhaled gas and Rome III subtype (Le Neve
et al Am J Gastro 2013; oral communication UEGW 2013).
AIMS & METHODS: The aim was to further characterize the two IBS clusters
previously identified. We included 100 patients with IBS (Rome III) and 38
healthy controls. The fasted subjects were served a test meal consisting of a
400ml liquid breakfast (Nutridrink, 1.5 kcal/ml) containing 25g lactulose.
The severity of gastrointestinal (GI) symptoms, fatigue, somatization, anxiety
and depression were evaluated by questionnaires before the test (IBS-SSS,
GSRS, VSI, FIS, PHQ-15, HAD), as well as visceral sensitivity (barostat) and
fecal microbiota composition (16S rRNA pyrosequencing). The intensity of eight
GI symptoms, the overall level of digestive comfort and the amount of exhaled
H2/CH4 were assessed every 15min during 4h after meal intake. A mapping of the
eight GI symptoms was done using a Principal Components Analysis (4h mean
score). Independently, a hierarchical cluster analysis was performed on the same
parameters to identify GI symptom-based IBS clusters.
RESULTS: The combined nutrient and lactulose challenge test discriminated
IBS from healthy controls. The challenge also allowed clustering of IBS patients
in two subgroups i.e High GI symptom (HGS) and Low GI symptom (LGS)
based on intensity of GI symptoms, in line with our previous study. Patients in
the HGS group (n 39; mean 4h pain 9.3, bloating 10.3, distension 11.2,
discomfort 11.8) displayed higher IBS-SSS score (353.7 vs. 236.8; p50.0001)
and higher levels of anxiety (9.0 vs. 7.0; p50.05), fatigue (71.3 vs. 42.2; p50.001)
and somatization (14.7 vs. 11.8; p50.01) as well as lower overall digestive com-
fort (8.0 vs. 12.8; p50.001) than patients in the LGS group (n 61; mean 4h
pain 2.4, bloating 3.0, distension 3.4, discomfort 4.8; p50.001). Patients
in the HGS group displayed significantly higher rectal sensitivity compared to
both LGS patients and healthy controls (p50.001 for pain intensity at 12 and
24mm Hg). No significant difference was seen between IBS clusters for fecal
microbiota composition.
CONCLUSION: A test meal containing 25 g of lactulose allows clustering of IBS
patients according to their GI symptom response, which reflects visceral sensi-
tivity, IBS severity and psychological co-morbidity. This clustering cannot be
predicted by fecal microbiota composition. The lactulose challenge test appears
to be a promising tool to better define postprandial symptoms and the patho-
physiology of IBS, and to non-invasively assess visceral sensitivity.
Disclosure of Interest: B. Le Neve Other: Danone Research employee, R.
Brazeilles Other: Danone Research employee, M. Derrien Other: Danone
Research employee, J. Tap Financial support for research from: Danone
Research, D. Guyonnet Other: Danone Research employee, H. Tornblom:
None declared, L. Ohman: None declared, M. Simren Financial support for
research from: Danone Research, Consultancy for: Danone Research
P0390 NORMAL SIGMOID PENETRABILITY TO FLUORESCENT
BEADS THE SIZE OF BACTERIA IN PATIENTS WITH IRRITABLE
BOWEL SYNDROME
C. Wising1,*, E. Almqvist2, L. Eklund2, H. Tornblom2, M. Simren2,
M.E. Johansson1, G.C. Hansson1, H. Sjovall2
1
Institute of Biomedicine, 2Institute of Medicine, Sahlgrens Academy, University of
Goteborg, Goteborg, Sweden
Contact E-mail Address: henrik.sjovall@medfak.gu.se
INTRODUCTION: Altered intestinal barrier function has been suggested to play
an important role in the pathophysiology of IBS, but the properties of one of the
most important components of the intestinal barrier, the intestinal mucus layer,
have not been studied in IBS. The colonic mucosa is covered by a thick mucus
layer consisting of an inner adherent layer and an outer loose layer. The inner
layer is normally devoid of bacteria. We tested the hypothesis that the penetr-
ability of colonic mucus in situ to fluorescent beads the size of bacteria is
increased in patients with irritable bowel syndrome (IBS).
AIMS & METHODS: Sigmoid biopsies were taken from unprepared colon in 12
healthy controls (mean age 28 years, 5 males and 7 females) and 14 IBS patients
(2 males and 12 females), 2 IBS-C, 2 IBS-D and 10 IBS-M). 21 patients who
underwent colonoscopy for other reasons (e.g. bleeding of unknown origin), with
prepared colon, and 27 patients with ulcerative colitis (UC) in remission served as
positive controls. The biopsies were mounted horizontally in an oxygenized per-
fusion chamber. After 20 minutes, a standardized amount of fluorescent beads
with a size similar to that of bacteria (2 and 1 and 0.5 um) were added on the
mucosal side. 40 minutes later, bead distribution was assessed by confocal laser
microscopy at three laser frequencies, 488, 555 and 639 nm. The confocal images
were transferred into Matlab and were processed by customized software. Mean
bead intensity per 10 mm slice was calculated as a function of distance from end
of crypt openings and the distance of this slice from end of tissue was used as a
marker for bead penetrability. Mucus thickness was also measured repeatedly
over time in a horizontal perfusion chamber using a micropipette after addition
of charcoal particles to the apical side of the biopsy.
RESULTS: When measured repeatedly over time using carbon powder and a
micropipette ruler, mucus thickness after 60 min was 54065 mm in the controls
and 61050 in the IBS patients (p 0.19). When studied with fluorescent
microbeads, the distance of the slice with maximal bead intensity from the
mucosa at 60 minutes was 40060 mm in the controls and 47080 mm in the
IBS patients (p 0.50). In the control patients, with prepared colon, the corre-
sponding value was 50060 mm (n.s.). In contrast, in prepared colon from UC
patients in remission the distance was 28060 mm (p50.01 versus other groups).
Three different bead sizes were used to test the occurrence of size-dependent
United European Gastroenterology Journal 2(5S)
permeability. However, no significant differences in impermeable layer thickness
were found between the three bead sizes in any of the groups.
CONCLUSION: The values for mucus thickness in unprepared colon obtained
with the micropipette ruler carbon powder and the data obtained with the
fluorescent microbeads agree closely, with slightly lower values obtained with the
microbeads. In this small sample, sigmoid mucus from patients with IBS symp-
toms tended to have a mucus layer slightly thicker than in healthy controls (n.s.
with both techniques), while the UC patients in remission had a markedly
reduced thickness of the bead-impenetrable mucus layer.
REFERENCES
Johansson ME, Sjovall H and Hansson GC. The gastrointestinal mucus system
in health and disease. Nat Rev Gastroenterol Hepatol 2013; 10: 352-361.
Disclosure of Interest: None declared
P0391 A PILOT RANDOMIZED PLACEBO-CONTROLLED
MULTICENTER STUDY ON THE EFFECT OF PALMITOYL-
ETHANOLAMIDE AND POLYDATIN IN PATIENTS WITH
IRRITABLE BOWEL SYNDROME
C. Cremon1,*, G. Barbara1, L. Bellacosa1, M.R. Barbaro1, J. Santos2,
M. Vicario2, M. Pigrau2, C. Alonso2, S. Bruley des Varannes3, M. Neunlist3,
D. De Filippis4, T. Iuvone4, V. Di Marzo5, R. De Giorgio1, R. Corinaldesi1,
V. Stanghellini1
1
Department of Medical and Surgical Sciences, University of Bologna, Bologna,
Italy, 2Institut de Recerca de lHospital, Vall dHebron, Barcelona, Spain, 3Institut
des Maladies de lAppareil Digestif, Hotel Dieu, Nantes, France, 4Department of
Pharmacy, University of Naples Federico II, Naples, 5Institute of Biomolecular Hospital, Tongji University School of Medicine, shanghai, China
Chemistry, Consiglio Nazionale delle Ricerche, Pozzuoli (Naples), Italy
Contact E-mail Address: cesare.cremon@aosp.bo.it
INTRODUCTION: Intestinal immune activation and mast cell intestinal infil-
tration play a pathophysiological role in the irritable bowel syndrome (IBS).
Palmithoylethanolamide (PEA), the saturated fatty acid ethanolamide of palmi-
tic acid, structurally related to the endocannabinoid anandamide, exerts anti-
inflammatory and anti-nociceptive actions and inhibits mast cell activation.
Polydatin (PD) acts synergistically with PEA in reducing mast cell release of
cytokines and related T cell activation.
AIMS & METHODS: We designed a pilot, phase 2, randomized, double-blind,
placebo-controlled, multicenter study evaluating the efficacy and safety of PEA/
PD in patients with IBS. Patients with Rome III confirmed IBS and healthy age-
and gender-matched subjects (HC) were recruited from 5 European study centers
(Bologna, Nantes, Barcelona, Tuzla, and Zagreb). After a 2-week run-in, the
patients were randomly assigned to oral tablets micronized PEA/PD 200 mg/
20 mg or placebo, b.i.d for 12 weeks. The efficacy evaluation included the assess-
ment of: 1) mast cell infiltration and endocannabinoid system in patients with
IBS vs. HC. 2) the effect of active treatment vs. placebo on mast cell infiltration,
endocannabinoid system, and symptoms in patients with IBS. Colonic mucosal
biopsies were obtained during at screening visit and at the end of the study.
Biopsies were processed for quantitative immunohistochemistry for mast cells,
and for biomolecular analysis of the endocannabinoid system (by liquid chroma-
tography and western blot).
RESULTS: A total of 54 patients with IBS (29 allocated to PEA/PD and 25 to
placebo) and 12 HC were recruited in the study. Mast cell counts were significantly
increased in patients with IBS in comparison with HC (5.3%2.7% vs. 3.21.3;
p 0.013). Compared to HC, expression of the peripheral cannabinoid receptor
CB2 in the tissue was higher in IBS (p 0.012) while the fatty acid amide oleoy-
lethanolamide was significantly reduced (p 0.007). The logistic model for repeated
measures did not reveal statistically significant effects of PEA/PD on mast cells and
endocannabinoid system. Nonetheless, compared with placebo, PEA/PD improved
abdominal pain severity (repeated measure ANOVA test; P50.05).
CONCLUSION: Our study suggests that PEA/PD is a promising effective treat-
ment in the management of pain in patients with IBS. Whether the PEA/PD
effect is secondary to mast cell stabilising or to modulation of the endocannabi-
noid system remains to be further investigated. ClinicalTrials.gov Identifier:
NCT01370720.
Disclosure of Interest: None declared
P0392 ASSOCIATION BETWEEN CHANGES OF INTESTINAL
MICROBIOTA, CHARACTERISTICS OF ANORECTAL MOTILITY
AND RECTAL SENSITIVITY DISTURBANCES USING HIGH-
RESOLUTION ANORECTAL MANOMETRY (HRAM) IN PATIENTS
WITH DIARRHEA-PREDOMINANT IRRITABLE BOWEL
SYNDROME
E. Polouektova1,*, S. Kuchumova1, V. Ivashkin1, E. Kostryukova 2,
O. Storonova1, O. Liashenko1, A. Troukhmanov 1, V. Govorun2, O. Shifrin1,
A. Sheptulin1
1
I. M. Sechenov First State Moscow Medical University, 2Scientific Research
Institute of Physical-Chemical Medicine, Moscow, Russian Federation
Contact E-mail Address: polouektova@rambler.ru
INTRODUCTION: At present the role of changes of the intestinal microbiota in
pathogenesis of irritable bowel syndrome (IBS) is widely discussed. Impact of
microbiome on the gastrointestinal motility and visceral hypersensitivity is
assumed. However the relevant data have been investigated insufficiently.
AIMS & METHODS: To estimate correlation between changes of the composi-
tion of intestinal microbiota, anorectal motility disorders and visceral hypersen-
sitivity in patients with diarrhea-predominant IBS (IBS-D).
31 patients with IBS-D (clinical type was determined according to the ROME III
criteria) and 15 healthy volunteers were studied. All subjects were analysed by
examining sequencing data of the 16s rRNA from fecal samples, the hydrogen
A239
breath test with lactulose to determine small intestinal bacterial overgrowth
(SIBO), high-resolution anorectal manometry (HRAM) using 20 channel
water-perfused catheter with a polyethylene balloon (Solar GI, MMS, the
Netherlands).
RESULTS: By sequencing of the 16s rRNA differences were found in the com-
position of intestinal microbiota between the IBS-D patients and healthy volun-
teers. In patients with IBS Bacteroides (18.9%), Coprococcus (7.2%) and Blautia
(5.4%) were detected more often, the control group showed prevalence of Blautia
(17.1%), Prevotella (8.3%) and Faecalibacterium (6.9%) (p50.05). A positive
result of breath test (the presence of SIBO) was found in 20 patients with IBS-
D (62.5%) and was not detected in the control group. A negative correlation was
revealed between positive result of the breath test and the following parameters
of rectal sensitivity and function of the anal sphincter: average pressure of the
anal sphincter, average maximum compression pressure of the anal sphincter, the
threshold for strong urge to defecate and maximum tolerable volume (p50.05).
CONCLUSION: Disruptions in the qualitative and quantitative composition of
intestinal microbiota are found in patients with IBS-D; these changes are corre-
lated with the parameters of anorectal motility and rectal sensitivity.
Disclosure of Interest: None declared
P0393 INSULAR HTR1A-NR2B PATHWAY MEDIATE THE VISCERAL
HYPERSENSITIVITY INDUCED BY CHRONIC STRESS IN RATS
H. Sun1,*, L. Yi1, L. Zhou1, Y. Chen1, Y. Jiang1, P. Wu2, S. Xu1
1
Department of Gastroenterology, Tongji Institute of Digestive Diseases, Tongji
Hospital, Tongji University School of Medicine, 2Clinical Nutrition, Tongji
Contact E-mail Address: s-haijie@163.com
INTRODUCTION: In many clinical studies, 5-HT1A receptor (HTR1A) of the
central nervous system (CNS) was thought to be important in the pathogenesis of
chronic stress related functional gastrointestinal disorders (FGIDs), but its
potential mechanism is still not clear. Some studies thought the abnormality of
HTR1A in CNS, through changing neuron activities of visceral sensory area such
as insular cortex, mediated visceral hypersensitivity which was an important
pathophysiological mechanism of stress-related FGIDs. NR2B was perhaps
one key downstream signaling molecule of HTR1A. Insular HTR1A-NR2B
pathway is inferred to be important in modulating the visceral hypersensitivity
induced by chronic stress.
AIMS & METHODS: This study aimed to determine if insular HTR1A-NR2B
pathway influences the activity of insula and mediates the visceral hypersensitiv-
ity induced by chronic stress in rats. Chronic water avoidance stress (WAS) was
used to establish visceral hypersensitivity rat models. Visceral sensitivity was
determined by measuring the visceromotor response (VMR) amplitude to
60mmHg colorectal distention (CRD). The HTR1A agonist 8-OH-DPAT and
the HTR1A antagonist WAY100635 were microinjected into the left or right
insular cortex. The expression levels of 5-HT, HTR1A, NR2B and c-fos were
observed by RT-PCR, Western Blot or immunohistochemical staining.
RESULTS: Compared with sham WAS and normal rats, the expression levels of
5-HT and HTR1A in the bilateral insular cortex of WAS rats were significantly
lower (p50.05), but the expression levels of c-fos and NR2B were significantly
higher in the bilateral insular cortex of WAS rats (p50.05). After 8-OH-DPAT
intervention of left or right insular cortex, the VMR amplitudes to 60mmHg
CRD could be significantly reduced in WAS rats (p50.01). After WAY100635
intervention of left or right insular cortex, the VMR amplitudes have no signifi-
cant changes in WAS rats (p40.05). The expression levels of bilateral insular
NR2B and c-fos in 8-OH-DPAT intervention group were significantly lower than
that in WAY100635 intervention group (p50.05).
CONCLUSION: Through regulating the activity of insular neuron, HTR1A-
NR2B pathway has a critical role in mediating the visceral hypersensitivity
induced by chronic stress in rats.
Disclosure of Interest: None declared
P0394 HIGHER FREQUENCY OF NEGATIVE SELF-ESTEEM AND
INFERIOR COPING STRATEGIES FOUND AMONG IBS PATIENTS
A. Faresjo1,*, L. Viktorsson2, V. Tegelstrom3, T. Faresjo1, M.P. Jones4,
S. Walter5, E. Grodzinsky3
1
Medicine and Health, linkopings University, Community medicine, 2Medicine and
Health, Linkopings universitet, 3Unit of Research and development, County
Council of Ostergotland, Linkoping, Sweden, 4Psychology Department, Macquarie
University, Sydney, Australia, 54Institution of Clinical and Experimental Medicine,
Division of Gastroenterology, Linkoping, Sweden
Contact E-mail Address: ashild.olsen.faresjo@liu.se
INTRODUCTION: A positive self-image is one of the key components for good
health and wellbeing. Irritable Bowel Syndrome has been reported to be asso-
ciated with altered psychological and cognitive functioning such as mood dis-
turbances somatization, catastrophizing or altered visceral interoception by
negative emotions and stress (1,2).
AIMS & METHODS: Aims to investigate the psychosocial constructs of self-
esteem and sense of coherence among IBS patients compared to non-IBS
patients. A case-control study in primary care setting among IBS patients meet-
ing the ROME III criteria (n 140) compared to controls i.e non-IBS patients
(n 213) in primary care without any present or previous gastrointestinal com-
plaints. The data were collected through self-reported questionnaires of psycho-
social factors.
RESULTS: IBS patients reported significantly higher frequency of more negative
self-esteem than controls (p50.0001), had lower scores on the positive self-
esteem measurement (p50.0001), and lower sense of coherence (p50.0001)
than the controls. The IBS cases were also less likely to report good health
A240
status (p50.0001) and less likely to report a positive belief in the future
(p50.0001). After controlling for relevant confounding factors in multiple
regressions, the more negative self-esteem for IBS patients remained statistically
significant (p 0.02), as were the lower scores for sense of coherence for IBS
cases (p 0.04).
CONCLUSION: The more frequently reported negative self-esteem and inferior
coping strategies among IBS patients found in this study suggest the possibility
that psychological therapies such as cognitive behavior therapy might be helpful
for these patients. However these data do not indicate the causal direction of the
observed associations. More research is therefore warranted to determine whether
these psychosocial constructs are more frequent personality traits in IBS patients
or if the disease itself lowers self-esteem and leads to inferior coping strategies.
REFERENCES
1. Bengtsson M, Sjoberg K, Candamio M, et al. Anxiety in close relationships is
higher and self-esteem lower in patients with irritable bowel syndrome compared
to patients with inflammatory bowel disease. Eur J Intern Med 2013; 24: 266-272.
2. Lackner JM, Gudleski GD, Firth R, et al. Negative aspects of close relation-
ships are more strongly associated than supportive personal relationships with
illness burden of irritable bowel syndrome. J Psychosom Res 2013; 74: 493-500.
Disclosure of Interest: None declared
P0395 LABOUR PRODUCTIVITY LOSS BECAUSE OF IRRITABLE
BOWEL SYNDROME COMPLAINTS
C. Flik1,*, W. Laan1, A. Smout2, N.de Wit1
1
Julius Center, Health Sciences and Primary Care, University Medical Centre,
Utrecht, 2Gastroenterology and Hepatology, Academic Medical Centre,
Amsterdam, Netherlands
Contact E-mail Address: c.e.flik@umcutrecht.nl
INTRODUCTION: Irritable Bowel Syndrome (IBS) is the most prevalent
chronic functional bowel disease. IBS often results in a substantial disease
burden for the patient and leads to considerable medical costs. Systematic
reviews reporting economic consequences of IBS focus on direct medical costs
and indirect societal costs, such as loss of productivity. When calculating indirect
costs for IBS most researchers only take the costs for loss of labour days into
account. In our view disease-related loss of labour productivity should also con-
sider the IBS-related impact on work productivity on the days that the IBS
patient is present at work.
AIMS & METHODS: We report the overall impact of IBS on labour produc-
tivity, i.e. the combined number of sick leave days and the loss of efficiency
during the days IBS patients did work with active IBS complaints.
207 adult patients (18-65 years of age) with IBS, meeting Rome III criteria, who
were recruited for a randomized controlled trial on hypnotherapy were selected.
The impact of IBS on work was measured with four questions of the Trimbos/
iMTA questionnaire for Costs associated with Psychiatric Illness (Tic-P): ques-
tion 1 is about absenteeism from work because of IBS in the past two weeks (yes/
no), Q2 about absenteeism for more than two weeks (yes/no),Q3 assessed if one
was hindered by IBS complaints when working in the past two weeks (no, not at
all; yes, somewhat; yes considerably) and Q4 assessed how efficient one has
worked with the IBS complaints (from zero, indicating maximally inefficient
up to 10: as efficiently as normal).
RESULTS: Of the 140 patients who had a job, 104 (74.3%) were women and 36
(25.7%) men. Of these female IBS patients 19 (18.2%) were absent from work
because of IBS complaints, 10 (9.6%) less than two weeks, 9 (8.7%) more than
two weeks. Eleven of these patients had moderate and 8 patients had severe IBS.
Five of the male IBS patients (13.9%) were absent from work because of IBS com-
plaints, 3 (8.3%) less than two weeks, 2 (5.6%) more than two weeks; one had
moderate and four severe IBS. IBS subtype was known of 131 working IBS patients,
21 (16%) had IBS-Constipation, 33 (25.2%) had IBS-Diarrhea and 77 (58.8%) had
IBS-Mixed type. Of the patients with IBS-C 2 (9.5%) were absent less than two
weeks, 0% more than two weeks; of the patients with IBS-D 3 (9.1%) were absent
less than two weeks and 2 (6.1%) more than two weeks; of the patients with IBS-M 8
(10.4%) were absent for less than two weeks and 8 (10.4%) for more than two weeks.
In 20% of the female and 7% of the male working IBS patients IBS complaints
had no impact on their labour productivity, 64% of women and 23% of men
were hindered to some extent and 16% of women and 23% of men were hindered
very much by their IBS complaints in performing their job; 33.3% of women and
52.8% of men indicated that they worked less efficiently than normal (score  6)
because of their IBS complaints.
CONCLUSION: IBS complaints do not only result in substantial absenteeism
from work, but also in severe loss of efficiency among those IBS patients who do
not report sick, but continue working. When quantifying disease-related loss of
labour productivity both aspects should be taken into account.
Disclosure of Interest: None declared
P0396 EXTENSIVE OVERLAP AMONG PATIENTS WITH IRRITABLE
BOWEL SYNDROME WITH CONSTIPATION, CHRONIC
IDIOPATHIC CONSTIPATION, FUNCTIONAL DYSPEPSIA, AND
GASTROESOPHAGEAL REFLUX DISEASE: A CROSS-SECTIONAL,
POPULATION-BASED SURVEY
N. Vakil1, J.M. Johnston2,*, M. Stelwagon2, E. Shea2, S. Miller3
1
University of Wisconsin School of Medicine and Public Health, Madison,
2
Ironwood Pharmaceuticals, Cambridge, 3Lieberman Inc., Great Neck, United
States
INTRODUCTION: Individuals with functional gastrointestinal disorders
(FGIDs) may report symptoms of more than one FGID as well as symptoms of
gastroesophageal reflux disease (GERD). This US cross-sectional Internet-based
survey assessed overlap of these disorders and sufferers symptom experience.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: A random sample of 10,030 US citizens completed an
online screening questionnaire to identify those meeting Rome III criteria for
irritable bowel syndrome with constipation (IBS-C), chronic idiopathic constipa-
tion (CIC), and/or functional dyspepsia (FD), and/or who reported GERD
(defined as heartburn or regurgitation twice/week in the absence of treatment).
Survey responses were weighted for age and gender to be representative of the US
census. Respondents who met criteria for 1 condition completed a detailed
questionnaire including a symptom checklist and questions about bothersome-
ness, severity and frequency of symptoms and healthcare-seeking behaviour.
Respondents reported symptoms experienced in the past 12 months, rating
them on a scale from less than 5 days a year to everyday. Overall and
individual gastrointestinal (GI) symptom bothersomeness was reported on a 5-
point scale from not at all to extremely bothersome.
RESULTS: A total of 2641 respondents met criteria for 1 condition. Including
those with overlapping conditions, 328 met criteria for IBS-C, 552 for CIC, 1690
for FD and 1337 for GERD; 56.5%, 39.9%, 44.7% and 44.2%, respectively,
reported very/extremely bothersome GI symptoms. Overall, 1592 (60.3%) met
criteria for a single condition, 832 (31.5%) met criteria for 2 conditions and 217
(8.2%) met criteria for 3. Of the 4 conditions, respondents with IBS-C were the
most likely to have overlapping conditions. Overall bothersomeness of symptoms
increased with condition overlap: 22.5-30.4% of respondents with 1 condition
had very/extremely bothersome symptoms, compared to 37.1-65.7% of those
with 2 conditions, and 65.1-73.5% of those with 3 conditions. With the exception
of heartburn/acid reflux, the frequency and bothersomeness of individual symp-
tomsincluding abdominal pain, bloating, diarrhea, and constipationalso
increased with condition overlap.
TABLE 1. Condition Overlap
IBS-C CIC FD GERD
N (total 2641) (n 328) (n 552) (n 1690) (n 1337)
One Condition Only 57 (17%) 207 (38%) 721 (43%) 607 (45%)
and IBS-C1 247 (15%) 137 (10%)
and CIC1 289 (17%) 160 (12%)
and FD1 247 (75%) 289 (52%) 650 (49%)
and GERD1 137 (42%) 160 (29%) 650 (38%)
3 conditions 113 (34%) 104 (19%) 217 (13%) 217 (16%)
CONCLUSION: Functional GI disorders frequently overlap with each other and
with GERD. Patients with overlapping FGIDs have more frequent and bother-
some symptoms and greater symptom burden. Results of clinical trials in FGIDs
may be modified by overlapping FGIDs; baseline symptom severity may be
affected by FGID overlap and global response measures may mask therapeutic
response in one or the other FGID. (Study sponsored by Forest Laboratories, Inc.,
and Ironwood Pharmaceuticals, Inc.)
Disclosure of Interest: N. Vakil Financial support for research from: Pfizer,
Consultancy for: Astra Zeneca, Ironwood, Otsuka, Takeda, Shareholder of:
Meridian (stock ownership), J. Johnston Shareholder of: Ironwood
Pharmaceuticals, Other: Employee Ironwood Pharmaceuticals, M. Stelwagon
Shareholder of: Ironwood Pharmaceuticals, Other: Employee Ironwood
Pharmaceuticals, E. Shea Shareholder of: Ironwood Pharmaceuticals, Other:
Employee Ironwood Pharmaceuticals, S. Miller Consultancy for: Astra Zeneca,
Ironwood, Otsuka, Takeda, Pfizer
P0397 THE PATH FROM GI SYMPTOMS TO DEPRESSED MOOD AND
ELEVATED STRESS: IS IT SPECIFIC TO IBS?
M. Jones1,*, S. Walter2, E. Grodzinsky3, L. Viktorsson3, N.J. Talley4, A. Faresjo5
1
Psychology Department, Macquarie University, North Ryde, Australia,
2
Institution of Clinical and Experimental Medicine, 3Department of Medical and
Health Sciences, Linkoping University, Linkoping, Sweden, 4Faculty of Health &
Medicine, University of Newcastle, Callaghan, Australia, 5Dept of Medicine and
Health Sciences, Linkoping University, Linkoping, Sweden
Contact E-mail Address: mike.jones@mq.edu.au
INTRODUCTION: The irritable bowel syndrome (IBS) has been associated with
depressed mood1 and elevated levels of perceived life stress2, presumably via the
adverse effects of the gastrointestinal (GI) symptoms associated with the disor-
der. However some degree of GI symptoms are also present in non-IBS indivi-
duals, including healthy community members.
AIMS & METHODS: We aimed to determine whether the path from GI symp-
toms to disordered mood leading to elevated perceived stress was different in IBS
and non-IBS or undifferentiated between these groups.
Subjects (n 192, 16% IBS, 84% controls) were all patients at primary health
care clinics in one of three Swedish cities as part of the Twin Cities study based
at Linkoping University. Rome II criteria were assessed by the standard Rome
Foundation questionnaire. GI symptom burden was assessed by 14 day diary and
measures included percent of days with record of nausea, bloating, any abdom-
inal pain (AP), moderate AP and intense AP. Maximum recorded pain intensity
was also noted. Mood was assessed via questions addressing depression symp-
toms and the EuroQol 5 questionnaire. Stress was measured via the Perceived
Stress Scale (PSS). A Structural equation model (SEM) was used to model latent
variables for GI symptom burden predicting mood, which then predicted stress.
Standardized path coefficients are reported along with measures of model fit.
RESULTS: In the combined sample GI symptom burden was found to predict
mood (b 0.184, SE 0.076) and mood was found to predict stress (b 0.591,
SE 0.080). When stratified, the model path coefficients were not different in
any significant respect between IBS and non-IBS patients. GI symptoms
United European Gastroenterology Journal 2(5S)
predicting mood yielded: IBS (b 0.163, SE 0.176) and control (b 0.219,
SE 0.090) while for mood predicting stress: IBS (b 0.708, SE 0.141) and
control (b 0.582, SE 0.089). Model fit did not differ significantly between
the combined and stratified models, indicating that the subtle observed differ-
ences in path coefficients were consistent with random chance. The latent vari-
ables representing GI symptoms and mood provided an adequate representation
of the GI and mood constructs (c2/df 1.73, CFI 0.99, RMSEA 0.06). This
was equally true in the IBS and control groups.
CONCLUSION: Our data support the general hypothesis that symptom experi-
ence is associated with elevated mood disturbance which is associated with ele-
vated levels of psychological stress. However while it has been assumed that there
is something special about IBS symptomatology that induces mood disorder, our
data suggests that while IBS is associated with higher levels of symptoms, the
association between GI symptoms and mood, thence perceived stress exists
equally in IBS and non-IBS individuals.
REFERENCES
1. Blanchard, EB, et al. The role of anxiety and depression in the irritable bowel
syndrome. Behav Res Ther 1990; 28: 401-405.
2. Murray, CD, et al. Effect of acute physical and psychological stress on gut
autonomic innervation in irritable bowel syndrome. Gastroenterology 2004; 127:
1695-1703.
Disclosure of Interest: None declared
P0398 FUNCTIONAL SYMPTOMS IN THE GENERAL POPULATION
DIARY VERSUS QUESTIONNAIRE
M. Jones1,*, S. Walter2, N. Talley3, L. Agreus4, A. Andreasson4,5
1
Department of Psychology, Macquary University, North Ryde, Australia,
2
Institution of Clinical and Experimental Medicine (IKE), Linkoping University,
Linkoping, Sweden, 3Faculty of Medicine, University of Newcastle, Newcastle,
Australia, 4Karolinska Institutet, Centre for Family Medicine, Huddinge, 5Stress
Research Institute, Stockholm University, Stockholm, Sweden
Contact E-mail Address: anna.andreasson@ki.se
INTRODUCTION: Previous studies have found discrepancies between recall
and diary reports of symptoms[1]. While questionnaires are commonly used
and convenient they can also be prone to recall bias [2]. Since the standard
Rome criteria are symptom recall based, if the source of symptom information
tangibly changes the clinical picture it calls into question diagnostic criteria.
AIMS & METHODS: We investigated the concordance between the IBS-sup-
portive criteria pain relieved by defecation and onset of stools associated with
a change in stool consistency between questionnaire recall and prospective diary
reports. The present study population consists of 272 participants of a random
population based colonoscopy study. Pain relieved by defecation (PRBD) was
identified in 7 day diary records by selecting all hours when defecation was
reported then checking whether pain was reported in a two-hour window prior
to the hour in which defecation was reported but was absent in the two hour
window after defecation was reported. The Rome II IBS criterion of stool con-
sistency altered by pain was assessed by comparing the distribution of Bristol
stool scores (Bristol) on days when pain was reported to the distribution on days
when no pain was reported. Statistical contrasts, based on unconditional logistic
regression, are adjusted for repeated measurements on individuals using the
linearization method to yield correct standard errors and p-values.
RESULTS: Pain relieved by defecation: The PRBD pattern was ever identified in
3.4% of participants compared with the corresponding questionnaire item asking
whether pain was ever relieved by defecation in a 3-month recall period where the
prevalence was 55.3%. However concordance between diary and questionnaire
was only 66.1% and kappa was close to zero (0.07). The PRBD diary pattern was
seen significantly more often in persons who reported pain relieved by defecation
on the questionnaire (7.2%) than persons who did not (1.3%) indicating that
diary and questionnaire are not completely disconnected. Change in stool form
with pain: Among all participants, hard stools were more often reported on pain
days (OR: 4.06, 95% CI: 2.14-7.71, p50.001 for Bristol score 1 and OR: 2.67,
95% CI: 1.61-4.42, p50.001 for Bristol score 2). However this was true for all
participants, regardless of whether they reported onset of pain or discomfort
associated with hard stools on the questionnaire. No difference in the occurrence
of loose stools on pain versus non-pain days was observed, not even in partici-
pants who reported onset of pain associated with loose stools.
CONCLUSION: The poor concordance between prospective diary and retro-
spective questionnaire might be due to any of: 1) poor recall when completing
questionnaires, 2) symptoms fluctuate over short time scales or 3) a 7 day diary is
too short to accurately capture low prevalence conditions. Given the apparent
central importance of measurement methodology to prevalence of disease the
reasons for this poor concordance needs to be elucidated.
REFERENCES
1. Dinning PG, et al. The impact of laxative use upon symptoms in patients with
proven slow transit constipation. BMC Gastroenterol 2011; 11: 121.
2. Coughlin SS. Recall bias in epidemiologic studies. J Clin Epidemiol 1990; 43:
87-91.
Disclosure of Interest: None declared
P0399 EFFECT OF THE FODMAP-RESTRICTED DIET ON COLONIC
GAS PRODUCTION CAPACITY IN PATIENTS WITH FUNCTIONAL
GASTROINTESTINAL DISORDERS
M.L. Ones1,*, I. Thun1, F.Van Megen1, M.H. Morken1, G.E. Kahrs1,
G.M. Oldery1, T. Hausken1, J.G. Hatlebakk1
1
Department of Clinical Nutrition and Section of Gastroenterology, Department of
Medicine, Clinical Institute 1 (K1), University of Bergen, Haukeland University
A241
Hospital, Bergen, Norway
Contact E-mail Address: mon083@student.uib.no
INTRODUCTION: The FODMAP-(fermentable oligo-, di-, and monosacchar-
ides and polyols) restricted diet is used as a treatment for functional gastrointest-
inal disorders such as irritable bowel syndrome (IBS) [1], with the goal of
reducing fermentation and gas related symptoms. We wanted to investigate
whether the capacity for gas production changed over time when consuming a
FODMAP-restricted diet among patients with IBS or functional dyspepsia (FD).
AIMS & METHODS: 29 patients with IBS (n 19) or FD (n 10), were diag-
nosed according to ROME III criteria for IBS and FD (24F/5M, age 3411y).
Participants were instructed thoroughly about the diet from a clinical dietician
and followed closely for 6  1 weeks. Repeated 4 days prospective food records
(baseline and 6 weeks) were used to measure diet changes and adherence to the
diet. Lactulose breath test was performed before, and during the last week of the
diet. Participants were adviced to not drink/eat/smoke 10 hours before the test
(usually at 8:30). After baseline breath test they consumed 10 g of lactulose
dissolved in 120 ml water and breath samples were collected every 15 min for
180 min. Hydrogen and methane gas was analysed in a Model SC Quintron Gas
Chromatograph. The area under the curve (AUC) was used as a measurement for
gas production, and breath samples before lactulose intake were used to study
adherence with the diet. Statistical test used were paired t-test, Wilcoxon signed
rank and Spearman and Pearson correlation test.
RESULTS: The FODMAP intake significantly decreased from median 8 g/d to
0.25 g/d (p 5 0.0001), and good adherence was also verified by baseline breath
samples for hydrogen which decreased from median 6 to 2 ppm (p 0.0124), and
methane from median 25 to 18 ppm (n.s. p 0.6797). 28 (18 IBS/10 FD) had
hydrogen production and there was a significant reduction from median 4418 to
1710 ppmxmin (p 0.0035) during the diet intervention. 9 (7 IBS/2FD) partici-
pants had methane production, with a reduction from median 9495 to 6750
ppmxmin (n.s. p 0.5415). Correlation between the change in FODMAP
intake and the change in hydrogen (r -1609, p 0.4045) or methane production
was not significant (r -0.1019, p 0.7943).
CONCLUSION: The FODMAP-restricted diet was associated with a reduction
in the capacity for hydrogen gas production in patients with IBS or FD, which
might indicate a shift in colonic microbiome
REFERENCES
1. Halmos EP, et al. A diet low in FODMAPs reduces symptoms of irritable
bowel syndrome. Gastroenterology 2014; 146: 67-75 e5.
Disclosure of Interest: None declared
P0400 WORK PRODUCTIVITY AND ACTIVITY IMPAIRMENT IN IBS: A
MULTIFACETED PROBLEM
A. Frandemark1,*, G. Ringstrom1, H. Tornblom1, M. Simren1
1
Deparment of Internal Medicine & Clinical Nutrition, Institute of Medicine,
Sahlgrenska Academy, University of Gothenburg, Goteborg, Sweden
Contact E-mail Address: asa.frandemark@gmail.com
INTRODUCTION: IBS is one of the most prevalent functional gastrointestinal
disorders. Earlier studies have shown that IBS patients are more likely to be
impaired at work and during daily activities compared to non-IBS patients.
However, factors of importance for this impairment have not yet been fully
examined.
AIMS & METHODS: Our aim was to investigate the relationship between work
impairment and other factors related to IBS. We included 533 patients with IBS
(median age 34 (17-80) years, 420 females). The patients completed the Work
Productivity and Activity Impairment Questionnaire:IBS (WPAI:IBS), as well as
questionnaires to assess IBS symptom severity (IBS-SSS), GI-specific anxiety
(VSI), somatic symptoms (PHQ-15), depression and anxiety (HAD), and fatigue
(MFI). Uni- and bivariate analyses were performed, as well as linear regression
analyses to determine factors independently associated with the work productiv-
ity and activity impairment measures.
RESULTS: The IBS patients reported 719% (meanSD) absenteeism (actual
work time missed), 3325% presenteeism (impairment while at work), 3627%
overall work productivity loss and 4627% activity impairment. Female IBS
patients reported greater activity impairment than males (4727 vs. 4127%;
p50.05), but no other gender differences were found. A weak, but statistically
significant negative association was noted between age and activity impairment
(rho -0.11; p50.05), but otherwise age was not associated with the work pro-
ductivity and activity impairment. No differences between IBS-subtypes were
found. With increasing severity of IBS symptoms, somatic symptoms and GI-
specific anxiety, higher degrees of absenteeism, presenteeism, overall work pro-
ductivity loss and activity impairment were seen (p50.0001 for all). Among the
fatigue measures, physical fatigue, general fatigue and reduced activity demon-
strated the strongest associations with the work productivity and activity impair-
ment (rho 0.28-0.47; p50.01). Weaker, but still statistically significant
associations were seen between general anxiety and depression and presenteesim,
overall productivity loss and activity impairment (rho 0.19-0.30; p50.05).
Using linear regression analysis, IBS symptom severity, GI-specific anxiety and
general fatigue were independently associated with presenteeism (R2 0.36;
p50.05) and overall productivity loss (R2 0.42; p50.05), while activity impair-
ment was independently associated with IBS symptom severity and general fati-
gue (R2 0.40; p50.05).
CONCLUSION: Work productivity and activity impairment is a substantial
problem in patients with IBS. A combination of IBS and somatic symptom
severity, fatigue and psychological factors seem to impact the IBS patients abil-
ity to be active and productive at work. Based on this, a multidimensional
treatment approach for IBS patients seems logical.
Disclosure of Interest: None declared
A242
P0401 THE SEVERITY OF SYMPTOMS RELATED TO IRRITABLE
BOWEL SYNDROME IS A RISK FACTOR FOR THE
MISCLASSIFICATION OF SIGNIFICANT ORGANIC DISEASE
D. Carter1,2,*, E. Bardan1,2, E. Derazne 1, B. novis1,2, M. Beer-Gabel1,2
1
Sackler Faculty of Medicine, Tel Aviv, 2Gastroenterology, Chaim Sheba Medical
Center, Ramat Gan, Israel
Contact E-mail Address: dr.dancarter@gmail.com
INTRODUCTION: The diagnosis of Irritable Bowel Syndrome (IBS) is based
mainly of clinical evaluation. The reported incidence of misclassification of sig-
nificant organic diseases in previously diagnosed IBS patients differs between
studies.
AIMS & METHODS: We examined the incidence and risk factors for the diag-
nosis of significant organic diseases (inflammatory bowel disease (IBD), Celiac
disease, gastrointestinal malignancy and thyroid dysfunction) in a cohort of
2645 IBS.
RESULTS: During follow-up, organic disease was diagnosed in 27 subjects
(1.03%): IBD in 23, Celiac disease in 2, IBD and Celiac disease in one and
hypothyroidism in one. The mean interval from the diagnosis of IBS to the
diagnosis of an organic disorder was 13.088.51 months. Increased symptom
severity was the only significant risk factor for the misclassification of an organic
disease (HR 2.26, 95%CI 1.01-5.05 p 0.047). The risk ratio for misclassification
of organic diseases in moderate to severe IBS was increased by 2.575 (95%CI
1.10-6.51, p 0.027) in relation to mild IBS.
CONCLUSION: The incidence of misclassification of major organic disease in
IBS patients was low. Increased symptoms severity was the only significant risk
factor for the misclassification of organic disorders. Further gastrointestinal eva-
luation should be considered when symptoms are moderate to severe.
Disclosure of Interest: None declared
P0402 BILE ACID DIARRHOEA MASQUERADES AS DIARRHOEA-
PREDOMINANT IRRITABLE BOWEL SYNDROME: RESULTS
FROM A DUAL CENTRE PROSPECTIVE STUDY
I. Aziz1,*, S. Mumtaz2, H. Bholah2, F.U. Chowdhury3, D.S. Sanders1,
A.C. Ford2
1
Department of Gastroenterology, Royal Hallamshire Hospital, Sheffield, 2Leeds
Gastroenterology Institute, 3Nuclear Medicine Department, St Jamess University
Hospital, Leeds, United Kingdom
INTRODUCTION: Several studies have suggested that bile acid diarrhoea
(BAD) can present with symptoms that are compatible with diarrhoea-predomi-
nant irritable bowel syndrome (IBS-D). However, uncertainty exists as these have
often been retrospective, have not defined IBS-D according to accepted diagnos-
tic criteria, or have included patients with chronic diarrhoea in the analysis. We
have examined this issue in a well-characterised cohort of patients with rigor-
ously defined IBS-D.
AIMS & METHODS: This was a prospective cross-sectional survey conducted
among consecutive patients with IBS-D attending Gastroenterology clinics in
two hospitals in Sheffield and Leeds, UK. All patients underwent 23-seleno 25-
homo-tauro-cholic acid (SeHCAT) scanning according to local protocol, with a
retention of 515% at day 7 used to confirm BAD. The degree of BAD was
classed as severe if retention 55%, moderate if 5.0%49.9%, and mild if
10.0%414.9%. Presence of IBS-D was defined according to the Rome III cri-
teria. Patients with other known risk factors for BAD, including previous cho-
lecystectomy, terminal ileal Crohns disease, terminal ileal resection, pelvic or
abdominal radiotherapy, coeliac disease, or microscopic colitis, were excluded.
Participants completed the patient health questionnaire-15, a validated somatisa-
tion score, and the hospital anxiety and depression score. Demographic data,
including age, gender, lifestyle, and body mass index (BMI) were collected. The
effect of all these factors on presence or absence of BAD was examined by
multivariate logistic regression analysis, with results expressed as odds ratios
(ORs) with 99% confidence intervals.
RESULTS: This is an interim analysis of an ongoing study. In total, 51 patients
with IBS-D according to the Rome III criteria have been recruited to date (37
(72.5%) female, mean age 47.0 years). In total, 14 (27.5%) were found to have
BAD following SeHCAT scanning. Of these, nine (17.6%) had severe BAD, four
moderate, and one mild. Mean age, BMI, anxiety, depression, and somatisation
scores were not significantly different among those with, compared with those
without, BAD. No predictors of presence of BAD were identified following
multivariate logistic regression.
CONCLUSION: Our data suggest that more than one-in-four IBS-D patients, if
investigated, have definite evidence of BAD. In the majority, this is severe.
Failure to investigate patients to exclude BAD as an underlying cause of symp-
toms compatible with IBS-D results in misdiagnosis and a failure to institute
effective therapy, in the form of bile acid sequestrants. This suggests that future
IBS management guidelines should advocate diagnostic testing to exclude BAD
before a diagnosis of IBS-D is made.
Disclosure of Interest: I. Aziz: None declared, S. Mumtaz: None declared, H.
Bholah: None declared, F. Chowdhury: None declared, D. Sanders: This study
was funded by investigator-initiated grant from GE healthcare, A. Ford: This
study was funded by investigator-initiated grant from GE healthcare.
United European Gastroenterology Journal 2(5S)
P0403 VALIDATION OF THE USE OF THE ICD-10 DIAGNOSTIC CODE
FOR IRRITABLE BOWEL SYNDROME IN THE SWEDISH
NATIONAL PATIENT REGISTER
N. Jossan1,*, A.-S. Backman2, M. Linder2, M. Altman2, M. Simren2, O. Ole`n2,
H. Tornblom1
1
Dept of Internal Medicine, Institute of Medicine, Sahlgrenska Academy,
University of Gothenburg, Gothenburg, Sweden, Gothenburg, 2Clinical epidemiol-
ogy uniit, Dept of Medicine, Karolinska Institutet, Stockholm, Sweden
Contact E-mail Address: hans.tornblom@gu.se
INTRODUCTION: Irritable bowel syndrome (IBS) is a diagnosis based on
symptom criteria. In order to perform epidemiologic studies based on national
health-care registers there is a need to assess the accuracy of the diagnostic code
in clinical practice at different time points.
AIMS & METHODS: The aim of this study was to evaluate the positive pre-
dictive value of the ICD-10 (International Classification of Diseases, version 10)
code for IBS in Sweden in hospital based outpatient care during 2005 (using the
Rome II criteria) and 2010 (Rome III criteria). We identified all Swedish adults
that had received the ICD-10 code for IBS as the main diagnosis during hospital-
based outpatient care in 2005 and 2010 by use of the Swedish National Patient
Register. We excluded individuals from the IBS cohort if they had been diag-
nosed with predefined diagnoses, incompatible with IBS, during a time span of 6
months before or after the IBS diagnosis. The National Board of Health and
Welfare generated a random sample of 300 identities. Each medical record was
retrieved and read by two of the authors (N. J. and H. T.) who noted if symptoms
compatible with IBS according to Rome II criteria (2005 cohort) or Rome III
criteria (2010 cohort) could be identified.
RESULTS: We received a total of 248 medical records (2005, n 127; 2010,
n 121). In 173 patients (70%), the diagnosis fulfilled diagnostic criteria with
a high certainty and in 75 patients (30%) it did not. The proportions of valid
diagnoses were similar in 2005 (Rome II criteria, 68%) and 2010 (Rome III
criteria, 72%) (2 0.67, df 1, p .41). Out of the 75 cases that did not fulfill
diagnostic criteria, 24 were labeled probable IBS because of insufficient med-
ical data. There was no difference when comparing tertiary (72% correct) and
secondary care (69% correct) (p .62), but a significant difference in accuracy
was noted comparing departments of internal medicine (155/210, 74%) and non
internal medicine departments (18/38, 47%) (p .001). The most common rea-
sons for a diagnosis being judged as not valid were: insufficient patient data
available in 33 patients (13%), symptoms only including abdominal pain/discom-
fort or abnormal bowel habit in 19 patients (8%), an obvious misuse of the
diagnosis in 12 patients (5%) and too short duration of symptoms in 11 cases
(4%).
CONCLUSION: The use of the ICD-10 diagnostic code for IBS in Swedish
secondary and tertiary care has a high validity in departments of internal med-
icine but less so in other departments. This finding needs to be addressed when
planning and interpreting epidemiologic studies of IBS.
Disclosure of Interest: N. Jossan: None declared, A.-S. Backman: None declared,
M. Linder: None declared, M. Altman: None declared, M. Simren: None
declared, O. Ole`n: None declared, H. Tornblom Lecture fee(s) from: Almirall,
Shire, Consultancy for: Almirall, Danone, Shire
P0404 ALTERATIONS IN ENTERIC GLIA CELL PHENOTYPE AND
FUNCTIONS IN IRRITABLE BOWEL SYNDROME
N.L. Lilli1,*, Q. Lucille1, A. Philippe1, R.-D. Malvyne1, D. Tony1, K. Elise2,
B. Giovanni3, D.G. Roberto3, B.D. V. Stanislas2, C. Emmanuel2, N. Michel1
1
Inserm U913, 2IMAD, Nantes, France, 3Dimec, Bologna, Italy
Contact E-mail Address: libera.lilli@gmail.com
INTRODUCTION: Irritable bowel syndrome (IBS) is a complex disease char-
acterized by symptoms including chronic abdominal pain or discomfort and
alteration of bowel habit. Increasing evidence demonstrates a central role of
intestinal epithelial barrier (IEB) dysfunction, and especially increased paracel-
lular permeability, in the pathophysiology of IBS. The enteric nervous system
(ENS), and in particular enteric glial cells (EGC) play a pivotal role in the
maintenance of IEB.
AIMS & METHODS: The purpose of this study was to characterize the lesions
of the EGC in IBS patients and the putative causative role of soluble factors
produced by the colonic IEB microenvironment in these lesions. Methods:
Eighteen IBS patients (6 constipation-predominant IBS (IBS-C), 6 diarrhea-pre-
dominant IBS (IBS-D) and 6 mixed bowel habits IBS (IBS-M) patients) and 9
healthy controls (HC) were included. For each patient gastrointestinal symptoms
were assessed using the Rome III questionnaire and colonoscopy was performed
with 12 biopsies of left colon. Paracellular and transcellular permeability was
measured on 3 biopsies using the Ussing chambers. Supernatant was obtained
by incubation of 4 biopsies in Krebs-Hepes solution during 25 minutes at 37 C.
At the end of the incubation time, biopsies were processed for Western blot
analysis. Both total Glial fibrillary acidic protein (GFAP) expression and the
55-kDa band as well as S100b were analysed. The mRNA expression levels of
glial markers (Sox-10; S100b) and inflammatory cytokine TNF-a were measured
using real-time PCR. Intracellular calcium flux in response to adenosine tripho-
sphate (ATP) stimulation was measured using Fluo-4 probe in culture of rat
EGC after 48h incubation with patients and HC supernatants or protease-acti-
vated receptor agonists (SLIGRL and Thrombin), serotonin or histamine.
RESULTS: Paracellular and transcellular permeability of biopsies from all sub-
types of IBS patients was similar as compared to HC, except in the IBS-C sub-
type for which transcellular permeability was significantly increased. No
difference in S100b, total GFAP and the specific 55-kDa band expression was
observed for any subtype. Sox-10 and S100b mRNA expression was similar in
biopsies of all IBS subtypes as compared to HC. Interestingly, we observed a
United European Gastroenterology Journal 2(5S)
significant increase in TNF-a mRNA expression in IBS-M but not C or D sub-
type as compared to control. Intracellular calcium responses (maximal amplitude
and half max duration) to ATP were significantly decreased in rat EGC cultures
incubated with supernatants of IBS-D and M but not C subtypes as compared to
control. No difference in calcic response to ATP was observed in EGC cultures
after incubation with different SLIGRL, thrombin, serotonin and histamine
concentrations.
CONCLUSION: Our study demonstrates that enteric glial phenotype and func-
tions are altered in IBS in a subtype dependent fashion. The mediators respon-
sible for these changes as well as the functional consequences of these changes
remain to be identified.
Disclosure of Interest: None declared
P0405 ABDOMINAL PAIN VERSUS ABDOMINAL DISCOMFORT:
IMPLICATIONS FOR DIAGNOSTIC ASSESSMENT OF IRRITABLE
BOWEL SYNDROME (IBS)
O. Palsson1,*, S. Heymen1, W.E. Whitehead1
1
Department of Medicine, Division of Gastroenterology and Hepatology,
University of North Carolina, Chapel Hill, United States
Contact E-mail Address: opalsson@med.unc.edu
INTRODUCTION: Diagnostic questions in the current Rome criteria for IBS
inquire about frequency of abdominal discomfort or pain, whereas the U. S.
Food and Drug Administration guidelines for IBS clinical trials only reference
abdominal pain frequency. It is unknown to what extent people perceive abdom-
inal pain and discomfort differently or whether both are needed in GI diagnosis
questions.
AIMS & METHODS: We compared abdominal pain and discomfort ratings in a
U. S. nationwide internet community survey of 328 adults, containing the Rome
III diagnostic questions for IBS in the new response formats planned for Rome
IV diagnoses (Gastroenterology 2013;144(5) Suppl.1:S-916), including the stan-
dard in the past 3 months, how often did you have discomfort or pain anywhere
in your abdomen? and alternative forms of that question replacing abdominal
discomfort or pain with only pain or only discomfort. Also included was a Colorectal cancer (%)
multiple-choice question about the extent to which abdominal pain and discom-
fort are experienced as separate sensations, and demographic questions. To avoid
over-estimating agreement between alternative question forms, responses from
people who reported having neither pain nor discomfort in the abdomen in the
past 3 months were excluded from analysis, as well as those inconsistent on either
of two repeated quality-check questions, leaving 218 for analysis. Analysis cal-
culated percent agreement between alternate question forms, and also Cohens
Kappa (K-values) for diagnostic performance as this controls for rate of chance
agreement (K 4 0.8 excellent agreement).
RESULTS: The subjects (52.8% females; mean age 45.8, range 19-85 years)
varied widely in their perception of the relationship between abdominal pain and
discomfort: 33.9% stated they were entirely or mostly independent sensations,
27.1% that they were mostly or entirely the same sensation, and 39.0% that both
were equally true i.e., they could be either separate sensations or discomfort a
mild version of pain. Only about half of subjects rated frequency of pain alone
(52.8%) and discomfort alone (55.5%) as identical in intensity (i.e., same
response option chosen on the 9-point frequency scale) to ratings on the standard
pain or discomfort question. However, when the diagnostic frequency thresh-
old for IBS (43 days a month in the past 3 months) was compared, the agree-
ment with pain or discomfort on that threshold being met (when met by either
version) was 72.4% (K 0.63) for the pain alone and 76.8% (K 0.66) for
discomfort alone, and 81.3% between the latter two (K 0.74). When full IBS
criteria were examined using the 3 different question versions, the agreement with
the standard question version when at least one method qualified subjects as IBS
was 80.8% (K 0.85) for the pain-only version and 87.7% (K 0.90) for dis-
comfort-only, with the latter two also showing 87.7% agreement (K 0.90). IBS
diagnosis with discomfort alone diagnosed a slightly higher rate of IBS (71 cases)
compared to the other 2 versions (66 cases each).
CONCLUSION: The use of abdominal discomfort or pain as a criterion for
IBS diagnosis is ambiguous because there is no agreement among U. S. adults
regarding whether these are qualitatively different sensations. However, in 4 out
of every 5 cases the same individuals would be diagnosed IBS regardless of which
descriptor is used. [Supported by a grant from Salix Pharmaceuticals]
Disclosure of Interest: O. Palsson Financial support for research from: Salix
Pharmaceuticals, S. Heymen Financial support for research from: Salix
Pharmaceuticals, W. Whitehead Financial support for research from: Salix
Pharmaceuticals
P0406 PREVALENCE OF ORGANIC GASTROINTESTINAL DISEASE IN
SUSPECTED IRRITABLE BOWEL SYNDROME (IBS) VARIES
ACCORDING TO SUBTYPE
P. Patel1,*, P. Moayyedi2, P. Bercik2, M.-I. Pintos-Sanchez2, C. Bolino2,
D. Morgan3, A. Ford4
1
School Of Medicine, University of Leeds, Leeds, United Kingdom, 2Farncombe
Family Digestive Health Research Institute, Gastroenterology Division, McMaster
University, Health Sciences Center, 3Gastroenterology Department, St. Josephs
Healthcare, Hamilton, Canada, 4Leeds Gastroenterology Institute, St. Jamess
University Hospital, Leeds, United Kingdom
Contact E-mail Address: um10pp@leeds.ac.uk
INTRODUCTION: In patients who report symptoms compatible with IBS in the
absence of alarm symptoms, guidelines suggest the diagnosis can be made with-
out investigations. However, there are few validation studies of the current gold-
standard, the Rome III criteria, and the prevalence of organic gastrointestinal
(GI) disease in people with suspected IBS is unclear.
A243
AIMS & METHODS: We evaluated consecutive patients with Rome III-defined
IBS, and examined whether prevalence of organic GI disease varied according to
IBS subtype, or the presence or absence of alarm symptoms. Demographic and
symptom data were collected from 4224 patients with GI symptoms attending
outpatient clinics at two hospitals in Hamilton, Ontario. Participants completed
the Rome III diagnostic questionnaire for the functional GI disorders, which was
used to categorise IBS subtype. Individuals underwent colonoscopy, with asses-
sors blinded to symptom status. Patients with normal colonoscopy and no evi-
dence of coeliac disease were classed as having no organic GI disease. Prevalence
of organic GI disease was compared according to IBS subtype, and in patients
who did, compared with those who did not, report alarm symptoms (weight loss,
rectal bleeding, anaemia, or family history of colorectal cancer) using a 2 test.
RESULTS: 537 patients met Rome III criteria for IBS (mean age 42yrs, 404
(75.2%) females). Organic GI disease was present in 138 (25.7%), with the com-
monest finding Crohns disease (n 46 (8.6%)). 63 patients had IBS-C, 209 IBS-
D, and 265 IBS-M. Prevalence of organic GI disease was significantly lower in
IBS-C (n 8 (12.7%)) versus IBS-D (n 67 (32.1%)) or IBS-M (n 63 (23.8%))
(p 0.005) (Table). In the 410 patients who reported 1 alarm symptom, pre-
valence of organic GI disease was significantly higher (n 116 (28.3%)) com-
pared with 127 patients who did not report any alarm symptom (n 22 (17.3%))
(p 0.013). In IBS-D, there was a significantly higher prevalence of organic GI
disease in those with alarm symptoms (36.0%) compared with those without
(17.85%) (p 0.02). However, IBS-C and IBS-M prevalence of organic GI dis-
ease in patients with alarm symptoms versus those without was not significantly
higher (IBS-C 11.6% versus 15.0%, p 0.708; IBS-M 25.6% versus 17.7%,
p 0.202
Total IBS IBS-D IBS-C IBS-M
(n 537) (n 209) (n 63) (n 265)
No organic GI disease (%) 399 (74.3) 142 (67.9) 55 (87.3) 202 (76.2)
Ulcerative colitis (%) 34 (6.3) 19 (9.1) 1 (1.6) 14 (5.3)
Crohns disease (%) 46 (8.6) 21 (10.0) 2 (3.2) 23 (8.7)
14 (2.6) 5 (2.4) 2 (3.2) 7 (2.6)
IBD unclassifiable (%) 24 (4.5) 11 (5.3) 2 (3.2) 11 (4.2)
Microscopic colitis (%) 12 (2.2) 8 (3.8) 0 (0) 4 (1.5)
Coeliac disease (%) 8 (1.5) 2 (1.0) 2 (3.2) 4 (1.5)
CONCLUSION: Patients with suspected IBS-C are unlikely to have underlying
organic GI disease, compared with IBS-D or IBS-M. Although the incorporation
of the absence of alarm symptoms into the diagnostic criteria for IBS reduced the
likelihood of organic GI disease, this was only for IBS-D and, because alarm
symptoms are so common, 60% of patients still have normal investigations.
Better ways of diagnosing IBS are needed.
Disclosure of Interest: None declared
P0407 SOMATISATION LEVEL VARIES ACCORDING TO IRRITABLE
BOWEL SYNDROME (IBS) SUBTYPE AND DRIVES BLOATING
SEVERITY
P. Patel1,*, P. Moayyedi2, P. Bercik2, M.-I. Pintos-Sanchez2, C. Bolino2,
D. Morgan3, A. Ford4
1
School Of Medicine, University of Leeds, Leeds, United Kingdom, 2Farncombe
Family Digestive Health Research Institute, Gastroenterology Division, McMaster
University, Health Sciences Center, 3Gastroenterology Department, St. Josephs
Healthcare, Hamilton, Canada, 4Leeds Gastroenterology Institute, St. Jamess
University Hospital, Leeds, United Kingdom
Contact E-mail Address: um10pp@leeds.ac.uk
INTRODUCTION: Literature suggests that somatisation is strongly associated
with IBS. However, it remains unclear whether the degree of somatisation varies
according to IBS subtype. Furthermore, whether there is an association between
higher levels of somatisation and more severe IBS symptoms is unknown.
AIMS & METHODS: Demographic and symptom data were collected from
4224 adult patients attending gastrointestinal (GI) outpatient clinics at two hos-
pitals in Hamilton, Ontario. Participants completed the Rome III diagnostic
questionnaire for the functional GI disorders. Somatisation data were collected
via the Patient Health Questionnaire-15 (PHQ-15), comprising 15 somatic symp-
tom items. To avoid overestimation of the severity of somatisation we excluded
the 3 GI items from the original PHQ-15 questionnaire to form the PHQ-12.
Somatisation severity was categorised according to total PHQ-12 (minimal 3,
low 4-7, medium 8-12 and high 13) with a maximum somatisation score of 24.
Mean somatisation score and total number of somatic symptoms reported were
compared between IBS subtypes (diarrhoea-predominant (IBS-D), constipation-
predominant (IBS-C), and mixed stool pattern (IBS-M)) using analysis of var-
iance. The effect of level of somatisation on the severity of individual IBS symp-
toms, including lower abdominal pain or discomfort, stool frequency, stool
consistency, bloating or abdominal distension, tenesmus, and urgency was com-
pared according to IBS subtype using a 2 test with P values of 50.01 denoting
statistical significance.
RESULTS: 840 patients met the Rome III criteria for IBS and provided complete
somatisation data (mean age 38.3 years, 702 female (83.6%)). Of these, 289
patients had IBS-D, 138 IBS-C, and 413 had IBS-M. Mean PHQ-12 scores
were significantly higher in those with IBS-M (n 10.35), compared with IBS-
C (n 8.94) or IBS-D (n 9.24) respectively (P50.001). Mean number of PHQ-
12 symptoms reported was also significantly higher in IBS-M patients (7.2) com-
pared with patients with IBS-C (n 6.2) or IBS-D (n 6.4) respectively
(P50.001). High level of somatisation was present in 222 patients (26.4%).
A244
The prevalence of a high level of somatisation was significantly greater in patients
with IBS-M (131 patients (31.7%)) compared with IBS-C (31 (22.5%)) or IBS-D
(60 (20.8%)) respectively (p 0.003). For all subtypes of IBS, high levels of
somatisation were associated with a greater severity of bloating or abdominal
distension (P50.001 for IBS-M and IBS-D, and p 0.004 for IBS-C respec-
tively). For patients with IBS-M, high levels of somatisation were also associated
with a significantly greater prevalence of likelihood of reporting 53 stool per
week (p 0.001). No other significant associations between somatisation severity
and symptom severity were observed.
CONCLUSION: IBS-M is strongly associated with higher levels of somatisation.
The number of reported somatic symptoms reported is higher in IBS-M com-
pared with other IBS subtypes. Severity of bloating or abdominal distension
reported by all patients with IBS is strongly associated with high levels of soma-
tisation. This suggests psychological stress may drive the severity of this com-
monly reported symptom in IBS, and may partly explain why it can be difficult to
treat.
Disclosure of Interest: None declared
P0408 INTESTINAL AND SYSTEMIC IMMUNE MARKERS IN
PATIENTS WITH IRRITABLE BOWEL SYNDROME
Z. Mujagic1,2,*, E.F. Tigchelaar1,3, A. Smolinska1,4, A.A. Masclee2,
S. Zhernakova1,3, F.-J. van Schooten1,4, C. Wijmenga1,3, D.M. Jonkers1,2
1
Top Institute Food and Nutrition (TIFN), Wageningen, 2Division
Gastroenterology-Hepatology, Department of Internal Medicine, NUTRIM School
for Nutrition, Toxicology and Metabolism, Maastricht University Medical Center
(MUMC), Maastricht, 3Department of Genetics, University of Groningen,
Groningen, 4Department of Toxicology, NUTRIM School for Nutrition,
Toxicology and Metabolism, Maastricht University Medical Center (MUMC),
Maastricht, Netherlands
Contact E-mail Address: z.mujagic@maastrichtuniversity.nl
INTRODUCTION: Immune activation (low grade inflammation) and an altered
intestinal microbiota are postulated to be involved in the multi-factorial patho-
physiology of Irritable Bowel Syndrome (IBS), especially in the diarrhea predo-
minant subtype. Fecal calprotectin and plasma cytokines, as markers of intestinal
inflammation and systemic immune activation, respectively, and the antimicro-
bial protein human beta defesin-2 (HBD-2), have previously been assessed in IBS
patients, but results were inconsistent and numbers were too small for subtype
analyses.
AIMS & METHODS: The aim of our study was to compare fecal calprotectin,
HBD-2 and plasma cytokines levels of a large well characterized IBS cohort to
healthy controls (HC), and to assess differences between subtypes.
Fecal and blood samples were obtained from IBS patients (Rome III) and age-
and gender-matched HC. Calprotectin and HBD-2 levels in fecal samples were
analyzed by ELISA, while non-stimulated levels of IL-1, IL-6, IL-8, IL-10, IL-
12P70 and TNF- were assessed by Luminex assay. Kruskal Wallis test was used
for multi-group comparison and Mann-Whitney U test for 2-group comparisons,
with post-hoc Bonferroni correction (for multiple testing).
RESULTS: We included 164 HC and 264 IBS patients (IBS5SUB4TOTAL5/
SUB4): 92 diarrhea predominant (IBS-D), 48 constipation predominant (IBS-
C), 105 with mixed stools (IBS-M) and 19 with undefined subtype (IBS-U). IBS-
U was not analyzed separately due to small numbers. Calprotectin was higher in
IBS5SUB4TOTAL5/SUB4 compared to HC (median [IQR]: 40.3 [19;81] vs.
20.4 [5-48] ug/g, p 50.001, resp), and in all IBS-subtypes compared to HC. HBD-
2 levels were lower in IBS5SUB4TOTAL5/SUB4 compared to HC (31.0
[18;48] vs. 37.5 [27;60] ng/g, p 50.01), which was also true for IBS-D vs. HC.
The cytokines IL-1 (0.11 [0.11;1.12] vs. 0.11 [0.11;1.46] ug/l, p 50.01) and IL-6
(0.19 [0.19;0.19] vs. 0.52 [0.19;3.13] ug/l, p 50.01) were lower in
IBS5SUB4TOTAL5/SUB4 vs. HC, while IL-12p70 (0.08 [0.08;3.52] vs.
0.08 [0.08;1.53] ug/l, p 50.01) and TNF- (0.45 [0.26;0.69] vs. 0.67 [0.38;8.32]
ug/l, p 50.01) were higher IBS5SUB4TOTAL5/SUB4 compared to HC.
The IL10/12 ratio was also lower in IBSTOTAL compared to HC (0.45
[0.26;0.69] vs. 0.67 [0.38;8.32], p 50.01). The findings were consistent for all
subtypes, apart for TNF- being only increased in IBS-D and no differences
found between all subtypes and HC for IL-1. No significant differences were
found for IL-8 and -10.
CONCLUSION: Calprotectin levels were significantly higher, but mildly ele-
vated, in IBS patients and all subtypes compared to HC, pointing to low grade
mucosal inflammation in IBS. The overall cytokine levels were low, but com-
bined systemic cytokine data point to a pro-inflammatory state in the total group
of IBS patients as well as in all subtypes. Interestingly, HBD-2 levels were lower
in IBS patients compared to HC, especially in IBS-D, suggesting an altered host-
microbe interaction.
In conclusion, our data point to a low-grade mucosal and systemic inflammatory
state with reduced intestinal defensin levels in IBS patients when compared to
healthy controls. The findings did not depend on dominant bowel habits, indi-
cating that immune activation may plays a role in the pathophysiology of all IBS
subtypes.
Disclosure of Interest: Z. Mujagic: None declared, E. Tigchelaar: None declared,
A. Smolinska: None declared, A. Masclee Consultancy for: Pentax medical,
Grunenthal GmbH, Ferring, S. Zhernakova: None declared, F.-J. van
Schooten: None declared, C. Wijmenga: None declared, D. Jonkers: None
declared
United European Gastroenterology Journal 2(5S)
P0409 ENDOSCOPIC FINDINGS AND CLINICOPATHOLOGIC
CHARACTERISTICS OF ISCHEMIC COLITIS: A PORTUGUESE
CENTER EXPERIENCE
C. Leitao1,*, A. Santos1, H. Ribeiro1, J. Pinto1, A. Caldeira1, R. Sousa1,
J. Tristan1, E. Pereira1, A. Banhudo1
1
Servico de Gastrenterologia, Hospital Amato Lusitano - Unidade Local de Saude
de Castelo Branco, Castelo Branco, Portugal
Contact E-mail Address: catia.f.leitao@gmail.com
INTRODUCTION: Ischemic colitis (IC) is the most common vascular disorder
of the intestinal tract and the second most common cause of lower digestive
bleeding. The clinical disease course of ischemic colitis may vary from self-limit-
ing to life-threatening and has a wide spectrum of endoscopic findings.
AIMS & METHODS: In this study, we made a retrospective analysis of endo-
scopy Endings and clinicopathologic characteristics of IC in the endoscopy center
of our hospital during the last 10 years (2002 to 2012) and try to identify the
predictors of endoscopic severity of IC. The data collected included demographic
(age, gender), clinical (symptoms, comorbidities and medication), laboratory
(hemoglobin, leucocytes, C-reactive protein, lactate dehydrogenase), and endo-
scopic findings (localization, extension, severity of the lesions) and outcomes
(length of hospitalization stay, treatment and death).
RESULTS: The study included 194 patients (92 women; 62 men), with mean age
of 75 years. The most common comorbid disease was hypertension (56.5%),
followed by cardiovascular disease (21.5%), arrhythmias (14.8%) and cerebro-
vascular disease (6.6%). The majority of patients had a history of drug use
(89.6%), 23.4% of them nonsteroidal anti-inflammatory agents and 13.6% digi-
talis preparations. Hematochezias (79.2%) and abdominal pain (73.3%) were the
most common presentation symptoms. The average elapsed time between the
beginning of the symptoms and the diagnosis was 2,1 days. Ischemic lesions
were located mainly in the left colon (77.3%) and were found in more than 2
colonic segments in 42.9%. The endoscopic lesions were grade I in 57.1%, grade
II in 39.6% and grade III in 3.2% of patients. The involvement of more than 2
colonic segments (50.0001), the involvement of sigmoid and descendent colon
(50.0001), anemia (50.04), and mortality (50.0001) were significantly
higher in patients with severe endoscopic lesions. Death occurred in 4 patients
(2.6%) and surgery was performed in only 1 patient. The mean length of hospital
stay was 7.5 days. The involvement of more than 2 colonic segments (p40.0001),
longer elapsing time between the beginning of symptoms and the diagnosis
(p40.0001), antibiotics use (p40.009) and age higher than 80 years (p
50.001) were related to longer hospitalization.
CONCLUSION: In our study, the majority of patients were female, over 50
years of age and with several risk factors. The clinical disease course was self-
limiting and was associated a low mortality. The involvement of more than 2
colonic segments, the involvement of sigmoid and descending colon and anemia
may be predictive factors of endoscopic severity in IC. An intimate knowledge of
endoscopic findings and pathologic characteristics of ischemic colitis plays a
pivotal role in decreasing the misdiagnosis rate of ischemic colitis.
Disclosure of Interest: None declared
P0410 THE CLINICAL CHARACTERISTICS OF PATIENTS WITH
PNEUMATOSIS CYSTOIDES INTESTINALIS IN JAPAN
M. Miura1,*, D. Saito1, M. Hayashida1, A. Sakuraba1, Y. Yamada1,
G. Koyama1, S. Takahashi1
1
The Third Department of Internal Medicine, Kyorin University School of
Medicine, Tokyo, Japan
INTRODUCTION: Pneumatosis cystoides intestinalis (PCI) is a relatively rare
disease, in which multilocular or linear pneumatic cysts developed under the
mucosa or serosa of the intestinal wall. In recent years, with the advances in
imaging technologies, the number of reported cases of PCI has been increasing.
Here, we investigated the clinical characteristics of patients with PCI.
AIMS & METHODS: 55 patients were diagnosed as PCI at Kyorin University
Hospital during the 6-year period from September 2007 to August 2013. We
conducted a retrospective analysis of the clinical characteristics of these patients,
including sex, age, the site of lesion, symptoms and treatments.
RESULTS: The male to female ratio was 29:26 and the median age was 64.7
years. The diagnosis was made by CT(47 cases), or colonoscopy (8 cases). In
regard to the site of lesion, the stomach was 2 patients, small intestine was 18
patients, ascending colon was 26 patients, transverse colon was 4 patients, des-
cending colon was 2 patients and the sigmoid colon was 2 patients. 31 patients
complained of symptoms of abdominal pain (18), abdominal distension (9), fever
(2), diarrhea (2), and melena (1). There were 20 patients whose condition was
idiopathic and 35 patients whose condition was secondary to other underlying
diseases including diabetes (12), malignant tumors (9), intestinal tract necrosis
(9), collagenosis (7), constipation (1), chronic obstructive pulmonary disease (1)
and ileus (1). Eleven patients had a history of steroid use, and 12 patients had a
history of treatment with -glucosidase inhibitors. Thirty-four patients received
in hospital treatment including conservative treatments such as nil by mouth,
treatment with prokinetic agents, supplemental oxygen in 24 patients and
abdominal operation in 11 patients. Portal venous gas (HPVG) was observed
in 9 patients, and 8 of these had underlying intestinal tract necrosis.
CONCLUSION: In most patients, PCI is mild, asymptomatic and resolves spon-
taneously. The principally used treatment strategy for PCI is conservative treat-
ment. Appropriate consideration of the indications for operation is important for
avoiding unnecessary invasive treatment. However, especially in cases of PCI
complicated by HPVG, underlying intestinal tract necrosis should be borne in
mind and it seems to be important to promptly determine whether emergency
surgery is needed. There are numerous unresolved issues in respect of the patho-
logical characteristics of PCI, therefore, further accumulation and examination
United European Gastroenterology Journal 2(5S)
of cases are necessary. Further elucidation of the pathological characteristics and
establishment of suitable treatments are expected.
Disclosure of Interest: None declared
P0411 PROFILE AND OUTCOME OF PATIENTS WITH ISCHEMIC
COLITIS
R. Oprita1,*, F. Musat1, A. Ragea1
1
Gastroenterology, Bucharest Clinical Emergency Hospital, bucharest, Romania
Contact E-mail Address: ruxandraa@netscape.net
INTRODUCTION: - Ischemic colitis incidence is most likely underestimated
because the mild form often is of transient nature and misdiagnosed when
patients suffer from other diseases such as inflammatory bowel disease or infec-
tious colitis.
AIMS & METHODS: We prospectively studied patients referrd for colonoscopy
for lower gastro-intestinal bleeding from January 2013 until January 2014.
There were enrolled 74 patients (27 females and 47 males), aged between 20 to 75
years old, with a median age of 51 years old.
The findings at colonoscopy will depend on the stage and severity of ischemia. In
the early stages of ischemia, petechial hemorrhages are interspersed with areas of
pale, edematous mucosa. Later, segmental erythema, with or without ulcerations
and bleeding, may be observed. The colon single-stripe sign, a single longitudinal
ulcerated or inflamed colon strip, may characterize milder disease. With more
severe ischemia, the mucosa appears cyanotic, dusky, gray, or black.
Pseudopolyps and pseudomembranes may be appreciated, as well. A chronic
stage of ischemia characterized by stricture, decreased haustrations, and mucosal
granularity may occur several weeks or months later.
There are no endoscopic findings that are specific for ischemia, thus the clinical
setting must be considered.
RESULTS: Conditions mandating anticoagulation, such as atrial fibrillation or
dilated cardiomyopathy, were identified in 32% of case patients. Conditions
requiring antiarrhythmic therapy were identified in 25% of case patients; in 4
of the patients, cocaine was identified as the leading cause.
Of 74 patients, 5 required immediate surgery and 3 of them were positive for
clostridium difficile.
CONCLUSION: Ischemic colitis occurs as the result of a compromise in intest-
inal blood flow that can produce a spectrum of injury from transient self-limited
ischemia to fulminant ischemia or transmural infarction. Its diagnosis requires a
high index of suspicion, and the clinician should consider the diagnosis in
patients with acute abdominal pain and bloody stools.
REFERENCES
Reinus JF, Brandt LJ and Boley SJ. Ischemic diseases of the bowel. Gastroenterol
Clin North Am 1990; 19: 319.
Hourmand-Ollivier I, Bouin M, Saloux E, et al. Cardiac sources of embolism
should be routinely screened in ischemic colitis. Am J Gastroenterol 2003; 98:
1573.
Longstreth GF and Yao JF. Diseases and drugs that increase risk of acute large
bowel ischemia. Clin Gastroenterol Hepatol 2010; 8: 49.
Disclosure of Interest: None declared
P0412 CHRONIC KIDNEY DISEASE AND HIGH ECOG PERFORMANCE
STATUS ARE RISK FACTORS FOR SEVERE ISCHEMIC COLITIS
S.R. Jee1,*, S.R. Choi2, G.A. Song3, S.J. Park4, C.S. Song5, H.U. Park6
1
gastroenterology, INJE UNIVERSITY COLLEGE OF MEDICINE, 2Dong-A
University, 3gastroenterology, Busan national University, 4gastroenterology, Kosin
University, 5gastroenterology, Good Samsun hospital, 6gastroenterology,
Maryknoll Hospital, Busan, Korea, Republic Of
Contact E-mail Address: tokimom@nate.com
INTRODUCTION: Ischemic colitis is most frequent form of intestinal ischemic
disease. However, there have been debates about prognostic factors of ischemic
colitis
AIMS & METHODS: The aim of this study was to identify risk factors of severe
ischemic colitis. From January 2000 to December 2011, a retrospective study was
undertaken of patients with ischemic colitis hospitalized at 4 university hospitals
and 2 secondary hospitals at Busan, Korea. Patients with colon ischemia were
divided into two groups: those with mild disease and those with severe disease.
Data collected included age, sex, symptoms (abdominal pain, hematochezia and
abdominal angina), cormobidity (hypertension, diabetes mellitus, ischemic heart
disease, stroke, arrhythmia, congestive heart failure, peripheral vascular disease,
chronic obstructive lung disease, chronic kidney disease, hemodialysis, peritoneal
dialysis, hyperthyroidism, hypothyroidism and irritable bowel syndrome),
laboratory findings (total cholesterol, TG, LDL, HDL, total protein, albumin,
Hg, WBC count, Platelet count, ESR and CRP), endoscopic fidings (location of
lesions), and ECOG performance status.
RESULTS: A total of 292 patients were enrolled (mild group: 259, severe group:
33). In univariate analysis, location (involving Rt. Colon), chronic kidney disease
(stage V), ECOG, Platelet count, CRP were significant risk factors for severe
ischemic colitis. In multivariate analysis, chronic kidney disease (stage V) (OR,
5.289; 95% CI 1.308-21.378; p 0.019), ECOG (OR, 1.690; 95% CI 1.108-2.579;
p 0.015) were significant risk factors for severe ischemic colitis.
CONCLUSION: Chronic kidney disease (stage V) and high ECOG performance
status were independent risk factors for severe ischemic colitis. More caution
would be necessary when treatment of patients with ischemic colitis having
these factors.
Disclosure of Interest: None declared
A245
P0413 RESECT AND DISCARD (RD) STRATEGY FOR COLONIC
POLYPS- AN ASIAN PERSPECTIVE, ARE WE READY?
C.T. W. Chia1, Y.M. Yun2,*, S. Thrumurthy3, S.K. K. Tsao1
1
Gastroenterology & Hepatology, Tan Tock Seng Hospital (TTSH), Singapore,
Singapore, 2Monash University, Victoria, Australia, 3University of Aberdeen,
Scotland, United Kingdom
Contact E-mail Address: christopher_tw_chia@ttsh.com.sg
INTRODUCTION: The current practice of routinely resecting all diminutive (1-
5mm) and small (6-9mm) colonic polyps and submitting them for histopathologic
assessment has several disadvantage in terms of cost-effectiveness and risks from
repeated colonoscopies. The resect-and-discard (RD) strategy has been proposed
to reduce retrieval of diminutive polyps (1-5mm) for histology which has been
deemed not to have advanced histologic features. RD strategy for small polyps
(6-9mm) are still controversial. The prevalence of advanced histologic features in
the diminutive and small polyp category remains small but not clearly defined.
AIMS & METHODS: In this cross-sectional study, we aim to find the prevalence
of small & diminutive polyps resected that shows advanced histologic features
such as high grade dysplasia (HGD) or carcinoma to determine if RD policy is
feasible in the local Asian tertiary setting. Data was retrieved from Jan-Dec 2009
with assistance from the Pathology Department to identify all submitted colonic
polyp specimens. Each patient also had their colonoscopy report (s) and detailed
histology report reviewed by 2 separate colleagues within the team to ensure data
consistency. The variables captured include demographics, total polyp number,
polyp distribution in the colon, histology, polyp size and respective number in
each histology subtype and concurrent colorectal carcinoma (CRC).
RESULTS: There were a total 1482 polypectomy specimens retrieved for histol-
ogy from 871 patients. The colonic distribution of the polyps was 45.4% right
sided, 46.1% left sided and 8.5% rectal.
Please refer to Table 1 for summary of polyp distribution and dysplasia.
Tubular Tubulovillous Villous Serrated
Adenoma Adenoma Adenoma Adenoma
Colonic polyp histology (TA) (TVA) (VA) (SA) Hyperplastic
Low grade dysplasia (LGD) 79.2% 26.7% 0.0% 83.9% NA
High grade dysplasia (HGD) 20.8% 73.3% 100.0%
No dysplasia NA NA NA 16.1% 100.0%
Total number (1482) 1067(72%) 150(10.1%) 3(0.2%) 118(8.0%) 144(9.7%)
There were 844 diminutive polyps (1-5mm), 447 small polyps (6-9mm) and 191
large polyps (10mm). The proportion of HGD seen in each of these groups
were 18.7%, 37.6% and 56.5% respectively. The percentage of HGD present in
diminutive and small polyps was relatively high and significant. There were no
concurrent carcinomatous features seen in all the polyps.
CONCLUSION: These findings showed that a significant proportion of diminu-
tive polyps (18.7%) and small polyps (37.6%) harboured features of HGD, which
is significantly higher than previous findings of 1% for diminutive polyps in some
literatures. Based on size alone without the aid of narrow band imaging (NBI) or
other forms of image enhanced endoscopy (IEE), we find that RD strategy for
diminutive or small polyps may miss a significant group of patients with
advanced neoplastic histology who needs earlier colonoscopic surveillance.
There may be merits in the RD approach but this would require incorporation
of other real-time endoscopic modalities such as IEE and more robust evaluation
REFERENCES
Rex DK. Risks and potential cost savings of not sending diminutive polyps for
histologic examination. Gastro Hepatol 2012; 8: 128130.
Zauber AG, et al. Colonoscopic polypectomy and long-term prevention of CRC
deaths. N Engl J Med 2012; 366: 687-696.
Disclosure of Interest: None declared
P0414 THE STRAY PATIENT DEMOGRAPHIC LABEL: IMPLICATIONS
FOR PATIENT SAFETY AND QUALITY IN THE ENDOSCOPY UNIT
D.C. Sadowski1,*, G. Lutzak1
1
Division of Gastroenterology, Royal Alexandra Hospital, Edmonton, Canada
INTRODUCTION: Over a 6-month period, 3 separate incidents occurred in our
unit where the wrong patient demographic labels were affixed to the endoscopy
biopsy requisition form (EBRF), the biopsy specimen container (BSC) or both.
This type of incident can have a significant impact on patient safety and is an
indicator of poor quality in the specimen control process.
AIMS & METHODS: The purpose of this study was to identify factors contri-
a n
buting to this medical error and to develop a process to prevent future occur-
w
rences. A Quality Assurance Review (QAR) was conducted to determine the
r
i t h d
systems issues that contributed to these incidents. This review was carried out
at the Royal Alexandra Hospital, Edmonton, Canada. The endoscopy unit at this
W
hospital performs about 18,000 procedures per year. A QAR using Systems
Analysis Methodology (SAM) was conducted to identify issues that contributed
to the patient-specimen mismatches. SAM identified the following system issues:
a) variation in the set-up of nursing workspaces, b) variation in where and when
the EBRF was completed, and c) the occurrence of stray patient demographic
labels. The QAR identified several recommendations to prevent future mislabel-
ing: a) standardize how nursing workspaces are set up, b) develop a checklist to
ensure proper patient identification prior to procedure initiation, proper labeling
of EBRF and BSC, completion of EBRF, and c) remove all patient demographic
labels from the theatre immediately after the conclusion of the procedure.
A246
RESULTS: Since EBRF and BSC mislabeling incidents are rare events; we uti-
lized indicators of EBRF information quality as surrogate markers for effective-
ness of the QAR recommendations. We deemed the following factors as key
quality indicators of EBRF information: a) completion of clinical history by
physician, b) correct identification of specimen anatomic site, c) avoidance of
ra w n
ambiguous terminology, and d) correct patient label on EBRF and BSC. We
tracked these indicators daily. We reported the data weekly to physician leaders
ithd
and other healthcare providers in order to engage them in this initiative. We used
the Reporting and Learning System (RLS) for patient safety to monitor report-
W
ing of similar incidents. Prior to implementation of the QAR recommendations,
the average number of EBRFs containing deficient information was 16.6/month.
Subsequent to the implementation of QAR recommendations, this number
decreased to 6.4/month (p 0.02). However, in the 7 months subsequent to the
QAR recommendation implementation, we had 4 further incident of mislabeling
with the wrong patient label and 3 episodes of unlabeled specimen containers.
CONCLUSION: Stray patient data labels are a significant contributing factor to
EBRF and BSC mislabeling. QARs can reduce the incidence of this medical error
and improve quality of EBRF completion; however, without health care provider
engagement, serious incidents may still occur.
Disclosure of Interest: None declared
P0415 A NOVEL SAMPLING DEVICE FOR COLLECTING
MUCOCELLULAR MATERIAL FROM THE UNPREPARED RECTUM
J. Booth1,*, J. Lacy-Colson2, M. Norwood3, C. Murray1
1
Origin Sciences Ltd, Cambridge, 2Surgery, Royal Shrewsbury Hospital,
Shrewsbury, 3Surgery, Leicester Royal Infirmary, Leicester, United Kingdom
Contact E-mail Address: jodie.booth@originsciences.com
INTRODUCTION: Earlier detection of colorectal and other gastrointestinal
malignancies is an urgent objective. Currently much effort is directed at the
development of in vitro diagnostic tests that evaluate informative protein or
DNA biomarkers in blood or stool samples. Stool samples are relatively incon-
venient to collect, require special handling facilities, and additionally suffer from
contamination that may interfere with molecular assays. Blood samples, while
more convenient, may not be as informative early in the disease process. Several
studies have shown that significant numbers of exfoliated cells and their products
are retained in a muco-cellular layer overlying the colonic mucosa but distinct
from the stool itself, and that this material flows toward the rectum, where it can
be captured for analysis
AIMS & METHODS: Origin Sciences has developed a novel sampling device,
which incorporates an inflatable nitrile membrane. Following insertion into the
unprepared rectum via a standard proctoscope, the membrane is inflated to make
contact with the rectal mucosa for 10 seconds. The membrane is then deflated
and retracted into the device prior to removal from the patient. Upon retraction
the material sampled from the rectal mucosa is retained on the inverted mem-
brane, which acts as a receptacle for the addition of buffer to preserve the
material for subsequent analysis.
RESULTS: The sampler has now been tested in over 2000 patients and healthy
volunteers, and has shown excellent patient acceptability. Tests and in vitro
experiments with monolayers of cultured human cells indicate that the membrane
captures intact cells, which are easily washed off the membrane for further inves-
tigation. Detailed evaluation of the mucous-associated soluble material captured
by the device in both normal and diseased states, shows it to be rich in protein
and nucleic acids. Levels of soluble protein material present in the buffer vary
between 90 and 3000 g/mL, with a mean of 710 g/mL. As part of a pro-
gramme to identify novel cancer biomarkers, Origin Sciences has evaluated the
presence of auto-antibodies in the proteinaceous component of the preparation,
and has detected informative auto-antibody isotypes IgA, IgG and IgM by
ELISA. The preparation is also rich in nucleic acids. DNA is found in amounts
ranging from 0.5 to 21.9 ug/mL. Laboratory experiments have shown that this
DNA retains a high degree of integrity and is suitable for PCR amplification, and
subsequent sequencing, since we have been able to detect a number of genes by
quantitative PCR.
CONCLUSION: The sampling device represents a novel and minimally invasive
means of capturing biomarker-rich material from the unprepared rectum. Since
there is minimal contamination by stool, the material collected is readily analy-
sable, in principle lending itself to Point of Care tests for a wide range of indica-
tions, including infectious and inflammatory diseases of the GI tract in addition
to malignancy. The device can be used as a robust means of collecting material
for later analysis by a wide range of technologies.
Disclosure of Interest: None declared
P0416 SYMPTOM-SPECIFIC REFERRAL CONTENT: WHAT DOES THE
GASTROENTEROLOGIST NEED?
S.L. Eskeland1,*, L. Aabakken2, T.de Lange1
1
Department of Medical Research, Brum Hospital, Vestre Viken Hospital Trust,
2
Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo,
Norway
Contact E-mail Address: s.l.eskeland@medisin.uio.no
INTRODUCTION: Low quality referrals are a challenge for gastroenterologists
when assessing and prioritizing the patients. However, it is not known which
information the gastroenterologists rely on for this task. We wanted to identify
what gastroenterologists considered the most important variables to include in
the referral letters for 9 common indications.
AIMS & METHODS: 25 Norwegian gastroenterologists completed a web-based
survey where they were asked to select the 15 most important variables out of a
list of 29-36 potential variables.
United European Gastroenterology Journal 2(5S)
RESULTS: For all 9 indications, information about duration, current medical
treatment and weight loss were selected. The remaining selected variables were
for:
Dyspepsia: Medical history, nausea/vomiting, reflux, hematemesis, dysphagia,
abdominal pain, effect of anti-acid treatment, general condition, abdominal pal-
pation (AP), previous gastroscopies and lab-analyses for anaemia and faecal
occult blood (FOBT).
Dysphagia: Progression (intermittent, stable, progressive), texture provoking dys-
phagia, subjective localization of obstruction, hematemesis, regurgitation of
undigested foods, presence of reflux, stimulantia, ulcerogenic medication, general
condition, previous endoscopies and radiology and lab-analyses for anaemia.
Diarrhoea: Hematochezia, nocturnal diarrhoea, recent antibiotic treatment, gen-
eral condition, digital rectal exploration (DRE), previous endoscopies and lab-
analyses for anaemia, FOBT, celiac disease, infection/inflammation, inflamma-
tory bowel disease (IBD) and faecal bacteria/parasites.
Bowel changes: Type of change, hematochezia, abdominal pain, B symptoms
(fever, night sweat, weight loss), AP, DRE, general condition, previous endosco-
pies and lab-analyses for anaemia, celiac disease, IBD and FOBT.
Hematochezia: Blood colour, location of blood (on paper/on faeces/in faeces),
percentage of bowel movements with observed blood, bowel changes, symptoms
from upper or lower GI-tractus, hematemesis, AP, DRE, previous endoscopies
and lab-analyses for anaemia, IBD and FOBT.
Chronic abdominal pain: Medical history, characterization and location of pain,
nocturnal pain, relation to meals, presence of bowel changes, AP, general con-
dition, previous radiology/endoscopies and lab-analyses for anaemia, liver/pan-
creatic function, IBD and FOBT.
Constipation: Main complaint (hard/ rare/slow etc), frequency and consistency of
bowel movements, hematochezia, abdominal pain, effect of treatment-attempts,
predisposing factors, AP, DRE, previous endoscopies and lab-analyses for anae-
mia, thyroid disease and FOBT.
Jaundice: Medical history, exposure liver-toxic substances, stimulantia, colour
changes urine/faeces, abdominal pain, AP, liver stigmata, previous radiology
and lab-analyses for liver/pancreatic function, hepatitis serology, specific liver
diseases and infection/inflammation.
Weight loss: Presence of any abdominal symptoms, B symptoms, abdominal
pain, appetite, food intake, general condition, AP, symptoms/findings from
other organ-systems, previous radiology and lab-analyses for anaemia, celiac
disease and FOBT.
CONCLUSION: We identified 15 variables considered essential by gastroenter-
ologists for each of the 9 most common reasons for referrals. Validation of the
relation between the findings and the quality of referrals remains unknown, and
need further assessments.
Disclosure of Interest: None declared
P0417 PREVIOUS SCREENING EPISODE PREDICTORS OF REPEAT
PARTICIPATION IN THE NHS BOWEL CANCER SCREENING
PROGRAMME
S.H. Lo1, S.P. Halloran2,3,*, J. Snowball2, H.E. Seaman2,3, J. Wardle1,
C.von Wagner1
1
Department of Epidemiology and Public Health, Health Behaviour Research
Centre, University College London, London, 2NHS Bowel Cancer Screening
Southern Programme Hub, 3University of Surrey, Guildford, United Kingdom
Contact E-mail Address: s.halloran@nhs.net
INTRODUCTION: Effective colorectal cancer (CRC) screening using faecal
occult blood (FOB) tests requires adherence to a programme of repeat participa-
tion. This study investigated previous screening episode predictors of screening
uptake among previous responders.
AIMS & METHODS: The NHS Bowel Cancer Screening Programme (BCSP) in
England offers biennial screening using a guaiac FOB test. Uptake data for the
second (R2) and third (R3) biennial invitation round were studied among 62,099
individuals (aged 60-64) in the Southern Hub of the BCSP. R3 invitees comprised
three subgroups: Consistent Screeners (screened in R1 and R2), Dropouts
(screened in R1, not screened in R2) and Late Entrants (not screened in R1,
screened in R2). Predictors of uptake derived from previous screening episodes
included late return of the test kit (after more than 28 days), test results and
compliance with follow-up investigations (usually colonoscopy). Age, gender,
area-level socioeconomic deprivation and screening history were included in
multivariable logistic regression analyses.
RESULTS: Overall uptake among previous responders was 86.6% in R2 and
88.6% in R3. In R3, repeat uptake was 94.5% among Consistent Screeners,
59.8% among Dropouts and 78.0% among Late Entrants (differences between
groups, p50.001). Returning the test kit after more than 28 days in a previous
episode was associated with a reduced likelihood of repeat uptake in R2 (82.3%
vs. 88.7%, p50.001) and R3 (84.5% vs 90.5%, p50.001). Receiving an abnor-
mal test result was also strongly associated with reduced repeat uptake in R2
(61.4% vs. 86.8%, p50.001) and R3 (65.7% vs. 88.8%, p50.001). Furthermore,
repeat uptake in R2 and R3 was particularly low among subjects who had not
attended their follow-up test (R2: 24.3% vs. 67.1%, p50.001; R3: 43.2% vs.
69.9%, p50.001).
CONCLUSION: Previous screening episode factors related to various stages of
the screening process have been implicated in subsequent uptake. These previous
screening episode predictors could be used to identify individuals at risk of
dropping out of screening and provide an opportunity to tailor invitation and
reminder letters to elicit increased uptake by selected sub-populations.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0418 CAN WE EXPLAIN THE APPARENT DECLINE IN UPTAKE OF
INVITATIONS FOR COLORECTAL CANCER SCREENING IN
ENGLAND?
J. Snowball1, H.E. Seaman1,2, S.P. Halloran1,2,*
1
NHS Bowel Cancer Screening Southern Programme Hub, 2University of Surrey,
Guildford, United Kingdom
Contact E-mail Address: s.halloran@nhs.net
INTRODUCTION: The NHS Bowel Cancer Screening Programme (BCSP) pro-
vides biennial guaiac-based faecal occult blood test (gFOBT) screening for color-
ectal cancer (CRC) to individuals aged 60-74 years (inclusive). Uptake of
screening invitations in England, which averages about 55%, is affected by indi-
vidual factors that include screening history, sex and level of social deprivation.
Data for 2013 indicate a marked decline in uptake in England during the second
half of 2013. The BCSP in England is co-ordinated by five regional Hubs; each
works with local screening centres that provide follow-up investigations (usually
colonoscopy) for individuals with a positive gFOBT result. The Southern Hub
provides the screening service to about 26% of the population in England (14.6
million); it sends over one million invitations for screening and analyses about g
million test kits every year. Uptake in the Southern Hub averages 61% (2012/
2013) but demonstrates the decline since June 2013 reported across the rest of the
country, an observation investigated by the Southern Hub research team.
AIMS & METHODS: All BCSP screening activity is recorded on the Bowel
Cancer Screening System (BCSS). Data for the period 2009-2013 were analysed
to investigate patterns of uptake according to age, sex, screening episode, index
of multiple deprivation (IMD) and screening centre.
RESULTS: Amongst individuals aged 60-74 years, although subject to marked
fluctuations throughout each year, the overall trend was towards increased
uptake until June 2013, after which uptake declined sharply. Uptake amongst
first-time invitees aged 60 years was the most consistent (55%) between 2009 and
2012, although a marked fall in uptake was evident from mid-2013. The most
deprived showed the greatest fall in the first invitation episode (60-year-olds) and
there was no change in uptake by the least deprived individuals. Different pat-
terns observed across screening centres may reflect different start dates resulting
in a different mix of episodes, with the population with the longest screening
history possibly subject to screening fatigue.
CONCLUSION: We have not explained the decline in uptake of CRC cancer
screening invitations during 2013. A decline in CRC screening uptake has been
observed by the other BCSP Hubs and by the NHS screening programmes for the
breast and cervix (personal communication), although the decline in uptake of
breast and cervix screening has been more gradual. It may be that the public is
reacting to adverse publicity about the benefits of screening surrounding breast
screening, in particular, although data from the Scottish programme do not
demonstrate the decline observed in England (personal communication). The
benefits of CRC screening are well-recognised and efforts to improve uptake
of screening invitations and close monitoring of uptake should continue.
Disclosure of Interest: None declared
P0419 PATIENT PREFERENCES FOR TERMINOLOGY USED TO
IDENTIFY FECAL INCONTINENCE
S. Heymen1,*, O. Palsson1, S.M. Kim1, S. Twist1, W.E. Whitehead1
1
Medicine, University of North Carolina, Chapel Hill, United States
Contact E-mail Address: steve_heymen@med.unc.edu
INTRODUCTION: Fecal incontinence (FI) affects 9% of non-institutionalized
U. S. adults, but fewer than 30% have discussed this problem with their physi-
cian. This is unfortunate because effective treatments are available. Two factors
that may contribute to low consulting rates are embarrassment about this taboo
topic and unfamiliarity with the terms used by physicians.
AIMS & METHODS: Our goal was to identify terms that are the most accep-
table and understandable to FI patients to make it easier for clinicians to inquire
about and discuss FI with patients, and easier for patients to disclose the pro-
blem. Thirty patients with FI (29 women) recruited by advertisement participated
in internet chat rooms of 1-5 persons. They were asked: What words do you use
to describe your FI when you are talking to doctors, family members, or
friends? with requests to rate 3 domains on a 0-10 scale: 1) the understandability
of these terms, 2) their appropriateness for discussions with others, and 3) the
patients level of discomfort (embarrassment) in using the term. Based on focus
group input, 29 terms were selected for participants to evaluate for a national
survey. Thirty-one terms were not included because the investigators deemed
them to be offensive (e.g., squirts, shits, taco butt) or because they were adjectives
describing emotional reactions to FI or characteristics of FI (e.g. Embarrassing,
Disgusting). This sample was stratified by FI status, age, sex, and race/ethnicity.
RESULTS: The national survey recruited 560 participants (42% with FI). Sixty-
four participants were excluded for answering identical questions inconsistently.
The remaining 496 participants had a mean age of 47.5 (range 18-91) years, 48%
of participants were males, and race/ethnicity was 69.6% Caucasian, 15.7%
Hispanic, and 14.7% African American. Participants were also divided into
three age groups for analysis: 35 and younger (n 146), 36-64 (n 243) and 65
and older (n 106). Appropriateness ratings are reported here. When we com-
pared the ratings from participants with FI and without FI, four of the top five
rated terms were the same for both groups (Bowel Incontinence, Bowel Control
Issues, Accidental Bowel Leakage, and Diarrhea). Women rated all of these
terms as significantly more Appropriate than men did. A consistent race/ethnicity
pattern showed highest Appropriateness ratings for Caucasians, then Hispanics,
and lowest by African Americans on all of these terms. Ratings also differed
significantly by age group, increasing with age across the three groups for all of
these terms. Ratings differed on only one of these terms due to Education level
(Bowel Control Issues) or Income (Bowel Incontinence).
A247
CONCLUSION: We recommend excluding the term Diarrhea as it is not specific
to leakage of diarrhea. The remaining top three terms were ranked identically for
participants with and without FI: 1) Bowel Incontinence, 2) Bowel Control
Issues, 3) Accidental Bowel leakage. All three terms scored below the median
on the Uncomfortableness domain. The term used most often by providers, fecal
incontinence, did not score in the top 10 on any of the 3 domains. Accidental
Bowel leakage, recently described as patients preferred term, ranked 3rd. This
information may help improve communication between patients and providers
and enable more patients to receive treatment. Supported by Salix
Pharmaceuticals.
Disclosure of Interest: None declared
P0420 SORD OVEREXPRESSION AND OTHER ASPECTS OF
DYSREGULATED PROTEIN EXPRESSION IN HUMAN
PRECANCEROUS COLORECTAL NEOPLASMS: A QUANTITATIVE
PROTEOMICS STUDY
T. Staiano1,*, A. Uzozie2, P. Nanni2, M. Giancarlo2
1
ENDOSCOPY AND GASTROENTEROLOGY UNIT, A. O. ISTITUTI
OSPITALIERI DI CREMONA, CREMONA, Italy, 2ENDOSCOPY AND
GASTROENTEROLOGY UNIT, University of Zurich, zurig, Switzerland
Contact E-mail Address: terrystaiano@libero.it
INTRODUCTION: Colorectal adenomas are cancer precursor lesions of the
large bowel. A multitude of genomic and epigenomic changes have been docu-
mented in these preinvasive lesions, but their impact on the protein effectors of
biological function has not been comprehensively explored.
AIMS & METHODS: Using shotgun quantitative MS, we exhaustively investi-
gated the proteome of 30 colorectal adenomas and paired samples of normal
mucosa. Total protein extracts were prepared from these tissues (prospectively
collected during colonoscopy) and from normal (HCEC) and cancerous (SW480,
SW620, CACO2, HT29, CX1) colon epithelial cell lines. Peptides were labeled
with isobaric tags (iTRAQ 8-plex), separated by OFFGEL electrophoresis, and
analyzed by LC-coupled tandem MS. Non-redundant protein families (4325 in
tissues, 2017 in cell lines) were identified and quantified. Principal component
analysis of the results clearly distinguished adenomas from normal mucosal
samples, and cancer cell lines from HCEC cells.
RESULTS: Two hundred twelve proteins displayed significant adenoma-related
expression changes (q-value 5 0.02, mean fold change vs. normal mucosa /-
1.4), which correlated (r 0.74) with similar changes previously identified by our
group at the transcriptome level. Fifty-one (25%) proteins displayed direction-
ally similar expression changes in colorectal cancer cells (vs. HCEC cells) and
were therefore attributed to the epithelial component of adenomas. Although
benign, adenomas already exhibited cancer-associated proteomic changes: 69
(91%) of the 76 protein upregulations identified in these lesions have already
been reported in cancers. One of the most striking changes involved sorbitol
dehydrogenase (SORD), a key enzyme in the polyol pathway.
CONCLUSION: Validation studies revealed dramatically increased SORD con-
centrations and activity in adenomas and cancer cell lines, along with important
changes in the expression of other enzymes in the same (AKR1B1) and related
(KHK) pathways. Dysregulated polyol metabolism may represent a novel facet
of the metabolome remodeling associated with tumorigenesis.
Disclosure of Interest: None declared
P0421 KNOWLEDGE AND PERCEPTION OF DOCTORS ON RISK
FACTORS AND SCREENING OF COLORECTAL CANCER (CRC)
Y.J. Wong1,*, Z. Poh1, M.L. Ong1, K.L. Shum1, V. Namasivayam1, K.L. Ling1
1
Gastroenterology, Singapore General Hospital, Singapore, Singapore
Contact E-mail Address: eugene.wong@mohh.com.sg
INTRODUCTION: CRC has claimed 214,675 lives Europe and is expected to
rise by 12% by 20201. Knowledge and perception of doctors is important to
future success of CRC screening program as early detection of CRC improve
survival. However, little is known about doctors knowledge and perception
towards CRC. We aim to determine current knowledge and perception of color-
ectal cancer screening amongst junior doctors.
AIMS & METHODS: 169 junior doctors practicing across 7 specialties at a local
academic institution were recruited from July -September 2013. Standardized
questionnaires consisting of 44 questions were administered during structured
resident teaching sessions that were unrelated to CRC. Individual responses
were collected. Absent doctors were contacted via email. Standard statistical
techniques were employed.
RESULTS: 74% (125/169) of junior doctors responded. Respondents mean age
was 27.7 years (23-35). Mean duration of practice locally was 3.2 years (1-8).
Majority (97.6%) were aware that CRC is curable if treated early, and 85.6%
recognized that CRC screening reduces mortality. Only 78.4% recognized CRC
as the commonest cancer locally. Most CRC risk factors (CRC-RFs) such as age,
family history, smoking, inflammatory bowel disease and colonic polyps were
correctly identified (84.8-100%). However, knowledge of modifiable CRC-RFs
was poor. Few recognized diabetes mellitus (5.6%), sedentary lifestyle (39.2%)
and obesity (43.2%) as CRC-RFs. In addition, 10.4% wrongly identified tradi-
tional medicine as a CRC-RF, and only 45.7% correctly identified the recom-
mended age for CRC screening according to local guidelines. More fresh
graduates (PGY1) correctly identified 80% of CRC-RFs compared to the
rest (40% vs 21.9%; p 0.044). Only 90.4% and 88% identified colonoscopy
and fecal occult blood test (FOBT) as acceptable CRC screening methods. 94.2%
felt FOBT had poor test performance. Physicians concerns for colonoscopy
included cost (76.9%), risk of perforation (61.5%), bleeding (46.2%), and incon-
venient bowel preparation (66.7%). In spite of this, 80.8% will offer colonoscopy
while only 68% will offer FOBT for CRC screening to their patients. There was
A248
no difference in attitudes and practice patterns between doctors of different post-
graduate years.
CONCLUSION: Majority of junior doctors correctly identified CRC as a sig-
nificant healthcare burden, and that CRC screening and early detection reduces
mortality. However, knowledge on modifiable CRC-RFs is still lacking. Many
had concern about FOBT test performance, and more will offer screening colo-
noscopy. Continual medical education for junior doctors on modifiable CRC-RF
and importance of CRC screening should be emphasized for continual success of
CRC screening.
REFERENCES
1. GLOBOCAN. Estimated cancer incidence, mortality and prevalence worldwide
in 2012, 2012.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
NERVE GUT AND MOTILITY I POSTER EXHIBITION HALL
XL_____________________
P0422 OSMOTIC LAXATIVES ARE ASSOCIATED WITH LOWER
RIGIDITY IN IDIOPATHIC PARKINSONISM
A. Augustin1,*, A. Charlett2, C. Weller1, S.M. Dobbs1,3, D. Taylor1, M. Ibrahim4,
I. Bjarnason3, R.J. Dobbs1,3
1 CORTICOTROPIN-RELEASING FACTOR
Pharmaceutical Science, Kings College London, 2Statistics Unit, Centre for
Infectious Disease Surveillance and Control, Public Health England,
3
Gastroenterology, Kings College Hospital, 4Diagnostic Immunology Laboratory,
Kings College and St Thomass Hospitals, London, United Kingdom
Contact E-mail Address: sylvia.dobbs@kcl.ac.uk
INTRODUCTION: In idiopathic parkinsonism (IP), flexor rigidity is greater the
higher the circulating natural-killer cell count, an effect modulated by CD4
count.1 These counts are higher with hydrogen-breath-test positivity for small-
intestinal-bacterial-overgrowth. Two-thirds of IP-patients are positive at
presentation.
AIMS & METHODS: Improving intestinal transit with laxatives might reduce
rigidity by reducing overgrowth.
Relationships of interventions for constipation to rigidity and overgrowth were
explored using generalised linear mixed models. Surveillance yielded 1378 objec-
tive measures of arm rigidity in 74 IP-patients over 343 person years, with 437 2-h
lactulose-hydrogen-breath-tests in 48. Maintenance osmotic laxative (macrogols)
was exhibited in 50 (176 person years); bulk-forming laxative (ispaghula husk/
methylcellulose/sterculia) in 52 (196); enterokinetic agent (prucalopride) in 25
(45); and guanylate cylase-C receptor agonist (linaclotide) in 8 (12).
RESULTS: Osmotic laxative was the only intervention associated with a change in
rigidity. Flexor rigidity increased (by 6.8 (4.3, 9.4) % per year, p 0.001) where not
exhibited, stabilised where exhibited (1.4 (95% CI -0.9, 3.8) % per year, p 0.2).
Bulk-forming laxative had no additional effect on rigidity (p 0.5). Similarly, the
ratio, flexor to extensor rigidity, indicating tendency to simian posture, increased
(3.2 (0.7, 5.7) % per year, p 0.01) where osmotic laxative was not exhibited,
stabilised where exhibited (-1.6 (-3.9, 0.8) % per year, p 0.2). Bulk-forming laxa-
tive had no additional effect on the ratio (p 0.6).
Only bulk-forming laxative was associated with change in breath-hydrogen. Peak
hydrogen was lower by 11 (1. 20) ppm (p 0.03) where exhibited, with no differ-
ential effect of time (p 0.9). (Odds ratio for a positive breath-test where exhib-
ited compared with where not: 0.55). Osmotic laxative had no additional effect
on peak hydrogen (p 0.3).
CONCLUSION: Osmotic laxative may reduce rigidity by reducing inflamma-
tion, directly, or by removing an inhibitory effect on anti-parkinsonian medica-
tion. Any effect of overgrowth on rigidity may relate to organisms not flagged by
hydrogen-breath-test.
REFERENCES
1. Dobbs RJ et al. Leukocyte-subset counts in idiopathic parkinsonism provide
clues to a pathogenic pathway involving small intestinal bacterial overgrowth. A
surveillance study. Gut Pathogens 2012; 4: 12.
Disclosure of Interest: None declared
P0423 DOES BODY POSITION MODIFY ANORECTAL PRESSURE
VALUES RECORDED BY THREE-DIMENSIONAL HIGH-
RESOLUTION ANORECTAL MANOMETRY?
A. Benezech1,2,*, M. Bouvier1,2, J.-C. Grimaud1,2, N. Lesavre3, K. Baumstarck4,
V. Vitton1,2
1
Centre dExploration Fonctionnelle Digestive, Service de Gastroenterologie,
Hopital Nord, 2Interface de Recherche Translationnelle en Neurogastroenterologie,
CRN2M, UMR 7286, Aix-Marseille Universite, 3Centre dInvestigation Clinique
9502, Hopital Nord, 4Unite dAide Methodologique a` la Recherche Clinique,
EA3279, Laboratoire de Sante Publique, Aix-Marseille Universite, Marseille,
France
INTRODUCTION: Anorectal manometry is the gold standard in the physiolo-
gical exploration of anorectal disorders. In recent years, three-dimensional high-
resolution anorectal manometry (3DHRAM) was developed. However, exams
(conventional manometry or 3DHRAM) are traditionally made in the left lateral
decubitus position while anorectal symptoms (dyschezia and anal incontinence)
occur in the standing or sitting position.
AIMS & METHODS: The aim of our prospective study was to compare the
pressure values obtained by 3DHRAM in the lying position (left lateral decubitus
position) and in the standing position.
All patients referred to our center to explore anal incontinence or dyschesia by
3DHRAM and EUS were eligible. Patients with a history of anorectal surgery or
suffering from anal pain were excluded. The 3DHRAM was performed by the
United European Gastroenterology Journal 2(5S)
same operator successively in the left lateral decubitus position and in the stand-
ing position. The EUS was perfomed the same day. KESS and Wexner scores
were routinely rated, as well as size and weight of the patients. The calculated
number of patients required for this study was 40.
RESULTS: These are preliminary results (20 patients included in the 40 to be
included). 17 females and 3 males, with a median age of 41 years (20-73) and a
median body mass index of 23 kg/m2 (17-36) were included. The indication of
examinations was anal incontinence in 8 patients and constipation in 12 cases,
with a median KESS score of 20 (9-32) and a median Wexner score of 9 (7-20).
No manometric measured parameters was significantly different in the supine or
standing position, whatsoever in the subgroup of incontinent patients or in the
subgroup of constipated patients.
CONCLUSION: These preliminary results showed no significant difference
between the pressure values measured by 3DHRAM in the supine and standing
position. At this stage of study, two hypotheses can be advanced: 1) the lack of
power related to the low effective since we have included only half of the patients
required; 2) no difference whatever the position of the patient when the measure-
ments are made with 3DHRAM. Analysis of the results when all patients will be
included will provide the answer to this question.
Disclosure of Interest: None declared
P0424 BUSERELIN INDUCES ENTERIC NEURONS TO EXPRESS
B. Ohlsson1,*, C. Karlsson2, U. Voss3, G. Molin2, S. Ahrne2, E. Ekblad3,
E. Sand3
1
Department of Clinical Sciences, Lund University, Division of Internal Medicine,
Malmo, 2Food Hygiene, Dept of Food Technology, Engineering and Nutrition,
Division of Applied Nutrition, Lund University, 3Department of Experimental
Medical Science, Neurogastroenterology Unit, Lund University, Lund, Sweden
Contact E-mail Address: bodil.ohlsson@med.lu.se
INTRODUCTION: Treatment with gonadotropin-releasing hormone (GnRH)
analogs have led to severe dysmotility, which implicates roles for the reproductive
peptide/hormones in the gastrointestinal tract. Administration of the GnRH
analog buserelin to rats leads to neurodegeneration and ganglioneuritis.
During these experiments, we have observed that the treated rats have exhibited
a more stressed behavior than controls. Stress has been shown to increase secre-
tion of corticotropin-releasing factor (CRF) and to increase intestinal permeabil-
ity in humans, and to increase locomotion, rearing, pellet excretion, and altered
colonic microbiota in rodents. CRF is highly expressed in the enteric nervous
system in humans and rodents, and has been shown to abolish the vasoactive
intestinal peptide (VIP)-induced neuronal survival.
AIMS & METHODS: The aim of the present study in rat was to evaluate the
effect of the GnRH analog buserelin on enteric neurons immunoreactive to CRF
and the intestinal microbiota.
Forty rats were given either buserelin (B) (20 g, 1 mg/ml) or saline (C) sub-
cutaneously, once daily for five days, followed by three weeks of recovery, repre-
senting one session of treatment. Two weeks after the fourth session, the animals
were euthanized. Gastrointestinal tissue were collected and analyzed for neuronal
survival and CRF immunoreactivity. Microbial DNA (16S rRNA genes) was
extracted from the colonic mucosa and analyzed with molecular genetic methods.
The Terminal Restriction Fragment Length Polymorphism (T-RFLP) method
was used to analyze microbial diversity. Bacterial abundance of the bacterial
groups Clostridium leptum and Enterobacteriaceae was estimated using separate
quantitative PCR assays.
RESULTS: Body weight transiently increased by buserelin treatment at week 5
and 9 (p 5 0.001). Enteric neurons were reduced in number by approximately
40% in both submucous and myenteric ganglia of ileum and colon. Enteric
neurons in colon immunoreactive to CRF increased in submucous ganglia
(C 10 (6-16)%, B 21 (14-25)%, p 5 0.05) and in myenteric ganglia (C 7
(5-9)%, B 19 (18-23)%, p 5 0.01) due to buserelin treatment. In submucous
ganglia, the number of neurons immunoreactive to both nitric oxide synthase
(NOS) and CRF increased due to buserelin treatment (p 5 0.05). In the myen-
teric ganglia, the number of neurons immunoreactive to NOS or VIP, in addition
to CRF, tended to increase after buserelin treatment (p 5 0.14 and p 5 0.08,
respectively). The CRF fiber density was unaffected by buserelin treatment
throughout all the different layers of the bowel wall. The total amount of bacteria
and diversity in colon did not differ between groups. The number of bacteria in
the group of Enterobacteriaceae was significantly lower in buserelin-treated rats
compared to saline-treated rats (p 5 0.05), whereas the total amount of bacteria
in the groups of Clostridium leptum did not differ between broups.
CONCLUSION: The relative number of enteric neurons expressing CRF was
increased after induction of enteric neuropathy. The enteric nervous system
shows proof of plasticity, since NOS-immunoreactive neurons starts to express
CRF after buserelin treatment. Despite a marked enteric neuropathy, no signs of
bacterial overgrowth or diminished diversity are at hand in colon.
Disclosure of Interest: None declared
P0425 FUNCTIONAL CONSEQUENCES AFTER BUSERELIN-INDUCED
ENTERIC NEUROPATHY IN RAT
B. Ohlsson1,*, E. Ekblad2, B. Roth1, B. Westrom3, P. Bonn2, E. Sand2
1
Department of Clinical Sciences, Lund University, Division of Internal Medicine,
Malmo, 2Department of Experimental Medical Sciences, Neurogastroenterology
Unit, Lund University, 3Department of Biology, Functional Biology, Lund
University, Lund, Sweden
Contact E-mail Address: bodil.ohlsson@med.lu.se
INTRODUCTION: Women treated with gonadotropin-releasing hormone
(GnRH) analogs develop in some cases enteric neuropathy with ensuing severe
United European Gastroenterology Journal 2(5S)
dysmotility. Administration of GnRH analog to rats leads to similar degenerative
changes and ganglioneuritis.
AIMS & METHODS: The aim of the present study in rat was to evaluate the
enteric neuropathy, in terms of affected neuronal subpopulations and gastroin-
testinal function, and to investigate levels of zonulin and titers of GnRH and
luteinizing hormone (LH) and their receptors in plasma.
Forty rats were given either the GnRH analog buserelin (B) (20 g, 1 mg/ml) or
saline (C) subcutaneously, once daily for five days, followed by three weeks of
recovery, representing one session of treatment. Two weeks after the fourth
session, the animals were euthanized. Prior to sacrifice, feces were analyzed for
weight and fat, and GI transit time and galactose absorption were studied.
Neuronal subpopulations and survival were analyzed in GI tissue. Blood samples
were analyzed for zonulin, GnRH and LH and their receptors.
RESULTS: Body weight transiently increased by buserelin treatment at week 5
and 9 (p 5 0.001). Buserelin increased estradiol in plasma and uterine muscle
layers were thickened, implicating high estrogen activity. Enteric neurons were
reduced in number by approximately 40% in both submucous and myenteric
ganglia of ileum and colon. Feces weight decreased in buserelin-treated rats
(C 4.3 (3.4- 5.9) g; B 3.2 (2.4-3.6) g, p 5 0.01) whereas fat content in feces
increased (C 2.8 (2.9-3.9)%; B 3.6 (2.6-3.2)%, p50.01), compared to saline-
treated rats. Total GI transit time and galactose absorption were not affected by
buserelin treatment. Studies on the various neuronal subpopulations in colon
showed increased relative number of somatostatin immunoreactive neurons in
submucous, but not myenteric, ganglia while the numbers of cocaine-ampheta-
mine-related transcript (CART), calcitonin gene-related peptide (CGRP), gala-
nin, gastrin-releasing peptide (GRP), neuropeptide Y (NPY), nitric oxide
synthase (NOS), serotonin, substance P (SP) and vasoactive intestinal peptide
(VIP) were unchanged. The levels of zonulin in plasma and the titers of anti-
bodies against GnRH, LH or their receptors were unaffected by buserelin
treatment.
CONCLUSION: A marked enteric neuropathy is at place with only modest
effects on gastrointestinal function after buserelin treatment. Altered feces
weight and fat content is suggested as early signs of dysfunction.
Disclosure of Interest: None declared
P0426 CHARACTERIZATION OF BIOMECHANICAL PROPERTY OF
INTESTINAL SMOOTH MUSCLE USING HILL-TYPE MUSCLE
MODEL; ANIMAL STUDY
S.-J. Nam1, H.J. Chun1, J.H. Hong2, J.J. Seo2, S.Z. Yoon3, S.H. Kim1, J.M. Lee1,
I.K. Yoo1, H.S. Choi1, E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, C.D. Kim1,*,
S.W. Lee1, J.-J. Park1
1
Internal Medicine, Korea University College of Medicine, 2Control and
Instrumentation Engineering, Korea University, 3Anesthesiology, Korea University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: pinetrees@daum.net
INTRODUCTION: Various treatment modalities for GI motility disorders have
been developed so far including medications and electrical stimulation. But little
is known about biomechanical properties of gastrointestinal smooth muscle, in
contrast to vascular or respiratory smooth muscle. In this study, we made a novel
actuator model for characterization of biomechanical property of small intestinal
smooth muscle.
AIMS & METHODS: In the order to characterize active and passive properties
of intestinal smooth muscle, we performed tensile test and isometric, isotonic
experiments using viable small intestines of 3 month old pig. In the tensile testing,
we connected excised intestinal samples to the universal testing machine devel-
oped by our own group only for soft tissue measurement. In isometric and
isotonic experiments, porcine small intestine was bathed in HTK-solution for
preservation of energy source. After connection of the sample to sensor,
muscle contraction was induced by acetylcholine chloride. Contractile force
and velocity were measured by isometric force transducer and isotonic
transducer.
RESULTS: In tensile experiment, tensile stress was maximum at the 1.67 times
its original length and 0.702N at break point. In isometric experiment, maximum
contractile force was observed at the resting length which was 12.350.5 mN
after 50min of acetylcholine stimulation. Intestinal smooth muscle contraction
was sustained for 55min. In isotonic experiment, intestinal smooth muscle was 10
to 100 times slower than skeletal muscle contraction. We calculated contractile
velocity for various loads and acquired load free contractile velocity by curve
fitting method (0.4952 mm/min). Finally, we combined previously acquired pas-
sive and active parameters of intestinal smooth muscle to make a comprehensive
intestinal smooth muscle model.
CONCLUSION: In this study, we characterized active and passive parameters
and applied them to modified Hill type muscle model for making a novel actua-
tor of intestinal smooth muscle. This study would provide basic tool for under-
standing biomechanical properties of intestinal smooth muscle, and we can utilize
this as basic data for development of a more efficient GI electrical stimulator.
Disclosure of Interest: None declared
A249
P0427 5HT SELECTIVE RECEPTOR AGONISTS AND GALLBLADDER
MOTILITY IN PATIENTS WITH MIGRAINE
D. Georgescu1,*, C. Georgescu2, R. Buzas1
1
Internal medicine, University of Medicine, 2Neurology, County Hospital,
Timisoara, Romania
Contact E-mail Address: dgeorgescu@hotmail.com
INTRODUCTION: Some 5HT selective receptor agonists (triptans) are reported
to have gastric motor effects but less is known about their role on gallbladder
(GB) motility.
AIMS & METHODS: Assessment of GB motility in patients treated with oro-
dispersable triptans .30 patients diagnosed with mild to moderate migraine: 15
with with aura (3 men, 12 women, mean age 43.1317.72 years) and 15 without
aura ((1 man, 14 women, mean age 47.7318.50 years), with an ejection frac-
tion (EF) of GB 5 60%, previously measured by elipsoid ultrasound Dodds
method, without prokinetic treatments, collagen or thyroid disease, diabetes
mellitus, cardiac, liver or kidney failure, undertook this study. The same mea-
surements were made while having a migraine attack, before and every 15 min-
utes till 90 minutes after receiving 5 mg of orodispersable zolmitriptan.
RESULTS: There was no statistical significant difference between initially EF of
the two groups (p 0.8190). Patients with migraine with aura showed before ther-
apy a mean EF 42.534.31%; after therapy the mean EF improved significantly:
48.803.23% (p 0.0001). Patients with migraine without aura displayed an initi-
ally mean EF 42.533.27% and had a very statistically significant response to
therapy with increasing of EF to 61.477.07% (p50.0001). There was also a
statistically significant difference of respose to therapy in patients with migraine
without aura (61.477.07% vs 48.803.23%; p50.0001).
CONCLUSION: 5HT selective receptor agonists increased GB motility in
migraine attacks with a better response in patients without aura.
REFERENCES
1. Dodds WJ, Groh WJ, Darweesh RM, et al. Sonographic measurement of
gallbladder volume. Am J Roentgenol 1985; 145: 1009-1011.
2. Bigal ME, Ferrari M, Silberstein SD, et al. Migraine in the triptan era: lessons
from epidemiology, pathophysiology, and clinical science. Headache 2009;
49(Suppl. 1): S21-33.
3. Cipolla G, Sacco S, Crema F, et al. Gastric motor effects of triptans: open
questions and future perspectives. Pharmacol Res 2001; 43: 205-210.
4. Moroa E, Cremaa F, De Pontib F, et al. Triptans and gastric accommodation:
pharmacological and therapeutic aspects. Dig Liver Dis 2004; 36: 8592.
5. Deixler E and Helmke K. Extrahepatic cholestasis during therapy with zolmi-
triptan. Z Gastroenterol 2005; 43: 1045-1049.
Disclosure of Interest: None declared
P0428 NEUROPATHOLOGICAL ANALISYS AND CLINICAL FEATURES
OF CHRONIC CONSTIPATION IN PATIENTS WITH PARKINSON
DISEASE
F. Giancola1,*, C. Sorteni2, F. Torresan3, A. Ioannou3, M. Guarino4,
G. Barbara3, C. Cremon3, R. Latorre3, R. Chiocchetti2, C. Vallorani2,
P. Clavenzani2, P. Cortelli5, V. Stanghellini3, C. Sternini6, R. De Giorgio3
1
Dept Vet Med Sci and Dept Med Surg Sci, 2Dept Vet Med Sci, 3Dept Med Surg
Sci, University of Bologna, 4Neurology Unit, St. Orsola-Malpighi Hospital, 5Dept
Biom and Neuromot Sci, University of Bologna, Bologna, Italy, 6CURE/Dig Dis
Res Center, Div Dig Dis, Depts Med Neurobiol, David Geffen School of Medicine,
University of California at Los Angeles, Los Angeles, California, United States
Contact E-mail Address: fiorella.giancola2@unibo.it
INTRODUCTION: Chronic constipation (CC) represents one of the most
common gastrointestinal (GI) complaints in Parkinsons disease (PD), being
diagnosed in about 80% of patients. Furthermore, CC often precedes the somatic
motor impairment in PD. The enteric nervous system (ENS), controlling gut
functions, can be a target of the PD although the precise neurochemical ENS
abnormalities underlying CC/PD patients remain largely unknown.
AIMS & METHODS: In CC/PD patients we aimed to: 1) characterize constipa-
tion by assessing colonic transit time (TT) and anorectal manometry (AM); 2)
analyze colonic submucosal neurons of PD patients vs controls, particularly
assessing the secretomotor neuron component.
GI symptoms were evaluated by the Rome III questionnaire, while PD was estab-
lished by a Unified Parkinsons Disease Rating Scale (part III). CC was studied in 25
PD patients (7F, 18M; age range: 64-85 yrs) by TT, AM and colonoscopy; 14 control
subjects (4F, 10M; age range: 33-77 yrs) undergoing screening colonoscopy were also
enrolled in the study. Using routine biopsies during colonoscopy, we obtained sub-
mucosal specimens with related neural network in 10 CC/PD patients and 10 controls.
The submucosal plexus was studied by immunohistochemistry on whole mount pre-
parations using a mouse monoclonal anti-HuC/D as pan-neuronal marker
(Invitrogen, 1:50) and two rabbit polyclonal anti-VIP (vasoactive intestinal peptide-
7913; CURE/DDRC, UCLA, 1:2500) and anti-pChAT (peripheral choline acetyl
transferase, Justus-Liebig-University Giessen, Germany; 1:100) antibodies.
RESULTS: Four groups of CC/PD patients were characterized: a) 55% with a
delayed TT and altered AM; b) 15% with a delayed TT; c) 20% with an altered
AM; d) the remaining 10% with no evident functional impairment. There were
no significant differences in the number of HuC/D immunoreactive (-IR) neu-
rons/ganglion between CC/PD (4.70.8) and controls (5.51.5); however, a
reduced number of HuC/D/VIP-IR neurons was found in CC/PD (73.317.1)
vs controls (86.010.9) (P50.05). No significant changes were detected for HuC/
D/ChAT neurons in both groups (85.611.1 vs. 91.210.1).
CONCLUSION: Most (90%) of CC/PD patients has a marked impairment of
colonic motor and rectal sensory functions. Neurochemical changes in a subset of
VIP containing secretomotor neurons suggest that altered secretory mechanisms
may accompany sensorymotor dysfunction in PD-related CC pathophysiology.
A250
Disclosure of Interest: None declared
P0429 EHLERS-DANLOS SYNDROME AND IBS - SAME GI
SYMPTOMS, DIFFERENT DISEASES
G. Mohammadian1,2,*, J. Lunding3, G. Lindberg2,3
1
Center of Digestive Diseases, Karolinska Universtity Hospital, 2Institution of
Medicine, Huddinge, KAROLINSKA INSTITUTET, 3Center of digestive dis-
eases, Karolinska University Hospital, Stockholm, Sweden
Contact E-mail Address: ghazaleh.mohammadian.kermani@ki.se
INTRODUCTION: Ehlers-Danlos syndrome (EDS) is usually an autosomal
derived disease with defects in the collagen synthesis. It is divided into six sub-
groups according to the Brighton criteria. The most common subtype gives
hypermobility of the joints, frequent luxations and fractures. It is also connected
with gastrointestinal symptoms, most commonly abdominal pain and other
symptoms that are included in the functional symptom spectrum. Patients with
EDS fulfil the Rome III criteria for functional gastrointestinal disorders in 84%.
So far there are no systematic studies of GI physiology and treatment for GI-
disorders in these patients.
AIMS & METHODS: To evaluate symptoms, gastrointestinal work up, opioid
therapy, treatment response to octreotide, and findings on 24h ambulatory small
bowel manometry in patients with EDS.
Information obtained from patient database and retrospectively acquired infor-
mation from the medical record system in the out- and inpatient clinic in Center
of Digestive Diseases, Karolinska University Hospital, Stockholm, Sweden.
RESULTS: The search found 24 patients from 2001 to 2014, all but one were
female. Abdominal pain was present in 100%, change of bowel habits in 19/24.
Ten had done small bowel manometry, 3 of them were classified as enteric
dysmotility and 5 patients had some changes of MMC phase III. Ten of the
patients had tried octreotide and seven of them had clinical response and con-
tinued the octreotide treatment. Eleven patients were unable to do small bowel
manometry due to use of opioids and three are on the waiting list for the
manometry.
CONCLUSION: We show that patients with EDS have a high frequency of
changes in small bowel manometry and high prevalence of enteric dysmotility.
Treatment with octreotide is effective, even without having enteric dysmotility.
Abdominal pain in patients with EDS should not be considered as IBS but EDS
should be considered in patients with joint hypermobility and abdominal pain.
Further studies are needed for evaluation of gastrointestinal physiology of
patients with EDS.
Disclosure of Interest: None declared
P0430 COMBINED EFFECT OF EARLY LIFE STRESS AND ACUTE
STRESS AS A NEW MODEL FOR FUNCTIONAL DYSPEPSIA
H. Abdel-Aziz1, W. Wadie2, H.F. Zaki2, J. Muller1, M.T. Khayyal3,*
1
Scientific Department, Steigerwald Arzneimittelwerk, Darmstadt, Germany,
2
Pharmacology, Faculty of Pharmacy, Cairo University, Cairo, 3Pharmacology,
Faculty of Pharmacy, Cairo University, Darmstadt, Egypt
Contact E-mail Address: heba.abdelaziz@gmail.com
INTRODUCTION: Functional dyspepsia (FD) is one of the most common GI
disorders. Because of the chronic relapsing nature & lack of effective treatment
options, FD is associated with significantly impaired quality of life and consider-
able health care costs.
Based on the central role stress seems to be playing in functional GI diseases,
available animal models for FD rely on exposing animals to various types of
stress either in the neonatal period or in adulthood.
However, clinical studies have shown that adverse physiological or psychological
experiences in early life are associated with the development of FD symptoms, as
well as acute stressful conditions in adulthood. Hence, childhood traumatic
experiences followed by later exposure to acute stress may play key roles in the
development & in modulation/ maintenance of FD.
AIMS & METHODS: In the present study, we tried to mimic this situation by
combining early life stress (neonatal maternal separation, NMS) and acute stress
in adulthood (restraint stress, RS) in rats, in the hope of developing a multi-
dimensional experimental model of FD with closer resemblance to the clinical
situation.
To explore the validity of this sequential stress model in trying to develop new
drugs for FD, we tested the effects of STW5, a multicomponent herbal prepara-
tion widely used to treat FD with strong clinical evidence, as a standard drug.
RESULTS: Fundus strips from rats subjected to the combined stress showed
significantly reduced responses to adrenaline, carbachol, KCl and 5HT as com-
pared to those from normal rats or animals subjected to either stressor. Animals
treated with STW5 showed normalized response to adrenaline, carbachol and
5HT. Combined stress also markedly increased plasma levels of CRF to twice as
much as either stressor alone. The elevation of CRF was associated with a
corresponding increase in plasma corticosterone. Pretreatment with STW5 pro-
tected against the increase in both CRF and corticosterone. None of the treat-
ments significantly affected active plasma Ghrellin.
CONCLUSION: These data indicate that combined early life stress and acute
stress effectively induce stomach motility disorders as well as hormonal derange-
ments that might be more representative of the complex clinical situation and
might represent a model for the screening of new FD drugs.
Disclosure of Interest: H. Abdel-Aziz Other: Employee of Steigerwald
Arzneimittelwerk GmbH, W. Wadie: None declared, H. Zaki: None declared,
J. Muller Other: Employee of Steigerwald Arzneimittelwerk GmbH, M. Khayyal
Financial support for research from: Steigerwald Arzneimittelwerk GmbH
United European Gastroenterology Journal 2(5S)
P0431 RECIPROCAL MODULATION OF INTESTINAL SMOOTH
MUSCLE CELL CONTRACTILITY BY TH17 AND TH1 CYTOKINES
H. Akiho1,*, K. Ohbuchi2, K. Tsuchiya2, E. Ihara3, K. Nakamura3,
M. Yamamoto2
1
Gastroenterology, Kitakyushu Municipal Medical Center, Kitakyushu, 2Tsumura
Research Laboratories, Tsumura & Co., Ibaraki, 3Medicine and Bioregulatory
Science, Kyushu University, Fukuoka, Japan
INTRODUCTION: Gastrointestinal motility disorders, such as infection, IBD,
ileus, achalasia and functional gastrointestinal disease, have been associated with
immune activation. We have previously reported that the hypercontractility of
small intestinal (SI) smooth muscle cells (SMC) is mediated by IL-17A-induced
NFkB/IkBz-RGS4 signaling resulting in down regulation of RGS4 activity.
RGS4 is known to suppress Gaq/11 signaling triggered by stimulation of the
acetylcholine (muscarinic 3) receptor. On the contrary, IL-1, which is known
to induce hypomotility of SMC, upregulates RGS4 expression and function.
However, these opposite effects by IL-17A and IL-1 both have been found to
be mediated by NFkB/IkBz activation. In the present study, we have investigated
the mechanism by which IL-17A- and IL-1-induced NFkB/IkBz activation pro-
duces the different outcomes.
AIMS & METHODS: Murine SMCs were isolated, cultured, and treated with
various chemical probes, IL-17A, IL-1, and IL-4 (1050 ng/ml). Contraction
was assessed using a cell imaging analyzer on a temperature-responsive UpCell
96-well plate. Activation of NFB was evaluated by the strength of the nuclear
NFB p65 immunosignal. Activation of RGS4, myosin light chain (MLC) and
MAPKs were determined by immunoblotting.
RESULTS: IL-17A significantly enhanced carbachol-induced contractile
responses, concomitant with increased phosphorylated MLC (p-MLC) and
decreased RGS4 activity. IL-1 significantly decreased p-MLC and increased
RGS4 activity. These effects of IL-17A and IL-1 were both abrogated by an
NFB inhibitor and IB siRNA. Screening of activated MAPK using a pro-
teome profiler revealed that IL-1 activated p38MAPK and JNK but IL-17A
activated p38MAPK only. The effect of IL-17A was abrogated by p38MAPK
inhibitors but not by JNK inhibitors. The effect of IL-1 was abrogated by JNK
inhibitors but enhanced by p38MAPK inhibitors. Anisomycin, a p38MAPK
activator induced hypercontractility.
CONCLUSION: These data suggest that the balance of relative activity levels of
JNK and p38MAPK is critical for determining the direction of contractile
response and that NFB/ IB signaling fuels the movement of MAPK-triggered
molecular events toward/against hypercontractility of SI SMC. The relatively
stronger activation of p38MAPK may result in hypercontractility, induced by
IL-17A, and that of JNK may result in hypocontractility, induced by IL-1. Our
findings may lead to the development of new pharmacotherapeutic strategies for
gastrointestinal motor dysfunctions.
Disclosure of Interest: None declared
P0432 EXPECTATIONS OF PATIENTS WITH IRRITABLE BOWEL
SYNDROME (IBS): A PROSPECTIVE SURVEY OF THE FRENCH
ORGANIZATION OF IBS PATIENTS
J.-M. Sabate1,*, P. Ducrotte2, T. Piche3, F. Zerbib4, M. Dapoigny5, S. Bruley
Des Varannes6, B. Bonaz7, F. Mion8, F. Iglicki1, D. Denhez1, D. Tchatat1,
S. Facon9, P. Jouet1
1
Hepatogastroenterology, Hopital Louis Mourier, Colombes,
2
Hepatogastroenterology, CHU de Rouen, Rouen, 3Hepatogastroenterology,
Hopital LArchet, Nice, 4Hepatogastroenterology, Hopital Saint Andre, Bordeaux,
5
Hepatogastroenterology, CHU de Clermont Ferrand, Clermont-Ferrand,
6
Hepatogastroenterology, CHU de Nantes, Nantes, 7Hepatogastroenterology,
CHU de Grenoble, Grenoble, 8Service des Explorations Fonctionnelles, Hopital
Edouard Herriot, Lyon, 9Association des Patients Souffrant du Syndrome de
lIntestin Irritable, Hopital Louis Mourier, Colombes, France
Contact E-mail Address: jean-marc.sabate@lmr.aphp.fr
INTRODUCTION: IBS may be responsible for an impaired quality of life (QoL)
and represents an economic burden for society. Efficacy of treatments is poor
and patients often feel isolated and dissatisfied with medical care1. This work
aims to describe the characteristics of IBS in members of the French organization
of IBS patients (APSSII, www.apssii.org) and to compare their expectations to
their past experiences with health care providers.
AIMS & METHODS: From January to June 2013 all members of APSSII were
asked (once, by mail or online) to answer a questionnaire with a description of:
IBS, treatments, impact on QoL, expectations and experiences in relation to the
disease and health care system.
RESULTS: 222 out of 330 members (67%) responded (women 68.5%, age
46.517.7 years, disease duration 8.80.7 years, IBS-D 33.6%, IBS-C 26.7%,
IBS-A 38.2%). A colonoscopy was performed in 87%, and diagnosis was made
by a physician in 88%. Patients were followed up by a doctor in 65% (specialist
57% or GP 38%), and 82% had consulted for IBS in the last 12 months. Past or
current treatments were antispasmodics (46%), laxatives (25%), antidepressants
(25%), probiotics (38%), homeopathy (34%), hypnosis (15%), relaxation (31%),
osteopathy (28%), acupuncture (25%) and 46% were on a diet. IBS was severe
(IBS-SSS 4 300) in 53% and major depression was present in 45% (HAD score
4 19). QoL was impaired (FDDQL score 4114), more frequently in women
(44.914 vs. 40.214.4 (p 0.039), with no difference according to IBS subtype,
and was correlated with disease severity and HAD score (r -0.707 and r -
0.484, p50.001; respectively). Patients expectations about IBS were improved
health, information on the causes and treatments for 94%, and better dis-
ease recognition for 86%. Expectations vs. experiences (%) in relation to the
medical providers were: sufficient information (94% vs. 16%), listening with
empathy (97% vs. 36%), providing hope (85% vs. 9%), improved health
United European Gastroenterology Journal 2(5S)
(95% vs 15%). Patients thought that their doctors had good knowledge on IBS
in 18%, believed in their symptoms in 47% and suggested to them that "it was
in their head" in 65%. Only 16% were satisfied with the health care system for
IBS management and 68% considered that an improvement in the management
of symptoms would have an impact on overall IBS cost. There was a discrepancy
between the desired information sources on IBS (more information via the
doctor) and the reality: internet 84%, specialist 47.9% and GP 32%.
CONCLUSION: These French data on expectations of IBS patients from a
survey conducted among members of a patients organization show 1) a severe
disease with frequent psychological impact and impaired QoL, 2) many unsatis-
fied expectations with respect to the disease and health care professionals, and 3)
a need for improving the quality of patient-physician relationship.
REFERENCES
1. Halpert et al. Dig Dis Sci 2010; 55: 375-383.
Disclosure of Interest: None declared
P0433 PROTECTIVE EFFECTS OF SACRAL NERVE STIMULATION
AGAINST TNBS-INDUCED ACUTE INTESTINAL INFLAMMATION
J. Bregeon1,*, A.C. Cordeiro1, P. Aubert1, J. Jaulin1, J. Chevalier1, J. Hervouet2,
D. Minault2, E. Coron1, M. Neunlist1, G. Meurette1
1
Inserm U913, Digestive Diseases Institute, Nantes University Hospital, 2Inserm
U1064, Laboratoire des grands animaux, Nantes University Hospital, NANTES,
France
INTRODUCTION: Inflammatory Bowel Diseases (IBD) dramatically alter the
quality of life for the young adult and have a high societal cost. Treatments of
IBD have made recent progress but their adverse side effects are numerous and
relapse prevention remains a problem. Enhancing intestinal epithelial barrier
(IEB) functions emerges as a promising new therapeutic approach. The enteric
nervous system (ENS), a key regulator of gut homoeostasis, exhibits major bar-
rier protective effects. Sacral nerve stimulation (SNS), probably via activation of
the ENS, has been reported to enhance IEB resistance (1) but its putative pro-
tective effects in response to inflammatory challenge remain unknown.
AIMS & METHODS: Therefore, the aim of this study was to determine whether
SNS protects barrier dysfunction as well as modulates intestinal inflammation
induced by an acute inflammatory stress induced by TNBS. Twelve pigs were
implanted for percutaneous bilateral SNS (S3 stimulation) (Medtronic 041828-
004, Minneapolis, USA; 14 Hz, 210ms). Six pigs were stimulated 3 hours prior
and 3 hours after administration of rectal enemas of TNBS (15 mg/ml). Control
animals (CT) were implanted but not stimulated and also received TNBS enema.
Rectal panparietal biopsies were performed before (T0) and 1h, 3h, 24h after
enema. Intestinal para- and transcellular permeability was assessed in Ussing
chambers. In vivo, intestinal inflammation was evaluated by endoscopy and con-
focal endomicroscopy (CEM) scores. Impact of SNS upon the mucosal changes
induced by TNBS was evaluated by combining histological and transcriptomic
approaches.
RESULTS: In CT, a significant and transient increase in rectal para- and trans-
cellular permeability was measured as early as 3h following TNBS enema. 24h
after enemas permeability was still increased in CT as compared to its T0 value.
In SNS pig, a significant and transient increase in para- and transcellular perme-
ability occurred as early as 1h following TNBS enema. However, 24h after
enemas permeability was similar to its T0 value. At 24h, similar results were
observed at the rectosigmoidal hinge level. Consistently, the SNS pigs exhibited
a trend toward a lower UCEIS score (p 0.07, n 5) as compared to CT. At 24h,
CEM scores revealed that TNBS induced alterations in crypt circularity, tortu-
osity and brightness were significantly reduced by SNS as compared to control
(p 0.05, n 6; p 0.008, n 6, respectively). Furthermore, epithelial desqua-
mation and edema formation was significantly larger in CT as compared to SNS
pigs (p 0.03, n 6, both measures). Finally, mRNA expression of key tight
junction proteins such as Claudin-1 (p 0.04, n 6) and ZO-1 (p 0.03, n 6)
were significantly increased in SNS (p 0.04, n 6; p 0.03, n 6, respectively)
as compared to CT pigs. Western blot analysis of ZO-1 also showed that ZO-1
protein expression was increased in SNS as compared to CT animals (p 0.018,
n 6).
CONCLUSION: Altogether these results show that SNS exhibit major repara-
tive properties on mucosal lesions induced by acute inflammatory stress. These
identify SNS as a putative alternative or complementary therapy targeting dis-
eases such as IBD.
REFERENCES
(1) Neurogastroenterol Motil 2012; 24: 267e110.
Disclosure of Interest: None declared
P0434 FAECAL INCONTINENCE IN TYPE 2 DIABETICS: COMPARISON
WITH NON DIABETIC HEALTHY INDIVIDUALS AND ANALYSIS
OF RELATED FACTORS
J.X. Jorge1,2,*, L.S. Fernandes3, C.C. Almeida2, F.J. Delgado4, E.A. Panao5,
M.A. Simoes2
1
Faculty of Medicine, Agostinho Neto University, Luanda, Angola, 2Faculty of
Medicine, University of Coimbra, Coimbra, 3Medicine Urgency, Hospital
Fernando Fonseca, Lisboa, 4Medicine, Hospital de Alcobaca, Alcobaca,
5
Gastroenterology, Hospital dos Covoes, Coimbra, Portugal
Contact E-mail Address: cambombo@hotmail.com
INTRODUCTION: Faecal incontinence is a complaint that some type 2 diabetic
patients frequently refer1. The factors involved with are not well known.
AIMS & METHODS: The aim of this study was to compare the frequency of
faecal incontinence between type 2 diabetic patients and non diabetic healthy
individuals and to analyse some factors involved in this perturbation in diabetics.
A251
A questionnaire of Gastrointestinal Symptoms Rating Scale2 was completed by
to 140 type 2 diabetics and 132 non diabetic healthy individuals, matched by age
and gender.
RESULTS: The frequency of faecal incontinence in diabetics vs. non diabetics
was 14.3% vs. 3.1%, p 50.01. According to the severity, the frequency of faecal
incontinence between diabetics vs. non diabetics was as follows: minor symp-
toms, 3.6% vs. 2.3%; moderate symptoms, 7.9% vs. 0.8%; severe symptoms,
2.1% vs. 0.0%; very severe symptoms, 0.7% vs. 0.0%, p 0.03.
When analysing the frequency of faecal incontinence in diabetics according to the
disease duration, 5/ 10 years vs. 410 years the results was 9.5% vs. 24%, p
50.01. The symptoms for severity was also significantly higher in diabetics with
more than 10 years of disease, p 0.01. In diabetic patients, age, gender and
glycaemia control did not influence the frequency and severity of faecal
incontinence.
CONCLUSION: 1- Faecal Incontinence is more frequent and severe in type 2
diabetics than non diabetic healthy individuals. 2- Diabetes duration influences
the frequency and the severity of faecal incontinence. 3- Age, gender and glycae-
mia control did not influence the frequency and the severity of faecal inconti-
nence in type 2 diabetic patients.
REFERENCES
1 Ditah I, et al. Clin Gastroenterol Hepatol 2014; 12: 636-643.
2 Strid H, et al. Nephrol Dial Transplant 2002; 17: 1434-1439.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
OESOPHAGEAL, GASTRIC AND DUODENAL DISORDERS I POSTER EXHIBITION
HALL XL_____________________
P0435 PHENOTYPIC PLASTICITY OF ALVEOLAR MACROPHAGES IN
GASTROESOPHAGEAL REFLUX DISEASE WITH PULMONARY
MANIFESTATIONS AND ITS COMBINATION WITH ASTHMA
I.V. Maev1,*, S.V. Lyamina2, I.Y. Malyshev3
1
Propaedeutics of Internal Diseases and Gastroenterology, 2Pathophysiology,
Propaedeutics of Internal Diseases and Gastroenterology, 3Pathophysiology,
Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: svlvs@mail.ru
INTRODUCTION: To date it is known that in spite of different points of view
on etiology and variety of cellular and molecular pathogenetic components of
pulmonary manifestations in gastroesophageal reflux disease (GERD) and com-
bination of GERD and asthma there is a key feature of inflammation and the
immune response disorder in the form of Th1/Th2 imbalance in the pathogenesis
of the disease. Th1 or Th2 direction of immune response is mainly predetermined
by innate and adaptive immune response cells - macrophages. Considering the
concept of M1/M2 programming in changing microenvironment, macrophages
can obtain either pro-inflammatory L1 phenotype, or alternatively anti-inflam-
matory M2 phenotype and change their phenotype in the disease formation. So
we can suppose that Th1/Th2 imbalance is mainly due to impairment ability of
macrophages to adequate change their phenotype, i.e. with impaired phenotypic
plasticity of macrophages.
AIMS & METHODS: Assessment of alveolar macrophages (AM) phenotypic
plasticity in GERD and its combination with asthma and healthy volunteers
under the influence of different serum (FBS) concentrations. Methods: In vitro
experiments were carried out on AM, isolated from BALF of patients with
GERD (n 15, 46.414.18 y.o.), combination of GERD and asthma (n 16,
49.303.64 y.o.) and healthy volunteers (HV) (n 10, 51.833.52 y.o.). AM
phenotype was assessed by flow cytometry (Beckman Coulter, FC500) by cyto-
kine production of proinflammatory M1, anti-inflammatory L2 and bivalent
L1/L2 cytokines in culture medium (CM) of AM (BenderMedSystems,
BMS810FF). Phenotypic plasticity of AM was measured as percentage change
of markers during 36 hours of AM reprogramming in the presence of 0%, 10%,
40% standard fetal bovine serum, containing endogenous reprogramming factor
surfactant protein D.
RESULTS: Pooled analysis of M1 and M2 phenotypic plasticity in GERD and
its combination with asthma against HV showed maximum of M1 phenotypic
plasticity in GERD M1/M2 index of the macrophages ability to change their
phenotype towards M1 was 5.33 and this was 8.5 times increased vs combination
of GERD and asthma (p50.05). Maximum macrophage phenotypic plasticity
towards M2 phenotype was observed in combination of GERD and asthma and
M1/M2 index of phenotypic plasticity was 5.45 times higher than in GERD.
CONCLUSION: The ability of AM to change their phenotype under the influ-
ence of the microenvironment in GERD and its combination with asthma was
changed as compared to healthy volunteers. In GERD macrophages possess
more possibilities to obtain M1 phenotype than M2, but the in combination of
GERD and asthma macrophages are more predisposed to obtain M2 phenotype.
So the studied ability of macrophages to adapt their phenotype to the micro-
environment and to reprogram the phenotype of the cells can be thought of as the
base for new therapy approach in personalized medicine influencing the initial
links of inflammatory response and Th1/Th2 imbalance even in initial stages of
pathological process.
Disclosure of Interest: None declared
A252
P0436 INCREASED LEPTIN SIGNALING IN ESOPHAGEAL
ADENOCARCINOMA CELL LINE TREATED WITH PERITUMORAL
ADIPOSE TISSUE-DERIVED CONDITIONED MEDIUM
E. Trevellin1, M. Scarpa2,*, A. Carraro3, L. Saadeh2, M. Cagol2, R. Alfieri2,
U. Tedeschi3, C. Castoro2, R. Vettor1
1
Dept. of Medicine DIMED, University of Padova (Italy), 2Oncological Surgery
Unit, Oncological Institute (IOV-IRCCS), Padova, 3Dept. of General Surgery and
Odontoiatrics, University of Verona, Verona, Italy
INTRODUCTION: Obesity is associated with an increased risk of cancer and it
has been hypothesized that the action of adipokines (e.g. leptin and adiponectin)
may influence tumor invasiveness.
AIMS & METHODS: Our aim is to investigate if peritumoral adipose tissue may
play a direct role by altering the expression of genes involved in migratory/
mesenchymal transition processes in human esophageal adenocarcinoma cells.
Human esophageal adenocarcinoma cells (OE33) were cultured with conditioned
medium (CM) derived from adipose tissue fragments of peritumoral and distal
(omental) depots of 15 patients with esophageal adenocarcinoma, undergoing
surgical resection. After 48h we measured mRNA levels of leptin receptor
(ObR), adiponectin receptor (AdipoqR), alpha-smooth muscle actin (-SMA)
and E-cadherin (CDH1) in OE33 cells using Real Time quantitative PCR.
RESULTS: Gene expression of ObR, AdipoqR, -SMA and CDH1 were dra-
matically increased in OE33 cells cultured with CM, compared to control cells.
Moreover, expression of ObR, AdipoqR -SMA and CDH1 was significantly
higher in OE33 cells cultured with CM of peritumoral depot, compared to cells
cultured with CM of omental depot. Interestingly, ObR and -SMA expression
was significantly increased in OE33 cells cultured with CM of peritumoral depot
derived from patients with lymph node involvement (N), compared to peritu-
moral CM of patients with no positive lymph node (N-).
CONCLUSION: Our results suggest that peritumoral adipose tissue may influ-
ence esophageal adenocarcinoma cells, through the action of secreted factors. In
particular, leptin signaling may be involved in the induction of -SMA expres-
sion in esophageal adenocarcinoma cells, possibly promoting a more aggressive
behaviour of tumor.
REFERENCES
Prieto-Hontoria PL, et al. Role of obesity-associated dysfunctional adipose tissue
in cancer: a molecular nutrition approach. Biochim Biophys Acta 2011; 1807: 664-
678.
Jeong YJ, et al. Expression of leptin, leptin receptor, adiponectin, and adiponec-
tin receptor in ductal carcinoma in situ and invasive breast cancer. J Breast
Cancer 2011; 14: 96-103.
Zhao L, et al. Possible involvement of leptin and leptin receptor in developing
gastric adenocarcinoma. World J Gastroenterol 2005; 11: 7666-7670.
Howard JM, et al. Associations between leptin and adiponectin receptor upre-
gulation, visceral obesity and tumour stage in oesophageal and junctional ade-
nocarcinoma. Br J Surg 2010; 97: 1020-1027.
Disclosure of Interest: None declared
P0437 SURFACTANT PROTEIN D AND ALVEOLAR MACROPHAGES
PHENOTYPE AS ADDITIONAL MARKERS IN DIAGNOSTICS OF
GASTROESOPHAGEAL REFLUX DISEASE WITH PULMONARY
MANIFESTATIONS AND ITS COMBINATION WITH ASTHMA
S. V. Lyamina1,*, I.V. Maev2, I.Y. Malyshev3
1
pathophysiology, Propaedeutics of Internal Diseases and Gastroenterology, 2
Propaedeutics of Internal Diseases and Gastroenterology, 3pathophysiology,
Moscow State University of Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: svlvs@mail.ru
INTRODUCTION: Actual pathogenesis studies of pulmonary manifestations in
gastroesophageal reflux disease (GERD) and its combination with asthma
showed that respiratory system inflammation and imbalance between Th1 and
Th2 immune responses are the main pathologic components of the process.
Considering the present-day concept of Th1/Th2 Paradigm and M1/M2 macro-
phages programming, immune response disorders depend largely on the balance
of functional phenotypes of alveolar macrophages (AM). One of significant
bivalent regulatory components of AM activity is surfactant protein D (SP-D).
So we suppose that pooled analysis of AM phenotype with quantitative and
qualitative analysis of SP-D composition in broncho-alveolar lavage fluid
(BALF) will add to research in pathogenesis of pulmonary manifestations in
GERD and can be used as additional biomarker in GERD and its combination
with asthma.
AIMS & METHODS: This study evaluated pooled data of AM phenotype and
quantitative/qualitative composition of SP-D in BALF in patients with pulmon-
ary GERD manifestations and its combination with asthma in comparison with
healthy volunteers. Methods: Pooled analysis of AM phenotype in patients with
GERD (n 15, 46.414.18 y.o.), combination of GERD and asthma (n 16,
49.303.64 y.o.) and healthy volunteers (HV) (n 10, 51.833.52 y.o.) was per-
formed by flow cytometry (Beckman Coulter FC500) by expression of M1 and
M2 AM phenotypes CD markers (CD25, CD80 and CD163, CD206, respec-
tively) and cytokine production of proinflammatory M1, anti-inflammatory L2
and bivalent L1/L2 cytokines in culture medium (CM) of AM
(BenderMedSystems, BMS810FF). Quantitative analysis of SP-D in BALF
was performed by ELISA. Qualitative assessment of SP-D oligomeric forms in
BALF was performed by western blot analysis using tris-acetate gels (Invitrogen,
NuPAGE, # EA03752BOX).
RESULTS: Analysis of AM phenotype in patients with GERD, its combination
with asthma vs. HV showed that pooled M1/M2 ratio of AM CD markers and
cytokine production was 2.16 and 2.52, 0.91 and 0.84 vs. HV, respectively. The
results indicates shift of AM towards M1 phenotype vs HV in GERD and
United European Gastroenterology Journal 2(5S)
towards M2 phenotype vs HV in combination of GERD and asthma. SP-D
level in BALF in patients with GERD was 2.66 times decreased vs patients with
combination of GERD and asthma (155.8318.13 ng/ml vs 414.7250.22 ng/ml,
p50.05) and 3.42 times decreased vs. HV (155.8318.13 ng/ml vs 533.2021.12,
p50.05). Qualitative analysis of SP-D oligomeric forms in GERD and its com-
bination with asthma showed predominance of monomeric forms vs HV with
monomeric and multimeric SP-D oligomers.
CONCLUSION: In GERD with pulmonary manifestations and combination of
GERD and asthma AM phenotype and quantitative and qualitative composition
of SP-D in BALF vary against healthy volunteers and each other. Shift of AM
phenotype towards M1 vs healthy and significant maximum decreased SP-D level
in BALF are typical for GERD with pulmonary manifestations, whereas shift of
AM phenotype towards M2 and less decreasing SP-D level in BALF are specific
for combination of GERD and asthma. There were no significant differences in
qualitative oligomeric composition of SP-D in BALF in GERD and its combina-
tion with asthma.
Disclosure of Interest: None declared
P0438 INITIAL EXPERIENCE WITH HEMOSPRAY IN THE
TREATMENT OF ACUTE UPPER GASTROINTESTINAL BLEEDING
B. Disney1,*, A.K. Kurup1, S. Ishaq1, S. Shetty1, H. Muhammad1
1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom, Dudley,
United Kingdom
INTRODUCTION: Upper gastrointestinal bleeding remains a medical emer-
gency. Endoscopic therapies such as adrenaline injection, heater probe and
clips are used to achieve haemostasis. However, accurate delivery of these
endotherapies can be challenging. Hemospray (Cook Medical, Winston-Salem,
North Carolina, USA), an inorganic haemostatic powder, is licensed for use in
non-variceal acute upper GI bleeding. The delivery system allows a wide area of
coverage, negating the need for accuracy, and has promising results.
AIMS & METHODS: Retrospective analysis of all upper GI bleeds utilising
Hemospray following its introduction to Russells Hall Hospital in July 2013.
Patients were identified using the Unisoft endoscopy database and endoscopy
unit logbooks. Data on the use of Hemospray, bleeding lesion identified and use
of other therapeutic modalities were collected. Outcomes including mortality,
primary haemostasis and rebleeding were obtained. The aim of this study was
to assess the effectiveness of Hemospray in the real-life setting.
RESULTS: Hemospray was used 17 times in 13 patients with acute upper GI
bleeding (mean age 69 years, range 37-96 years; 69% male). The patients had a
median Blatchford score of 10 (range 5-13) and Rockall score of 7 (range 3-8).
Three patients had Hemospray used on more than one occasion.
The cause of bleeding was peptic ulcer in 10/17 patients (58.8%), upper GI malig-
nancy in 6/17 patients (35.3%) and unknown source in 1/17 patients (5.9%).
Hemospray was used as primary endotherapy in 11/17 patients (65%) achieving
initial haemostasis in 16/17 cases (94%). Technical failure occurred in one patient
with the cartridge failing to operate and deliver Hemospray. Rebleeding within 30
days occurred with 6/17 uses (35%); 5 of these in the context of peptic ulcer disease
and 1 in upper GI malignancy. When Hemospray was used as primary therapy
rebleeding occurred on 4 occasions compared to 2 when used as second line therapy
(p 0.57). Blatchford scores were higher in those patients suffering from rebleeding
(12 versus 10, p 0.21). No significant differences in rebleeding was noted between
malignant and non-malignant causes of acute upper GI bleeding. 30-day mortality in
this patient cohort was 2/13 (15.4%). There were no documented complications of
Hemospray therapy.
CONCLUSION: Hemospray is a safe, and easy to use, endoscopic therapy with
excellent initial haemostasis as both a primary or second line treatment. In the
context of bleeding as a result of upper GI malignancy Hemospray provided
good palliation. Although there appeared to be a higher rebleeding rate seen
when Hemospray was used as primary therapy this was not significant and
may reflect the low numbers in the study.
REFERENCES
1. Leblanc S, Vienne A, Dhooge M, et al. Early experience with a novel hemo-
static powder used to treat upper GI bleeding related to malignancies or after
therapeutic interventions. Gastrointestinal Endoscopy 2013; 78.
2. Chen YI, Barkun AN, Soulellis C, et al. Use of the endoscopically applied
hemostatic powder TC-325 in cancer-related upper GI hemorrhage: preliminary
experience. Gastrointestinal Endoscopy 2012; 75.
Disclosure of Interest: None declared
P0439 CORRECT USE OF PROTON-PUMP INHIBITORS FOR STRESS
ULCER PROPHYLAXIS IN INTENSIVE CARE UNIT: NO GI
BLEEDING AND NO CL. DIFFICILE?
S. Segato1,1, L. Bardelli1, C.C. Cortelezzi1,*, M. Parravicini1, M. Montanari1,
S. Piana1, S. Bonecco1, S. Segato1, G. Bisso1, G. Minoja2
1
Gastroenterology, 2Intensive Care Unit, Azienda Ospedaliero Universitaria
Macchi Varese, Varese, Italy
Contact E-mail Address: sergio.segato@ospedale.varese.it
INTRODUCTION: Despite limited data about their use in critically ill patients,
proton pump inhibitors (PPIs) have become the first line therapy in stress ulcer
prophylaxis (SUP). PPIs may increase the risk of hospital-acquired pneumonia
and enteric infections, especially Clostridium difficile related diarrhoea. Many
studies showed an overuse of acid suppressive therapy in Intensive Care Unit
(ICU), with unintended consequences of therapy.
AIMS & METHODS: The aim of the study was to evaluate the current practice
of SUP, the correlation with the evidence-based American Society of Health-
System Pharmacist (ASHP) guidelines and the occurrence of GI hemorrhage,
pneumonia, and CDI in critical care setting.
United European Gastroenterology Journal 2(5S)
The study was made on 300 consecutive patients (186 men, 114 women, medium
age 63.9 yrs, range 23-99 yrs, median ICU stay 11.42 days range 3-45 days)
admitted to ICU of the teaching hospital Macchi Varese between January 1st
and June 30th 2012 and January 1st and June 30th 2013; patients admitted to
neurocritical care unit and children under 18 yrs were excluded. Data about
clinical indications, drug assumption and outcomes (gastrointestinal haemor-
rhage, pneumonia and enteric infections) were collected during ICU stay.
RESULTS: Mechanical ventilation for more than 48h was the reason for initiat-
ing prophylaxis in 294 patients (98%); 6 pts. had a platelet count under 50.000/
mm3.
281 pts (93.6%) used PPIs (omeprazole 40mg daily i.v.), 19 pts (6.3%) H2RAs
(ranitidine 150 mg every 8 hours i.v.), 296 pts (98.6%) antibiotics, 166 pts
(55.3%) vasoactive drugs.
32 patients (10.6%) developed nosocomial pneumonia; 26 of them had other risk
factors (1 asthma, 14 chronic obstructive lung disease, 1 AIDS, 10 were older
than 75 years). One pt had Clostridium difficile related dyarrhea. One pt with a
history of active duodenal ulcer had ulcer bleeding.
CONCLUSION: All SUP were classified as appropriate according to the ASPH
guidelines. PPIs represent the first line therapy. Bleeding from stress ulceration is
extremely uncommon; Clostridium difficile related dyarrhea is unexpectedly rare
too. Patients who developed hospital-acquired pneumonia during acid-suppres-
sive therapy, usually had other risk factors linked to this kind of infection. In this
prospective observational study, the occurrence of GI bleeding and symptomatic
CDI in critically ill patients, treated following ASHP guidelines, is lower than
reported in other studies. More data from well-designed randomized clinical
trials are needed before any change in practice.
Disclosure of Interest: None declared
P0440 A COMPARISON OF THE GLASGOW-BLATCHFORD SCORE
AND AIMS65 SCORE IN PREDICTING NEED FOR CLINICAL
INTERVENTION AND MORTALITY IN ACUTE NON-VARICEAL
UPPER GI BLEEDS: A RETROSPECTIVE COHORT STUDY
A.J. Palmer1, F. Moroni1,*, S. McLeish1, G. Campbell1, J. Bardgett1, J. Round1,
C. McMullan1, M. Rashid1, R. Clark1, D. De Las Heras 2, C. Vincent2
1
Medicine, Raigmore, 2Medicine, Raigmore Hospital, Inverness, United Kingdom
Contact E-mail Address: andrew.palmer1@nhs.net
INTRODUCTION: The early use of risk stratification scores is recommended by
the International Consensus Upper Gastrointestinal (GI) Bleeding Group for
patients presenting with acute non-variceal upper GI bleeds (ANVUGIB) 1.
Such models permit identification of patients who are suitable for early hospital
discharge or even outpatient care. The most widely used is the Glasgow-
Blatchford Score (GBS) 2. The score ranges from 0 to 23 and the risk of requiring
clinical intervention and death has been shown to increase with increasing score 3.
More recently a simpler scoring system known as AIMS65 was devised, which is
based on serum Albumin (530g/dl), INR 41.5, altered Mental status
(GCS514), Systolic BP (590) and age 465. One point is scored for the presence
of each variable and it has been shown to accurately predict mortality, length of
stay, and be superior to the GBS in predicting mortality 4,5. However, its ability
predict the need for clinical intervention has yet to be established.
AIMS & METHODS: The aim of this study was to examine the ability of the
AIMS65 score in predicting the need for clinical intervention and mortality in
comparison to the GBS. To do this we performed a retrospective analysis of 150
adults who presented to a single district general hospital in Scotland with a
primary diagnosis of ANVUGIB and who underwent upper GI endoscopy
between March 2008 & April 2013. GBS and AIMS65 scores were calculated
and requirement for clinical intervention, defined as the need for endoscopic
treatment, blood transfusion and/ or surgery was recorded. The area under the
receiving-operator characteristic curve (AUROC) was calculated for each score.
RESULTS: Of the 150 patients 62% were male and 38% female. The mean age
was 68 years (SD 16), GBS 7.9 (SD 4.6) and AIMS65 score 1.0 (SD 1.0). The
overall mortality was 6%. The GBS had a high predictive accuracy and was
superior to AIMS65 in predicting requirement for any clinical intervention
(AROC 0.81 vs. 0.70), blood transfusion (AROC 0.85 vs. 0.67) and endoscopic
therapy (AROC 0.67 vs. 0.58). With respect to mortality, AIMS65 was superior
to the GBS (AROC 0.79 vs. 0.68). Patients with a GBS 54 experienced no
mortality, GBS 4 58 2.6% and for those with GBS 8 10.1%. For the GBS
these cut off values maximised the sensitivity and specificity for inpatient mor-
tality. Patients with low risk AIMS65 scores (0 or 1) experienced mortality (4%)
questioning its use as a risk stratification tool for safe, early, hospital discharge.
CONCLUSION: In our population the GBS was superior to the AIMS65 score
in terms of predicting the need for any clinical intervention, blood transfusion or
endoscopic therapy. We identified potential cut off values for the GBS that allow
stratification of patients into low, medium and high risk groups on the basis of
predicted mortality. This warrants further investigation.
REFERENCES
(1) Barkun et al. Ann Intern Med 2010; 152: 101-113.
(2) Blatchford et al. Lancet 2000; 356: 1318.
(3) Srygley et al. JAMA 2012; 307: 1072.
(4) Saltzman et al. Gastrointest Endosc 2011; 74: 1215.
(5) Hyett et al. Gastrointest Endosc 2013; 77: 551.
Disclosure of Interest: None declared
A253
P0441 OUTCOMES AND PREDICTIVE FACTORS OF
TRANSCATHETER ARTERIAL EMBOLIZATION FOR NON-
VARICEAL UPPER GASTROINTESTINAL BLEEDING
H.H. Lee1,*, J.M. Park1, C.-H. Lim1, J.S. Kim1, Y.K. Cho1, B. I. Lee1, I.S. Lee1,
S.W. Kim1, M.-G. Choi1
1
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea,
Republic Of
Contact E-mail Address: hanyee99@hanmail.net
INTRODUCTION: Transcatheter arterial embolization (TAE) has been consid-
ered a therapeutic option for upper gastrointestinal (GI) bleeding when endo-
scopic treatment fails.
AIMS & METHODS: We aimed to assess the efficacy and clinical outcomes of
TAE for acute nonvariceal upper GI bleeding and to identify predictors of
recurrent bleeding within 30 days.
Transcatheter angiography was performed in 66 patients (42 men, 24 women;
mean age, 60.3  12.7 years) who experienced acute nonvariceal upper GI bleed-
ing during a 7-year period. Clinical information was reviewed retrospectively.
Outcomes included technical success rates, complications, and 30-day rebleeding
and mortality rates.
RESULTS: TAE was feasible in 59 patients. The technical success rate was
98.3%. Rebleeding within 30 days was observed in 46.6% and was managed
with reembolization in 8 patients, endoscopic intervention in 5, surgery in 2,
and conservative care in 12. The 30-day overall mortality rate was 42.4%. Of
the 34 patients whose initial endoscopic hemostasis failed, 31 (91.2%) underwent
angiographic embolization, which was successful in 30. Rebleeding occurred in
15 patients (50.0%), mainly because of malignancy. Two factors were indepen-
dent predictors of rebleeding within 30 days by multivariate analysis: coagulo-
pathy (OR, 4.37; CI, 1.2515.29; P 0.021) and embolization in 32 territories
(OR, 4.93; CI, 1.4317.04; P 0.012). Catheterization-related complications
included hepatic artery dissection and splenic embolization.
CONCLUSION: TAE controlled acute nonvariceal upper GI bleeding effec-
tively. TAE may be considered when endoscopic therapy is unavailable or unsuc-
cessful. Coagulopathy and embolization of 32 territories were significant
predictors of angiographic failure. Correction of coagulopathy before TAE is
recommended.
REFERENCES
1. Loffroy R, Guiu B, Cercueil JP, et al. Refractory bleeding from gastroduode-
nal ulcers: arterial embolization in high-operative-risk patients. J Clin
Gastroenterol 2008; 42: 361-367.
2. Rockall TA, Logan RF, Devlin HB, et al. Incidence of and mortality from
acute upper gastrointestinal haemorrhage in the United Kingdom. Steering
Committee and members of the National Audit of Acute Upper
Gastrointestinal Haemorrhage. BMJ 1995; 311: 222-226.
3. Hearnshaw SA, Logan RF, Lowe D, et al. Acute upper gastrointestinal bleed-
ing in the UK: patient characteristics, diagnoses and outcomes in the 2007 UK
audit. Gut 2011; 60: 1327-1335.
Disclosure of Interest: None declared
P0442 DOES DISCHARGE HEMOGLOBIN AFFECT OUTCOME OF
PATIENTS WITH ACUTE NON-VARICEAL UPPER
GASTROINTESTINAL BLEEDING?
J.M. Lee1, H.J. Chun1,*, I.K. Yoo1, S.J. Nam1, S.H. Kim1, H.S. Choi1,
E.S. Kim1, B. Keum1, Y.T. Jeen1, H.S. Lee1, C.D. Kim1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine,
Korea University College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: jmlee1202@gmail.com
INTRODUCTION: Many patients with gastrointestinal bleeding show anemia
and usually need red blood cell transfusion. Several studies suggested that restric-
tive transfusion strategy and low hemoglobin threshold for transfusion showed
acceptable outcomes in patients with acute upper gastrointestinal bleeding [1,2].
But clinicians are concerned about low hemoglobin affects prognosis and clinical
outcome after discharge. This study aimed to assess whether discharge hemoglo-
bin influences on outcomes, or not, in patients with acute non-variceal gastro-
intestinal bleeding.
AIMS & METHODS: Retrospective analysis was carried out on patients who
had upper gastrointestinal bleeding between January 2011 and December 2012.
We analyzed the patients who had lowest hemoglobin below 10 g/dL during
admission. Patients with variceal bleeding, stroke, or cardiovascular disease
were excluded. We divided the patients into two groups by discharge hemoglobin
(Low discharge hemoglobin group; 8 g/dL  hemoglobin 510 g/dL, High dis-
charge hemoglobin group; 10 g/dL  hemoglobin 512 g/dL) and compared
clinical outcomes and hemoglobin level changes.
RESULTS: A total of 212 patients with upper gastrointestinal bleeding had
undergone the endoscopic hemostasis during study periods. One hundred two
patients had satisfied the inclusion criteria. Fifty patients discharged with hemo-
globin level under 10 g/dL and fifty two patients discharged with hemoglobin
level over 10 g/dL. There was no significant difference of endoscopic findings
between two groups. Patients in low discharge hemoglobin group showed a lower
consumption of pRBC(Low discharge Hb group; 3.2  1.4 pint, High discharge
Hb group; 4.1  1.8 pint, P Value 0.01) and shorter hospital days (Low dis-
charge Hb group; 4.3  2.5 days, High discharge Hb group; 5.6  4.2 days).
Hemoglobin levels were not fully recovered at out-patient department until 7
days after discharge. But, most patients showed hemoglobin recovery at 45
days after discharge (Low discharge Hb group; Hb 12.2  2.0 g/dL at OPD
45, High discharge Hb group;; Hb 11.9  2.0 g/dL at OPD 45). Clinical symp-
toms after discharge were presented no significant difference between two groups.
A254
CONCLUSION: In patients with acute gastrointestinal bleeding, discharge
hemoglobin between 8 to 10 g/dL was showed favorable outcomes during out-
patient department follow-up. It seems to be tolerable level without additional
pRBC transfusion. Despite of high hemoglobin over 10 g/dL at discharge, there
was no significant advantage in clinical outcome. Our result can increase the
evidence available to support restrictive transfusion strategies in patients with
acute non-variceal upper gastrointestinal bleeding.
REFERENCES
1. Villanueva C, Colomo A, Bosch A, et al. Transfusion strategies for acute upper
gastrointestinal bleeding. New Eng J Med 2013; 368: 11-21.
2. Rockey DC. To transfuse or not to transfuse in upper gastrointestinal hemor-
rhage? That is the question. Hepatology 2014. doi: 10.1002/hep.26994.
Disclosure of Interest: None declared
P0443 EVALUATION OF THE PREDICTIVE VALUE OF REBLEEDING
RATE OF FORREST SIMPLIFIED CLASSIFICATION
J. Moleiro1,*, A. Ferreira2, J. Torres3, E. Barjas3, M. Cravo3
1
Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco Gentil, E.
P. E., Lisboa, 2Gastroenterology, Centro Hospitalar do Algarve, Portimao,
3
Gastroenterology, Hospital Beatriz Angelo, Loures, Portugal
Contact E-mail Address: joana_moleiro@hotmail.com
INTRODUCTION: A simplification of the Forrest classification (FC) into three
levels (high risk: Ia; increased risk: Ib to IIc; low risk: III) has recently been
proposed (1).
AIMS & METHODS: Our aim was to evaluate the prognostic value of this new
simplified classification (SC) in predicting re-bleeding of peptic ulcer (PU) and to
compare it with the traditional FC. We retrospectively identified patients
admitted to our unit between 07/2012 to 02/2014 with upper gastrointestinal
bleeding due to PU. Demographic, clinical, laboratorial and endoscopic data
were collected. Therapeutic interventions and cases of re-bleeding and mortality
within a 30 days period were registered. The predictive value of the FC and SC
were compared using logistic regression and ROC curves.
RESULTS: 81 patients underwent upper gastrointestinal endoscopy due to
bleeding PU; the mean age was 70  16 years; 61 (75%) were men. Clinical
presentation of PU bleeding was melena in 33 cases (41%), hematemesis in 29
(36%), symptomatic anemia in 8 (10%), hematochezias in 7 (9%) and hemody-
namic instability in 4 (5%). The mean hemoglobin at admission and heart rate
were 8.75 g/dL and 94 bpm, respectively. Forty-eight percent of the ulcers were
located in the stomach and 52% in the duodenum. Endoscopic therapy was
performed in 39 patients (49%), and was effective in 38. One patient (1.2%)
required surgery. At the 30th day, re-bleeding occurred in 15 patients (19%)
and the mortality rate was 6%. Re-bleeding occurred in 1 of 2 patients with
Forrest Ia ulcer (high risk) and 8 (38%) with Forrest IIa (increased risk). The
odds ratio for re-bleeding of high risk and increased risk ulcers was 33.00 and
14.30 (p 0.013), respectively. The AUROC (for re-bleeding) was 0.733 for SC
and 0.723 for FC.
CONCLUSION: FC maintains its predictive value in determining re-bleeding in
PU. The proposed SC maintains the prognostic value of the FC, and therefore is
an alternative to assess the risk of re-bleeding.
REFERENCES
Groot NL, Oijen MG, Kessels K, et al. Reassessment of the predictive value of
the Forrest classification for peptic ulcer rebleeding and mortality: can classifica-
tion be simplified? Endoscopy 2014; 46: 46-52.
Disclosure of Interest: None declared
P0444 SURVIVAL OUTCOMES AFTER IMPLEMENTATION OF THE UK
IMPROVING OUTCOMES GUIDANCE (IOG) FOR OESOPHAGEAL
AND GASTRIC CANCERS
R.K. Fofaria1,*, J. Deacon1, A.Z. Al-Bahrani2, A. Polychronis3, I.R. Sargeant1,
D. Morris1
1
Gastroenterology, Lister and QEII Hospitals, Stevenage, 2General Surgery,
Watford Hospital, Watford, 3Medical Oncology, Mount Vernon Cancer Centre,
Northwood, United Kingdom
Contact E-mail Address: rishi.fofaria@nhs.net
INTRODUCTION: Oesophago-gastric (OG) cancer is the 3rd most common
cause of cancer-related death in the UK. Historically, it has been suggested
that the UK may have lagged behind European OG survival outcomes because
of fragmentation of service provision, suboptimal access to leading specialist
centres and delayed presentation and referral of patients from primary care.
The Improving Outcomes Guidance (IOG) for Upper GI Cancers (2001) and
Manual for Cancer Services (2004, 2011) recommended centralising curative
therapies, reconfiguring access to diagnostic/staging services and formalising
the role of the Cancer Network and peer-reviewed Network Site Specific
Groups. Lister and QE2 District Hospitals (part of the Mount Vernon Cancer
Network) cover a catchment population of 600,000 people and reconfigured their
upper GI cancer services in mid-2009.
AIMS & METHODS: Aims: To assess survival outcomes in patients with OG
cancer over a 9-year period before and after the reconfiguration of a local upper
GI cancer network.
Methods: The medical, endoscopic and computerised notes of multi-disciplinary
team meetings of all patients diagnosed with OG cancer between 1 January 2004 -
31 March 2013 were retrospectively analysed. Age, sex, histology, tumour site,
treatment intent and number of patients surviving at 6, 12, 24 and 42 months and
at 1 April 2014 were noted. The 2 (Chi-Square) test was used to analyse the
significance of survival outcomes.
RESULTS: From January 2004 - December 2008 there were: 139 gastric cancers
(27% curative therapeutic intent) and 234 oesophageal cancers (23% therapeutic
United European Gastroenterology Journal 2(5S)
intent; 63.6% adenocarcinoma), with overall 12-month survival of 30% and 42%
and 42-month mortality of 12% and 15%, respectively. From January 2009
March 2013 there were: 111 gastric cancers (18% curative therapeutic intent;
68.5% male; average age 75) and 230 oesophageal cancers (26.5% therapeutic
curative intent; 65.2% male; average age 72; 69.1% adenocarcinoma) with over-
all 12-month survival of 40% and 36% and 42-month mortality of 16% and 8%,
respectively (p40.05 for all corresponding follow-up intervals). Sub-group ana-
lysis shows increased survival in the 2009-2013 gastric cancer cohort treated with
curative intent at 6 months (p50.05) and palliative therapy at 12 months
(p50.05). There was no significant decrease in survival outcome at any stage
of follow up in both cancer groups and cohorts.
CONCLUSION: These findings are in keeping with national outcomes and show
that the institution of recommendations from the IOG, including centralisation
of curative therapies and access to specialist services, show no significant decrease
in survival outcome for OG cancer. Indeed, there is a modest increase in short-
term gastric cancer survival. The lower percentage of patients treated with cura-
tive intent, compared to national data, may reflect the late presentation of OG
cancers and partially explain survival outcomes in this population.
REFERENCES
Improving outcomes in upper GI cancers: the manual NHS Executive, DoH,
UK, January 2001.
Manual for cancer services: upper GI measures National Cancer Action Team,
2004, 2011.
Cancer Research UK. http://www.cancerresearchuk.org (accessed 22 April 2014)
National Oesophago-Gastric Cancer Audit (NOGCA), UK The RCS, AUGIS,
BSG, RCR, HSCIC (2010, 2012, 2013)
Disclosure of Interest: None declared
P0445 THE FLAME MODEL: SUPPORTING ENDOSCOPY TRAINING
IN LOW RESOURCE SETTINGS
S. Goddard1,*, J. Ansell1, N. Hawkes2
1
School of Postgraduate Medical and Dental Education, Cardiff University,
2
Gastroenterology Department, Royal Glamorgan Hospital, Cardiff, United
Kingdom
Contact E-mail Address: goddardsg@cardiff.ac.uk
INTRODUCTION: Simulation permits selective breakdown of key motor skills
for a clinical procedure into basic steps, which is better for acquisition, teaching
and assessing. (1, 2) Environment doesnt significantly affect skills transfer,
implying endoscopy can be learnt outside the clinical setting. Basic endoscopic
competencies can be taught with ex-vivo animal models. (3) The British Society
of Gastroenterology supported an excursion to Kurdistan whose remit to train-
the-trainers required provision of a suitable model.
AIMS & METHODS: Develop and Validate: Flexible Lightweight Animal
Model for gi Endoscopy (FLAME), to support hands-on endoscopy training
in a low-resource setting, specifically, to facilitate training in GI haemostasis,
variceal banding and polypectomy. Pilot prototyping indicated use of a light-
weight, mouldable, plastic frame with selected ports for the attachment of pre-
made animal tissue patches with bespoke defects. Potential port sites were ana-
lysed to optimise access and offer different technical challenges. A foil plate and
cling film wrap-around supported use of diathermy and prevented fluid leakage.
The model was housed in foam and enclosed in a lightweight box. External
Velcro straps provided further anchorage. The model was validated during a
hands-on training course conducted in Erbil, Iraq in February 2014. Attendees
completed 11-point realism (visual, anatomical and mechanical) surveys based on
a 7 point Likert scale,(4) separately for GI haemostasis, variceal banding and
polypectomy. Analysis using Wlicoxon signed rank test (PASW Statistics 18) for
non-parametric data reported scores against a hypothetical mean of 4.0 for
statistical significance (n 17 gave 490% power to detect a difference of 1
point).
RESULTS: 20 delegates (6 consultants, 14 trainees) completed the surveys. For
polypectomy all scores were greater than 1 point above the 4.0 hypothethical
mean, range 5.26-5.76 (score of 7 indicates strong agreement with realism). Mean
overall score was 5.59 [p50.05; CI 4.96-6.22]. For both variceal banding and GI
haemostasis, all mean scores were above 4.0 though the overall reality scores did
not reach significant difference; variceal banding - range 4.62-5.31, overall score
4.62; GI haemostasis range 4.5-5.83, overall score 4.56. Separate evaluation of
the overall training course revealed high levels of delegate satisfaction, principally
the hands-on model training elements.
CONCLUSION: The FLAMEs initial evaluation in a course setting demon-
strates face and content validity for polypectomy. Whilst banding and GI hae-
mostasis values didnt achieve statistical significance ratings for all parameters,
all were higher than the hypothetical mean. The model is cost-effective, easy to
transport, robust in practice and was highly valued by delegates in course eva-
luation. We plan further adaptations with follow-up validation studies.
REFERENCES
1. Hamdorf J and Hall J. Acquiring surgical skills. Br J Surg 2000; 87: 28-37.
2. Kopta J. An approach to the evaluation of operative skills. Surgery 1971; 70:
297-303.
3. Parra-Blanco A, Gonzalez N, Gonzalez R, et al. Animal models for endo-
scopic training: do we really need them? Endoscopy 2013; 45: 478-484.
4. Sedlack R, Baron T, Downing S, et al. Validation of a colonoscopy simulation
model for skills assessment. Am J Gastroenterol 2007; 102: 64-74.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0446 THE FIRST REPORT ON THE GASTROPROTECTIVE EFFECT
OF TRIPEPTIDE T-34 UNDER CONDITIONS OF WATER-
IMMOBILISATION STRESS IN RATS
C. Nasadyuk1,*, A. Sklyarov1
1 1
Biochemistry, DANYLO HALYTSKY LVIV NATIONAL MEDICAL
UNIVERSITY, Lviv, Ukraine
Contact E-mail Address: nasadyukch@gmail.com
INTRODUCTION: There is accumulating evidence that a number of short pep-
tides are envolved in the regulation of the function of gut and may be considered
as new pharmacological drugs for the prevention and treatment of gastric
ulceration.
AIMS & METHODS: Objective of our research was to explore the effect of
tripeptide T-34 (H-Glu-Asp-Gly-OH) on the area of water-immobilisation
stress (WIS)-induced gastric lesions in rats and activities of NO-synthases
(NOS) and lipid peroxidation processes in gastric mucosa (GM).
The studies were conducted on white male rats. 30 min before the exposure to
WIS rats were pretreated with T-34 introduced intragastrically (IG) in dose 10mg
(n 5) or intraperitoneally (IP) - 2mg (n 5). Control rats were injected 0.5 ml of
saline (n 5). After 5 hours of WIS, rats were sacrificed, gross inspection of GM
was conducted and NOS activity, NO and MDA content in GM were deter-
mined. In blood plasma L-arginine concentration was measured.
RESULTS: WIS caused the formation of gastric lesions (181.9 mm), accom-
panied by acute rise of NO-synthase activity (p50.05), in particular its inducible
isoform iNOS (p50.01), increased production of NO and MDA (p50.05) in
GM compared to intact rats. The concentration of L-arginine, NO precursor, in
blood plasma decreased (p50.05). Pretreatment with T-34 IG caused 27%
(p50.05) decrease of ulceration area, at that NOS activity decreased for 45%
(p50.05), iNOS activity diminished for 60% (p50.01) in GM compared to
control rats. Decrease of NO (p50.05) and tendency to decrease of MDA con-
tent in GM were also noted, whereas L-arginine concentration in plasma
increased (p50.05). Pretreatment with T-34 IP also resulted in the decrease of
iNOS activity in GM (p50.05) but no statistically significant difference of the
area of GM damage was evaluated compared to saline-treated rats exposed to
WIS.
CONCLUSION: T-34 decreased the indices of nitrooxidative stress in GM under
the conditions of WIS-induced gastric lesions in rats. IG administration of T-34
was superior to IP injection of this compound towards reduction of gastric
mucosa damage. Deeper studies on the elucidation of the cytoprotective effect
of tripeptide T-34, optimization of dosage and route of application are required.
Disclosure of Interest: None declared
P0447 THE FREQUENCY AND TYPE OF HISTOLOGICAL GASTRIC
CHANGES IN PATIENTS WITH FUNCTIONAL DYSPEPSIA
I. Korendovych1,*, A. Svintsitskyy1, O. Kuryk2,3, G. Solovyova1,2
1
Internal Medicine #3, Bogomolets National Medical University, 2Oberig clinic,
3 1
Morbid Anatomy, Bogomolets National Medical University, Kyiv, Ukraine
Contact E-mail Address: ira-korendovych@yandex.ru
INTRODUCTION: Though the symptoms of functional dyspepsia (FD) are not
considered to correlate with mucosa changes the histopathological evaluation
seems to be fundamental not to miss the early onset of atrophic-metaplastic
transformation.
AIMS & METHODS: Our aim was to assess the frequency and type of histolo-
gical changes in patients with functional dyspepsia. This work was a part of a
randomized superiority trial in which combined treatment using eradication ther-
apy (ET) plus antidepressant by comparison with ET for patients with FD was
assessed. Adult patients (18 - 65 years) with confirmed diagnosis of FD by the
Rome III criteria (2006) were eligible to participate. Exclusion criteria: the pre-
sence of red flag signs and other comorbidities that could explain the symp-
toms. Biopsy specimens were taken from stomach following the Houston-
updated gastric biopsy sampling protocol for the next histological examination.
One expert gastrointestinal pathologist, blinded to all patient clinical but not
endoscopic information, assessed all tissue samples. The degree of inflammatory
changes was scored by the 4-grade Visual Analogue Scale, atrophy - following
Operative Link for Gastritis Assessment (OLGA) and metaplasia - following
Operative Link on Gastric Intestinal Metaplasia (OLGIM) staging systems. All
patients were tested for H. pylori using two methods (rapid urease test and by
morphological examination).
RESULTS: 75 patients fulfilled all criteria and were included into the study.
Mean age was 40.33.9; males 26 (34.7%). H. pylori was detected in all 75
patients. The main location of H. pylori infection was antral part. Patients had
mainly a mild degree of mucosal inflammation (84%) which in most cases was
limited to antral part. Atrophy was statistically significant more frequently diag-
nosed in antrum (64.0%) than in corpus (12.0%) (p50.0001) and in all cases
didnt exceed OLGA stage I. Metaplasia of intestinal type was found in 26
(34.7%) patients in antral part and was not detected in corpus (p50.0001). No
case of dysplasia was detected. We also tried to collate the degree of gastritis and
the stage according to OLGA (2008) in antrum and corpus with the presence of
such clinical syndromes of FD as postprandial distress and epigastric pain. No
statistically significant correlation was found (p40.05).
CONCLUSION: As in most studies, we also didnt find the correlation between
stage and degree of gastritis and clinical symptoms of FD. But we shouldnt
forget about possible microscopic changes of mucosa when dealing with func-
tional patients, thus conducting a primary prophylaxis of gastric cancer.
Disclosure of Interest: None declared
A255
P0448 THE IMPACT OF ERYTHROMYCIN ON MYOELECTRIC
ACTIVITY IN EXPERIMENTAL PIGS
T. Douda1,*, J. Kvetina2, I. Tacheci1, M. Pavlik3, M. Kunes4, M. Kopacova1,
S. Rejchrt2, J. Bures2
2nd Department of Medicine- Gastroenterology, 22nd Department of Medicine,
Charles University Faculty of Medicine & University Teaching Hospital, Hradec
Kralove, Czech Republic, 3Centre of Advanced Studies, University of Defence,
Faculty of Military Health Service, 4Biomedical Research Centre, University
Teaching Hospital, Hradec Kralove, Czech Republic
Contact E-mail Address: tomas.douda@fnhk.cz
INTRODUCTION: Surface electrogastrography (EGG) is a non-invasive
method for the assessment of gastric myoelectrical activity. Erythromycin, as a
potent prokinetic drug, increases the dominant frequency of EGG both in
humans and experimental pigs. The aim of this study was to evaluate the effect
of erythromycin on the porcine EGG power (assessed by areas of amplitudes)
and power ratio (simple fraction ratio of the areas of amplitudes after and before
erythromycin administration).
AIMS & METHODS: Six mature female pigs (3 months old, mean weight
23.22.1, median 23 kg) were included in the study. All EGG recordings were
performed under general anaesthesia in the morning after 24 hours of fasting (by
means of the MMS EGG System, Enschede, the Netherlands). The baseline EGG
recording lasted 15 min., erythromycin ethylsuccinate (1,500 mg) was subse-
quently administered by gastric tube into the stomach. The EGG trial recording
lasted 150 min. (ten 15-minute intervals: P1 to P10) after erythromycin adminis-
tration. Running spectral analysis (based on Fourier transform) was used for
initial evaluation of the EGG. The gastric myoelectric activity was estimated
by EGG power analysis and by power ratio assessment.
RESULTS: Erythromycin increased the EGG power significantly after 15 to 30
min. from the baseline mean value 828633 (V^2) to 15834238 (at P1) and
11022077 (P2 interval), p 0.003. Afterwards, the EGG power decreased to its
minimum at P4 (237200), p50.001; and increased to 7091213 V^2 after 150
min. (at P10), p50.001. The EGG power ratio reached the highest values at P1
(1.643.98) and P2 (1.914.27), decreased significantly at P4 (0.290.27; p50.001)
and balanced out after 150 min. at P10 interval (1.152.48; NS: p 0.668).
CONCLUSION: A medium single dose of erythromycin caused a significant
increase in the EGG power and power ratio after 15 to 30 min. after intragastric
administration. Both myoelectrical markers decreased after 60 min. and returned
close to the initial values after 150 min.
Acknowledgement
The study was supported by research grant IGA NT/14270-3.
Disclosure of Interest: None declared
P0449 FUNCTIONAL MOTOR-SECRETORY LIGAMENTS OF
DIGESTIVE ORGANS
Y. I. Reshetilov1,*, S.N. Dmitrieva1, H.Y. Vasilchenko1, N.N. Protsenko1
Family Medicine and Gastroenterology Department, State Institution
Zaporizhzhya Medical Academy of Postgraduate Education, Ukraine, Zaporozhye,
Ukraine
INTRODUCTION: Definition of motor stomach and duodenum disorders role
in gastroduodenal zone development process is interesting for peculiarities of
digestive system disorder clinical realization. Phase structure of interdigestive
motility reflects changes of digestive system activity and inactivity periods; influ-
ences interdigestive cycle duration and essentially changes during gastric and
duodenum diseases.
AIMS & METHODS: Patients with functional diseases (65), chronic gastritis/
gastroduodenitis (184) and duodenal peptic ulcer (55) took part in study of
stomach and duodenum motility (GDM). Also 30 healthy men took part in
this testing. GDM was studied by the special bougie. Electrodes were based in
duodenum, antrum and in body of stomach. External probe ends were connected
with polygraph strain gauge, which registered GDM and defined interdigestive
cycle periods of inactivity (I phase) and activity (II phase intermittent motility,
III phase rhythmic phase).
RESULTS: Correct alternation of GDM was diagnosed among healthy men: I
phase 22.42.0; II phase 42.62.6; III phase 5.61.7 min, in case of inter-
digestive cycle total time is 69.72.3 min. Amplitude and frequency character-
istics of stomach and GDM were lowest during I phase (1-4 low-amplitude
contractions per min), but they became higher during II phase (3-8 contractions
of different height per min) and during III phase (9-15 rhythmic amplitude
signals per min). Phase research of intragastric pH in basal conditions showed,
that stomach pH decreases till 1.00.10 during II phase and it increases till
1.70.12 during the third one, as maximal realization of acidogenesis stomach
function at the beginning of working period. Patients were separated in 3 obser-
vation groups: with heightened, preserved and reduced acidogenesis stomach
function. The I group endurance period of inactivity (1 phase) lasted for
15.61.0 min, working period of II and III phase was increased till 50.61.0
and 6.20.9 min, properly (P50.05). Patients of the II group had phase indexes,
which essentially did not differ from control group results (20.61.6-42.32.3-
5.21.3; P40.05). In the group motor indexes and interdigestive total time did
not statistically differ from check ones (P40.05). Patients from the III group had
these results: I phase lasted for 27.30.9 min, II phase 38.50.7 and III phase
was shortened to 4.11.1 min; the inactive period increase was determined by
means of working period, which was equivalent to gastroduodenodyskinesia.
CONCLUSION: In case of inflammatory gastroduodenum pathology, GDM
structure changes according to the picularities of stomach acidogenesis during
intagastral cycle. This fact can be explained by secretory and motor function of
digestive system functional correlation.
Disclosure of Interest: None declared
A256
P0450 HIGH ONE-YEAR RESPONSE RATE TO PERMANENT GASTRIC
ELECTRICAL STIMULATION AND IMPROVED QUALITY OF LIFE
IN PATIENTS WITH NON-ESTABLISHED INDICATIONS FOR
TREATMENT SELECTED BY A TEMPORARY STIMULATION
PERIOD
B. Serrano Falcon1,2,*, S. Kilincalp3, M. Simren4, G. Ringstrom4,
H. Abrahamsson4, H. Tornblom4
1
Dept of Internal & Clinical Nutrition, Institute of Medicine, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden, 2Servicio de Aparato
Digestivo, Hospital Clnico San Carlos, Madrid, Spain, 3Department of gastroen-
terology, Diskapi Yildirim Beyazit Education Hospital, Ankara, Turkey, 4Dept of
Internal Medicine & Clinical Nutrition, Institute of Medicine, Sahlgrenska
Academy, University of Gothenburg, Gothenburg, Sweden
Contact E-mail Address: hans.tornblom@gu.se
INTRODUCTION: Gastric electrical stimulation (GES) with the Enterra system
is a therapeutic alternative for patients with therapy refractory nausea and vomit-
ing secondary to diabetic or idiopathic gastroparesis (GP). Some patients with
normal gastric emptying also benefit from GES (Andersson et al, 2011) after
selection with a temporary percutaneous stimulation (TPGES) test.
AIMS & METHODS: The aim of this study was to assess response rate and
quality of life after one year of treatment with GES in patients selected by a
TPGES test period. We used the TPGES technique described by us previously in
a randomized double blind crossover design with 2 weeks stimulation ON (5-7
mA range) followed by stimulation OFF, or the opposite order. Treatment
response was defined as a symptom reduction 50% during the ON period
compared to the OFF period for one or both of weekly nausea hours (WNH)
and weekly vomiting frequency (WVF). Non-responders to blinded TPGES were
offered an open treatment period with increased stimulation (5-10 mA as toler-
ated). The response to permanent GES was judged by the same response defini-
tion but comparing one-year data with baseline symptom registration. Quality of
life was evaluated by use of the SF36 questionnaire at baseline and after 12
months of GES therapy.
RESULTS: Twenty-eight patients (22 female (78.6%), median age 43.5 years
(range 20-70)) with therapy refractory nausea and vomiting were included.
Gastric emptying was normal in 17 patients (61%) and delayed in 11 (39%).
Ten patients (36%) were responders after blinded TPGES and 18 were not. Six
accepted an open stimulation period during which two more were responders and
two were judged as responders by patient preference, both of whom had diabetes
mellitus. Thus, a total of 14 patients (50%) were offered and accepted a perma-
nent device (Table 1). After one year of GES treatment, 11 patients (79%) were
still responders. Response to treatment could not be predicted by gastric empty-
ing status, neither after TPGES (p .70) nor after GES (p .61). Responders to
GES had a significant improvement in quality of life after one year comparing
with baseline in terms of bodily pain (p .017), vitality (p .035), social func-
tioning (p .026), role emotional (p .038), mental health (p .024) and general
health (p .017).
Table 1. Clinical diagnosis, gastric emptying status, TPGES response and one-
year response number in patients selected for permanent GES.
Responders
TPGES Responders
Diagnosis (n) Gastroparesis (open stim) 1 year GES
Diabetes mellitus (5) 0 3 (2) 3 IIIb (p 0.591). There were no significant differences in oesophageal body moti-
Idiopathic gastroparesis (3) 3 1 1 swallow test was normal in 47.4% in HH IIIa and in 75% in HH IIIb (p 0.055).
Postsurgical nausea or vomiting (7) 5 3 (1) 2
Functional dyspepsia (9) 0 5 (1) 3
Enteric dysmotility (4) 3 2 2
United European Gastroenterology Journal 2(5S)
from 30 to 40 mm. After each dilation symptoms were assessed to evaluate
whether a subsequent dilation with a larger balloon size was required. Patients
with recurrent or persistent symptoms (Eckardt score 43) after treatment with a
40-mm balloon were identified as failures.
RESULTS: 12 patients presented with achalasia type I, 6 with achalasia type II
and 2 with achalasia type III (Chicago classification). Median relapse time was 4
years after Heller myotomy (IQR: 7 years and 9 months). 3 patients were not
suitable for PD; 1 patient was morbidly obese and 2 had a mega-oesophagus. 5
patients were successfully treated with one 30-mm balloon dilation (median
follow-up time: 2 years; IQR: 7 years). 8 patients required dilations with 30-
and 35-mm balloons (median follow-up time: 6 years; IQR: 6.5 years). 4 patients
underwent 3 dilations with balloon sizes up to 40 mm, and all failed on the 40-
mm balloon as well. Thus, PD was successful for 13 out of the 17 patients who
could be treated, resulting in a success rate of 76% for treatable patients or 65%
for all patients. Patients successfully treated with a 30-mm balloon all suffered
from achalasia type I. Baseline LOS pressure (before dilation) was not different
between successfully treated patients (Median: 15.0 mmHg; IQR: 11.5 mmHg)
and those that failed (median: 12.5 mmHg; IQR: 6.5 mmHg) treatment (p40.05).
Furthermore, baseline Eckardt scores were not predictors of successful treat-
ment; there was no difference between successful (median: 6; IQR: 2) and
failed (median: 5.5; IQR: 3.25) treatment. Baseline symptom pattern was not a
predictor of successful treatment either.
CONCLUSION: Pneumodilation for recurrent symptoms after previous Heller
myotomy has a success rate of 76%, using 30- and 35-mm balloons. Patients with
recurrent symptoms after pneumodilation with 35-mm balloon are likely to also
fail after dilation with a 40-mm balloon.
Disclosure of Interest: None declared
P0452 IS DIFFERENTIATING BETWEEN HIATUS HERNIA IIIA AND
IIIB IN HIGH RESOLUTION MANOMETRY USEFUL IN CLINICAL
PRACTICE?
C. Ciriza De Los Rios1,*, F. Canga1, I. Castel1, G. Castellano1
1
gastroenterology, HOSPITAL UNIVERSITARIO DOCE DE OCTUBRE,
Madrid, Spain
Contact E-mail Address: constanzacarpa@gmail.com
INTRODUCTION: Oesophageal high resolution manometry (HRM) is a useful
tool for the detection of hiatus hernia (HH) as two high pressures zones, lower
oesophageal sphincter (LOS) and crural diaphragm (CD) can be clearly identi-
fied. Two types of HH have been described in HRM, type IIIa, associated with a
further decrease in LOS pressure during inspiration, and IIIb associated with an
increase in LOS pressure during inspiration.
AIMS & METHODS: The aim of this study is to determine if these HRM
classifications for hiatus hernia are useful in clinical practice.
39 consecutive patients with HH detected by HRM were included. HRM
(Manoscan; Given) was performed in supine and analyzed according to 2012
Chicago classification criteria. HH was defined as a separation 4 2 cm between
LOS and CD at inspiration. Upper endoscopy was performed on all patients and 24
hours pH-monitoring on 30 (76.9%) of them. Statistical analysis: U Mann Whitney;
Chi-Square.
RESULTS: Clinical data, HRM and pH-monitoring results are expressed in the
table. Hypotensive LOS (resting pressure 5 10 mmHg) was found in 42.8% HH
IIIa and in 27.8% HH IIIb; oesophagogastric junction (OGJ) obstruction (IRP-4
415 mmHg) at the level of the CD was found in 19.1% HH IIIa and in 16.7%
lity (normal 76.2% in HH IIIa and 61.1% in HH IIIb; p 0.457). Multiple water

CONCLUSION: TPGES is a good selection tool for patients with non-estab-

lished indications for GES treatment and results in a high one-year response rate.
A significant improvement in quality of life after 1 year of GES therapy was also
shown in the responder group.
Disclosure of Interest: B. Serrano Falcon: None declared, S. Kilincalp: None
declared, M. Simren: None declared, G. Ringstrom: None declared, H.
Abrahamsson: None declared, H. Tornblom Lecture fee (s) from: Almirall,
Shire, Consultancy for: Almirall, Danone, Shire

P0451 EFFICACY OF PNEUMODILATION IN ACHALASIA AFTER

FAILED HELLER MYOTOMY
C. Saleh1,*, F. Ponds1, M. Schijven1, A. Smout1, A. Bredenoord1
1
gastroenterology and hepatology, academic medical center (AMC), Amsterdam,
Netherlands
Contact E-mail Address: c.m.saleh@amc.uva.nl
INTRODUCTION: Heller myotomy is an effective treatment for the majority of
achalasia patients. However, a small proportion of patients suffers from persis-
tent or recurrent symptoms after surgery and they are usually subsequently trea-
ted with pneumodilation (PD).
AIMS & METHODS: The efficacy of PD as secondary treatment for achalasia
has scarcely been studied. This study therefore aimed to investigate the efficacy of
PD as treatment for achalasia patients suffering from persistent or recurrent
symptoms after Heller myotomy. 20 patients with recurrent or persistent symp-
toms (Eckardt score 43) after Heller myotomy were selected. Patients were
treated with PD, using a graded distension protocol with balloon sizes ranging
United European Gastroenterology Journal 2(5S) A257
always associated with an abnormal last MRS swallow according to CC criteria
(premature swallow, n 4; rapid contraction, n 3; hypercontractile swallow,
HH IIIa (n 21) HH III b (n 18) p-value n 1; failed, n 1). This was observed also in the only case with normal MRS.
CONCLUSION: MRS was a useful complementary test during HRM in order to
Clinical data detect esophageal motility abnormalities in patients with either normal or abnor-
Age 63.8 [57.4-70.1] 58.6 [51.8-65.3] 0.234 mal standard manometry. Moreover, MRS was superior to standard assessment
Sex (F) 13 (58.9%) 9 (50%) 0.455 in provoking esophageal symptoms in patients with NCCP or dysphagia and
BMI (kg/m2) 30.7 [27.9-33.5] 27.2 [25.2-29.2] 0.037 permitted to correlate them to abnormal motor function.
Abdominal perimeter (cm) 105.7 [100.8-110.6] 97.4 [91.2-103.5] 0.078 Disclosure of Interest: None declared
Co-morbidity 1 (4.8%) 2 (11.1) 0.873
No 20 (95.2%) 16 (88.9%) 0.424
Yes 19 (90.5%) 15 (83.3%) 0.311 P0454 VALIDATION OF THE CHICAGO CLASSIFICATION FOR THE
Previous PPI treatment 10 (47.6) 12 (66.8%) DIAGNOSES OF PRIMARY ESOPHAGEAL MOTILITY DISORDERS
Upper endoscopy 2 (9.5%) 1(5.5%) BASED ON OUTCOME DATA
Normal 4 (19.1%) 4 (22.2%) G. Capovilla1, R. Salvador1, M. Costantini1, L. Nicoletti1, G. Zaninotto2,
Peptic esophagitis 2 (9.5%) 1 (5.5%) E. Savarino1,*
Barrett 1 (4.8%) 1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Ring/Stenosis 2 (9.5%) Padua, Italy, 2Imperial College, London, United Kingdom
Diverticulum
Other (gastritis, ulcer) INTRODUCTION: Early comparisons between 8-channel water-perfused (WP)
HRM parameters conventional manometry and 36 pressure transducers solid-state (36-SS) high-
Resting pressure (mmHg) 12.6 [8.7-16.5] 12.5 [9-12,3] 0.945 resolution manometry (HRM) showed that high spatial resolution increases the
IRP-4s 8.9 [6.1-11.8] 6.7 [3.7-9.8] 0.112 diagnostic yield and accuracy for clinically relevant esophageal motility disorders
OGJ total length (cm) 7.3 [6.3-8.3] 7.7[6.3-9.1] 0.791 (EMD). Thus, a new classification of EMD based on HRM findings, the Chicago
Oesophageal length (cm) 20.5[19.4-21.7] 20.8[19-22.7] 0.813 Classification (CC), has been proposed. Limited data are available on the clinical
Sac length 3.3 [2.5-4] 3.1 [2.1-4.2] 0.646 impact of this classification in terms of patients outcome.
DCI (mmHg.cm.s) 1474.4 [1027.5-1921.2] 2070 [868.7-3272.7] 1 AIMS & METHODS: We aimed to prospectively assess the clinical value of the
VFC (cm/s) 3.8 [2.8-4.8] 4.2[2.9-5.4] 0.626 CC comparing the diagnoses of EMD obtained by using the 36-SS and the 24-
IBP (mmHg) 18.6 [14.4-22.8] 23.1[14.9-31.3] 0.967 channel WP system in a group of patients with esophageal symptoms and eval-
Distal Latency (s) 5.4 [4.8-6.1] 5.9[5.6-6.3] 0.119 uating their clinical outcome at 1-year after treating them based on 36-SS HRM
findings. Diagnoses of EMD have been collected from a prospective, rando-
pH-monitoring result mized, double blind, crossover study aimed to measure and compare normal
Abnormal 7 (43.8%) 7 (50%) 0.509 values of conventional and high-resolution manometry metrics as well as to
Positive symptom index 3 (18.7%) 3 (21.4%) 0.558 assess the inter-rater and inter-device agreement for the diagnoses of EMD
between the 36-SS (Given Imaging, US) and the 24-WP system (EB Neuro,
Italy). Twenty patients [11M/9F; 48 (43-55)] underwent both procedures blinded
and in random order. Two expert reviewers (RS, ES) performed a blind analysis
CONCLUSION: There were no significant differences between the two HH types of the patients plots. Diagnoses based on CC were obtained. Inter-rater and
in the clinical data, in upper endoscopy, HRM and pH-monitoring results inter-device agreement for each reviewer were evaluated. Then, according to
although patients with HH IIIa are more obese and tend to have a more hypo- CC-based diagnoses at 36-SS HRM plus impedance-pH features in case of sus-
tensive LOS. The differentiation between both subtypes is therefore not useful for pected reflux disease, patients were empirically treated and followed-up for 1
routine clinical practice. year. Outcome was evaluated as positive (50% of symptomatic relief) or nega-
Disclosure of Interest: None declared tive (550%) based on validated disease-related questionnaires.
RESULTS: Diagnostic inter-device agreement was moderate for both reviewers
[k (RS) 0.5; k(ES) 0.4], whereas diagnostic inter-rater agreement was higher
P0453 MULTIPLE RAPID SWALLOWING IS A USEFUL for the 36-SS (k 1) than for the 24-WP (k 0.68) system. As to the outcome
COMPLEMENTARY TEST TO CORRELATE SYMPTOMS TO evaluation at 1-year, we found that 17/20 (85%) patients had a positive outcome.
ESOPHAGEAL MOTILITY ABNORMALITIES Among them, 7 patients had dysphagia with achalasia (type II, n 5; type III,
E. Savarino1,1,*, C.de Cassan1, F. Galeazzi1, R. Salvador1, E. Marabotto2, n 1; type I, n 1) and were surgically (n 4) or endoscopically (n 3) treated,
M. Furnari2, P. Zentilin2, N.de Bortoli3, S. Marchi3, R. Bardini1, 7 patients had reflux symptoms with normal peristalsis (NP; n 4) or frequent
G.C. Sturniolo1, V. Savarino2 failed peristalsis (FFP; n 2) or weak peristalsis (WP; n 1) and were surgically
1
Department of Surgery, Oncology and Gastroenterology, University of Padua, (n 2, Nissen Fundoplication) or medically (n 5, PPI plus alginate) treated, 1
Padua, 2Department of Internal Medicine, University of Genoa, Genoa, patient had chest-pain with WP and was treated with PPI plus prokinetic and,
3
Department of Internal Medicine, University of Pisa, Pisa, Italy finally, 2 patients had dysphagia with FFP and outflow obstruction (OO) and
were treated with prokinetic and endoscopic dilatation, respectively. Out of 3/20
INTRODUCTION: Although esophageal motor disorders (EMD) are associated (15%) patients with a negative outcome, 1 had dysphagia with NP (also at 24-WP
with non-cardiac chest pain (NCCP) and dysphagia, minimal data support a HRM) and was treated with PPI plus prokinetic, 1 had regurgitation with OO
direct relationship between abnormal motor function and symptoms. Indeed, a (normal peristalsis at 24-WP HRM) and was treated with PPI plus prokinetic,
recent study failed to observe a correlation between high-resolution manometry and 1 had chest-pain with distal esophageal spasm (FFP at 24-WP HRM) and
(HRM) metrics and symptoms during the manometric protocol. On the other was treated with endoscopic dilatation.
hand, multiple rapid swallowing (MRS) has been recently suggested as a com- CONCLUSION: The 36-SS HRM was more accurate and reproducible than the
plementary test during HRM in order to observe abnormalities in inhibitory or 24-WP system for diagnosing clinically relevant EMD based on the CC.
excitatory esophageal mechanisms that could potentially underlie esophageal Moreover, the Chicago classification has been found greatly useful as diagnostic
symptoms. Limited data are available on the role of MRS in eliciting NCCP tool in order to obtain good outcome in patients reporting esophageal symptoms.
or dysphagia during HRM testing. Disclosure of Interest: None declared
AIMS & METHODS: We aimed to evaluate the yield of MRS to provoke
esophageal symptoms in patients with normal or abnormal standard manometry.
Consecutive patients with NCCP or dysphagia without previous surgery were P0455 CLINICAL AND ENDOSCOPIC CHARACTERISTICS CAN HELP
enrolled. All patients underwent HRM as follows: after a 5-min baseline record- DISTINGUISH PSEUDOACHALASIA FROM ACHALASIA
ing to locate and assess the esophago-gastric junction, the subjects took 10 single F.A. Ponds1,*, I.M. van Raath1, A.J. Smout1, A.J. Bredenoord1
water swallows (5 mL) at 30-s intervals (standard assessment) and two MRS (one 1
Department of Gastroenterology and Hepatology, Academic Medical Centre
swallow every 23s) while 10mL of water was injected steadily into their mouths Amsterdam, Amsterdam, Netherlands
through a syringe. Symptoms reported were recorded and graded based on a 5- Contact E-mail Address: f.a.ponds@amc.uva.nl
point Likert scale (0-4) and a 10-cm visual analogue scale (VAS). The tracings
were analyzed based on Chicago Classification (CC) criteria for EMD and, INTRODUCTION: Pseudoachalasia is a condition in which clinical and mano-
further, MRS were analyzed for completeness of esophageal body inhibition metric signs of idiopathic achalasia are mimicked by another abnormality, most
and for augmentation of contraction after the last MRS swallow. Also the last often a malignancy. An underlying malignancy should be recognized early to
swallow during MRS was classified according to the CC criteria. prevent inappropriate therapeutic intervention and delay in appropriate treat-
RESULTS: We enrolled 31 [18M/13F; mean age 55 (35-78)] patients complaining ment. However, clinical identification of pseudoachalasia can be challenging.
of NCCP (n 14) and dysphagia (n 17) as major symptom. Fourteen (45%) AIMS & METHODS: The aim of our study was to identify characteristics that
patients had incomplete esophageal body inhibition, whereas 13 (42%) patients suggest potential pseudoachalasia caused by malignancy. Patients diagnosed with
failed to increase wave amplitudes after MRS. Overall, 18 (58%) patients had achalasia by manometry were retrospectively included between 2000 - March
abnormal MRS, with 5 (16%) of them having normal peristalsis. No patient 2014 in a single centre. Manometric criteria for achalasia were defined as aper-
complained of NCCP or dysphagia during standard assessment. In contrast, 9 istalsis and dysrelaxation of the lower oesophageal sphincter (LOS).
(29%) patients reported either NCCP [n 5; mean Likert scale 3.0 (range 2.0-4.0) Pseudoachalasia was diagnosed in patients with clinical and manometric signs
and VAS scale of 7.7 (6.6-9.2)] or dysphagia [n 4; mean Likert scale 2.8 (range of achalasia that were found to have an underlying malignancy. Clinical (Eckardt
2.0-3.0) and VAS scale of 7.6 (5.2-8.8)] during at least one MRS (p 0.0020). symptom score), manometric, endoscopic and radiological findings were
Among them, at standard manometric assessment, we found normal peristalsis reviewed and compared between patients with pseudoachalasia versus achalasia.
(n 2), Jackhammer Esophagus (n 3), distal esophageal spam (n 2), outflow RESULTS: In total 205 patients with achalasia were included (116 male, median
obstruction (n 1), and absent peristalsis (n 1), whereas MRS resulted to be age 52 (39-64) (median (IQR)). Pseudoachalasia was diagnosed in 10 patients
abnormal in 8 cases. Interestingly, when symptoms were reported, they were (4.9%, 8 male) and caused by oesophageal adenocarcinoma (n 3), oesophageal
A258
squamous cell carcinoma (n 3), adenocarcinoma of the cardia (n 3) or pan-
creatic adenocarcinoma (n 1). The underlying malignancy was found at EUS
(30%), at a second or third endoscopy with biopsies (20%) or during a treatment
session (30%; 2x Heller myotomy, 1x pneumodilation). In 20% of the patients a
CT-scan after achalasia treatment, performed because of quick recurrence of
symptoms, eventually showed the malignancy. Patients with pseudoachalasia
were older at time of diagnosis compared to achalasia patients (68 (50-72) vs
51 (38-63), p 5.05)), had a shorter clinical history (6 (5-12) months vs 24 (11-68)
months, p 5.01) and lost more weight (12 (10-20) kg vs 6 (0-10) kg, p 5.01). The
Eckardt symptom score was higher in the group with pseudoachalasia (9 (8-10) vs
7 (6-9), p 5.05). However when the score was corrected for weight loss no
difference was seen (6 (6-7) vs 5 (5-7), p 4.05). Manometries in both groups
showed aperistalsis and dysrelaxation of the LOS, with no difference in LOS
pressure (33 (19-35) mmHg vs 23 (18-32) mmHg, p 4.05). In 80% of patients
with pseudoachalasia a barium oesophagography was performed and in 75% it
was suggestive of achalasia showing an enlarged diameter, narrowing of the LOS
and stasis of contrast compared to 91% in idiopathic achalasia. All patients with
pseudoachalasia underwent 1 or more endoscopies and in 80% the LOS was
difficult or even impossible to pass. In achalasia patients the LOS was difficult
to pass during endoscopy in only 22%.
CONCLUSION: Advanced age, short clinical history, considerable weight loss
and difficulty in passing the LOS during endoscopy are characteristics that
should arouse a higher suspicion of pseudoachalasia and warrant additional
investigations. It is not possible to distinguish pseudoachalasia from achalasia
with the conventional diagnostics used for achalasia such as manometry and
barium oesophagography.
Disclosure of Interest: None declared
P0456 DEVELOPMENT OF AN ENDOSCOPY- AND HISTOLOGY-
BASED ACTIVITY INDEX FOR EOSINOPHILIC ESOPHAGITIS
A. Schoepfer1,*, A. Straumann2, R. Panczak3, C. Kuehni3, Y. Romero4,
J. Alexander4, I. Hirano5, N. Gonsalves5, G. Furuta 6, E. Dellon7, J. Leung8,
M. Collins9, C. Bussmann10, P. Netzer3, S. Gupta11, M. Chehade 12,
F. Moawad13, S. Aceves14, J. Wo15, M. Zwahlen3, E. Safroneeva3 on behalf of
International Eosinophilic Esophagitis Activity Index Study Group
1
University Hospital Lausanne / CHUV, Lausanne, 2University Hospital Basel,
Basel, 3University of Bern, Bern, Switzerland, 4Mayo Clinic Rochester, Rochester,
5
Northwestern University of Chicago, Chicago, 6University of Colorado, Aurora,
7
University of North Carolina, Chapel Hill, 8Tufts Medical Center, Boston,
9
Cincinnati Children Hospital, Cincinnati, United States, 10Viollier Pathology
Basel, Basel, Switzerland, 11Indiana University of Medicine, Indianapolis, 12Mount
Sinai Food Allergy Institute, New York, 13Walter Reed Army Hospital, Bethesda,
14
University of California, San Diego, 15Indiana University, Indianapolis, United
States
Contact E-mail Address: alain.schoepfer@chuv.ch
INTRODUCTION: A validated instrument to assess severity of eosinophilic
esophagitis (EoE) in clinical trials and observational studies is urgently needed.
The international Eosinophilic Esophagitis Activity Index (EEsAI) study group
is currently developing an activity index for adult EoE patients. Three instru-
ments have been developed to assess endoscopic, histologic, and clinical EoE
activity.
AIMS & METHODS: We aimed to develop instruments that assess endoscopic
and histologic findings and the corresponding score based on the items that best
explain the variability in the physician global assessment (PGA) of EoE severity.
To assess whether items of the patient-reported outcomes (PRO) instrument,
which is designed to assess symptom severity, also help to explain the variability
of the PGA. We sought input from the experts and patients to generate the item
list to be included into 3 different instruments. Physicians provided PGA that
took into account symptoms, endoscopy, and histology and was assessed on a
Likert scale from 0 to 10. Using the physician instrument, severity of EoE-asso-
ciated endoscopic features including white exudates, rings, edema, furrows, and
strictures was graded. Severity of EoE-associated histologic findings including
peak eosinophil counts, eosinophil abscesses, basal layer enlargement, and sub-
epithelial fibrosis was assessed by the means of histopathology instrument. The
dysphagia characteristics and behavioral adaptations associated with consump-
tion of foods of different consistencies, among others, were assessed using the
PRO instrument. Linear regression and analysis of variance (ANOVA) was used
to evaluate the extent to which variations in the severity of EoE-associated
endoscopic and histologic features explain the variability in PGA. ANOVA
was used to examine the extent to which variations in symptom severity help
to explain the variability in PGA over and above variations in severity of endo-
scopic and histologic features.
United European Gastroenterology Journal 2(5S)
RESULTS: The physician, histopathology, and PRO instruments were evaluated
in 153 adult EoE patients (72.5 % males, median age 38 years) recruited in
Switzerland and in the United States. Variations in severity of endoscopic fea-
tures including white exudates, rings, edema, furrows, and strictures explained
52 % of the PGA variability. Variations in severity of histologic features includ-
ing the peak esophageal eosinophil numbers and eosinophilic microabscesses
explained additional 9 % of the variability in PGA. Variations in symptom
severity (7 items of the PRO module recalled over the last 7 days) explained an
additional 10 % of the variability in PGA.
CONCLUSION: The variations in severity of EoE-associated endoscopic and
histologic features explained most variability in physician global assessment of
EoE severity (total of 61 %).
Disclosure of Interest: None declared
P0457 DIETARY TREATMENTS FOR INDUCING REMISSION OF
EOSINOPHILIC ESOPHAGITIS. A SYSTEMATIC REVIEW AND
META-ANALYSIS
A.J. Lucendo1,*, A. Arias2, J. Gonzalez-Cervera3, J.M. Tenias2
1
Gastroenterology, Hospital General de Tomelloso, Tomelloso, 2Research Support
Unit, Hospital General La Mancha Centro, Alcazar de San Juan, 3Allergy,
Hospital General de Tomelloso, Tomelloso, Spain
Contact E-mail Address: alucendo@vodafone.es
INTRODUCTION: Eosinophilic esophagitis (EoE) is a chronic esophageal
immune/allergy-mediated disorder, which represents a distinctive form of food-
allergy. Various dietary interventions have been used to treat patients with EoE,
yielding varied results.
AIMS & METHODS: This systematic review assesses the efficacy of different
dietary therapies in inducing disease remission of EoE in adult and pediatric
patients with the disease.
A systematic search was performed in MEDLINE, EMBASE, and SCOPUS for
studies investigating the efficacy of various dietary interventions in inducing
remission (515 eosinophils/hpf) of inflammatory infiltration as observed in eso-
phageal biopsies from both pediatric and adult EoE patients. Summary esti-
mates, including 95% confidence intervals (95% CI), were calculated for
exclusive feeding with amino acid-based elemental formulas, allergy testing-direc-
ted food elimination diets, and six-food elimination diets (SFED). A fixed or
random effects model was used depending on heterogeneity (I2); publication bias
risks were assessed by means of funnel plot analysis.
RESULTS: The search yielded 578 references, of which 30 were included in the
quantitative summary. All told, the studies described 1,285 EoE patients (1,124
children and 161 adults) undergoing different dietary treatments. Elemental diets
were effective in 90.4% of cases (95% IC: 84.795.5%, I2: 2.3%), SFED in 73%
(66.678.9%; I2: 0%), and allergy testing-directed food elimination induced
remission in 46.3% of cases (35.657.1%; I2: 7 6.4%). Additional dietary therapy
strategies (elimination of cows milk and gluten-free diets) were also evaluated.
Overall, no significant differences in remission rates were documented between
children and adults (67.4% vs. 71.5%).
CONCLUSION: Dietary treatment is effective in achieving histological remis-
sion in patients with EoE. Elemental diets and SFEDs were the most consistent
alternatives, achieving 515 eosinophils/hpf in 90.4 and 73% of treated patients,
respectively.
Disclosure of Interest: None declared
P0458 IS EOSINOPHILIC ESOPHAGITIS CORRELATED WITH
ALLERGIC RHINITIS?
A. Soylu1,*, H. Kaya2, S. Cakmak1, S. Poturoglu3, A. Altntas2, I. Sevindir1
1
Gastroenterology, 2Otorhinolaryngology, Bakirkoy Dr Sadi Konuk Research and
Training Hospital, 3Gastroenterology, Haseki Research and Training Hospital,
Istanbul, Turkey
Contact E-mail Address: aliyesoylu@superonline.com
INTRODUCTION: Eosinophilic esophagitis (EoE) is a rare disorder and is
reported to be associated with concurrent allergic disorders. In this study, we
aimed to evaluate the prevalance EoE in patients with allergic rhinitis and to
assess clinical features in those patients having EoE.
AIMS & METHODS: Patients with allergic rhinitis were questioned with respect
to esophageal and gastric symptoms (i.e., epigastric pain, gastroesophageal reflux
(GER), dysphagia), and underwent upper gastrointestinal (GI) endoscopy and
serum IgE level measurement. Multiple tissue samples were taken from the
upper, middle and lower esophagus, gastric corpus and antrum, and duodenum
during upper GI endoscopy. EoE was defined as the presence of eosinophilic

P0457

Dietary Treatment Overall effect N Children N Adult N

All 67.9% (57.9% 77.1%) 42 67.4% (55.9% - 78%) 34 71.5% (53.3% - 86.7%) 6
Elemental diets 90.8% (84.7% - 95.5%) 13 90.4% (83.5% - 95.5%) 12 94.4% (17/18) 1
Allergy testing-direct elimination diets 46.3% (35.6% - 57.1%) 13 47.9% (36.8% - 59.1%) 12 26.6 (4/15) 1
SFED 73% (66.6% - 78.9%) 6 72.8% (62.5% - 82%) 4 73.1% (64.8% - 80.7%) 2
Gluten-free diet 52.2% (15.3% - 87.8%) 6 45.5% (2.6% - 93.8%) 4 100% (1/1) 1
Milk elimination diet 68.2% (47.8% - 85.6%) 3 66.6% (44.7% - 84.8%) 2 100% (1/1) 1
Subgroups according to quality Medium/High - High 69.8% (58.4% - 80.1%) 32 70.3% (56.5% - 82.4%) 26 70.6% (51.1% - 86.8%) 5
Low Medium/Low 60.6% (35.3% - 83.1%) 10 58.5% (32.2% - 82.3%) 9 100% (1/1) 1
United European Gastroenterology Journal 2(5S)
infiltration in the squamous epithelium of the esophagus (eosinophil number
15/HPF for patients using PPI and 20/HPF for patients not using PPI) and
the absence of eosinophilic infiltration in corpus, antrum and duodenum.
Reexamination with upper GI endoscopy was performed after a 2-month
proton pump inhibitor (PPI) therapy. Allergy test results were recorded.
Symptoms, serum IgE levels, allergy test positivity, Helicobacter pylori positivity,
endoscopic findings and histologic findings were compared between patients with
EoE and those without EoE.
RESULTS: Sixty seven patients were included in the study. Of them, 15 were
male. Mean age of male and female patients were similar (p 0.129).
Histopathological diagnosis of EoE was made in 7 patients (10.4%) and none
of them had a history of PPI usage prior to diagnosis. Symptoms of GER and
dysphagia were present in 71.4% and 28.57% of patients with EoE, while they
were present in 28.30% and 1.67% of those without EoE. In patients with
histologically proven EoE (n 7), 4 had endoscopic findings compatible with
EoE (57%), 2 had grade A reflux esophagitis (28.6%) and 1 had normal endo-
scopic findings. In patients without EoE (n 60), 1 had endoscopic findings
compatible with EoE and 3 had grade A reflux esophagitis. All patients with
EoE had eosinophil number 20/HPF in tissue samples from upper and middle
portion of the esophagus. Serum IgE levels were significantly higher in patients
with EoE than in those without EoE (281.59204.12 vs 105.75161.6)
(p 0.013). H. pylori positivity were similar (p 0.816). Allergy test positivity
was 85.7% in patients with EoE and 50% in those without EoE.
CONCLUSION: GER is the most common symptom in patients with EoE.
EoE may be present even in patients with normal endoscopic findings
Serum IgE levels are higher and allergy test positivity are more common in
patients with allergic rhinitis and EoE.
EoE is common in patients with allergic rhinitis.
It is important to question patients with respect to EoE symptoms in patients
with allergic rhinitis and high serum IgE levels, especially when corticosteroid
therapy is considered.
Disclosure of Interest: None declared
P0459 CLINICAL AND HIGH RESOLUTION MANOMETRY DATA
SUPPORT THE HYPOTHESIS THAT PROTON PUMP INHIBITOR-
RESPONSIVE ESOPHAGEAL EOSINOPHILIA REPRESENT A
GERD-RELATED PHENOMENON
O. Bartolo1, C.de Cassan1, R. Caccaro1, F. Galeazzi1, T. Morbin1, S. Tolone1,
R. Salvador1, G.C. Sturniolo1, M. Costantini1, E. Savarino1,*
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, Italy
INTRODUCTION: Eosinophilic esophagitis (EoE) and Proton Pump Inhibitor-
response esophageal eosinophilia (PPI-REE) present similar phenotypic appear-
ance, similar histopathology but different response to antisecretory therapy.
Thus, it is unclear if PPI-REE is a gastro-esophageal reflux disease (GERD)-
related phenomenon, a subtype of EoE, or a completely unique entity. High
resolution manometry (HRM) is a novel technique that has been recently
shown to provide new insights on GERD pathogenesis. In particular, eso-
phago-gastric junction (EGJ) morphology different from type I and weak peri-
stalsis have been strongly associated with GERD.
AIMS & METHODS: We aimed to compare HRM features of patients with EoE
and PPI-REE. Consecutive patients with symptoms suggestive of EoE underwent
upper endoscopy in order to assess the presence of at least 15 eos/hpf on oeso-
phageal biopsies at mid/proximal esophagus and, then, were treated with twice-
daily PPI for at least 8 weeks. Thereafter, patients repeated upper endoscopy and
were stratified into two groups: EoE, in case of persistence of at least 15 eos/hpf
on oesophageal biopsies, and PPI-REE, in case of less than 15 eos/hpf and a 50%
decrease from baseline. Patients underwent also HRM with a 5-min baseline
recording to assess the EGJ and 10 single water swallows (5 mL) at 30-s intervals
to evaluate the esophageal peristalsis. Tracings were analyzed based on Chicago
Classification and each EGJ was classified as: Type I, no separation between the
Lower Esophageal Sphincter and the Crural Diaphragm; Type II, minimal
separation (41 and 52 cm); Type III, 42 cm of separation.
RESULTS: Thirty-one patients were identified as having EoE [24M/7F; mean
age 28 (18-75)], whereas 10 patients were diagnosed with PPI-REE [9M/1F; mean
age 38 (20-64)]. The two cohorts had similar dysphagia for solids (EoE 71% vs.
PPI-REE 66%, p 0.6979), bolus impaction (65% vs. 60%, p 1.000) and chest-
pain (23% vs. 20%, p 1.000), but different heartburn (26% vs. 60%,
p 0.0485) and regurgitation (16% vs. 50%, p 0.0446). Endoscopic features
had the same frequency between EoE and PPI-REE: rings (45% vs. 50%,
p 1.000), furrows (26% vs. 10%, p 0.4101) and plaques (23% vs. 40%,
p 0.4132). Esophageal strictures tended to be more frequent in EoE (52% vs.
10%, p 0.0592). At HRM testing, EoE patients had higher mean integrated
relaxation pressure [9 (2-16) vs. 6 (2-16), p 0.0616] and LES basal pressure [26
(10-54) vs. 17 (1-34), p 0.0388], but similar mean distal contraction integral
[1094 (522-2653) vs. 1763 (483-5281), p 0.5613] compared to patients with
PPI-REE. Type II and III EGJs were less common in EoE than in PPI-REE
patients (9% vs. 50%, p 0.0129). Manometric diagnoses were similar between
EoE and PPI-REE: weak peristalsis including large or small breaks and frequent
failed peristalsis (16% vs. 40%, p 0.2221), absent peristalsis (3% vs. 10%,
p 1.0000) and distal esophageal spasm (3% vs. 0%, p 1.0000).
CONCLUSION: Typical reflux symptoms and HRM features GERD-related are
more common in patients with PPI-REE than in patients with EoE. These data
support the hypothesis that PPI-REE may represent a GERD-related phenom-
enon rather than a subtype of EoE or a separate entity. Further larger studies are
needed to confirm these findings.
Disclosure of Interest: None declared
A259
P0460 LONG-TERM EFFICACY OF PROTON-PUMP INHIBITOR
THERAPY IN ADULT PATIENTS WITH PPI-RESPONSIVE
ESOPHAGEAL EOSINOPHILIA
J. Molina- Infante1,*, J. Martinek2, M.D. Rivas3, J. Krajciova2, F.J. Moawad4,
C. Martinez-Alcala1, B.D. van Rhjin5, J. Barrio6, J. Zamorano3,
A.J. Bredenoord5, E.S. Dellon7
1
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, Spain,
2
Gastroenterology, Institutu Klinicke a Experimentaln Medicny, Prague, Czech
Republic, 3Research Unit, Hospital San Pedro de Alcantara, Caceres, Spain,
4
Gastroenterology, Walter Reed National Military Medical Center, Bethesda,
United States, 5Gastroenterology, Academic Medical Center, Amsterdam,
Netherlands, 6Gastroenterology, Hospital Rio Hortega, Valladolid, Spain,
7
Gastroenterology, Center for Esophageal Diseases and Swallowing, University of
North Carolina School of Medicine, Chapel Hill, United States
Contact E-mail Address: xavi_molina@hotmail.com
INTRODUCTION: Proton pump inhibitor-responsive esophageal eosinophilia
(PPI-REE) is diagnosed in at least a third of patients with a phenotype suggestive
of eosinophilic esophagitis (EoE). However, neither long-term response to PPI
therapy in PPI-REE patients nor influencing factors have been evaluated yet.
AIMS & METHODS: We aimed to determine the long-term efficacy of PPI
therapy in PPI-REE and its association to CYP2C19 genotype status.
Retrospective multicenter study in PPI-REE adult patients, defined by consensus
guidelines. After a diagnosis of PPI-REE, PPI therapy was tapered and main-
tained at the lowest dose with the target endpoint of clinical remission.
Histological remission was defined by 5 15 eos/HPF. Follow-up endoscopy
was performed at 12 months or longer on PPI maintenance dose. CYP2C19*2
and CYP2C19*17 were determined from blood samples in Spanish patients.
RESULTS: 46 PPI-REE patients were included (mean follow-up time: 27 months
(12-79)). While on clinical remission on low-dose PPI therapy, 34/46 (74%) had
sustained histologic remission (19 double-dose PPI, 21 single-dose PPI). In 8/12
relapsers (66%) on maintenance PPIs, esophageal eosinophilia recurred exclu-
sively at the distal esophagus. Compared to patients with sustained PPI-response
(n 13), this subset of distal relapsers showed borderline significant higher rates
of CYP2C19*2 rapid metabolizer genotype (100% vs. 53%, P 0.07) and reflux
esophagitis at baseline (50% vs. 0%, P 0.08). All distal relapsers re-achieved
histological remission after PPI-dose intensification (omeprazole 40 mg bid).
CONCLUSION: 74% of adult PPI-REE patients had persistent clinico-histolo-
gical remission on low-dose maintenance PPI therapy. While on clinical remis-
sion, two thirds of relapsers showed eosinophilic inflammation limited to the
distal esophagus. Baseline reflux esophagitis and a CYP2C19 rapid metabolizer
genotype were associated to this relapsing pattern and histological remission was
re-achieved after PPI-dose intensification in all patients.
Disclosure of Interest: None declared
P0461 RESULTS OF LIQUID CYTOLOGY IN THE DIAGNOSIS AND
MONITORING EOSINOPHILIC OESOPHAGITIS
J. Rodr guez Sanchez1,*, B. Lopez Viedma1, E.de la Santa Belda1, P. Olivencia
Palomar1, J. Olmedo Camacho1, M. Garc a Rojo2
1
Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real,
2
Pathology, Hospital de Jerez de la Frontera, Jerez de la Frontera, Spain
Contact E-mail Address: joakinrodriguez@gmail.com
INTRODUCTION: Esophagoscopy with biopsy is considered the only method
for diagnosis and monitoring EoE. Therefore it is important to find out less
invasive diagnostic methods. Regarding this issue, obtaining oesophageal cytol-
ogy is a way to explore to design in the future devices that allow to obtain
samples without endoscopy and biopsy. The aim of the study was to analyze
the accuracy of liquid-based cytology (LC) of the esophagus in the diagnosis and
monitoring EoE histological activity.
AIMS & METHODS: LC specimens were obtained in patients with active EoE
(AEoE) (15 eo/hpf) and EoE in remission (EoER) (515 eo/hpf) by oesopha-
geal aspirate samples collected after instillation of 50 cc of saline solution suc-
tioned by bronchioalveolar lavage system adapted to the gastroscope. The
samples were collected in Cytolyt solution (Hologic), obtaining Papanicolaou
and May-Grunwald/Giemsa that were assessed by two independent pathologists.
EoE specimens were compared with LC obtained from patients with GERD.
RESULTS: Specimens of 36 patients (69.4% male, mean age 30.88 years) were
included. AEoE (17, 47.2%), EoER (11, 30.5%) and GERD (8, 22.2%). Eo / hpf
proximal oesophageal biopsies (AEoE 28.58 vs EoER 2.09 vs GERD 1.25, p5
0.001) and distal (AEoE 23.33 vs EoER 2.36 vs GERD 2.50, p 0.002). LC Eo/
hpf (AEoE 9.23 vs EoER 1.54 vs GERD 2, p 0.01). Linear correlation between
Eo/hpf average biopsy and LC Eo/hpf: r 0.57, p 5 0.001. For diagnosis of
EoE,  3 Eo/hpf in LC obtained a Sensitivity 70%, specificity 81%, PPV 86%
and NPV 60% (AUC 0.81, p 0.01). For detection of AEoE,  3 Eo/hpf in LC
obtained a sensitivity 70%, specificity 82%, PPV 81% and NPV 66%
(AUC 0.87, p 0.001).
CONCLUSION: LC in oesophageal aspirate obtained by a cutoff in 3 eo/hpf
seems to be effective for the diagnosis and monitoring activity in EoE. These
results open the door to the development of non endoscopic devices that allow us
the diagnosis and monitoring of disease noninvasively.
Disclosure of Interest: None declared
A260
P0462 CORRELATION BETWEEN CLINICAL, HISTOLOGIC AND
ENDOSCOPIC ACTIVITY IN EOSINOPHILIC OESOPHAGITIS.
PRELIMINARY RESULTS OF SENECA PROJECT (SPANISH STUDY
OF ENDOSCOPY AND EOSINOPHILS CORRELATION
ASSESSMENT)
J. Rodr guez Sanchez1,*, J. Molina Infante2, J. Barrio Andres3, I. Perez were thus considered the control group. Patients underwent standard stationary
Mart nez4, A. Bouhmidi Assakali5, J.A. Olmos Jerez6, B. Madrigal Rubiales7,
E.de la Santa Belda1, B. Lopez Viedma1, J. Olmedo Camacho1
1
Gastroenterology, Hospital General Universitario de Ciudad Real, Ciudad Real,
2
Gastroenterology, Hospital San Pedro de Alcantara, Caceres, 3Gastroenterology,
Hospital del Rio Hortega, Valladolid, 4Gastroenterology, Hospital Universitario
Central de Asturias, Oviedo, 5Gastroenterology, Hospital Santa Barbara,
Puertollano, 6Gastroenterology, Hospital Rey Juan Carlos, Mostoles, 7Pathology,
Hospital del Rio Hortega, Valladolid, Spain
Contact E-mail Address: joakinrodriguez@gmail.com
INTRODUCTION: Esophagoscopy with biopsies is considered the gold stan-
dard for diagnosis and monitoring EoE. This is due to lack of correlation
between histology, endoscopy and clinical manifestations of the disease. A
novel endoscopic classification for assessment of eosinophilic esophagitis (EoE)
activity has been recently proposed (EREFs). We aimed to address the correla-
tion of clinical and endoscopic EoE activity scores with histological response
after different therapeutic interventions.
AIMS & METHODS: Spanish multicenter prospective study in consecutive
patients with EoE, according to consensus guidelines. Clinical (Dysphagia
Symptom Score (DSS) Scale) and endoscopic (EREFS) disease activity, along
with eosinophil peak count, were assesed at baseline and after topical steroids or
elimination diet, including food reintroductions. Histological remission was
defined by 5 10 eos/HPF at both distal and proximal esophagus. Patients
were subclassified: Group A (Baseline), Group B (No histological remission
after therapy/food reintroduction) and Group C (Histological remission after
therapy/food reintroduction).
RESULTS: 79 patients undergoing 128 upper endoscopies have been included so
far (77.2% male, age 34.7 years-old, dysphagia 100%). Group A: 47 (36.7%),
Group B: 61 (47.7%) and Group C: 20 (15.6%). DSS score was significantly
higher in Group A (A 7.16, B 5.15, C 3.70; p 0.006), but no differences IMPEDANCE-PH MONITORING REVISITED
were observed between groups B and C (p 0.12). Regarding endoscopic find-
ings, inflammatory features were significantly decreased after histological remis-
sion (furrows: A 63.8%, B 72.1%, C 40%; p 0.034 / exudates (grade 2): Contact E-mail Address: ang_daphne@yahoo.com
A 10.6%, B 18%, C 5%;p 0.002), but not fibrostenotic features (pseudor-
ings: A 68.1%, B 55.4%, C 55%;p 0.44/stricture: A 10.6%, B 9.8%, INTRODUCTION: Non-response to proton pump inhibitor (PPI) therapy in
C 5%;p 0.75). Mucosal edema was common at baseline and persistent
regardless of histological remission (A 61.7%, B 78.7%, C 60%; p 0.09). Impedance-pH (MII-pH) monitoring clarifies the symptom profile and evaluates
CONCLUSION: EoE clinical activity significantly decreased after different ther-
apeutic interventions, with no differences between patients showing eosinophilia
remission or persistence after therapy. Histological remission was correlated with
significant decrease of inflammatory endoscopic features, but not of fibrostenotic
findings. Mucosal edema was mostly persistent regardless of histological remis-
sion, suggesting it might belong to the fibrotic remodelling spectrum.
REFERENCES
Disclosure of Interest: None declared
P0463 IN PATIENTS WITH GASTROESOPHAGEAL REFLUX DISEASE,
GLOBUS IS ASSOCIATED WITH ABNORMAL OROPHARYNGEAL
ACID EXPOSURE
M. Di Stefano1, C. Mengoli1,*, M. Bergonzi1, E. Pagani1, E. Miceli1,
G.R. Corazza1
1
1st Department of Internal Medicine, IRCCC Policlinico S. Matteo, University of
Pavia, Pavia, Italy
Contact E-mail Address: m.distefano@unipv.it
INTRODUCTION: Globus, a persistent or intermittent non-painful sensation of
a lump or foreign body in the throat, is frequently associated with gastroesopha-
geal reflux disease (GERD): it is estimated that up to 68% of GERD patients
suffer from globus. However, previous esophageal pH and pH-impedance studies
failed to define a causative role of acid or non-acid reflux in globus
pathophysiology.
Table to P0464
Group 1
Typical
(N39M,55F)
Raised AET 9/94 (9.6%)
No. of AR events (mean, SEM) 22.6  2.3
No. of NAR events (mean, SEM) 26.1  2.7
p50.05 compared to group 3
No of proximal reflux events (mean,SEM) 25.5 2.3
p50.05 compared to group 3
Total no. of reflux events 48.6  3.9
p50.005 compared to group 3
Total bolus exposure time (mean, SEM) 1.7  0.2
Positive symptom association for acid reflux 45/94(47.8%)
p50.05 compared to groups 2
Positive symptom association for non-acid reflux 43/94 (45.7%)
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: The aim of this study was to investigate both distal and
proximal, oropharyngeal acid exposure, with a new device, in patients with non-
erosive reflux disease (NERD) with and without globus.
A group of 37 patients affected by NERD was enrolled. The presence of reflux
symptoms was evaluated and severity was graduated by VAS. In eight patients,
globus was the main symptom; in the other 29, globus was not present and they
esophageal manometry (6 channelssleeve) and 24-hr pH-impedance esophageal
monitoring (Sleuth, Sandhill Scientific) combined with 24-hr oropharyngeal pH
monitoring (Restech Dx-pH Measurement System).
RESULTS: Distal esophageal acid exposure (pH 54), number of acidic and
weakly acidic reflux episodes and proximal extension of refluxate were similar
between patients with and without globus. On the contrary, patients with globus
showed a significantly longer oropharyngeal exposure to pH55.5 (total duration
of acid exposure: 222 min  230 min vs 47 min  88 min, p50.05; and percent of
recording: 16.0716.2% vs 3.566.84%, p50.05), compared to patients without
globus; the longest episode of oropharyngeal acid exposure was significantly
longer in patients with globus than in patients without globus (110 min  115
min vs 15 min  25 min; p50.05). A higher score for heartburn was evident in
the group of patients without globus (3.453.31 vs 1.311.44, p50.05); no
difference was found in regurgitation, cough, sore throat, or thoracic pain
score. Finally, the prevalence of esophageal motor disorders was similar in the
two groups.
CONCLUSION: Oropharyngeal acid exposure could have an important patho-
physiological role in globus onset. Oropharyngeal pH monitoring seems a more
accurate diagnostic tool than the standard 24-hr pH-impedance study to define
the role of acid exposure in this subgroup of patients.
REFERENCES
1. Selleslagh M, van Oudenhove L, Pauwels A, et al. Nat Rev Gastroenterol
Hepatol 2014; 11: 220-233.
2. Chevalier JM, Brossard E and Monnier P. 2003; 260: 273-276.
Disclosure of Interest: None declared
P0464 UNDERSTANDING THE CAUSE OF PERSISTENT GERD
SYMPTOMS DESPITE PROTON PUMP INHIBITOR THERAPY:
D. Ang1,*, I. Hussain1, F. Kwong Ming1
1
Gastroenterology, Changi General Hospital, Singapore, Singapore
patients with reflux symptoms and a normal gastroscopy remains a challenge.
patients objectively for acid reflux (AR) and non-acid reflux (NAR).
AIMS & METHODS: To study MII-pH characteristics in patients referred for
GERD evaluation who remain symptomatic despite PPIs, and study mechanisms
related to persistent symptoms. Methods: Between January 2009-December 2013,
consecutive patients with typical symptoms (group 1); atypical symptoms (group
2) and non-cardiac chest pain (NCCP, group 3) underwent 24 hour MII-pH after
PPI washout. Prevalence of (i) oesophageal acid exposure time (AET)44.2%; (ii)
bolus exposure (BE41.4%), (iii) high reflux numbers (473) and/or (iv) positive
symptom marker based symptom index (SI 50%) and/or symptom association
probability (SAP 95%) for AR or NAR events was compared between groups
by chi-square and student t-testing.
RESULTS: 208 patients (80M, mean age 45.9  12.5) were studied (Table 1).
Elevated AET occurred in 24 (11.5%). 120 (57.7%) recorded a positive study on
MII-pH evaluation despite a normal overall AET. Group 1 and 3 patients had
significantly more symptomatic AR events (p50.05) compared to group 2.
Symptomatic NAR related events did not differ significantly different between
groups. Patients with a positive symptom association for AR events were more
likely to have abnormal BE (p 0.01) and abnormal reflux numbers (p50.05).
Table 1.
CONCLUSION: Use of MII-pH in PPI non-responders identifies AR and NAR
events and serves as an important diagnostic modality to evaluate the symptom
profile and guide appropriate therapy, which may extend beyond PPIs.
Disclosure of Interest: None declared
Group 2
Atypical Group 3
(N34M,50F) Non cardiac chest pain (N7M,23F)
13/84(15.5%) 2/30(6.7%)
21.2  1.9 18.3  3.0
23.1  1.5 17.1  2.1
p50.05 compared to group 3
23.7  1.7 17.1  2.8
p50.05 compared to group 3
44.0  2.5 35.4 3.8
1.5  0.1 1.2  0.2
23/84 (27.4%) 19/30(63.3%)
p50.05 compared to groups 2
39/84(46.4%) 10/30(33.3%)
United European Gastroenterology Journal 2(5S)
P0465 ACID AND NON ACID REFLUXES MODIFY THE BASELINE
IMPEDANCE VALUES IN A LARGE SERIES OF NERD PATIENTS
F.P. Zito1,*, P. Andreozzi1, A. DAlessandro1, I. Arnone1, M. Pesce1, E. Efficie1,
G. Affinito1, D. Esposito1, G.D. De Palma1, G. Sarnelli1, R. Cuomo1
1
Clinical Medicina and Surgery, UNIVERSITY OF NAPLES " FEDERICO II",
Naples, Italy
Contact E-mail Address: francescozito1@hotmail.com
INTRODUCTION: Esophageal baseline impedance (BI) may be considered as
an indirect way to express macroscopic and/or microscopic mucosal integrity
since recent evidence has shown that patients with both erosive or non erosive
esophagitis have lower level of BI than healthy subjects.
AIMS & METHODS: The aim of our study was to evaluate how BI is transiently
influenced by the nature of reflux events.
We studied 60 patients (28 M - mean age 45.8  16.1) with typical GERD-
symptoms (heartburn and regurgitation) and negative endoscopy, who per-
formed a 24h-pH impedance monitoring from January to March 2014. Among
these, 33 exams were performed on therapy with proton pump inhibitor, while 27
were off-therapy. For each patient, 24 hours esophageal BI was calculated during
the first period of 60 seconds without an impedance event (swallow or reflux)
every four hours. Then, we calculated BI immediately before and 1 minute after
the end of the same reflux event. Pre and post-reflux BI for acid and non acid
were calculated in off and on-therapy patients, respectively. Moreover, for each
reflux episode, the minimum pH reached was also registered.
RESULTS: 24 hours BI and pre-reflux BI were similar for both acid and non
acid events (2422641 vs 2424758m and 2386497 vs 2384639 m, respec-
tively, all p NS). On the contrary, a significant reduction between pre and post-
reflux BI for acid and a significant increase was registered for non acid reflux
(2424758 vs 2130721 m, p 0.001 and 2384640 vs 2767489 m,
p 0.004, respectively). The same results were observed in the subgroups of
subjects off and on therapy (Off-therapy: 2330766 vs 2083684 m, p50.01;
On therapy: 2187478 m vs 2713503 m, p50.01, respectively).
Most interestingly differences between pre and post-reflux BI of all patients were
positively correlated to the pH nadir of each reflux event (p50.0001, r2 0.42).
CONCLUSION: Baseline impedance may be transiently influenced by the nature
of reflux episodes, being acid and non-acid refluxes respectively associated with a
decrease and an increase of baseline impedance. Our data indicate that nature of
refluxes is able to differently affect BI, likely, if this phenomenon underlies
changes in mucosal integrity or it is associate with abnormal perception deserves
further investigation.
Disclosure of Interest: None declared
P0466 PATIENTS WITH ACTIVE CELIAC DISEASE HAVE ALTERED
INTERCELLULAR SPACES AND TIGHT JUNCTION STRUCTURE
OF THE LOWER ESOPHAGUS THAT MAY EXPLAIN THE HIGH
PREVALENCE OF REFLUX SYMPTOMS IN THESE PATIENTS
G. I. Longarini1,*, F. Nachman2, S. Salim1, H. Hwang1, A.F. Costa1, M.
I. Pinto3, X.X. Wang3, H. Vazquez1, C. Fuxman2, M.L. Moreno1, S. Niveloni1,
E. Smecuol1, R. Mazure1, E. Maurino1, E. Verdu3, J.C. Bai1
1
Medicine, Hospital Udaondo, 2Fundacion Favaloro, Buenos Aires, Argentina,
3
Farncombe Institute, McMaster University, Hamilton, Canada
Contact E-mail Address: fdnachman@intramed.net
INTRODUCTION: Patients with untreated celiac disease (CD) often complain
of reflux symptoms, which in 30% of cases are considered moderate to severe
(CGH 2011; 9: 214-9). The gluten-free diet leads to a rapid and persistent
improvement in reflux symptoms and most cases do not require the use of
proton pump inhibitors. The mechanisms involved in the expression of reflux
symptoms in CD patients are unknown.
AIMS & METHODS: Objective: We explored symptomatic and mucosal mar-
kers of permeability of the lower esophagus in patients with newly diagnosed CD
at the time of diagnostic endoscopy, patients with symptoms of GERD but no
CD (GERD controls) and healthy controls without symptoms (healthy controls:
HC).
Methods: A cohort of 23 consecutive patients with active CD at the time of
diagnosis, 5 GERD control patients, and 11 HC subjects, were enrolled in the
study. Nine out of 23 CD patients had GERD symptoms considered as moderate
or severe (42 points in the GSRS questionnaire). Endoscopic biopsies from the
distal esophagus were obtained 2 cm above the z-line. Samples were assessed for
histological damage, dilated intercellular space (DIS) scores by optical micro-
scopy (OM) and electron microscopy (EM), and tight junction (TJ) mRNA
expression for zonnula occludens-1 (ZO-1) and claudin-2 and -3 (CL-2; CL-3)
using Real Time qRT-PCR.
RESULTS: Patients with active CD had increased DIS scores compared to HC
subjects (OM: 8.03.1 vs. 2.22.5; p50.003 and EM: 31.79.5 vs. 15.05.1;
p50.04) but similar to GERD controls. CD patients without GERD symptoms
also had higher DIS scores compared to HC (OM: p50.006; EM: p50.03) but
similar to those in CD patients with GERD symptoms. Overall CD patients had
lower expression of ZO-1 than HC (CD patients with and without GERD symp-
toms: p50.003 and p40.05; respectively). A non-statistical trend for higher CL-2
and CL-3 expression was observed in CD patients compared with GERD con-
trols and no differences were detected between CD subgroups with or without
GERD symptoms. CD patients had similar expression of CL-2 and CL-3 com-
pared to HC.
CONCLUSION: Our study suggests an impairment of mucosal permeability in
the distal esophagus of patients with active CD irrespective of the presence of
GERD symptoms. The altered expression of ZO-1, and CL-2 and CL-3 may
underlie loss of TJ integrity in the esophageal mucosa, an expression pattern
that is reminiscent of intestinal permeability abnormalities observed in CD,
A261
and that may contribute to reflux symptom expression and its reversion by the
gluten-free diet.
Disclosure of Interest: G. Longarini: None declared, F. Nachman: None declared,
S. Salim: None declared, H. Hwang: None declared, A. Costa: None declared,
M. Pinto: None declared, X. X. Wang: None declared, H. Vazquez: None
declared, C. Fuxman: None declared, M. Moreno: None declared, S. Niveloni:
None declared, E. Smecuol Financial support for research from: Astra Zeneca,
Lecture fee(s) from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, R.
Mazure: None declared, E. Maurino: None declared, E. Verdu: None declared, J.
Bai: None declared
P0467 RECEPTOR MODULATION AND MAP-KINASE SIGNALING
INDUCED BY STW5 AND BY THE PROTON-PUMP INHIBITOR
OMEPRAZOL IN A RAT MODEL FOR GASTROESOPHAGEAL
REFLUX DISEASE AND IN HET1A-CELLS
H. Abdel-Aziz1,*, O. Kelber 2, M.T. Khayyal 3, G. Ulrich-Merzenich4
1
University of Munster, Munster, 2Steigerwald Arzneimittelwerk GmbH,
Darmstadt, Germany, 3Cairo University, Cairo, Egypt, 4Medical Clinic III, UKB,
University of Bonn, Bonn, Germany
Contact E-mail Address: gudrun.ulrich-merzenich@ukb.uni-bonn.de
INTRODUCTION: We had earlier demonstrated that STW5 affects multiple
chemokine families on genome and proteome level reducing inflammation in
the esophageal tissue in our rat model for gastroesophageal reflux disease
(GERD)1.
AIMS & METHODS: Here we investigated selected receptors and which signal-
ing cascades are activated during the anti-inflammatory processes by STW5 and
by the proton-pump inhibitor Omeprazole (O). Methods: Rats were pretreated
with either STW5 (0.5 or 2ml/kg) or O (30mg/kg). Esophagitis was induced
surgically followed by a further 10d treatment. On day 10 animals were sacrificed
and whole cell lysates of the esophagi were evaluated by Western Blot analysis for
the receptors GPR 84 and LOX-1 (lectin-like oxidized low density lipoprotein
receptor 1) and the stress induced mitogen activated kinase (MAPK) p38.
Further investigations were undertaken with the human esophageal squamous
cell line HET-1A. Inflammation was induced with Capsaicin (50mM, 18hrs) and
cells were treated with either STW5 (0.17; 0.5; 1.7; 5ml/ml) or O (10mg/ml; 30mg/
ml). MAPKs p38, ERK1 and 2 were determined. Data were normalized either
with the respected unphosphorylated protein or with -Actin.
RESULTS: The LOX-1 receptor was only detected in the esophagi of rats with
esophagitis, but not in the esophagi of sham operated or treated rats. The GPR
84 receptor was increased in the esophagitis group compared to the sham group
and down regulated by STW5 and O. In the sham group neither total p38 MAPK
nor the phosphorylation of p38 was increased. The treatment of STW5 inhibited
the phosphorylation of p38 MAPK in the tissue, but did not influence the
increase in the total amount of p38 of the esophagitis group. In HET1A cells
capsaicin slightly increased the expression of GPR84 which was reduced by the
high concentration of STW5. Capsaicin induced an increase in the phosphoryla-
tion of ERK1/2 compared to the control. This increase was inhibited in the
presence of STW5 as well as in the presence of O.
CONCLUSION: The LOX-1 and the GPR 84 receptor activation contribute to
experimental GERD. They are targeted like P38, which is known to be acid
sensitive in GERD2, by STW5. Data further substantiate differential
MAPKinase signaling in GERD. They support the classification of GPR84 as
proinflammatory receptor with a link to the immune response in oesophageal
tissue.
REFERENCES
1 Abdel-Aziz, et al. United Eur Gastroenterol J 2013; 1: A113OP380.
2 Rafiee, et al. Am J Physiol Cell Physiol 2006; 291: C931-C945.
Disclosure of Interest: H. Abdel-Aziz Other: employee of Steigerwald
Arzneimittelwerk GmbH, O. Kelber Other: employee of Steigerwald
Arzneimittel GmbH, M. T. Khayyal Financial support for research from:
Steigerwald Arzneimittelwerk GmbH, G. Ulrich-Merzenich Financial support
for research from: Steigerwald Arzneimittelwerk GmbH
P0468 EXPRESSION OF VEGF AND VEGFR IN EROSIVE AND
NONEROSIVE REFLUX DISEASE
J. Wasielica-Berger1,*, A. Pryczynicz2, J. Daniluk1, P. Rogalski1, A. Kemona2,
A. Dabrowski1
1
Department of Gastroenterology and Internal Medicine, 2Department of
Pathomorphology, Medical University of Bialystok, Bialystok, Poland
Contact E-mail Address: jwasielica@o2.pl
INTRODUCTION: Up to 70% of patients with gastro-esophageal reflux disease
do not have erosions visible in conventional endoscopy. They are classified as
non-erosive reflux disease (NERD). Studies on endoscopy with optical magnifi-
cation described a variety of minimal changes in NERD patients, also concerning
vessels. Until now it is not clear why some patient develop erosions and others do
not. Differences in self-defense mechanisms may matter. Vascular endothelial
growth factor (VEGF) is a signal protein working through its receptor
(VEGFR) promoting angiogenesis and wound healing.
AIMS & METHODS: We evaluated squamous epithelium above Z line in mag-
nification up to 105 times in 20 patients with NERD, 12 patients with erosive
esophagitis (EE) and 5 controls (patients without reflux disease). The magnified
images were analyzed with respect to: visibility of palisade blood vessels, appear-
ance of intrapapillary capillary loops (IPCLs) and white points seen as whitish
pinpoint spots encirculating IPCLs or independent from IPCLs. Biopsy speci-
mens for the histopathologic examination were taken 1-2 cm above Z line. In
histology presence of inflammation was evaluated in a scale from 0 (absent) to 3
(severe). Expression of VEGF and VEGFR in squamous epithelium was
A262
evaluated by immunohistochemistry method. The reaction of VEGF and
VEGFR proteins was defined as low if positive in less than 33% of vessels,
moderate if positive in 33-66% of vessels and high if positive in over 66% of
vessels. Statistics was executed with Fisher exact test.
RESULTS: Expression of VEGF and VEGFR was significantly higher in EE
than NERD group (p50.05). Control group had comparatively low expression
of VEGF and VEGFR.
VEGF expression VEGFR expression
Number of
patients Low * Moderate High * Low ** Moderate High **
EE 0 (0%) 5 (42%) 7 (58%) 1(8.3%) 4 (33.3%) 7(58.3%)
NERD 8 (40%) 8 (40%) 4 (20%) 11 (55%) 5 (25%) 4 (20%)
Controls 2 (40%) 3 (60%) 0 (0%) 3 (60%) 1 (20%) 1 (20%)
Enlarged IPCLs, white points or diminished visibility of palisade vessels seen in
magnification endoscopy did not correlate with expression of VEGF and
VEGFR, neither did the grade of esophagitis evaluated in plain histology.
CONCLUSION: VEGF and VEGFR expression is higher in EE than NERD
patients. This phenomenon may be the part of esophageal mucosa healing in EE.
Disclosure of Interest: None declared
P0469 EXPRESSION OF EPIDERMAL GROWTH FACTOR RECEPTOR
IN PATIENTS WITH GASTRO-OESOPHAGEAL REFLUX DISEASE
AND IN THOSE WITH SYSTEMIC SCLEROSIS
P. Zentilin1,*, E. Marabotto1, L. Assandri1, F. Grillo2, L. Mastracci2,
M. Giuseppe3, A. Sulli4, E. Savarino5, V. Savarino1
1
Department of Internal Medicine, Gastroenterolgy Unit, 2Department of Surgical
Sciences and Integrated Diagnostics, Pathological Anatomy Unit, 3Department of
Internal Medicine, Internel Medicine Unit, 4Department of Internal Medicine,
Rheumatology Unit, Genova, 5Department of Surgery, Oncology and
Gastroenterology, Gastroenterolgy Unit, Padova, Italy
Contact E-mail Address: pzentilin@unige.it
INTRODUCTION: Epidermal growth factor (EGF) and its receptor (EGFR), a
tyrosine kinases receptors (TKs), are associated with epithelial proliferation and
restitution, the two key mechanisms involved in oesophageal epithelial defense
against reflux. It has been shown that EGFR expression increases with the pro-
gression from gastro-oesophageal reflux disease (GORD) to Barretts oesopha-
gus/adenocarcinoma. Systemic sclerosis (SSc) is characterized by deposition of
collagen and other extracellular matrix proteins in the connective tissues, imbal-
ance of the immune system, and microvasculature abnormalities. Besides TKs
physiological roles, they are key players in various diseases, including SSc.
Indeed, their pathological activation may drive carcinogenesis, vascular remodel-
ling, and fibrogenesis. No studies investigated the EGFR expression on oesopha-
geal mucosa of SSc patients.
AIMS & METHODS: We aimed to assess and compare the presence of EGFR
expression on oesophageal mucosa of GORD and SSc patients. We studied 24
SSc (22F, median age 56yrs) and 22 GORD (9F, median age 64yrs) patients.
They underwent upper endoscopy and multiple specimens (n 4) were taken
from the distal oesophagus (at the Z-line and 2 cm above it). Biopsies were
fixed in formalin and embedded in paraffin. After preparation, anti-human
EGFR monoclonal antibody, clone H11 (anti-EGFR) (Dako), was applied to
the slides and EGFR expression was considered positive when staining was
detected on the membrane. Patients were endoscopically classified as having
erosive oesophagitis (EO), non-erosive reflux disease (NERD, in case of no
mucosal breaks and GORD symptoms) or negative endoscopy (NE, in case of
no mucosal breaks and absence of GORD symptoms). Microscopic oesophagitis
(MO) was diagnosed by using a previously validated score.
RESULTS: At endoscopic evaluation, 3/24 (13%) SSc patients had EO, 11/24
(46%) had NERD and 10/24 (42%) had NE, whereas at microscopic evaluation 3
had evidence of erosive oesophagitis, 11 of MO and 10 of normal mucosa,
respectively. Among GORD patients, we found at endoscopic and microscopic
evaluation that 3/22 (14%) had EO with histological reply of 2 erosive oesopha-
gitis and 1 MO, 12/22 (55%) had NERD with evidence of MO and 7/22 (31%)
had normal findings at both measurements. Overall comparison of EGFR
expression between SSc and GORD patients was not significant, whereas com-
parison of EGFR expression between the 10/24 SSc and 7/22 GORD patients
without endoscopic and histological alterations was statistically significant
(p 0.0068). EGFR expression between the 14/24 SSc patients with erosive
and microscopic oesophagitis was higher than in the 10/24 with normal
mucosa (p 0.0177) as well as in GORD patients with and without oesophagitis
(p 0.0004). In GORD patients EGFR expression decreases proximally, while in
SSc patients it seems overexpressed.
CONCLUSION: In GORD patients, EGFR expression correlates with histolo-
gical findings and seems to play a major role in maintaining epithelial integrity.
In SSc patients, it is overexpressed and this can act as an inflammatory reactive
stimulus, even in the absence of microscopic lesions.
Disclosure of Interest: None declared
P0470 ACID INFUSION INTO THE STOMACH DOES NOT AFFECT THE
NUMBER OF MEAL-INDUCED TRANSIENT LOWER ESOPHAGEAL
SPHINCTER RELAXATIONS (TLESR)
P. Banovcin1,*, J. Halicka1, M. Halickova1, J. Androvic1, M. Duricek1,
R. Hyrdel1, M. Tatar1, M. Kollarik1,2
United European Gastroenterology Journal 2(5S)
1
JESSENIUS FACULTY OF MEDICINE, COMENIUS UNIVERSITY,
Martin, Slovakia, 2JOHNS HOPKINS SCHOOL OF MEDICINE, Baltimore,
United States
Contact E-mail Address: pbanovcin@gmail.com
INTRODUCTION: TLESRs are considered to be the most important mechan-
ism of gastroesophageal reflux (GER). However, the regulation of TLESRs by
acid is incompletely understood. We have recently reported that acid in the
esophagus enhanced TLESR (Abstract Tu1868, Digestive Diseases Week,
Gastroenterology Vol. 146[2014] suppl.). Specifically, we found that the acid
infusion into the esophagus increased the number of meal-induced TLESRs by
60% compared to control infusion.
AIMS & METHODS: In the present study we evaluated the effect of acid infu-
sion into the stomach on the meal-induced TLESRs. The study was carried out in
healthy subjects (age 23  0.3 years) None of the subjects had any esophageal
motility abnormality as defined by Chicago criteria. TLESRs were evaluated by
using high resolution manometry (HRM). The study was performed in sitting
position. For infusions a tube (O. D. 1mm) was attached to the HRM catheter
with the opening positioned in the stomach at least 5 cm below the manometri-
cally identified lower esophageal sphincter. Each subject was studied at two
occasions (control or acid infusion) separated by at least 7 days. Following a
standard meal (chicken sandwich and soda drink), acid (0.15 M HCl) or water
was infused into the stomach (8ml/min, 20 min) by using a perfusion pump.
TLESRs were counted during 2h following the completion of the infusion. In
some subjects TLESRs were also counted during 20 min of acid infusion. The
study conformed to Declaration of Helsinki. All subjects gave informed consent.
RESULTS: 10 subjects (7M/3F) completed the study. We found that acid infu-
sion into the stomach did not affect the number of meal-induced TLESRs. The
number of TLESRs (median[interquartile range]) during 2h following the control
vs. acid infusion was 17[12-18.75] vs. 15.5[12.25-20.25], n 10, p NS, Wilcoxon
Signed-Rank Test). The average duration of TLESRs was not changed
(16.3s0.4s, n 153 vs. 17.2s0.7s, n 151, P40.2, unpaired T-test). The
number of TLESRs during the acid infusion was also not affected (quantified
in 6 subjects, 4M/2F). The number of TLESRs during the 20 min of control vs.
acid infusion was 5.5[2.75-6] vs. 4[3.25-4.75], n 6, p NS, Wilcoxon Signed-
Rank Test).
CONCLUSION: We conclude that the acid infusion into the stomach does not
affect the meal-induced TLESR. These results are consistent with the notion that
the direct effects of acid in the stomach has limited role in the regulation of
TLESR. Our results also indicate that the substantial enhancement of TLESR
by acid infusion into the esophagus observed in our previous study was not due
to acid effect in the stomach.
Supported by BioMed Martin (ITMS: 26220220187) co-funded by EU.
Disclosure of Interest: None declared
P0471 EFFECT OF GHRELIN ON EXPERIMENTAL ESOPHAGITIS IN
RATS
P. Konturek1,*, K. Celinski2, G. Burnat1, S. Kwiecien3, M. Raithel4,
S. Konturek3, T. Brzozowski3
1
Department of Medicine II, Thuringia Clinic, Saalfeld, Germany, 2Department of
Gastroenterology, Medical Academy Lublin, Lublin, 3Institute of Physiology,
University School of Medicine, Cracow, Poland, 4Department of Medicine I,
University Erlangen-Nuremberg, Erlangen, Germany
INTRODUCTION: Both ghrelin and leptin are involved in the regulation of
food intake but their effect on the development of experimental reflux esophagitis
(RE) is unknown.
AIMS & METHODS: The present study was designed to assess; 1) the effects of
pre-treatment with ghrelin and leptin on lesion score and esophageal blood flow
in rats with RE; 2) the influence of ghrelin and leptin on mucosal gene expression
and release of proinflammatory cytokines (IL-1b, TNF-a and IL-6) and 3) the
influence of ghrelin and leptin on the expression of COX-2 and HSP70 in eso-
phageal mucosa during development of RE. RE was induced in rats (n 6/
group) according to technique proposed by Nakamura et al (Jpn J Pharmacol
1982, 32:445) by two ligation of 1) the duodenum at the pyloric sphincter and 2)
at the region between the forestomach and gastric corpus. Following treatment
groups were used: A) intact rats; B) rats with RE pretreated 1h before with saline
(control); C) rats pretreated with ghrelin (40 mg/kg i.p.) and D) leptin (40 mg/kg
i.p.) 1 h before exposure to RE. The lesion score (scale 0-5) and esophageal blood
flow using H2 gas clearance was measured. In addition, gene expression of IL-1b,
TNF-a, IL-6 and release of these cytokines was analyzed by quantitative RT-
PCR and ELISA. Furthermore, gene expression of COX-2 and HSP70 was
measured by RT-PCR.
RESULTS: Both ghrelin and leptin significantly attenuated (by 50%) the lesion
score induced by RE and this effect was accompanied by a significant increase in
esophageal blood flow. The expression of mRNA for COX-2 TNF-a, IL-1b and
IL-6 was negligible in the intact esophageal mucosa but was upregulated in
esophageal mucosa of rats with RE. The pretreatment with ghrelin and leptin
decreased the expression of mRNA for COX-2, TNF-a, IL-1b and IL-6. In
contrast, HSP70 was significantly downregulated in esophageal mucosa of rats
with RE and this effect was reversed in rats pretreated with ghrelin or leptin.
Ghrelin receptor (GHS-R) was detected both in intact and RE-inflamed esopha-
geal mucosa.
CONCLUSION: Appetite hormones, such as leptin and ghrelin, significantly
attenuate the inflammatory reaction in esophageal mucosa caused by pathologic
reflux of gastric acid. The anti-inflammatory effect of ghrelin and leptin is may be
attributed to their inhibitory effect on expression and release of proinflammatory
cytokines, COX-2 and the restoration of protective Hsp70 inhibited due to RE.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0472 ROLE OF ACID AND NON-ACID REFLUX IN ESOPHAGEAL
MUCOSAL DAMAGE (EROSIVE ESOPHAGITIS AND BARRETTS
ESOPHAGUS)
V. Kaibysheva1,*, A. Trukhmanov1, A. Ponomarev1, O. Storonova1,
M. Konkov1, V. Ivashkin1
1
FIRST MOSCOW STATE MEDICAL UNIVERSITY, Moscow, Russian
Federation
INTRODUCTION: The effect of acid reflux is commonly accepted nowadays.
Substantial experimental and clinical evidence strongly supports the importance
of acid and pepsin in causing esophageal mucosal injury. The role of weakly-acid
and duodenogastroesophageal reflux as an etiological factor of esophageal muco-
sal injury is not clarified until recently. With introduction of combined esopha-
geal pH-impedance monitoring, a precise diagnostic test for non-acid reflux is
now available.
AIMS & METHODS: The aim of this study was to assess the role of acid and
non-acid reflux in esophageal mucosal injury. 127 patients (75(59.1%) women
and 52(40.9%) men, averaging 48.6  14.9 years), off acid-suppressive therapy
underwent diagnostic work-up including upper-GI endoscopy with biopsy and
combined esophageal pH-impedance monitoring. According to data from pH-
impedance study patients were subdivided into three groups by predominant
characteristic of reflux: GERD with acid reflux (n 65; AR); GERD with
weakly-acid reflux (n 36, WR), and GERD with duodenogastroesophageal
reflux (n 26, DGR).
RESULTS: Rhe absence of endoscopically visible lesions or catarrhal esophagitis
(NERD) was found during endoscopy in 55.4%, 86.1%, and 76.9% for AR, WR,
DGR, respectively (p (AR-WR) 50.05). Erosive esophagitis (ERD) was found in
40%, 13.9% and 23.1% for AR, WR, DGR, respectively (p (AR-WR) 50.05).
Esophageal ulcers were found only in AR group in 4.6%. Moreover, AR and
DGR patients had significantly higher activity and degree of mucosal inflamma-
tion than patients in WR group (o50.05). Endoscopic changes indicating
Barretts esophagus with histologic presence of esophageal intestinal metaplasia
was found in 16%, 5.8%, and 42.9% for AR, WR, DGR, respectively (oAR-
DGR50.05; pWR-DGR50.05).
CONCLUSION: Higher frequency of esophageal mucosal injury in AR group in
comparison with patients in WR group suggests that acid is the key factor in
causing esophageal injury. While weakly acidic reflux does not contribute sig-
nificantly to esophageal mucosal damage. Similarly, the DGR patients had sig-
nificantly higher rate of intestinal metaplasia which indicates the important role
of duodenal content (bile or alkaline pancreatic secretions) in developing
Barretts esophagus.
Disclosure of Interest: None declared
P0473 IMPEDANCE-PH REFLUX PATTERNS IN PATIENTS WITH NON-
EROSIVE REFLUX DISEASE AND EROSIVE REFLUX DISEASE
V. Kaibysheva1,*, A. Trukhmanov1, V. Ivashkin1
1
FIRST MOSCOW STATE MEDICAL UNIVERSITY, Moscow, Russian
Federation
INTRODUCTION: Non-erosive reflux disease (NERD) and erosive reflux dis-
ease (ERD) are the most common phenotypic presentations of gastroesophageal
reflux disease.
AIMS & METHODS: To assess acid and non-acid reflux patterns in patients
with NERD and ERD using combined esophageal pH-impedance monitoring.
133 patients (off acid-suppressive medication) complaining of reflux symptoms
were underwent diagnostic work-up including upper gastrointestinal endoscopy
and ambulatory 24-h esophageal pH-impedance monitoring. According to data
of endoscopy patients were graded to NERD (90 patients (67.6%)) and ERD (43
patients, (32.3%)).
RESULTS: When compared to NERD, ERD patients showed a higher incidence
of acid reflux episodes in 24 h (72 (43;103) vs. 47 (21; 68), p50.05) and higher
duration of total esophageal acid exposure (10.8% (6.6; 19.4) vs. 4.5% (1.4;7.1),
p50.05). Reflux-related acid exposure (pH drops associated with reflux detected
by impedance) in ERD patients was twofold higher than in NERD patients
(2.2% (1.6; 2.9) vs. 1.08% (0.5;1.9), p50.05). Similarly, reflux-related alkaline
exposure (pH elevation (pH47) [1] associated with reflux detected by impe-
dance) was also higher in ERD patients (1.3% (0.8; 1.7) vs. 0.13% (0; 0.49),
p50.05). In contrast to ERD patients, NERD patients had significantly higher
(1.08% (0.46; 1.86) vs. 0.04% (0; 0.2), p50.05) reflux-related weakly acid
exposure (pH drops (pH57) [1] associated with reflux detected by impedance).
When compared with accepted normal values [1] NERD patients had signifi-
cantly higher mean number of weakly-acid refluxes (41(28;55)). Episodes of
weakly-acid reflux in NERD patients happened mainly at postprandial period.
Median acid (chemical) clearance time was twice higher in ERD patients (120
(76; 166) s.) in comparison to NERDs (60 (49; 116) s.) group. Meanwhile, there
was no significant difference in median volume clearance time between ERD and
NERD patients (23.3 (20.3; 27.6) vs. 19.1 (16.2; 23.6) s, p40.05). In both GERD
groups median volume clearance was significantly faster than median chemical
clearance (p50.05). Meanwhile, esophageal mucosas exposure to reflux volume
during 24 hour period, as assessed by impedance monitoring, was similar in both
ERD and NERD patients (3.8% vs.3.1%, p40.05).
CONCLUSION: While ERD and NERD patients have similar total esophageal
bolus exposure, ERD patients have an increased level of esophageal acid expo-
sure and reflux-related esophageal acid and alkaline exposure due to excessive
number of acid and alkaline reflux as well as long duration of chemical clearance.
Similarly, NERD patients have excessive number of postprandial weakly-acid
reflux and increased level of reflux-related esophageal weakly-acid exposure.
Consequently, this observation tends to support a notion that weakly-acid
reflux is less damaging to esophageal mucosa than acid reflux. Significant
A263
differences between acid and bolus clearances time may be caused by two dif-
ferent mechanisms of clearance. Volume clearance is achieved by peristalsis while
chemical clearance requires neutralization by saliva.
REFERENCES
1. Shay S, Tutuian R, Sifrim D, et al. Twenty-four hour ambulatory simulta-
neous impedance and pH monitoring: a multicenter report of normal values from
60 healthy volunteers. Am J Gastroenterol 2004; 99: 10371043.
Disclosure of Interest: None declared
P0474 CHARACTERISTICS OF NIGHTTIME REFLUX ASSESSED BY
USING MULTI-CHANNEL INTRALUMINAL IMPEDANCE PH
MONITORING AND A PORTABLE ELECTROENCEPHALOGRAPH
Y. Fujiwara1,*, Y. Kohata1, T. Tanigawa1, T. Watanabe1, K. Tominaga1,
T. Arakawa1
1
Osaka City University, Osaka, Japan
Contact E-mail Address: yasu@med.osaka-cu.ac.jp
INTRODUCTION: Nighttime reflux is strongly associated with sleep distur-
bances; however, the detailed characteristics of nighttime reflux occurring
during sleep have not been elucidated.
AIMS & METHODS: The present study aimed to analyze nighttime reflux by
using multi-channel intraluminal impedance pH (MII-pH) monitoring and a
portable electroencephalograph (EEG) in patients with gastroesophageal reflux
disease. Seventeen patients with heartburn and/or regurgitation were examined
by using MII-pH and a portable EEG simultaneously. Nighttime reflux was
divided based on reflux type, acidity, and extent. Phases of nighttime at bed
were divided as follows: (1) recumbent-awake before falling asleep; (2) nonrapid
eye movement (NREM); (3) rapid eye movement (REM); (4) awakening from
sleep; and (5) post-awakening in the morning.
RESULTS: A total of 184 nighttime refluxes were analyzed. Forty-three (23%)
refluxes occurred during recumbent-awake before falling asleep; 28 (15%) during
NREM; 14 (8%) during REM; 86 (46%) during awakening from sleep, with 50
(27%) during long awakening ( 5 min), and 13 (7%) during post-awakening in
the morning. Liquid reflux was common during awakening from sleep, NREM,
and REM. Prevalence of proximal migration was significantly lower in NREM
and REM than in the other phases. There was no difference in acidity and bolus
clearance time among the sleep phases. Nighttime reflux was highly prevalent
during long awakening (19/24, 79%). Among them, eight (42%) refluxes
occurred during the first epoch of long awakening.
CONCLUSION: Different reflux pattern at each phase during nighttime might
explain the pathogenesis of GERD and its related sleep disturbances.
Disclosure of Interest: None declared
P0475 THE CIRCULATING LEVEL OF CYTOKINES IN PATIENTS
WITH DIFFERENT FORMS OF GASTROESOPHAGEAL REFLUX
DISEASE: NON-EROSIVE REFLUX DISEASE, EROSIVE
ESOPHAGITIS AND BARRETTS ESOPHAGUS
Y. Evsyutina1,*, A. Truhmanov1, S. Lyamina2, I. Malyshev2, V. Ivashkin1
1
Sechenov First Moscow State Medical University., 2Moscow State University of
Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: uselina@mail.ru
INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most
common diseases and, according to recent epidemiological studies, clinical and
endoscopic GERD symptoms can be detected in 8-25% of the population
depending on country, race and gender. In the Russian Federation, the preva-
lence of GERD reaches 11-15%. Despite improvements in diagnosis and treat-
ment of GERD, there are still many unresolved issues. GERD is characterized by
disorders in immune response presented by misbalanced cellular (Th1) and
humoral (Th2) parts of immune response which depend on expression of
cytokines.
AIMS & METHODS: To determinate the circulating level of cytokines in
patients with different forms of gastroesophageal reflux disease (GERD): non-
erosive reflux disease (NERD), erosive esophagitis and Barretts esophagus. In
prospective cohort study were included 55 patients and randomized in 4 groups:
group 1 - 20 patients with NERD (11 men, 9 women; average age 37.75 12.04),
group 2 20 patients with erosive esophagitis (13 men, 7 women; average age
38.3312.55), 3 group 5 patients with Barretts esophagus (5 men; average age
34.259.88) and group 4 (control group) 10 healthy volunteers (5 men, 5
women; average age 33.379.39). In all enrolled patients were performed the
upper gastrointestinal endoscopy and the determination of plasma cytokines
(IL-4, IL-8, IL-10, IFN-, TNF-) by flow cytometry. Statistical analyses were
performed using SPSS 17.0 statistical package.
RESULTS: In patients with erosive esophagitis the median rate of IL-8 was 17.54
pg/mL (95% CI, 15.83 to 19.24), IFN- 72.97 pg/mL (95% CI, 15.24 to 130.7),
TNF- 16.31 pg/mL (95% CI, 14.03 to 18.58). The expression of IL-8 in patients
with erosive esophagitis was 2,3 times higher than in patients with NERD
(o 0.02) and 5,04 times higher than in patients with Barretts esophagus
(o 0.02). The expression of IFN- in patients with erosive esophagitis was
2,58 times higher than in patients with NERD (o 0.03) and 27,03 times
higher than in patients with Barretts esophagus (o 0.03). The expression of
TNF- in patients with erosive esophagitis was 2,22 times higher than in patients
with NERD (o 0.04) and 2,26 times higher than in patients with Barretts
esophagus (o 0.05). In patients with Barretts esophagus the median rate of
IL-4 was 14.95 pg/mL (95% CI, 12.75 to 17.15), IL-10 9.2 pg/mL (95% CI,
8.75 to 9.68). The expression of IL-4 in patients with Barretts esophagus was
2.36 times higher than in patients with erosive esophagitis (o 0.03) and 3.33
times higher than in patients with NERD (o 0.05). The expression of IL-10 in
patients with Barretts esophagus was 1.59 times higher than in patients with
A264
erosive esophagitis (o 0.03) and 2.53 times higher than in patients with NERD
(o 0.03).
CONCLUSION: In patients with erosive esophagitis in comparison with NERD
and Barretts esophagus we found overexpression of pro-inflammatory cytokines
(IL-8, IFN-, TNF-), that reflects their role in the Th1 immune response. In
patients with Barretts esophagus in comparison with NERD and erosive eso-
phagitis was the overexpression of anti-inflammatory cytokines (IL-4, IL-10),
that reflects their role in the Th2 immune response.
Disclosure of Interest: None declared
P0476 THE CIRCULATING LEVEL OF CYTOKINES IN PATIENTS
WITH REFRACTORY TO PROTON PUMP INHIBITORS
GASTROESOPHAGEAL REFLUX DISEASE
Y. Evsyutina1,*, A. Trukhmanov1, S. Lyamina2, I. Malyshev2, V. Ivashkin1
1
Sechenov First Moscow State Medical University, 2Moscow State University of
Medicine and Dentistry, Moscow, Russian Federation
Contact E-mail Address: uselina@mail.ru
INTRODUCTION: Gastroesophageal reflux disease (GERD) is one of the most
common diseases and, according to recent epidemiological studies, clinical and
endoscopic GERD symptoms can be detected in 8-25% of the population
depending on country, race and gender. In the Russian Federation, the preva-
lence of GERD reaches 11-15%. 50-60% of patients suffernig from refractory
GERD who despite the received therapy do not have improved clinical and
endoscopic picture, than can be explained with misbalance of Th1 and Th2
parts of immune response which depend on expression of cytokines.
AIMS & METHODS: To determinate the circulating level of cytokines in
patients with GERD depending on the response to standard proton pump inhi-
bitors (PPI) therapy. In prospective cohort study were included 50 patients ran-
domized in 3 groups: group 1 - 20 patients with non- refractory GERD (the
complete response to standard PPI therapy during 8 weeks which was defined
on disappearance of complaints) - 11 men, 9 women; average age 37.6610.02,
group 2 - 20 patients with refractory GERD (the partial response or absence of
response to standard PPI therapy during 8 weeks which was defined on main-
tenance of complaints) - 12 men, 8 women; average age 38.259.42, and group 3
(control group) 10 healthy volunteers (5 men, 5 women; average age
34.259.88). In all enrolled patients were performed the upper gastrointestinal
endoscopy and the determination of plasma cytokines (IL-4, IL-8, IL-10, IFN-,
TNF-) by flow cytometry. Statistical analyses were performed using SPSS 17.0
statistical package.
RESULTS: In patients with refractory to PPI gastroesophageal reflux disease in
comparison with patients with non- refractory GERD were higher levels of IL-8
(18.10 pg/mL vs. 6.66 pg/mL; o 0.02), IFN- (61.7 pg/mL vs. 24.10 pg/mL;
o 0.022), TNF- (14.77 pg/mL vs. 7.97 pg/mL; o 0.03). The high level of IL-8
is associated with relapse of erosive esophagitis within 2 years (p0.01).
CONCLUSION: In patients with refractory to PPI gastroesophageal reflux dis-
ease in comparison with non- refractory GERD was overexpressed IL-8, IFN-,
TNF-. Thus the high level of IL-8 was correlated with recurrent erosive eso-
phagitis within 2 years, and this cytokine can be used as the marker defining the
prediction of a course of a disease.
Disclosure of Interest: None declared
P0477 IS THERE A REAL RISK OF THE LONG TERM MEDICAL
TREATMENT OF GASTROESOPHAGEAL REFLUX DISEASE?
R. Kroupa1,*, M. Jecmenova1, M. Dastych1, J. Dolina1, A. Hep1
1 1
Department of Gastroenterology and Internal medicine, University Hospital Brno
and Faculty of Medicine Masaryks University, Brno, Czech Republic
Contact E-mail Address: rkroupa@fnbrno.cz
INTRODUCTION: A prolonged acid inhibition may be associated with the
important consequences like nutritional defects, increased risk of fractures or
infections and development of gastric polyps. The majority of data originate
from retrospective epidemiological studies only.
AIMS & METHODS: The aim of the study was to prospectively evaluate the
incidence of the possible risk events among patients during the long term acid
suppressive treatment.
A prospective observational study in gastroesophageal reflux disease (GERD)
patients requiring a long term treatment with proton pump inhibitors (PPI) was
performed. The development of fractures, pulmonary and enteric infection and
gastric polyps were recorded. The results were compared with control group
recruited from endoscopy outpatients without any history of the proton pump
inhibitor intake.
RESULTS: The cohort of 230 patients on maintenance GERD treatment (44%
female, age 53.8 14.4) was followed-up for 7.1 years (1631 patient-years).
Results were matched with 209 controls. The users of PPI were equally likely
to develop fractures 3.5% (OR 0.53; 95% CI 0.21-1.32) and bronchopneumonia
0.4% (OR 0.29; 95% CI 0.03-2.87) as the controls. The development of infectious
diarrhea was less frequent in PPI users than in controls (OR 0.11; 95% CI 0.01-
0.09). No case of hypomagnesemia was diagnosed in PPI users. Only a develop-
ment of fundic gland polyps was associated with PPI use in 12.6% of exposed
patients (OR 2.7; 95% CI 1.07-6.63).
CONCLUSION: A long term acid suppressing treatment of gastroesophageal
reflux disease did not increase the likelihood of fractures, infectious diarrhea,
bronchopneumonia and hypomagnesemia. Our results could encourage the
importance of prospective evaluation of risk events in subgroups according to
the indication of PPI use.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0478 30 MAY BE MORE APPROPRIATE THAN 45 FOR THE
CRITICALLY ILL PATIENTS RECEIVING MECHANICAL
VENTILATION AND ENTERAL NUTRITION
Y. Leng1,*, Y. Liiu1
1
Intensive care unit, Peking University Third Hospital, Beijing, China, Beijing,
China
Contact E-mail Address: lengyuxin1980@126.com
INTRODUCTION: Semi-recumbent position plays a pivotal role in prophylaxis
for the development of ventilator-associated pneumonia in the critically ills. In
the present study, we aimed to find a more appropriate semi-recumbent position
between 30 and 45 for the critically ill patients receiving mechanical ventilation
and enteral nutrition on balancing their advantages in ventilator-associated
pneumonia (VAP) prophylaxis and disadvantages in organ protection.
AIMS & METHODS: A prospective, randomized clinical study to investigate the
effect of different HOB (30 or 45 ) on all extent gastroesophageal reflux, prox-
imal gastroesophageal reflux and development of VAP; intra-abdominal pressure
(IAP), hemodynamic parameters [mean arterial pressure (MAP), abdominal per-
fusion pressure (APP), filtration gradient (FG)] and development of organ failure
was conducted on 86 consecutive patients admitted to a comprehensive intensive
care unit (ICU).
RESULTS: No significant differences in the incidence of VAP and number of all
extent reflux were found between 30 group and 45 group. However, the number
and percentage of proximal reflux in 45 group were unexpectedly higher than
30 group (Number: acid: p 0.022; weakly acidic: p 0.257; non acid:
p 0.168; Percentage: acid: p 0.000; weakly acidic: p 0.000; non acid:
p 0.000). Patients in 45 group had a trendency to develop new onset organ
failure more easily (45 vs. 30 : 11/42 vs. 5/44, p 0.077), accompanied with
higher IAPs measurement (17.645.32 mmHg vs.14.985.34 mmHg, p 0.023)
and lower MAP, APP, and FG (MAP, p 0.001; APP, p 0.000; FG, p 0.000).
CONCLUSION: For mechanically ventilated patients with enteral nutrition,
keeping the HOB at 45 doesnt show superiority over 30 . Elevating the HOB
from 30 to 45 cant reduce the incidence of VAP effectively but brings new
onset organ failure more easily.
REFERENCES
1. Leng YX, Zhang N, Zhu X, et al. Combined effects of elevated body position
on gastroesophageal reflux and intra-abdominal pressure in mechanical venti-
lated patients. Chin Crit Care Med 2011; 9: 534-537.
2. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the interna-
tional conference of experts on intra-abdominal hypertension and abdominal
compartment syndrome: I. Definitions. Intensive Care Med 2006; 32: 1722-1732.
3. Cheatham ML, Malbrain ML, Kirkpatrick A, et al. Results from the interna-
tional conference of experts on intra-abdominal hypertension and abdominal
compartment syndrome: II. Recommendations. Intensive Care Med 2007; 33:
951-962.
4. Sifrim D, Castell D, Dent J, et al. Gastro-oesophageal reflux monitoring:
review and consensus report on detection and definitions of acid, non-acid,
and gas reflux. Gut 2004; 53: 1024-1031.
Disclosure of Interest: None declared
P0479 DETECTION OF BURIED BARRETTS GLANDS AFTER
RADIOFREQUENCY ABLATION (RFA) WITH VOLUMETRIC
LASER ENDOMICROSCOPY (VLE)
A.-F. Swager1,*, D.F. Boerwinkel1, D.M. de Bruin2, D.J. Faber2, T.G.
van Leeuwen2, B.L. Weusten1, S.L. Meijer3, J.J. Bergman1, W.L. Curvers1
Gastroenterology and hepatology, 2Biomedical Engineering, 3Pathology,
Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: a.swager@amc.uva.nl
INTRODUCTION: The prevalence and clinical relevance of Buried Barretts (BB)
epithelium after radiofrequency ablation (RFA) in Barretts oesophagus (BO) is
questioned. Recent studies using small optical coherence tomography (OCT)
catheters for scanning underneath the neosquamous epithelium demonstrated a
high prevalence of tissue structures that might correspond to BB. Histological
correlation, however, is lacking. Volumetric Laser Endomicroscopy (VLE) is a
novel balloon-based OCT imaging technique that provides a 6-cm long circumfer-
ential volumetric scan of the oesophageal wall layers to a depth of 3 mm with a
resolution comparable to low-power microscopy.
AIMS & METHODS: To evaluate if post-RFA subsquamous structures,
detected with VLE, actually correspond to BB and to pursue direct histological
correlation of VLE images.
In-vivo VLE was performed to detect subsquamous structures suspicious for BB
in patients with 100% endoscopic regression of dysplastic Barretts epithelium
after RFA. Areas with suspicious subsquamous VLE structures were marked
with electrocoagulation after which in-vivo VLE was repeated to confirm that
the correct area was demarcated. These areas were subsequently resected endos-
copically, followed by immediate ex-vivo VLE scanning to reconfirm the pre-
sence of the subsquamous VLE structures. Extensive histological sectioning was
then performed and all histopathology slides were evaluated by an expert BO
pathologist (blinded for VLE images).
RESULTS: In 17 patients, 13 areas with suspicious subsquamous structures were
seen on in-vivo VLE and resected. Ex-vivo VLE of these 13 ER specimens
reconfirmed the presence of these subsquamous structures in 12 ER specimens.
Extensive histological sectioning of these areas showed BB in one area. The other
subsquamous VLE structures corresponded to dilated (ducts of) (sub)mucosal
glands or blood vessels.
CONCLUSION: VLE may potentially detect BB under endoscopically normal
appearing neosquamous epithelium. However, most post-RFA subsquamous
structures identified by in-vivo VLE did not correspond to BB. Further studies
United European Gastroenterology Journal 2(5S)
are required to identify VLE features that allow for differentiation of BB from
normal subsquamous structures.
Disclosure of Interest: None declared
P0480 VOLUMETRIC LASER ENDOMICROSCOPY IN BARRETTS
OESOPHAGUS: A STUDY ON HISTOLOGICAL CORRELATION
A.-F. Swager1,*, D.F. Boerwinkel1, D.M. de Bruin2, G.J. Tearney3,
C.L. Leggett4, B.L. Weusten1, D.J. Faber2, T.G. van Leeuwen2, S.L. Meijer5,
W.L. Curvers1, J.J. Bergman1
1
Gastroenterology and hepatology, 2Biomedical Engineering, Academic Medical
Center, Amsterdam, Netherlands, 3Pathology and Wellman Centre for
Photomedicine, Massachusetts General Hospital, Boston, 4Division of
Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States,
5
Pathology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: a.swager@amc.uva.nl
INTRODUCTION: Volumetric laser endomicroscopy (VLE) is a novel balloon-
based optical coherence tomography (OCT) imaging technique. It provides a 6-
cm long circumferential volumetric scan of the oesophageal wall layers to a depth
of 3 mm with a resolution that is comparable to low-power microscopy. VLE has
the potential for detection and delineation of early neoplastic lesions in Barretts
oesophagus (BO). In order to investigate this, it is important that structures
identified on VLE can be correlated with histology and -vice versa- that of
areas containing early neoplasia on histology the corresponding VLE features
can be studied. Most previous OCT studies lack such a direct correlation between
histology and OCT images.
AIMS & METHODS: To investigate the optimal approach for one-to-one cor-
relation of VLE images with histology.
BO patients with and without early neoplasia underwent endoscopic resection
(ER) of areas marked in-vivo with electrocoagulation markers (ECM).
Subsequently ER specimens underwent additional ex-vivo marking with several
different markers (ink, pin, ECM) followed by ex-vivo VLE scanning. Tissue
blocks were carefully sectioned guided by the placed markers. After further
histological processing a histopathology slide was sectioned from each block.
When necessary, extensive sectioning of tissue blocks was performed in order
to visualize all markers that were included in the tissue block on histology. All
histopathology and VLE slides were evaluated by 2 researchers and considered a
match if a)  2 markers were visible on both modalities and b) mucosal patterns
aside from these markers matched on both histology and VLE. All slides were
evaluated by an expert BO pathologist.
RESULTS: From 16 ER specimens (overall diagnosis: 7 non-dysplastic BO, 9
dysplastic BO (1 LGD, 4 HGD, 4 EAC)) 120 tissue blocks were sectioned of
which 57 contained multiple markers and thus could potentially be matched with
VLE. Based on several combinations of these markers in total 14 histology-VLE
matches could ultimately be constructed. Markers that achieved the best yield of
matches respectively were: in-vivo placed ECMs (8 matches with 12 markers),
pins (7 with 11), and ink (4 with 5). Histopathological evaluation was not hin-
dered by marker use. In this pilot study the last 6 ER specimens yielded 9/14
matches demonstrating a clear learning curve due to methodological improve-
ments in marker placement and tissue block sectioning.
CONCLUSION: One-to-one correlation of VLE and histology is complex but
feasible. The groundwork laid in this study will provide high-quality histology-
VLE correlations that will allow further research on VLE structures and VLE
features of early neoplasia in BO.
Disclosure of Interest: A.-F. Swager: None declared, D. Boerwinkel: None
declared, D. de Bruin: None declared, G. Tearney Financial support for research
from: Ninepoint Medical, Other: Massachusetts General Hospital has a licensing
arrangement with Ninepoint Medical. Dr. Tearney has the rights to receive roy-
alty income from this licensing arrangement., C. Leggett: None declared, B.
Weusten Financial support for research from: Ninepoint Medical, Other: Has
rights to receive royalty income from licensing arrangement between
Massachusetts General Hospital and Ninepoint Medical, D. Faber: None
declared, T. van Leeuwen: None declared, S. Meijer: None declared, W.
Curvers: None declared, J. Bergman: None declared
P0482
A265
P0481 SENSITIVITY TO OESOPHAGEAL MULTIMODAL
STIMULATION IN BARRETTS OESOPHAGUS PATIENTS
C. Lottrup1,*, A.L. Krarup1, P. Ejstrud2, M. Ostapiuk2, A.M. Drewes1
1
Mech-Sense, Department of Gastroenterology & Hepatology, 2Department of
Surgery, Aalborg University Hospital, Aalborg, Denmark
Contact E-mail Address: chlo@rn.dk
INTRODUCTION: Oesophageal sensitivity to mechanical and acid stimulation
in Barretts oesophagus has previously been shown to be decreased.
AIMS & METHODS: The aim was to investigate the oesophageal sensitivity in
Barretts oesophagus using a multimodal (mechanical, thermal, electrical, acid)
pain model.
Twenty-two patients with Barretts oesophagus (mean age: 64.6 years) were
compared to twelve healthy controls (mean age: 54.3 years) using oesophageal
multimodal pain stimulation following upper endoscopy. A probe with a poly-
urethane bag was placed in the lower oesophagus. The probe was then used to
apply mechanical, thermal, and electrical stimulation as well as a modified
Bernstein test with infusion of 0.1 N HCl. All stimulations were stopped when
the subject felt moderate pain, defined as 7 out of 10 on a visual analogue scale
(VAS 7).
RESULTS: Five of the Barretts oesophagus patients had oesophagitis (Los
Angeles grade A or B) on endoscopy.
For mechanical stimulation, the bag distension volume evoking VAS 7 was
significantly higher in the Barretts group (mean volume 42 vs 28 mL,
P 0.006). For thermal stimulation, there was a non-significant tendency in the
Barretts group towards a higher area under the curve to reach VAS 7 (949 vs.
677 s*oC, P 0.14). The stimulus required to reach VAS 7 during electrical
stimulation was significantly higher in the Barretts group (32.7 mA vs. 21.9
mA, p 0.03. During the modified Bernstein test, the acid volume required to
reach VAS 7 or a maximum infusion volume of 200 mL was lower in the
Barretts group (mean 77 vs. 127 mL, P 0.03). The time passed before feeling
the first burning sensation during acid infusion was shorter in the Barretts group,
but just failed to be significant (181 vs. 329 seconds, P 0.056).
The referred pain area defined by the subject immediately after sensing VAS 7
was insignificant between groups (P 4 0.05) for all 4 stimulation modalities.
CONCLUSION: Barretts oesophagus patients showed hyposensitivity to
mechanical, thermal and electrical stimulation, but hypersensitivity to acid sti-
mulation. This is to some degree different from earlier findings, but the latter
finding could indicate a sensitisation to acid because of oesophagitis underlying
the disease.
Disclosure of Interest: None declared
P0482 SURVEILLANCE IN PATIENTS WITH BARRETTS ESOPHAGUS:
A COST-EFFECTIVENESS ANALYSIS
F. Kastelein1,*, S.van Olphen1, E. Steyerberg2, M. Spaander1, C. Looman2,
E. Kuipers1, M. Bruno1, E.de Bekker-Grob2 on behalf of ProBar-study group
1
Gastroenterology and Hepatology, 2Public health, ERASMUS UNIVERSITY
MEDICAL CENTER, Rotterdam, Netherlands
Contact E-mail Address: f.kastelein@erasmusmc.nl
INTRODUCTION: Surveillance is recommended for Barretts esophagus (BE)
to detect esophageal adenocarcinoma (EAC) at an early stage.
AIMS & METHODS: The aim of this study was to evaluate the cost-effective-
ness of surveillance intervals and treatment strategies. 714 BE patients were
included in a multicenter prospective cohort study and followed during surveil-
lance according to the ACG guidelines. We used a multi-state-Markov model to
calculate misclassification and true progression rates from no dysplasia (ND) to
low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC. These pro-
gression rates were incorporated in a decision-analytic model, which included
costs and quality of life data associated with different surveillance strategies.
We evaluated different surveillance intervals for ND and LGD, endoscopic
mucosal resection (EMR) followed by radiofrequency ablation (RFA), RFA
alone or esophagectomy for HGD or early EAC and esophagectomy with neoad-
juvant chemoradiotherapy for advanced EAC. The incremental cost-effectiveness
ratio (ICER) was calculated in costs per quality-adjusted life year (QALY). The
willingness-to-pay threshold was set at E35.000 per QALY gained.

No dysplasia Low-grade dysplasia

Strategy Costs QALYs ICER Costs QALYs ICER

No surveillance E5.695 12.62 E4.823 E21.806 10.95 E4.040

Surveillance every 5 years with RFA E6.904 12.87 E61.821 E25.709 11.91 E28.741
Surveillance every 5 years with EMR and RFA E7.139 12.87 E104.668 E27.447 11.91 E31.073
Surveillance every 5 years with esophagectomy E13.965 12.64 E321.880 E50.909 11.33 E39.633
Surveillance every 4 years with RFA E7.695 12.89 E28.006 11.99 E72.257
Surveillance every 4 years with EMR and RFA E7.951 12.89 E29.959 11.99
Surveillance every 4 years with esophagectomy E15.229 12.63 E51.835 11.34
Surveillance every 3 years with RFA E8.868 12.90 E30.973 12.09
Surveillance every 3 years with EMR and RFA E9.148 12.90 E33.210 12.09
Surveillance every 3 years with esophagectomy E16.890 12.61 E52.851 11.34
Surveillance every 2 years with RFA E10.831 12.90 E34.956 12.19
Surveillance every 2 years with EMR and RFA E11.143 12.90 E37.575 12.19
Surveillance every 2 years with esophagectomy E19.325 12.59 E53.960 11.34
Surveillance every year with RFA E14.898 12.89 E40.542 12.27
Surveillance every year with EMR and RFA E15.257 12.89 E43.688 12.27
Surveillance every year with esophagectomy E23.686 12.54 E55.159 11.34
A266
RESULTS: The true annual progression rate for ND to LGD was 0.02, for LGD
to HGD or early EAC 0.03 and for HGD or early EAC to invasive EAC 0.36. In
patients with ND, surveillance every five or four years with RFA for HGD or
early EAC and esophagectomy for advanced EAC had ICERs of E4.800 and
E61.800 per QALY respectively. Strategies with shorter intervals provided higher
costs with similar QALYs gained. In patients with LGD, surveillance every five
to two years had ICERs of E4.040, E28.741, E31.073, and E39.633 per QALY
respectively. EMR prior to RFA was slightly more expensive, but had additional
value for tumor staging.
CONCLUSION: Surveillance with EMR and RFA for HGD or early EAC and
esophagectomy for advanced EAC is cost-effective with 5-year intervals for
patients with ND and 3-year intervals for patients with LGD, based on a will-
ingness-to-pay threshold of E35.000 per QALY.
Disclosure of Interest: None declared
P0483 BOTH ESOPHAGEAL POSTERIOR AND RIGHT WALL ARE THE
PREFERRED LOCALIZATIONS OF BARRETTS ESOPHAGUS
S. Bibbo`1, G. Ianiro1,*, L. Petruzziello2, C. Spada2, A. Larghi2, M.E. Riccioni2,
A. Gasbarrini1, G. Costamagna2, G. Cammarota1
1
Dept of Internal Medicine, Division of Gastroenterology, 2Department of Surgery
- Endoscopy Unit, CATHOLIC UNIVERSITY SCHOOL OF MEDICINE,
ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: Prevalence of Barretts esophagus (BE) is higher in patient
with gastroesophageal reflux disease (GERD) with a rate of prevalence of 10%.
The risk of cancer associated to this condition is estimated to be approximately
0.5% per year. For this reason a careful endoscopic surveillance assumes a
paramount importance. Only few literature data on the preferred esophageal
location of BE are available to date.
AIMS & METHODS: The aim of this study is to identify the preferred area
where BE can develop within esophageal circumference. We retrospectively ana-
lyzed patients with BE who underwent upper endoscopy between January 2010
and March 2014 at our Endoscopy Center. We included only patients with short
BE. In the case of multiple BE tongues, each lesion was considered individually.
The circumferential localization of the lesions was determined according to the
numbers of a clock face.
RESULTS: In the study period, a total of 204 subjects were newly diagnosed of
BE or had an endoscopic follow-up of BE. Twenty-four patients with circumfer-
ential lesions were excluded. Among the 180 remaining patients, multiple BE
lesions were diagnosed in 110 of them, for a total amount of 332 areas of mucosal
metaplasia. Our analysis of data showed a clear prevalence of BE in the position
near 3 oclock and 6 oclock of the endoscopic image. The area between 5 and 7
oclock (posterior wall) was the most affected (38.25% of the lesions). Other
localizations were respectively the arc between 2 and 4 oclock (right wall) with
27.71%, the arc 11 to 1 oclock 23.80% (anterior wall) and the arc 8 to 10 oclock
10.24% (left wall). For each of the four walls, difference between observed and
expected (dividing equally the number of lesions for the number of quadrants)
lesions was statistically significant (P50.0001 for each wall). Lesions were most
commonly located in the right (1 to 6 oclock) than in the left (7 to 12 oclock)
quadrant (207 versus 125 two-tailed P value 0.0189).
CONCLUSION: We first describe, in a large cohort of Italian patients, an
uneven localization of BE in the distal esophageal circumference, with an
higher prevalence on the posterior-right wall. Anatomical and environmental
factors could explain this finding. The circumferential asymmetry of LES pres-
sure (in particular, a lower pressure on the right quadrant) and the preference of
supine position during sleep are two situations that may promote the reflux of
gastric fluids preferably in the right and posterior wall of the distal esophagus. A
more accurate observation of such areas during endoscopic surveillance is advi-
sable in GERD patients.
Disclosure of Interest: S. Bibbo`: nothing to declare, G. Ianiro: nothing to declare,
L. Petruzziello: nothing to declare, C. Spada: nothing to declare, A. Larghi: noth-
ing to declare, M. E. Riccioni: nothing to declare, A. Gasbarrini: nothing to
declare, G. Costamagna: nothing to declare, G. Cammarota: nothing to declare
P0484 A STUDY ON THE LONG-TERM PROGNOSIS AND
PERFORMANCE ENDOSCOPIC SUBMUCOSAL DISSECTION FOR
ESOPHAGOGASTRIC JUNCTION ADENOCARCINOMA
H. Kaneko1,*, K. HIRASAWA1, R. KOBAYASHI1, M. MAKAZU1, C. SATO1,
A. KOKAWA1, S. MAEDA2
1
Division of Endoscopy, Yokohama City University Medical Center, 2department
of gastroenterology, Yokohama City University graduate school of medicine,
yokohama, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) was becoming
widespread as a treatment option for superficial adenocarcinoma of the esopha-
gogastric junction (EGJ) including Barretts esophageal adenocarcinoma; how-
ever, its long-term and treatment outcomes have not been fully evaluated.
AIMS & METHODS: The aim of this study was to assess the long-term and
treatment outcomes of ESD for patients with superficial adenocarcinoma of the
EGJ.
Between September 2000 and December 2013, we performed ESD for 104 super-
ficial adenocarcinoma of EGJ (type II tumor according to Siewerts classification)
in 103 patients. The rates of en bloc resection, positive for lateral and/or vertical
margin, curative resection, and overall and disease-specific survival rate after ESD
were evaluated during follow-up (median observation period 55.6 months).
We divided all patients into two groups, the adenocarcinoma of Barretts eso-
phagus (BE group: 20 lesions in 20 patients) and other adenocarcinoma of EGJ
(Non-BE group: 84 lesions in 83 patients), then each outcomes were evaluated.
United European Gastroenterology Journal 2(5S)
RESULTS: All lesions were treated by en bloc resection. None of BE group were
positive lateral margin and 7 of Non-BE group were positive lateral margin.
The rate of curative resection was 74% (77/104) in all patients, and BE group and
Non-BE group were 74% and 75%, respectively. The most frequent cause of
non-curative resection was tumor invasion into the deep submucosa.
Ninety three patients (93%) were traceable prognosis, and 5 year overall survival
rate was 91.2%. When we limited to the curative resections, 5 year overall survi-
val rates were 66.7% in BE group and 89.4% in Non-BE group. There was no
death of adenocarcinoma of EGJ, meaning that the disease-specific survival rate
was 100%.
There was no statistical difference of the rate of positive margin, curative resec-
tion and 5 year overall survival rates between BE and Non-BE groups.
CONCLUSION: The treatment outcomes of ESD for adenocarcinoma of EGJ
were favorable regardless of the evidence of Barretts esophagus. However, the
curative resection rate was relatively low. It was assumed that pre-operative
recognition of the tumor invasion into the submucosa might be difficult for
adenocarcinoma of EGJ.
Disclosure of Interest: None declared
P0485 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
MANAGEMENT OF PATIENTS WITH BARRETTS ESOPHAGUS: A
CLINICAL EVIDENCE-BASED CONSENSUS REPORT
J.P. Galmiche1, R. Arsenescu2, H. Bertani3, F. Caillol4, D. Carr-Locke5,
K. Chang6, E. Coron1,*, A. Dlugosz7, S. I. Gan8, M. Giovannini4, F.G. Gress9,
K. Ho10, V. Konda11, H. Neumann12, F. Prat13, P. Sharma14, S. Singh15,
K. Wang16, H. Wholfsen17
1
CHU Nantes, Nantes, France, 2Ohio State University Medical Center, Columbus,
United States, 3Nuovo Ospedale Civile SantAgositno Estense, Modena, Italy, 4I.
P. C, Marseille, France, 5Beth Israel Medical Center, New York, 6University of
California Irvine Medical Center, Irvine, United States, 7Karolinska University
Hospital Huddinge, Stockholm, Sweden, 8Virginia Mason Medical Center, Seattle,
9
N. Y Presbyterian Columbia University Medical Center, Brooklyn, United States,
10
National University Hospital, Singapore, Singapore, 11The University of Chicago
Medical Center, Chicago, United States, 12Universitatsklinikum Erlangen,
Erlangen, Germany, 13Cochin, Paris, France, 14VA Kansas City Medical Center,
Kansas City, 15VA Boston Healthcare System, Jamaica Plain, 16Mayo Clinic,
Rochester, 17Mayo Clinic, Jacksonville, United States
Contact E-mail Address: galmiche.jean-paul@orange.fr
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) is a recent technol-
ogy that provides microscopic imaging during endoscopy, thus in vivo and in real
time. The currently recommended Seattle protocol is intended to provide a com-
prehensive mapping of the Esophagus, but its inherent constraints have impaired
its application. CLE allows for unlimited sampling of the esophageal mucosa and
several recently published studies have shown its ability to provide a comprehen-
sive assessment of Barretts Esophagus (BE) lesions.
AIMS & METHODS: The aim of thi study is to develop consensus recommen-
dations on the role of CLE in the management of patients with BE.
Initial statements on the use of CLE for the characterization of BE were devel-
oped by a single CLE expert based on the available clinical evidence. Those
preliminary statements were edited and submitted by an external group of 20
GI physicians experts in CLE using a modified Delphi approach. After two
rounds of votes based on relevant data, quality of the evidence and strength of
recommendation, statements were validated if the threshold of agreement was
higher than 75%.
RESULTS: 12 recommendations were adopted and 4 were rejected. CLE should
be considered in the evaluation of BE. CLE is clinically indicated in patients with
BE dysplasia in lesions initially identified in surveillance, with or without elec-
tronic enhancement. CLE is able to distinguish cardia from intestinal metaplasia
(IM), based on the presence/absence of goblet cells. CLE is superior to White-
Light Endoscopy (WLE) in identifying IM. A negative CLE random sampling in
an endoscopically benign appearing Esophagus is sufficient to reduce the need
for a physical biopsy in patients with known BE. CLE can improve the yield for
neoplasia compared to standard WLE and random biopsies. CLE and WLE
targeted biopsies are superior to WLE targeted biopsies alone in the detection
of dysplasia. A positive CLE random sampling in an endoscopically neoplastic
appearing Esophagus is sufficient for therapeutic intervention. CLE can be used
to define location and lateral extent of neoplasia prior to therapy. CLE should be
cited as a valuable tool for an increased diagnostic yield in official surveillance
guidelines. CLE should be combined with red flag techniques.
CONCLUSION: The panel of experts that participated in this initiative strongly
believes that Confocal Laser Endomicroscopy is an important adjunct to the
current endoscopy practice. This technique can improve the management of
patients by more accurately characterizing neoplasia, identifying residual neopla-
sia in post-treatment surveillance and rationalizing the choice of the most appro-
priate treatment. This consensus report is based on a review of the clinical
evidence and on a consensus opinion.
Disclosure of Interest: J. P. Galmiche Consultancy for: Mauna Kea Technologies,
R. Arsenescu: None declared, H. Bertani: None declared, F. Caillol: None
declared, D. Carr-Locke: None declared, K. Chang Other: Medical Advisory
Board Mauna Kea Technologies, E. Coron Consultancy for: Has served as a
consultant for Mauna Kea Technologies, A. Dlugosz: None declared, S. I. Gan:
None declared, M. Giovannini: None declared, F. G. Gress: None declared, K.
Ho: None declared, V. Konda Other: Honorary for Mauna Kea Technologies,
H. Neumann: None declared, F. Prat: None declared, P. Sharma: None declared,
S. Singh: None declared, K. Wang: None declared, H. Wholfsen: None declared
United European Gastroenterology Journal 2(5S)
P0486 COST-EFFECTIVENESS OF CONFOCAL LASER
ENDOMICROSCOPY (CLE) FOR THE MANAGEMENT OF
BARRETTS ESOPHAGUS
C.L. Pen 1, J.P. Galmiche2,*, E. Coron 2
1
Universite Paris Dauphine, Paris, 2CHU Nantes, Nantes, France
Contact E-mail Address: claude.lepen@wanadoo.fr
INTRODUCTION: The clinical impact of CLE has been demonstrated for the
management of patients undergoing surveillance or treatment of Barretts
Esophagus. This study is the first one evaluating the economic impact of using
CLE in clinical practice in a European healthcare system.
AIMS & METHODS: The aim of this study was to evaluate the cost-effective-
ness of a CLE-based strategy compared to the standard Seattle protocol for the
management of patients with Barretts Esophagus and suspicion of neoplasia, in
the setting of the French public healthcare system.
We used the data published by Canto et al (1) on a multicentric randomized
controlled trial which compared 2 strategies: (i) high definition white light endo-
scopy (HD-WLE) CLE and targeted physical biopsies (CLE-based strategy)
and (ii) HD-WLE and random physical biopsies (Standard strategy). In that
study, the CLE-based strategy had a higher sensitivity for the diagnosis of
HGD/EC (95 versus 40%) without significant change in specificity (92%
versus 98% respectively). The average number of biopsies performed was
reduced from 5.91 to 1.26 per patient by the use of CLE. These data were entered
into a health economics model (piggyback study) to compare the costs of both
strategies when performed in public academic hospitals. French costs were asso-
ciated to each procedure in order to estimate the medical cost of the two strate-
gies from a public health payer perspective. CLE was priced as a therapeutic
endoscopy procedure that is valued 20% more than a standard diagnostic
endoscopy.
RESULTS: In spite of a higher procedure cost, the total costs for a cohort of 100
patients associated to the CLE-based strategy were 89,313.29 E compared to
90,658.90 E for the standard strategy. The cost per patient adequately diagnosed
and treated was also inferior for the CLE-based strategy (960.36 E vs. 1,054.17
E). Different sensitivity analyses (including a Monte-Carlo modeling) were per-
formed which confirmed the robustness of previous results.
CONCLUSION: In the restricted context of this evaluation, the CLE-based
strategy is not only more effective but also less costly than the standard strategy
i.e. corresponding to the definition of a dominant strategy.
REFERENCES
1. Canto MI, Anandasabapathy S, Brugge W, et al. In vivo endomicroscopy
improves detection of Barretts esophagus-related neoplasia: a multicenter inter-
national randomized controlled trial (with video). Gastrointest Endosc 2014; 79:
211-221.
Disclosure of Interest: C. Le Pen Consultancy for: Work as a consultant for
Mauna Kea Technologies, J. P. Galmiche Consultancy for: Work as a consultant
for Mauna Kea Technologies, E. Coron Consultancy for: Was consultant for
Mauna Kea Technologies
P0487 ENDOSCOPIC SUBMUCOSAL DISSECTION FOR SUPERFICIAL
BARRETTS ESOPHAGUS ADENOCARCINOMA: CLINICAL
OUTCOMES IN A LARGE SERIES OF EUROPEAN PATIENTS
J.-B. Chevaux1,*, H. Piessevaux1, A. Jouret-Mourin2, R. Yeung1, E. Danse3,
P.H. Deprez1
1
Hepato-Gastroenterology, 2Pathology, 3Radiology, Cliniques universitaires Saint-
Luc, Universite catholique de Louvain, Brussels, Belgium
Contact E-mail Address: jeanbaptistechevaux@gmail.com
INTRODUCTION: The role of endoscopic submucosal dissection (ESD) in
Barretts neoplasia has not yet been well defined, although this technique
could potentially achieve a higher curative resection rate and improved histolo-
gical assessment compared to endoscopic mucosal resection (EMR).
AIMS & METHODS: This study sought to assess ESD efficacy, safety, and
long-term results in a large patient cohort. Seventy-five consecutive Barretts
esophagus (BE) patients who underwent ESD between January 2007 and
February 2014 were retrospectively analyzed. ESD was performed for either
visible lesions that were multiple, over 15mm, or poor-lifting, or for suspected
submucosal infiltration. Primary endpoint was curative resection rate of carci-
noma (CRC).
RESULTS: Median patient age was 68 years (IQR, 61-76), median patient
follow-up was 20 months (IQR, 8.5-37.5), and median maximum specimen dia-
meter was 52.5mm (IQR, 43-71). Median maximum diameter of visible lesion was
20mm (IQR, 10-30). En bloc resection and CRC rates were 90% and 85%,
respectively. G3 differentiation and invasion 4pT1m2 were observed in 25%
and 55% of cases, respectively. Five early (548h) adverse events occurred
(two delayed hemorrhages; three perforations), all treated endoscopically. No
ESD-specific death was observed. Esophageal strictures manifested in 60% of
patients, all treated endoscopically. Additional treatment methods for residual
BE were proposed to 64% of patients, with a median number of two sessions
(IQR, 2-3). At latest follow-up, complete remission of neoplasia and intestinal
metaplasia was achieved in 92% and 73%, respectively.
CONCLUSION: ESD appears to be safe and effective, with a high curative
resection rate. ESD should be the favored treatment for Barretts neoplasia
cases at risk of incomplete resection or poor pathology assessment with conven-
tional EMR.
Disclosure of Interest: None declared
A267
P0488 AUTOFLUORESCENCE-TARGETED PROBE-BASED CONFOCAL
LASER ENDOMICROSCOPY CAN DETECT THE FIELD OF
MOLECULAR CHANGE IN BARRETTS OESOPHAGUS
M. Di Pietro1,*, E. Bird-Lieberman2, M. ODonovan1, H. Bertani3,
R. Fitzgerald1
1
MRC CANCER UNIT - University of Cambridge, Cambridge, 2Oxford
University Hospital, Oxford, United Kingdom, 3Endoscopy, Nuovo Ospedale Civile
S. Agostino Estense, Modena, Italy
INTRODUCTION: Probe-based confocal laser endomicroscopy (pCLE) allows
optical biopsies in Barretts oesophagus (BO) to predict histological outcome but
it is subject to sampling error if performed in a random fashion. We used auto-
fluorescence imaging (AFI) to direct pCLE and added molecular biomarkers to
the histopathological diagnosis.
AIMS & METHODS: The aims of this study were to assess the diagnostic
accuracy for dysplasia of AFI-targeted optical biopsies and to investigate the
correlation between pCLE patterns and field of molecular change.
53 patients with BO (non-dysplastic BO n 22, indefinite for dysplasia (ID)
n 5, low grade dysplasia n 13, high grade dysplasia (HGD) or intramucosal
cancer (IMC) n 13) were recruited at a single centre. Patients underwent high-
resolution endoscopy followed by AFI and then pCLE was performed on AFI
positive (AFI) areas. Targeted biopsies were taken from AFI areas, followed
by random biopsies as per Seattle protocol. pCLE sequences were graded accord-
ing to published criteria. Cyclin A and p53 expression were assessed by immu-
nohistochemistry and aneuploidy by flow-cytometry on AFI-targeted biopsies.
Statistical analyses were performed using chi-square test
RESULTS: AFI-targeted pCLE correctly classified all the HGD/EC patients and
had a sensitivity and specificity for any grade of dysplasia of 94% and 86%,
respectively. The Seattle protocol had similar sensitivity for HGD/IMC and any
grade of dysplasia (85% and 92.5%, respectively). For the per-location analysis,
a total of 185 endoscopic areas were analyzed with pCLE and molecular biomar-
kers. pCLE had a sensitivity and a specificity for HGD/IMC and any grade of
dysplasia of 100%/67% and 77%/77%, respectively. Overall, 40% of pCLE
irregular sequences corresponded to non-dysplastic areas (false positive). We
found a statistically significant enrichment (p50.001) of the three molecular
biomarkers in pCLE irregular areas. After exclusion of dysplastic areas, a sig-
nificant correlation between pCLE irregularity and biomarker positivity was
retained (p 0.008). The presence of at least 1 positive biomarker significantly
correlated with dysplasia both in pCLE irregular (p 0.01) and pCLE regular
areas (p 0.05). Using a cut-off of two positive biomarkers, this panel classified
as high risk all the patients with HGD/IMC and 45% of patients with LGD, but
none of the patients with ID and non-dysplastic BO
CONCLUSION: AFI-targeted pCLE has a high diagnostic accuracy for dyspla-
sia in BO. Tissue biomarkers are a useful adjunct to characterize the field of
molecular abnormality associated with optical dysplasia. These results suggest
that the presence of pCLE irregularity, even in the absence of histological dys-
plasia, relates to molecular changes and may warrant close follow up. A 3-bio-
marker is a useful adjunct to optical biopsy to provide further stratification
Disclosure of Interest: None declared
P0489 ROLE OF BODY COMPOSITION AND METABOLIC
DYSFUNCTION IN BARRETTS OESOPHAGUS AND
PROGRESSION TO CANCER
S. Di Caro1,*, L. Fini2, W.H. Cheung3, R. Haidry1, M. Keane1, L. Lovat1,
R. Batterham3, M. Banks1
1
Gastroenterology, UNIVERSITY COLLEGE HOSPITAL, LONDON, UK,
London, United Kingdom, 2Gastroenterology, Busto Arstizio Hospital, Milan,
Italy, 3Centre for Obesity Research, UNIVERSITY COLLEGE HOSPITAL,
LONDON, UK, London, United Kingdom
Contact E-mail Address: Simona. DiCaro@uclh.nhs.uk
INTRODUCTION: Oesophageal adenocarcinoma (OAC) arises within Barretts
oesophagus (BE). Obesity is associated with metabolic syndrome (MS) and
cancer progression. Body composition has a direct impact in obesity-related
diseases. Normal weight individuals with increased fat mass are considered meta-
bolically obese.
AIMS & METHODS: To evaluate the prevalence of obesity, altered body com-
position and metabolic indexes in patients (pts) with and without BE; and asso-
ciation with cancer progression in BE.
In sequential pts undergoing gastroscopy, MS, waist/hip ratio (WHR) and body
fat% (BF by bioimpedance analysis) were obtained. In BE pts, histological find-
ings were correlated with metabolic data. Pts were classified according to Body
Mass Index (BMI), abdominal obesity (AO by WHR) and in females, Normal
Weight Obese (NWO). Identified risk factors significantly associated with BE at
univariate analysis were subsequently entered into a multivariate logistic regres-
sion analysis.
RESULTS: 250 cases and 230 controls (F/M: 193/287) were enrolled. Age (cut
off: 57 years) and male gender (M/F 193/57; OR 5.01, p50.0001) were identified
risk factors for BE. AO (76 vs 51%; OR 3.13; p50.001), increased BF% (30.7 vs
17.6%; p 0.001), higher BMI (overweight: 39.6 vs 30%; OR 2.09; p 0.0008;
obese: 32 vs 22%; OR 2.3; p 0.004) and MS (33.2 vs 20%; OR 1.95; p 0.0017)
were significantly associated with BE. A positive trend, possibly related to the
small number of female cases, was demonstrated for NWO (28.1 vs 19.1%; OR
1.06; p 0.1). More cases were affected by hypertension (37.4 vs 21.3%; OR 2.4;
p5 0.001) and hyperlipidaemia (72.8 vs 53.9%; OR 2.28; p50001) but not
diabetes.
When adjusted by gender, age and race into a multivariate analysis, independent
risk factors for BE were BF% (OR 1.90; p 0.01) and AO (OR 1.67; p 0.03).
A268
Metaplasia and dysplasia were present in 57.2 and 42.8%. AO was the only
metabolic parameter independently correlated with high grade dysplasia (38 vs
21%; OR 2.44; p 0.001).
CONCLUSION: Abdominal obesity, and body fat mass are strong risk factors
for BE. A positive trend association was demonstrated in NWO. Furthermore,
abdominal adiposity plays a role in progression to OAC. BE might therefore be
considered in the metabolic syndrome spectrum and as such, in this group screen-
ing interventions may be considered.
REFERENCES
1. Ryan AM, Healy LA, Power DG, et al. Barrett esophagus: prevalence of
central adiposity, metabolic syndrome, and a proinflammatory state. Ann Surg
2008; 247: 909-15.1.
2. Anand G and Katz PO. Gastroesophageal reflux disease and
obesity.Gastroenterol Clin North Am 2010; 39: 39-46.
3. De Lorenzo A, Del Gobbo V, Premrov MG, et al. Normal-weight obese
syndrome: early inflammation? Am J Clin Nutr 2007; 85: 40-45.
4. Kendall B, Macdonald G, Hayward N, et al. The risk of Barretts oesophagus
associated with abdominal obesity in males and females. Int J Cancer 2013; 132:
2192-2199.
Disclosure of Interest: None declared
P0490 A NOVEL ENDOSCOPIC CLASSIFICATION SYSTEM USING I-
SCAN IMPROVES DYSPLASIA DETECTION IN BARRETTS
OESOPHAGUS
V. Sehgal1,*, D. Graham1, M. Banks1, R. Bisschops2, K. Ragunath3, L. Lovat1,
R. Haidry1
1
Gastroenterology, University College London Hospital (UCLH), London, United
Kingdom, 2Gastroenterology, University Hospitals Leuven, Leuven, Belgium,
3
Gastroenterology, Queens Medical Centre, Nottingham, United Kingdom
Contact E-mail Address: v.sehgal@ucl.ac.uk
INTRODUCTION: Dysplasia arising in Barretts oesophagus (BE) can lead to
oesophageal adenocarcinoma. Endoscopic surveillance is performed to detect
dysplasia in BE so early treatment can be offered. Current practice relies on
white-light endoscopy (WLE) to obtain random quadrant biopsies every 2cm
from the BE segment, sampling less than 5% of the surface and therefore poten-
tially missing areas of dysplasia.
An endoscopic image enhancement technology, i-Scan (PENTAX HOYA,
Japan), has been developed to help improve lesion recognition in the gastroin-
testinal tract. i-Scan utilises post-processing light filtering technology to provide
real-time analysis and enhancement of different elements of the mucosa and
microvasculature to improve dysplasia detection.
Previous endoscopic classification systems for BE have used image enhancement
technologies combined with magnification endoscopy. We report the accuracy of
a novel classification system using i-Scan without magnification amongst expert
endoscopists based at 3 high-volume European tertiary referral centres for detect-
ing BE dysplasia.
AIMS & METHODS: High definition (HD) video recordings were collected
from patients with non-dysplastic (ND-BE) and dysplastic (D-BE) BE under-
going endoscopy at University College London Hospital. A protocol was used to
record areas of interest and a corresponding biopsy was taken to confirm
pathology.
A simple classification system based on mucosal (M) and vascular (V) patterns
was used: M1 or M2 - regular oval or villous pits respectively (ND-BE), M3
irregular or featureless mucosa (D-BE); V1 regular vessels (ND-BE), V2
irregular (dilated, corkscrew) vessels (D-BE).
In a blinded manner, videos of normal and abnormal lesions were interpreted by
3 expert endoscopists using the above classification. Predicted pathology was also
recorded for each lesion. Acetic acid (ACA) chromoendoscopy was used in some
cases. Agreement in relation to predicted histology was calculated using 
statistics.
RESULTS: Videos from 47 patients (including 13 before and after ACA to
generate 60 videos in total) were analysed. 24 were ND-BE and 23 D-BE.
Cases in which ACA was used, 7 had ND-BE and 6 D-BE.
Experts accuracy for detection of D-BE and ND-BE was 69% (6272%) and
68% (39-80%) respectively. The sensitivity and specificity for dysplasia detection
using our classification system were both 68%. ACA improved the sensitivity and
specificity to 78% and 71% respectively. Inter-observer agreement for dysplasia
prediction in all cases was moderate ( 0.42) but improved to good ( 0.70)
with ACA.
CONCLUSION: Using a simple non-magnification endoscopic classification
system combined with i-Scan and ACA, experts are able to accurately diagnose
D-BE in 78% of cases. ACA chromoendoscopy appears to improve the sensitiv-
ity and inter-observer agreement for dysplasia detection over HD-WLE alone.
These data are comparable to similar classification systems using zoom enhanced
imaging and ACA previously published and could be used by the general endos-
copists performing BE surveillance to target sampling and improve dysplasia
detection. The addition of zoom endoscopy to i-scan has the potential to increase
the accuracy further.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0491 IMPACT OF ABLATION VS. SURVEILLANCE ON QUALITY OF
LIFE AND ILLNESS PERCEPTION IN PATIENTS WITH BARRETTS
OESOPHAGUS CONTAINING LOW-GRADE DYSPLASIA: A MULTI-
CENTER RANDOMISED CONTROLLED TRIAL
W. Rosmolen1,*, N. Phoa1, P. Nieuwkerk2, B. Weusten1,3, R. Bisschops4,
E. Schoon5, M. Sprangers 2, J. Bergman1
1
Gastroenterology and Hepatology, 2Medical Psychology, Academic Medical
Center, Amsterdam, 3Gastroenterology and Hepatology, Antonius Hospital,
Nieuwegein, Netherlands, 4Gastroenterology and Hepatology, University Hospital
Leuven, Leuven, Belgium, 5Gastroenterology and Hepatology, Catharina Hospital,
Eindhoven, Netherlands
Contact E-mail Address: j.j.bergman@amc.nl
INTRODUCTION: Patients with a confirmed histological diagnosis of low-
grade dysplasia in Barretts oesophagus have an increased risk of neoplastic
progression to high-grade dysplasia and oesophageal adenocarcinoma. We
recently reported on a multi-center randomised controlled trial, in which endo-
scopic radiofrequency ablation reduced neoplastic progression from 26.5% to
1.5% compared to endoscopic surveillance. As part of this trial, we prospectively
investigated whether these approaches also lead to differences in quality of life
and illness perception.
AIMS & METHODS: Patients with a confirmed histological diagnosis of low-
grade dysplasia in Barretts oesophagus were randomly assigned to ablation or
endoscopic surveillance. Quality of life and illness perception were assessed at
baseline, 2, 8, 14, 26, and 38 months follow-up. QOL was measured with the SF-
36 (general), the EORTC-QLQ-C30 (cancer-specific), and the EORTC-QLQ-
OES18 (esophageal cancer-specific). Illness perception was measured with the
brief-illness perception questionnaire (8 dimensions (scale 0-10); overall score
(scale 0-80)). To compare ablation with surveillance for longitudinal data with
repeated measurements, a linear mixed model was used.
RESULTS: Quality of life and illness perception were investigated in 96 patients
(47 ablation, 49 surveillance) with a median follow-up of 36 months. There were
no significant differences between the groups for SF-36 (general) and the
EORTC-QLQ-C30 (cancer-specific). Apart from less reflux symptoms in the
ablation group, there was no difference between the groups for EORTC-QLQ-
OES18 (esophageal cancer-specific).
Compared to surveillance patients, ablation patients perceived their disease as
lasting for a significantly shorter period of time (6.2 out of 10 vs 8.1 out of 10;
p50.001), experienced fewer symptoms (2.4 out of 10 vs 3.3 out of 10 p50.001),
had fewer concerns about their illness (3.6 out of 10 vs 5.2 out of 10; p50.001),
and were less emotionally affected by their illness (2.8 out of 10 vs 3.3 out of 10;
p 0.012). As a result, ablation patients experienced their disease as less threa-
tening compared to surveillance patients (overall illness perception score 26.6 out
of 80 vs 34.2 out of 80; p50.001).
CONCLUSION: In this multi-center randomised controlled trial of ablation
versus surveillance for low grade dysplasia in Barretts oesphagus, ablation not
only reduced the neoplastic progression by 25% compared to surveillance, but
also led to fewer concerns and a less threatening view of the illness during a
median follow-up of 36 months. This further strengthens the indication for pro-
phylactic ablation of confirmed low grade dysplasie in Barretts oesophagus.
Disclosure of Interest: W. Rosmolen Financial support for research from: Study
was sponsored by Covidien, N. Phoa Financial support for research from: Study
was sponsored by Covidien, P. Nieuwkerk: None declared, B. Weusten Financial
support for research from: Study was sponsored by Covidien, R. Bisschops
Financial support for research from: Study was sponsored by Covidien, E.
Schoon Financial support for research from: Study was sponsored by
Covidien, M. Sprangers: None declared, J. Bergman Financial support for
research from: Study was sponsored by Covidien
P0493 CLINICAL SIGNIFICANCE OF MEAN PLATELET VOLUME,
PLATELETCRIT, PLATELET-LYMPHOCYTE RATIO AND
NEUTROPHIL-LYMPHOCYTE RATIO IN THE DIFFERENTIATION
OF PATIENTS WITH GASTRIC PRECANCEROUS LESIONS
C. Kalkan1,*, C. Ates2, O. Keskin1, M. Yakut1, F. Karakaya1, X. Deda1,
I. Soykan1
1
Gastroenterology, 2Biostatistics, ANKARA UNIVERSITY, Ankara, Turkey
Contact E-mail Address: isoykan@medicine.ankara.edu.tr
INTRODUCTION: Before gastric cancer becomes clinically noticeable, a pro-
longed precancerous process takes place which includes atrophic gastritis and
intestinal metaplasia (IM). There is no validated evidence available to support
surveillance of gastric intestinal metaplasia. Therefore, the aim of this study was
to investigate whether systemic inflammatory response markers such as mean
platelet volume, plateletcrit, platelet/lymphocyte ratio (PLR) and neutrophil/
lymphocyte ratio (NLR) in peripheral blood may have a role in the differentia-
tion of patients with gastric precancerous lesions.
AIMS & METHODS: 1139 patients with atrophic gastritis, intestinal metaplasia
and gastric cancer were evaluated by means of mean platelet volume, plateletcrit,
PLR and NLR. Patients were further divided into four groups according to
updated Sydney classification: Group 0: IM negative, Group I: IM 1, Group
II: IM2, Group III: IM3, also two groups consisting of Group IV: gastric
cancer and Group V: atrophic gastritis were included into the study in order to
maintain approppriate comparisons.
RESULTS: As for PLR values, there were significant differences between groups
indicating that PLR was significantly higher in group IV compared to groups 0,
I, II, III, and V (209.4216.6 vs 131.461.7, 13160.4, 132.669.7, 13176 and
141.953. p 0.001, 0.001, 0.001, 0.001 and 0.048 respectively). NLR was also
significantly higher in group IV compared to groups 0, I, II, III, and V
(3.815.33 vs 2.41.65, 2.351.65, 2.421.91, and 2.341.57, p 0.001).
United European Gastroenterology Journal 2(5S)
Plateletcrit was significantly higher in group IV compared to group II (0.250.08
vs. 0.210.05%, p 0.01). However, there were no statistically significant differ-
ence between groups by means of mean platelet volume. Receiver operating
characteristic curve (ROC) analysis suggested that optimum PLR cut-off point
according to Youden index was 137.6 (AUC: 0.718) with a sensitivity and spe-
cificity of 0.67 and 0.68 respectively, and optimum NLR ratio cut-off point was
2.2 (AUC: 0.702) with a sensitivity and specificity of 0.71 and 0.60 respectively.
CONCLUSION: No evidence from randomised studies exists to support surveil-
lance of gastric intestinal metaplasia. Although sensitivity and specificity are not
high enough, PLR and NLR may be used in clinical practice in order to decide
which patients should be scoped and biopsied during the follow-up of patients
with IM and atrophic gastritis.
REFERENCES
1. Bhatti I, Peacock O, Lloyd G, et al. Preoperative hematologic markers as
independent predictors of prognosis in resected pancreatic ductal adenocarci-
noma: neutrophil-lymphocyte versus platelet-lymphocyte ratio. Am J Surg
2010; 200: 197203.
2. Ozgehan G, Kahramanca S, Kaya IO, et al. Neutrophil-lymphocyte ratio as a
predictive factor for tumor staging in colorectal cancer. Turk J Med Sci 2014; 44:
365-368.
3. Kwon H-C, Kim SH, Oh SY, et al. Clinical significance of preoperative
neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable
colorectal cancer. Biomarkers 2012; 17: 216222.
Disclosure of Interest: None declared
P0494 IMPACT OF CARCINOMATOSIS AND ASCITES STATUS ON
LONG-TERM OUTCOMES OF PALLIATIVE TREATMENT FOR
PATIENTS WITH GASTRIC OUTLET OBSTRUCTION CAUSED BY
UNRESECTABLE GASTRIC CANCER: STENT PLACEMENT VERSUS
PALLIATIVE GASTROJEJUNOSTOMY
C.H. Park1,*, E.H. Kim1, H. Chung1, J.Y. An2, H.-I. Kim2, S.K. Shin1,
S.K. Lee1, J.-H. Cheong2, W.J. Hyung2, Y.C. Lee1, S.H. Noh2, C.B. Kim2,
J.C. Park1
1
Department of Internal Medicine, Yonsei University College of Medicine,
2
Department of Surgery, Yonsei University College of Medicine, Seoul, Korea,
Republic Of
Contact E-mail Address: chan100@yuhs.ac
INTRODUCTION: Self-expandable metal stent (SEMS) placement and pallia-
tive gastrojejunostomy (GJJ) are palliative treatment options for malignant gas-
tric outlet obstruction.
AIMS & METHODS: We aimed to compare clinical outcomes of palliative
treatments for gastric outlet obstruction caused by unresectable gastric cancer
to identify optimal treatment modalities according to carcinomatosis and ascites
status. We analyzed 217 and 39 patients who underwent SEMS placement and
palliative GJJ, respectively, for gastric outlet obstruction caused by unresectable
gastric cancer.
RESULTS: Treatment modality was not an independently associated factor of
clinical success (P 0.992). Treatment modality, however, affected re-obstruc-
tion after clinical success (P 0.001). In addition, carcinomatosis with ascites was
an independent associated factor of clinical success (P 0.006) and re-obstruc-
tion (P 0.045). In a subgroup of patients with good performance who had
neither carcinomatosis nor ascites, patency duration and overall survival dura-
tion did not differ between the two groups. In patients with good performance
who had carcinomatosis without ascites, patency duration was longer in the
palliative GJJ group than in the SEMS placement group. Overall survival, how-
ever, did not differ between the two groups. In a subgroup of patients with good
performance who had carcinomatosis with ascites, both patency duration and
overall survival were longer in the palliative GJJ group than in the SEMS place-
ment group.
CONCLUSION: Long-term clinical outcomes of the palliative treatment mod-
ality for gastric outlet obstruction caused by unresectable gastric cancer were
affected by carcinomatosis and ascites status, according to which a palliative
treatment modality can be chosen.
Disclosure of Interest: None declared
P0495 HIGH PREVALENCE OF GASTROINTESTINAL STROMAL
TUMOURS (GISTS): A CASE SERIES IN UK SECONDARY CARE
C. Shekhar1,*, N.C. Fisher1
1
Gastroenterology, Russells Hall Hospital, Dudley, United Kingdom
Contact E-mail Address: drcshekhar@gmail.com
INTRODUCTION: Gastrointestinal Stromal Tumours (GISTs) are mesenchy-
mal tumours, predominantly affecting the GI tract. Diagnosis and classification
require specialist review and there are few published data on the incidence of
GIST in the UK. Reported incidences elsewhere vary between 6.5/ million/ year
in Norway and 14.5/ million/year in Sweden1,2. We have analysed our caseload of
GISTs in a UK secondary care setting with a population of approx 350,000, in
order to estimate incidence and review outcomes.
AIMS & METHODS: A retrospective case note reviews of all patients with
GIST, as identified from upper GI cancer multidisciplinary team meeting
(MDT) minutes, from 2008 to 2013 inclusive (6 years). The diagnosis of GIST
was considered valid, if characteristic imaging and/ or pathological features were
verified by CT scanning, endoscopic ultrasound (EUS) needle aspiration/ biopsy
and/ or surgical resection.
RESULTS: We identified 34 cases with a final diagnosis of GIST. The observed
incidence of presentation to hospital varied year on year, and estimated annual-
ised incidence was calculated at 16.2 / million/year. The age range was 28-91
years (M 15, F19). Nineteen cases (59%) presented with signs or symptoms of GI
A269
blood loss; five (15%) with other GI symptoms and remaining cases were found
incidentally. The size of GIST at presentation ranged from 1cm to 20 cm in
diameter. One case had metastasised at the time of diagnosis. EUS was used
for diagnosis and staging in 15 cases; 13 had fine needle aspiration, of which
10/13 were diagnostic. 26/34((76%) cases underwent resection surgery. 6 cases
were treated with Imatinib (Glivec). Case follow up range from 3 months to 6
years. Two patients died, one patient presented with metastatic disease other was
managed with palliative approach due to advance age and co-morbidities.
CONCLUSION: Our review suggests a higher than expected incidence of GISTs
in this population compared with other published series1,2. Most cases present
with GI blood loss and surgery is curative in most cases with good prognosis. The
incidence of GISTs in the UK is deserving of further study.
REFERENCES
1. Cancer Eidemiol 2011; 35: 515-520.
2. Cancer 2005; 103: 821-829.
Disclosure of Interest: None declared
P0496 ENDOSCOPIC CHARACTERISTICS PREDICTING
LYMPHOVASCULAR INVASION OF EARLY GASTRIC CANCER: A
RETROSPECTIVE COHORT STUDY USING PROPENSITY-SCORE
MATCHING
C.N. Shim1,*, P.-S. Kim1, H. Chung2, J.C. Park2, S.K. Shin2, S.K. Lee2,
Y.C. Lee2
1
Department of Internal Medicine, International St. Marys Hospital, Incheon,
2
Department of Internal Medicine, Institute of Gastroenterology, Yonsei University
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: kscn99@gmail.com
INTRODUCTION: The most important factor concerning endoscopic resection
(ER) for early gastric cancer (EGC) is the prediction of regional lymph node
(LN) metastasis before treatment. Of the main risk factors associated with LN
metastasis, lymphovascular invasion (LVI) of tumor is the strongest predictor for
LN metastasis in EGC. However, risk factors of LVI have not been securely
established. The purpose of this study was to evaluate endoscopic characteristics
predictive of LVI of EGC treated by ER.
AIMS & METHODS: A total of 1214 consecutive patients with 1240 EGCs
underwent ER between January 2007 to June 2013. The lesions studied were
grouped into groups of either no LVI group (n 1166) or LVI group (n 74),
according to the presence of LVI in ER specimen. Propensity-score matching for
adjustment of confounding variables including lesion size and submucosal inva-
sion yielded 148 matched patients. Endoscopic characteristics including macro-
scopic type, erythema, whitish discolorization, ulcer, marginal delineation, and
folds change were investigated among the matched cohort.
RESULTS: Lymphovascular tumor invasion was diagnosed in 6.0% of enrolled
lesions. Of clinicopathologic characteristics in the overall cohort, larger size
(P50.001) and submucosal invasion determined by endoscopic ultrasound
(P50.001) and histology (P50.001) were significantly higher in the LVI
group. In the 148 matched cohort after propensity-score matching, endoscopic
elevated macroscopic type (P 0.020) and whitish mucosal discolorization
(P 0.022) were significant endoscopic characteristics related to LVI of EGC,
while no significant difference of age, sex, lesion size, location of tumor, submu-
cosal invasion, and histology were detected between the matched two groups.
CONCLUSION: Endoscopic elevated macroscopic type and whitish mucosal
discolorization in EGC carry a significant risk for LVI of tumor, which results
in non-curative ER for EGC. Further prospective studies of preoperative predic-
tion for LVI are warranted.
Disclosure of Interest: None declared
P0497 MAGNIFYING ENDOSCOPY WITH CRYSTAL VIOLET
STAINING HAS NO ADDITIONAL DIAGNOSTIC VALUE
COMPARED WITH NARROW-BAND IMAGING IN THE DIAGNOSIS
OF SPORADIC NONAMPULLARY DUODENAL ADENOMA/
CARCINOMA
D. Maruoka1,2,*, M. Arai2, K. Okimoto2, S. Minemura2, T. Matsumura2,
T. Nakagawa2, T. Katsuno2, O. Yokosuka2
1
Clinical Research Center, Chiba University Hospital, 2Department of
Gastroenterology and Nephrology, Graduate School of Medicine, Chiba University,
Chiba City, Japan
Contact E-mail Address: d-maruoka@chiba-u.jp
INTRODUCTION: Sporadic nonampullary duodenal adenomas rarely occur
but are precancerous lesions [1]. It recently became clear that high-grade dyspla-
sia (HGD) shows a high risk of progression to adenocarcinoma [2]. Therefore,
HGD and intramucosal carcinoma (HGD/IMC) are indications for endoscopic
resection. We previously reported that magnifying endoscopy with narrow-band
imaging (NBI-ME) was extremely helpful in the differential diagnosis of sporadic
nonampullary duodenal low-grade dysplasia (LGD) or HGD/IMC. Magnifying
endoscopy with crystal violet staining (CV-ME) is useful for diagnosing color-
ectal adenomatous tumors [3], but no report has analyzed the utility of CV-ME
in diagnosing duodenal tumors.
AIMS & METHODS: In this study, we analyzed whether CV-ME has additional
diagnostic value compared with NBI-ME in the diagnosis of sporadic nonam-
pullary duodenal adenoma/carcinoma. The final diagnosis was determined by
histopathological analysis of endoscopically resected specimens. Nineteen
patients with sporadic nonampullary duodenal adenoma or adenocarcinoma
without polyposis syndrome who were treated by endoscopic resection between
November 2012 and October 2013 were prospectively evaluated. Twenty lesions
were diagnosed using CV-ME after NBI-ME and then resected. In NBI-ME, we
evaluated the presence of the following: (a) irregular villi of various sizes, (b)
A270
small villi area (alternatively tubule-like structures), (c) intravillous irregular
microvessels, and (d) network-like microvessels. If any one of these findings
was observed, we diagnosed HGD/IMC. On the other hand, we diagnosed the
lesion that had none of these findings as LGD. In CV-ME, we made a final
diagnosis by adding the findings of (a) and (b) using CV-ME in addition to
NBI-ME.
RESULTS: Eight of the 20 lesions were LGD, while 12 were HGD/IMC. The
following values were obtained for NBI-ME and integrated diagnosis, respec-
tively: sensitivity, 1.0 and 1.0; specificity, 0.375 and 0.500; positive predictive
value, 0.706 and 0.750; negative predictive value, 1.0 and 1.0; and accuracy,
0.750 and 0.800. No significant differences were noted between groups (chi-
squared test).
CONCLUSION: CV-ME does not have additional diagnostic value compared
with NBI-ME in the diagnosis of sporadic nonampullary duodenal adenoma/
carcinoma.
REFERENCES
1. Shepherd NA, et al. WHO classification of tumours of the digestive system.
Lyon: IARC Press, 2010, pp. 98-101.
2. Okada K, et al. Am J Gastroenterol 2011; 106: 357-364.
3. Kobayashi Y, et al. Int J Colorectal Dis 2011; 26: 1531-1540.
Disclosure of Interest: None declared
P0498 A ROLE OF PALLIATIVE SURGERY IN STAGE IV GASTRIC
CANCER
D. Yamaguchi1,*, S. Fujii1, T. Kusaka1
1
Department of Gastroenterology, Kyoto Katsura Hospital, Kyoto, Japan
Contact E-mail Address: tetsu_kumohayuni64000@msn.com
INTRODUCTION: Standard treatment for patients with Stage IV gastric cancer
is systemic chemotherapy. Some patients receive palliative surgery before che-
motherapy to relieve gastric obstruction or uncontrollable bleeding. However,
few data is available about the impact of palliative surgery on following che-
motherapy in patients with Stage IV gastric cancer.
AIMS & METHODS: We aimed to compare the clinical outcomes between
patients with advanced gastric cancer who initially received surgical resection
for their primary lesion and those who initiated palliative chemotherapy without
surgery. Data of consecutive 123 patients with pathologically confirmed
advanced gastric cancer who received palliative chemotherapy between January
2005 and March 2014 were reviewed. A total of 57 patients received palliative
chemotherapy following surgical resection for their primary lesion (Group A)
and 50 patients initiated palliative chemotherapy without surgery (Group B).
Overall survival was defined as the period between the date of surgery or che-
motherapy initiation and the date of death for any reason or the last follow-up
visit.
RESULTS: Both groups were similar in age and gender. Median survival time
was 13.2 months (95% CI 7.2-19.2) for Group A and 10.2 months (95% CI 8.4-
12.1) for Group B. In group A, 10 patients could not proceed to palliative
chemotherapy because of postoperative complications (n 3) and/or deterio-
rated general conditions (n 7). In group B, 15 patients (37.5%) developed
adverse events related to residual primary lesion: gastric hemorrhage (n 6),
gastric stenosis (n 6), gastric perforation (n 3). Among these 15 patients,
only 2 patients who developed gastric perforation could resume chemotherapy.
Duration of chemotherapy did not differ between two groups.
CONCLUSION: Our data suggested that surgical resection of primary lesion
before initiating palliative chemotherapy could reduce the risk of developing
severe adverse events related to residual primary lesion during chemotherapy
without hampering its efficacy.
Disclosure of Interest: None declared
P0499 CLINICAL APPLICABILITY OF PERIOPERATIVE
CHEMOTHERAPY IN RESECTABLE GASTRIC CANCER
RESULTS FROM A PORTUGUESE CANCER INSTITUTE
D. Trabulo1,2,*, J. Moleiro2, A. Ferreira3, A. Loureiro4, C. Cardoso5,
R. Dion sio6, A. Pimenta7, S. Mao-de-Ferro2, M. Serrano2, S. Ferreira2, show a tight correlation between the histologic grade, the level of the tumor
J. Freire5, A. Luis5, R. Casaca8, A. Bettencourt8, D. Pereira2
1
Gastroenterology, Hospital de Sao Bernardo - Centro Hospitalar de Setubal,
Setubal, 2Gastroenterology, Instituto Portugues de Oncologia de Lisboa Francisco
Gentil, EPE, Lisboa, 3Gastroenterology, Centro Hospitalar do Algarve, Portimao,
4
Radiology, 5Oncology, Instituto Portugues de Oncologia de Lisboa Francisco
Gentil, EPE, Lisboa, 6Oncology, Centro Hospitalar do Algarve, Faro,
7
Radiotherapy, 8Surgery, Instituto Portugues de Oncologia de Lisboa Francisco
Gentil, EPE, Lisboa, Portugal
Contact E-mail Address: danieltrabulo@yahoo.com
INTRODUCTION: The benefit of perioperative chemotherapy (POC) in
patients with resectable gastric cancer (GC) and esophagogastric junction
cancer (EGJC) was demonstrated in MAGIC trial (2006), which was associated
to high morbidity.
AIMS & METHODS: Aims: To evaluate the clinical applicability of periopera-
tive chemotherapy (POC) in patients with resectable gastric and esophagogastric
junction (EGJ) cancer treated in a Portuguese cancer institute, as stated in the
MAGIC Trial. Methods: Selection of patients with GC and EGJC referred to our
institution from 2009 to 2013. Patients were staged with thoraco-abdomino-
pelvic CT, endoscopic ultrassonography (if T53, N0 and M0) and laparoscopy
(if T42 or N and M0). POC was proposed to those staged as T42 or N and
M0 (3 pre and 3 postoperative cycles of epirrubicine, cisplatin and 5-fluorouracil;
surgery with D2 lymph node dissection). Non-surgical candidates or stage IV
patients received palliative care. Those staged as T1/2 and N0, age 4 80 years or
with an obstructive or bleeding tumor had direct surgery. Evaluation of clinical
United European Gastroenterology Journal 2(5S)
characteristics, adhesion, complications, survival and recurrence. Statistical ana-
lysis performed with chi2, t-Student tests, Kaplan-Meier.
RESULTS: We evaluated a total of 418 patients: 315 with GC and 103 with
EGJC; 57% males; mean age 65.4  21-93 years. POC proposed to 150 patients.
Preoperative chemotherapy in 143 patients; not performed due to disease progres-
sion-5; obstructive symptoms-1; associated diseases-1; major morbidity-7%,
mortality-3%. Surgery in 134 patients (94%); not performed due to death
during chemotherapy-4, toxicity-1, disease progression-1, refusal-2. R0 surgery
was performed in 102 patients (76.1%), R1 surgery in 5 patients and R2 surgery/
unressecable in 28 patients; major morbidity-16%, mortality-3%. Postoperative
chemotherapy in 74 patients (72.5%); not performed due to previous chemother-
apy/surgery complications in 26 patients and disease progression in 2 patients;
major morbidity-6%; mortality-0%. Median time from chemotherapy to surgery:
50 days; from surgery to chemotherapy: 35.5 days. Surgical complications were
identical in those that had direct versus perioperative chemotherapy resections.
Overall, 69 patients (47%) did not complete the proposed protocol. Survival at 36
months: a) general 37.4%; b) proposed to POC 51.2%; c) treated with curative
intention-66.5%, d) completed the proposed protocol-70.7%.
CONCLUSION: In our series, one third of all patients were eligible for POC.
The rates of treatment conclusion, R0 surgery and postoperative chemotherapy
were higher in our series, compared with those described in the MAGIC study.
POC is feasible and applicable in clinical practice, but similar to that described in
the MAGIC study, only half of patients completed the proposed protocol, either
due to complications of treatment, either due to disease progression.
Disclosure of Interest: None declared
P0500 THE PROGNOSTIC SIGNIFICANCE OF TUMOR
ANGIOGENESIS IN GASTRIC CANCER
D. Lazar1,*, S. Taban2, M. Cornianu2, I. Sporea1, I. Ratiu1, A. Goldis1
1
Gastroenterology, 2Pathology, UNIVERSITY OF MEDICINE AND
PHARMACY TIMISOARA, Timisoara, Romania
Contact E-mail Address: lazar_daniela@yahoo.com
INTRODUCTION: Angiogenesis, the process by which new blood vessels are
formed, plays an essential role in the survival of the malignant cells, in the local
expansion and tumor invasion, as well as in the appearance of distant metastases.
The intratumoral microvessel density (MVD), which can be evaluated immuno-
histochemically, seems to have an influence on the prognosis of various malig-
nant tumors. The forming of new intratumoral microvessels depends on the
elaboration of the angiogenic growth factors by the malignant cells (such as
vascular endothelial growth factor VEGF). These factors expression is corre-
lated with the tumor angiogenesis, neoplasia progression and severe prognosis.
Among the known angiogenic factors, VEGF plays a central role in angiogenesis
process control in cancerous disease.
AIMS & METHODS: We evaluated the relation between MVD, VEGF expres-
sion, the clinicopathologic factors and the survival in patients with gastric cancer.
A prospective study has been carried out, regarding the evolution and aggres-
siveness of gastric cancer, with a duration of five years, 61 patients that under-
went a surgery for gastric cancer being included in the study. The
immunohistochemical reactions for CD34 and VEGF were performed for all
gastric cancers cases included in the study group.
RESULTS: MVD has shown in the gastric carcinomas an average value signifi-
cantly higher in comparison to the normal mucosa (38.7 vs. 12.5, p50.001). In
the intestinal type we have noticed a much lower average MVD than the average
MVD in the diffuse type of gastric carcinomas (36.8 vs. 41.6) (p 0.024).
Anaplastic carcinoma and the signet ring cell carcinoma are differentiating as
histological forms associated to an intense neoangiogenesis activity. The neoan-
giogenesis activity is correlated with the histologic grade, the lymphovascular
invasion, the level of extend, the lymph node metastasizing, the distant metasta-
sizing and the TNM stage. Positive immunoreactions for VEGF are significantly
more frequent in gastric carcinomas, in comparison to the normal gastric mucosa
(65.6% vs. 6.5%, p50.001). The immunoreactions to the VEGF protein were
positive in 71.1% of the intestinal carcinomas, significantly more frequent in
comparison to the diffuse type carcinomas (52.9%) (p 0.018). Our results
invasion and the VEGF expression. Our results prove the major correlation
between the VEGF expression and the 5 year survival rate of the patients with
gastric cancer, the survival rate for the carcinomas with VEGF / being
significantly lower than for the VEGF negative ones (12.5% vs. 23,8%)
(p 0.027).
CONCLUSION: Our study proves a tight correlation between the VEGF expres-
sion and the MVD (p 0.039), these factors playing an important role in the
tumoral biologic behaviour, in the progression and the prognosis.
Disclosure of Interest: None declared
P0501 GASTRIC CANCER IN PATIENTS WITH TYPE I GASTRIC
CARCINOIDS
G. Esposito1,*, E. Lahner1, E. Pilozzi2, G. Galli1, V.D. Corleto3, E. Di Giulio3,
B. Annibale1
1
Digestive and Liver Disease, 2Pathology, 3Digestive Endoscopy, Sapienza
University, Rome, Italy
Contact E-mail Address: gle.esposito@gmail.com
INTRODUCTION: Type I gastric carcinoids (T1-GCs) are rare tumors which
may arise in pts with atrophic gastritis (AG). These tumors are well-differentiated
with low proliferative index and a generally benign behavior, and constitute up to
80% of all gastric carcinoids. A major pathogenetic factor for T1-GCs is hyper-
gastrinemia due to AG. Gastrin acts as a growth type factor for enterochromaf-
fin-like cells, which in AG are chronically induced to proliferate, through a
United European Gastroenterology Journal 2(5S)
Table to abstract P0501.
Diagnosis of gastric
PatientGenderAge, yearsType of lesion cancer Locali-zation
#1 F 40 Low-grade dysplasia Gastroscopy according Antrum
(intramucosal, endosco- to follow-up Antrum
pically normal mucosa, protocol
detected on random
biopsies)
Diffuse gastric cancer
(signet-ring cells) in situ
(endoscopically normal
mucosa, detected on
random biopsies)
#2 M 78 Intestinal-type adenocarci- New onset of anemia Angulus
noma (gastric ulcer, 3
cm)
#3 F 58 Intestinal-type adenocarci- New onset of epigastric Antrum
noma (gastric ulcer, 2 pain
cm)
#4 F 49 Intestinal-type adenocarci- Gastroscopy according Antrum
noma in situ (endosco- to follow-up
pically normal mucosa, protocol
detected on random
biopsies)
multistep process passing from hyperplasia to dysplasia and then to carcinoid.
Epidemiological data suggest that AG is associated not only with T1-GCs, but
also with intestinal-type gastric cancer. The occurrence of gastric cancer in AG
pts with type I gastric carcinoids has not yet been described.
AIMS & METHODS: The aim of this study was to describe in a retrospective
case-series the occurrence of gastric cancer in AG pts with type I gastric carcinoid
in a single tertiary referral center. Between 1994 and 2012, 17 new cases of T1-
GCs were diagnosed amongst a cohort of AG pts. The clinical charts of these 17
T1-GCs pts were retrospectively evaluated for the occurrence of gastric cancer at
follow-up (median 4.2 years, range 0.5-13). AG diagnosis was based on the
presence of hypergastrinaemia and atrophy of the body mucosa. Diagnosis of
T1-GCs was performed when enterochromaffin-like cells proliferation was
4500m (WHO 2010 criteria).
RESULTS: In 4/17(23.5%) T1-GCs pts (3F, age 40-78yrs), gastric cancer
occurred (median follow-up 5.9 yrs, range 5.1-13; Table1). Three cases were
intestinal-type adenocarcinomas and one a signet-ring cells diffuse gastric
cancer, localized in 3 cases in the antrum. In two pts it was detected on
random biopsies during follow-up-gastroscopy, in the other two gastroscopy
was performed due to new symptoms. All pts with gastric cancer had associated
autoimmune features (pernicious anemia, autoimmune thyroid disease and a
spared antrum), compared to 77%, 46% and 54% of those without gastric
cancer.
Table1. Pts with type I gastric carcinoid who developed an epithelial neoplastic
lesion
CONCLUSION: This case-series shows that in pts with T1-GCs gastric cancer
may frequently occur at long-term follow-up. Thus, these pts should be moni-
tored by a long-term surveillance programme, including an accurate bioptic
sampling of antral mucosa.
Disclosure of Interest: None declared
P0502 THERAPEUTIC OUTCOMES OF ENDOSCOPIC RESECTION IN
FOREGUT NEUROENDOCRINE TUMORS
H.J. Jung1,*, Y.S. Myung1, J.P. Han1, S.J. Hong1, B.M. Ko1, M.S. Lee1
1
Department of Internal Medicine, SoonChunHyang University School of
Medicine, Bucheon, Digestive Disease Centerand Research Institute, Bucheon,
Korea, Republic Of
Contact E-mail Address: 95970@schmc.ac.kr
INTRODUCTION: Endoscopic resection (ER) may benefit to treat the low
grade foregut neuroendocrine tumors (NETs). This study aimed to evaluate
therapeutic outcomes of ER for foregut NETs.
AIMS & METHODS: From January 2003 to February 2013, a total of 40
patients were confirmed histologically as foregut NETs from the ER
(stomach 16, duodenum 13) and surgical resection (SR, stomach 9,
duodenum 2). The clinicopathological characteristics and therapeutic outcomes
were evaluated retrospectively.
RESULTS: Of 29 patients underwent ER (EMR 23, ESD 6), 28 were diag-
nosed as NET-G1 and 1 as NEC. Of 11 patients underwent SR, 9 were diagnosed
as NET-G1 and 2 as NEC. Tumor size of ER group was significantly smaller
than SR group (7.4 mm vs. 18.2 mm, P50.01). Depth of invasion was limited to
mucosa and submucosa in 28 NETs of ER group, However, all NETs of SR
group invaded the submucosa or proper muscle. Complete resections were
achieved in 22 patients (75.9%) of ER group and achieved in 11 patients
(100%) of SR group. In ER group, immediate procedure-related complications
occurred in 2 cases (bleeding 1, perforation 1), and they were successfully
treated by conservative treatment. There was no complication in SR group.
There was no recurrence in 7 NETs reported as incomplete resection in
margin, but all of 3 NEC patients (ER 1, SR 2) had recurrence during
follow up period. They were treated by additional chemotherapy and had no
A271
Time of occurrence
after diagnosis of type
IGC, months (years) Outcome
17 (1.4) Gastric surgery alive
156 (13)
80 (6.7) No surgery due to comorbidities dead
63 (5.2) Gastric surgery dead (complications of surgery)
61 (5.1) Gastric surgery alive
more disease progression. One metachronous recurrence occurred after complete
ER, and it was treated by ER.
CONCLUSION: ER can be used as an effective method as treatment for a small
sized and low grade foregut NETs. However, additional treatment should be
considered in the patients who diagnosed as NEC from histological result after
endoscopic treatment because it has high risk of recurrence rate.
Disclosure of Interest: None declared
P0503 SELF-EXPANDABLE METAL STENTS VERSUS SURGICAL
GASTROENTEROSTOMY FOR PALLIATION OF MALIGNANT
DUODENAL OBSTRUCTION
H. Saito1,*, M. Ito1, M. Yoshioka1, S. Saito1, F. Masakuni1, S. Ishiyama1,
A. Fujiwara1, J. Nasu1, S. Junji1
1
Internal medicine, Okayama Saiseikai General Hospital, OKAYAMA, Japan
Contact E-mail Address: itoh777-lj@infoseek.jp
INTRODUCTION: Surgical gastroenterostomy used to be the first line treat-
ment for palliation of malignant gastroduodenal obstruction. Recently endo-
scopic placement of self-expandable metal stents (SEMS) has become a
broadly accepted treatment for patients with advanced malignant gastroduode-
nal obstruction as a minimally invasive therapy.
AIMS & METHODS: We attempted to elucidate the current status of endo-
scopic SEMS for palliation of malignant duodenal obstruction in comparison
with surgical gastroenterostomy. A total of 39 consecutive duodenal tumor
obstruction patients who were treated at Okayama Saiseikai General Hospital
from January 2006 to Dectmber 2011 were reviewed (23 pancreatic cancer, 5
gallbladder cancer, 4 duodenal cancer, 2 renal pelvis cancer, 2 colon cancer, 1
gastric cancer, 1 liver cancer, 1 occult primary cancer). 25 patients were treated
by SEMS and 14 patients by surgical gastroenterostomy. We compared proce-
dure time, time from the procedure to starting oral intake, time from the proce-
dure to starting chemotherapy, technical success rate, complication, hospital
stay, and mortality.
RESULTS: In each and every patients, treatment (eather endoscopic stent
implantation or surgical gastroenterostomy) was clinically successful.
Endoscopic stenting was found to be associated with a shorter time of procedure
(mean 31.7 vs. 146 min, P50.01), a shorter time from the procedure to starting
oral intake (mean 2.96 vs. 6.64 days, P 5 0.01) and a shorter hospital stay (mean
15.3 vs. 25.6 days, P 5 0.02) than the surgical gastroenterostomy. There was no
significant difference between the two groups in the analysis of mortality (mean
91.5 vs. 158.8 days, p 0.107) and time from the procedure to starting che-
motherapy (mean 8.6 vs. 13 days, p 0.177). A single case of complication was
seen in each group, one case of intestinal perforation in SEMS group (4%) and
one case of intra-abdominal abscess in surgical gastroenterostomy group (7%).
Both cases were able to recover by conservative treatment.
CONCLUSION: Endoscopic SEMS insertion was superior against surgical gas-
troenterostomy in terms of procedure time, start of oral intake period and the
length of hospital stay. SEMS in duodenal obstruction is a feasible alternative of
surgical gastroenterostomy for the palliation of inoperable malignant duodenal
obstruction. With a high clinical success and low complication rate, endoscopic
implantation of SEMS seems to be a safe and tolerable procedure for palliative
treatment of malignant duodenal obstruction.
Disclosure of Interest: None declared
A272
P0504 CLINICAL OUTCOMES OF SALVAGE ENDOSCOPIC THERAPY
AFTER CHEMORADIOTHERAPY FOR ESOPHAGEAL CANCER
H. Osumi1,*, Y. Toshiyuki1, K. Chin1, A. Ishiyama1, T. Tsuchida1, J. Fujisaki1,
M. Igarashi1
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: hiroki.osumi@jfcr.or.jp
INTRODUCTION: Chemoradiotherapy (CRT) for esophageal cancer, especially
at stage I, has comparable survival rates to surgery, with a median survival rate
of 5 years. Therefore, in some cases, it is chosen as a first-line treatment for stage
I, II, and III esophageal cancer. However, about 30% of patients who are admi-
nistered chemoradiotherapy experience a local recurrence after complete
response, so it is important to consider salvage therapy to treat such recurrences.
Commonly administered salvage therapies include surgery, endoscopic therapy,
and argon plasma coagulation (APC).
AIMS & METHODS: The aim of this study is to illuminate the results of
administering salvage endoscopic therapy in cases of recurrent esophageal
cancer that had previously been treated with chemoradiotherapy. 161 patients
with UICCI-III esophageal cancer who received chemoradiotherapy at the
Cancer Institute Hospital between 2005 and 2013 without previously being trea-
ted were retrospectively studied. 11 of these patients had local recurrences after
receiving chemoradiotherapy, and received salvage endoscopic therapy as treat-
ment for the recurrence. Their overall survival (OS) and time of recurrence after
CRT and salvage endoscopic therapy were studied. Kaplan-Meier analysis and
Cox proportional hazard modeling were used for statistical analysis.
RESULTS: The median observation period for the 11 patients studied was 75.2
months (39.1-107.6). The clinical stages of esophageal cancer of the 11 patients
studied were as follows (stage I/II/III: 6/1/4). The salvage endoscopic therapies
administered were as follows (EMR/ESD/APC: 7/3/1). The clinical responses of
the patients to chemoradiotherapy were as follows (CR/PR: 8/3). 5 patients
experienced local recurrences again after salvage endoscopic therapy (EMR/
ESD/APC: 4/0/1). Disease-free survival in patients who received salvage EMR
therapy was a median 24 months (8.9-50.1). Patients who were administered
salvage APC therapy experienced relapses twice, and recurrence-free survival
among those patients was a median 9 months (3.4-14.6). None of the patients
who were administered ESD experienced a relapse, and disease-free survival
among those patients was a median 25.3 months (13.3-32). The complications
usually associated with endoscopic therapies were also not observed. There was
no significant difference between salvage therapies in terms of overall survival
(EMR 74.8 months (46.1-100.1), ESD 78.9months (39.1-107.6), APC 66.5
months).
CONCLUSION: ESD can be considered to be a better salvage therapy than the
other endoscopic therapies as the local recurrence rate was lower than that for
either EMR or APC. Even for less serious cases of esophageal cancer, ESD is a
preferable choice as a salvage endoscopic therapy after chemoradiotherapy. It
should be noted, however, that there was no difference in the long-term prog-
noses among the different salvage therapies, even after recurrence. In some cases,
ESD may not be ideal as a treatment, such as in patients who have other pre-
existing diseases that make long-term treatment difficult, or in cases of esopha-
geal stenosis, which renders it difficult to use ESD scopes. For such cases, other
salvage therapies can be considered, including surgery and photo-dynamic ther-
apy (PDT).
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
H. PYLORI I POSTER EXHIBITION HALL XL_____________________
P0505 LOW-DOSE ASPIRIN-ASSOCIATED GASTRIC AND DUODENAL
ULCERS IN JAPANESE PATIENTS WITH NO PREVIOUS HISTORY
OF PEPTIC ULCERATION
A. Tanabe1,*, Y. Ito1, Y. Yamaguchi1, N. Okaniwa1, H. Noda1, K. Yanamoto1,
Y. Tamura1, Y. Kondo1, R. Masui1, S. Izawa1, Y. Hijikata1, K. Tokudome1,
N. Kawamura1, A. Iida1, N. Ogasawara1, Y. Funaki1, M. Sasaki1, K. Kasugai1
1 P0507 HELICOBACTER PYLORI INFECTION AMONGST
Aichi medical university, Nagakute, Japan
INTRODUCTION: Long-term administration of low-dose aspirin (LDA) is
associated with a greater risk of adverse events, including gastroduodenal
ulcers and their potentially fatal complications (e.g., gastrointestinal bleeding
and perforation). The identified risk factors for ulcer bleeding with aspirin use
are history of ulcer bleeding; aspirin dose; advanced age (470 years); concomi-
tant use of NSAIDs or anti-coagulants; use of dual anti-platelet therapy;
Helicobacter pylori infection; and history of alcohol abuse, diabetes, or renal
failure. Proton pump inhibitors (PPIs) are used to decrease LDA-associated
gastroduodenal mucosal and NSAID-induced injuries. In Japan, since 2011,
treatment with half-dose PPI (lansoprazole 15 mg/day) has been permitted as a
medical service under health insurance for the prevention of NSAID- or LDA-
induced peptic ulcers in patients in the high-risk group who have a history of
peptic ulcers. However, there are few reports in which the use of PPIs reduced the
risk of LDA-associated peptic ulcers in patients without pre-existing peptic ulcers
AIMS & METHODS: AIM: To assess the risk factors and the efficacy of med-
ications for development of peptic ulcer disease in Japanese with no prior history
of peptic ulceration.
METHODOLOGY: We conducted a matched background study using esopha-
gogastroduodenoscopy (EGD) record collected from January 2010 through
December 2010. Consecutive 219 outpatients receiving LDA (75 mg) who had
no peptic ulcer history were matched to 1 control by age and sex who were not
receiving LDA and had no peptic ulcer history. Clinical parameters, concomitant
drugs, the reason for endoscopy, and endoscopic findings were analyzed.
United European Gastroenterology Journal 2(5S)
RESULTS: Of 219 patients receiving LDA, 20 (20%) was diagnosed endoscopi-
cally with peptic ulceration, which was significantly higher than 7 (3.2%) of 219
patients not receiving LDA (OR, 3.0; 95% CI, 1.26 7.35; P 0.016). From
multiple logistic regression analysis, LDA smoking habit, NSAID, and PPI
were detected as increased and decreased risk factors for peptic ulcer, respectively
(OR, 9.6; 95% CI, 2.27 38.63; P 0.002), (OR, 3.9; 95% CI, 1.03 14.72;
P 0.045), (OR, 7.4; 95% CI, 1.73 31.67; P 0.007), (OR, 0.11; 95% CI,
0.02 0.45; P 0.002). Age, current alcohol consumption, H2-receptor antago-
nists, and abdominal symptom were not significantly associated with the presence
of peptic ulcers.
CONCLUSION: Long-term administration of LDA increases the risk of peptic
ulcer even in the patients who had no peptic ulcer history, and PPIs reduces the
risk of developing gastric or duodenal ulcers. However this risk is significantly
increased in patients with concomitant smoking habit and NSAID. These results
may help identify patients who require more intensive prophylaxis against
aspirin-induced ulcerations.
Disclosure of Interest: None declared
P0506 CORRELATION BETWEEN THE PREVALENCE OF GALLSTONE
AND HELICOBACTER PYLORI INFECTION
B.J. Kim1,*, J.G. KIM1, J.-H. Jung1
1
Internal Medicine (Gastroenterology), Chung-Ang University College of
Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: gikbj@cau.ac.kr
INTRODUCTION: Several studies have reported that the presence of
Helicobacter DNA in human bile sample, although its pathological role is not
clear. Moreover, little is known about the association between Helicobacter pylori
(H. pylori) infection and gallstone.
AIMS & METHODS: The aim of this study was to determine whether H. pylori
infection is associated with an increased risk of gallstone in an asymptomatic
population.
We examined 2782 subjects (1635 men and 1147 women) who underwent both
upper endoscopy with CLO test and abdominal ultrasound at the Health
Examination Center at Chung-Ang University Yong-san Hospital in Korea
from January 2007 to December 2009. We compared the prevalence of gallstone
on ultrasound and endoscopic findings such as reflux esophagitis, gastric diseases
in the H. pylori infected subjects with that of the H. pylori uninfected subjects.
RESULTS: The overall prevalence of H. pylori infection in our study was 45.6%
(1271/2782). When the subjects were divided into two groups according to the H.
pylori infection status, there was no significant differences of the baseline char-
acteristics between the two groups. The prevalence of gallstone in the H. pylori
infected subjects was higher than that of the H. pylori uninfected subjects (5.4%
vs 3.2%, P 0.032). The prevalence of peptic ulcer in the H. pylori infected
subjects was higher than that of the H. pylori uninfected subjects (8.2% vs
3.4%, P50.001). The prevalence of reflux esophagitis in the H. pylori infected
subjects was lower than that of the H. pylori uninfected subjects (6.2% vs 14.0%,
P 0.012).
CONCLUSION: These findings suggest that H. pylori infection is associated
with an increased risk of gallstone in asymptomatic population.
REFERENCES
1: Attaallah W, Yener N, Ugurlu MU, et al. Gallstones and concomitant gastric
Helicobacter pylori infection. Gastroenterol Res Pract 2013; 2013: 643109.
2: Takahashi Y, Yamamichi N, Shimamoto T, et al. Helicobacter pylori infection
is positively associated with gallstones: a large-scale cross-sectional study in
Japan. J Gastroenterol 2013 Jun 5.
3: Abro AH, Haider IZ and Ahmad S. Helicobacter pylori infection in patients
with calcular cholecystitis: a hospital based study. J Ayub Med Coll Abbottabad
2011; 23: 30-33.
4: Lee JW, Lee DH, Lee JI, et al. Identification of Helicobacter pylori in gall-
stone, bile, and other hepatobiliary tissues of patients with cholecystitis. Gut
Liver 2010; 4: 60-67.
Disclosure of Interest: None declared
ARAB
ISRAELI WOMEN WITH HYPEREMESIS GRAVIDARUM- A
PROSPECTIVE, CONTROLLED STUDY
D. Boltin1,*, S. Abu Elheiga2, T.T. Perez1, A. Sharony2, H. Shamly2, Y. Niv1,
R. Dickman1
1
Gastroenterology, Rabin Medical Center, Petah Tikva, 2Obstetrics and
Gynaecology, St. Vincent French Hospital, Nazareth, Israel
Contact E-mail Address: dboltin@gmail.com
INTRODUCTION: Helicobacter pylori has been associated with hyperemesis
gravidarum in some geographical regions. The prevalence of H. pylori in Arab
Israeli women in the Upper Galilee and its association with hyperemesis grav-
idarum, has not been previously studied.
AIMS & METHODS: The aim of this study was to examine whether H. pylori
infection is associated with hyperemesis gravidarum in Arab Israeli women.
Subjects with hyperemesis gravidarum carrying a singleton fetus, were prospec-
tively recruited. Women with an uncomplicated pregnancy served as controls. All
patients underwent C13-urea breath testing to assess for H. pylori infection.
RESULTS: A total of seventy two subjects, including 24 patients with hyperem-
esis gravidarum and 48 controls, aged 28.85.3 years, were included. H. pylori
infection was identified in 73.9% (17/24), and 60.4% (29/48) of cases and con-
trols, respectively (p ns). H. pylori infection did not correlate with age or the
number of previous pregnancies (p ns). Control subjects with a history of early
trimester vomiting were not more likely to be infected with H. pylori, compared
to controls without a history of early trimester vomiting (p ns).
United European Gastroenterology Journal 2(5S)
CONCLUSION: H. pylori does not seem to increase the likelihood of hyperem-
esis gravidarum in Arab Israeli women. However, given the apparently high
background prevalence of H. pylori in this population, a larger study is required
to corroborate these findings.
REFERENCES
1: Gungoren A, Bayramoglu N, Duran N, et al. Association of Helicobacter
pylori positivity with the symptoms in patients with hyperemesis gravidarum.
Arch Gynecol Obstet 2013; 288: 1279-1283.
2: Shaban MM, Kandil HO and Elshafei AH. Helicobacter pylori seropositivity
in patients with hyperemesis gravidarum. Am J Med Sci 2014; 347: 101-105.
3: Vikanes AV, Ster NC, Gunnes N, et al. Helicobacter pylori infection and
severe hyperemesis gravidarum among immigrant women in Norway: a case-
control study. Eur J Obstet Gynecol Reprod Biol 2013; 167: 41-46.
4: Mansour GM and Nashaat EH. Role of Helicobacter pylori in the pathogen-
esis of hyperemesis gravidarum. Arch Gynecol Obstet 2011; 284: 843-847.
1: Gungoren A, Bayramoglu N, Duran N, et al. Association of Helicobacter
pyloripositivity with the symptoms in patients with hyperemesis gravidarum.
Arch Gynecol Obstet 2013; 288: 1279-1283.
2: Shaban MM, Kandil HO and Elshafei AH. Helicobacter pylori seropositivity
inpatients with hyperemesis gravidarum. Am J Med Sci 2014; 347: 101-105.
3: Vikanes AV, Ster NC, Gunnes N, et al. Helicobacter pylori infection and
severe hyperemesis gravidarum among immigrant women in Norway: a case-
control study. Eur J Obstet Gynecol Reprod Biol 2013; 167: 41-46.
Disclosure of Interest: None declared
-
P0508 THE PREVALENCE OF HELICOBACTER PYLORI POSITIVITY
IN THE GENERAL POPULATION IN SWEDEN HAS DECREASED
FROM 38 PERCENT TO 16 PERCENT SINCE 1989
A. Andreasson1,2, N. Talley3, L. Engstrand4, B. Wallner5, A. Forsberg6,
P.M. Hellstrom7, L. Agreus1,*
1
Karolinska Institutet, Centre for Family Medicine, Huddinge, 2Stress Research
Institute, Stockholm University, Stockholm, Sweden, 3Faculty of Medicine,
University of Newcastle, Newcastle, Australia, 4Karolinska Institutet, Stockholm,
5
Umea University, Umea, 6Molecular Medicine and Surgery, Karolinska Institutet,
Stockholm, 7Uppsala University, Uppsala, Sweden
Contact E-mail Address: lars.agreus@ki.se
INTRODUCTION: It is assumed that the prevalence of Helicobacter pylori
(H.p.) is decreasing in wealthy countries. There are however no recent prospec-
tive population based studies confirming this.
AIMS & METHODS: We aimed to evaluate the prevalence of positive H.p.
serology in random population sample in a Swedish community over 23 years.
In 1989 we mailed the validated Abdominal Symptom Questionnaire (ASQ) (age
22-80), and 1097 (87%) responded. H.p.serology (HM-CAPTM immunoassay)
was measured on a stratified sample (n 145 with either dyspepsia, IBS or
symptom free) (1). In late 2011 the ASQ was mailed again with the same sam-
pling procedure in the same community (age 20) and 1175 (64%) replied. A
total of 388 out of 1034 participants 20-79 years of age and suitable for an upper
endoscopy had an upper endoscopy spring 2012. H.p. serology (H. pylori IgA/
IgG ELISA) was measured on 386, 32 of those had participated in 1989. The
effect of time on H.p. prevalence was calculated using random effects logistic
regression models using H.p. as the dependent variable and gender, age and time
as independent variables. All participants in all surveys are included in the ana-
lyses (499 participants, 531 observations).
RESULTS: The prevalence of H.p. positivity in 1989 and 2012 in total and in age
groups for the 499 participants who participated in either or both studies is
presented in the table. H.p. positivity decreased significantly with time, the
odds ratio for H.p. positivity corresponding to 0.25 per decade (OR:0.25;
95%CI:0.11-0.59, p .001) independent of gender and age. There was no differ-
ence in H.p. prevalence between men and women (OR:0.92; 95%CI:0.40-2.08).
The odds of H.p. positivity increased with age by 11% per year (OR:1.11;
95%CI:1.04-1.18, p 0.001).
Table. Prevalence of Hp positivity in 1989 and 2012 in total and by age group
1989 2012
N hp positive/total % N hp positive/total % intestinal metaplasia and/or gastric atrophy independently of the H. pylori
Total 55/145 37.9 61/386 15.8
20-39 8/47 17.0 4/60 6.7
40-59 21/40 34.4 17/161 10.6
60-80 26/37 70.3 40/165 24.4
CONCLUSION: In this random sample of the adult general population in
Sweden, H.p. prevalence has decreased radically over the last two decades
across all ages. Among adults below 40 years it has reached the level where the
test & treat strategy might be questioned (2). Among adults older than 60 years
the risk of complications (3) is most probably reduced.
REFERENCES
1. Storskrubb T, et al. Scand J Gastroenterol 2008; 43: 1448-1455.
2. Malfertheiner P, et al. Gut 2012; 61: 646-664.
3. Agreus L, et al. Scand J Gastroenterol 2012; 47: 136-147.
Disclosure of Interest: None declared
A273
P0509 OBESITY AND HELICOBACTER PYLORI INFECTION: IS THERE
A LINK?
M. Sanduzzi Zamparelli1,*, A. Rocco1, D. Angrisani1, D. Compare1,
O.M. Nardone1, M.G. Iannuzzi1, G. Nardone1
1
clinical medicine and surgery, Federico II University, naples, Italy
Contact E-mail Address: marcosanduzzizamparelli@yahoo.it
INTRODUCTION: The incidence of obesity is increasing worldwide. The invol-
vement of Helicobacter pylori (H. pylori) in the pathophysiology of obesity is still
debated. Among the possible related factors reported, H. pylori infection has
been proposed to play a role by interfering with the release of gastric hormones
involved in the regulation of appetite and food intake. However, the data avail-
able until now are conflicting are derive from small series of cases.
AIMS & METHODS: To analyze the distribution of H. pylori infection in a large
cohort of consecutive patients stratified according to sex, age and body mass
index (BMI).
We enrolled 4653 subject referred to our Gastroenterology Unit between January
2006 to January 2014 to perform 13C-urea breath test (13C-UBT). In all cases we
recorded: age, sex, weight, height, previous esophagogastroscopy results, pre-
vious eradication therapy and H. pylori status. BMI was calculated according
to the following formula: mass (Kg)/height (m)2. The 13C-UBT was performed
by administering a solution of 100 ml tap water containing 100 mg of 13C-urea
and 1.4 g of citric acid. Breath samples were taken at baseline and 30 minutes
after ingestion of the urea. The 13C enrichment in breath was determined by
isotope ratio mass spectrometer. The 13CUBT was considered positive if the
value over baseline at 30 minutes was 4 5%.
RESULTS: Overall, there were 1916 (41%) male. Mean age was 43.75 years
(range 3-88), 323 (7%) subject were 15 year-old. Forty-seven percent (2183)
subjects reported previous eradication therapy. BMI was  18 in 188 (4%),
18.1-25 in 2322 (50%), 25.1-30 in 1576 (35%) and 30.1 in the remaining
514 (11%) of the cases. H. pylori infection was detected in 1892 (40.7%) with a
progressive increasing trend according to BMI ( 18: 36%; 18.1-25: 34%,
25.1-30: 46% and 30.1: 56%; p50.0001).
CONCLUSION: H. pylori infection is significantly more frequent in obese than
in normal weight individuals, irrespective of sex and age.
Disclosure of Interest: None declared
P0510 HELICOBACTER PYLORI, DECREASED PEPSINOGEN AND
ATROPHIC GASTRITIS ARE NOT ASSOCIATED WITH BARRETTS
ESOPHAGUS AND EROSIVE ESOPHAGITIS
M. Selgrad1,*, A. Kandulski1, A. Roessner2, J. Bornschein1, P. Malfertheiner1
1
Department of Gastroenterolgy, Hepatology, 2Department of Pathology, OTTO-
VON-GUERICKE UNIVERSITY, Magdeburg, Germany
Contact E-mail Address: michael.selgrad@med.ovgu.de
INTRODUCTION: Helicobacter pylori (H. pylori) infection has been suggested
to protect against the development of erosive esophagitis (ERD) and Barretts
esophagus (BE). A possible explanation represents the development of corpus
pre-dominant and/or atrophic gastritis in the natural course of H. pylori infection
with an associated decrease in gastric acid secretion.
AIMS & METHODS: Aim of the study was to assess whether H. pylori infection,
decreased serum pepsinogen levels as a marker for gastric atrophy and different
forms of gastritis are associated with the occurrence of BE and ERD.
For this, we reviewed prospectively collected data of 332 patients with an age
above 50 years that underwent gastro-duodenoscopy and colonoscopy. H. pylori
status was determined by serology and serum pepsinogen I levels were measured
in fasting state by commercially available assay. Intestinal metaplasia (IM),
glandular atrophy and mucosal inflammation were diagnosed from histological
specimens and graded according to the updated Sydney-classification.
RESULTS: In H. pylori infected patients (n 101; 30.4%), the overall prevalence
of ERD (20.8%) was comparable to non-infected patients (25.5%) (p 0.215)
and the same accounted for BE (7.9% vs. 11.7%) (p 0.214). H. pylori infection
was not associated with an increased risk for both ERD (OR 0.76, 95% CI:
0.43-1.35) and BE (OR 0.65, 95% CI: 0.28-1.49). The histological proof of
status did not show an association to neither ERD (OR 0.61, 95% CI: 0.28-
1.49) or BE (OR 0.73, 95% CI: 0.32-1.67). The same accounted for the different
phenotypes of gastritis, including antrum- and corpus pre-dominant as well pan-
gastritis for both ERD and BE. Furthermore, no association was seen between a
decreased pepsinogen I level and the occurrence of ERD (OR 0.75, 95% CI:
0.37-1.54) and BE (OR 0.82, 95% CI: 0.31-2.22).
CONCLUSION: H. pylori infection does not show any association to the occur-
rence of ERD and BE. Furthermore, different types of gastric inflammation and
a hypoacid gastric function do not have an influence on the development of ERD
and BE.
Disclosure of Interest: None declared
A274
P0511 A RETROSPECTIVE STUDY OF HELICOBACTER PYLORI AND
PEPTIC ULCER DISEASE PREVALENCE IN AN UPPER
GASTROINTESTINAL ENDOSCOPY REVIEW BETWEEN 2002 AND
2014
S. Roy1,*, D.A. Fernando2, W. Ocen3, J. Oyenuga3, S. Law3
1
Gastroenterology, Queen Marys Hospital, Sidcup, Kent, 2Medical School, Kings
College London, 3Medical School, Imperial College London, London, United
Kingdom
Contact E-mail Address: sunilroy@hotmail.co.uk
INTRODUCTION: There is a well established association between Helicobacter
pylori (H. pylori) infection and peptic ulcer disease (PUD). This association is
known to be stronger in duodenal ulcers (DU) in comparison to gastric ulcers
(GU). Over recent years, trends worldwide have shown a decreasing prevalence
of H. pylori infection with some studies suggesting the rate of decline may be as
high as 26% per decade1. Consequently due to its prominent association with
PUD it would be interesting to identify the change in prevalence of PUD over the
same timescale.
AIMS & METHODS: Using oesophagogastroduodenoscopy (OGD) as our
chosen diagnostic tool, we have set out to determine whether the trend of
90% cure rate) and safe second-line strategy in patients whose
decreasing H. pylori prevalence has been reflected in our sample population
over the last 12 years and whether there has also been a decrease in PUD pre-
valence in particular with respect to duodenal ulcers.
1781 diagnostic OGD procedures carried out by the same endoscopist in a single
District General Hospital in the South East of England were analysed retrospec-
tively. For each procedure the age, gender, H. pylori status and PUD diagnosis
were recorded. Prevalence data was calculated for three sequential time periods
with comparable patient numbers: 2002 to 2005 (Period 1: n 346), 2006 to 2010
(Period 2: n 677), 2011 to 2014 (Period 3: n 681).
RESULTS: The data showed that prevalence of H. pylori infection decreased in
each successive period (p 0.0012). The prevalence across the three time periods
were as follows: period 1- 36 cases (10.4%), period 2- 38 cases (5.60%, p 0.005
with respect to (WRT) Period 1) and finally period 3: 32 cases (4.70%, p50.001
WRT Period 1, p 0.446 WRT Period 2).
The prevalence of PUD also decreased in each successive period (p50.001). The
prevalence across the three time periods were as follows: period 1 - 27 cases
(7.80%; DU 24; GU 3), period 2 - 32 cases (4.73%, p 0.046 WRT Period
1; DU 24; GU 8) and period 3 - 11 cases (1.62%, p50.001 WRT Period 1,
p 0.001 WRT Period 2; DU 8; GU 4). The prevalence of duodenal ulcers
decreased in each successive period (p50.001), however the prevalence of gastric
ulcers remained consistently low (p 0.502).
CONCLUSION: Prevalence of H. pylori has fallen significantly over the time
period studied. Key reasons for this include continually improving sanitation and
living conditions as well as more effective treatment of H. pylori infection,
making recurrence less frequent. The falling prevalence of H. pylori is likely to
have contributed to the significant decrease in prevalence of PUD in the same
time period. Other reasons for this trend include the introduction of effective H.
pylori treatment and increasing effective use of acid suppressive medication.
Another possible factor for the decrease in PUD prevalence is more careful
prescription of non steroidal anti-inflammatory drugs. The stronger association
between H. pylori and DU may explain the significant reduction in the prevalence
of DU in comparison to GU.
REFERENCES
1 Banatvala N, Mayo K, Megraud F, et al. The cohort effect and Helicobacter
pylori. J Infect Dis 1993; 168: 219221.
Disclosure of Interest: None declared
P0512 SECOND-LINE RESCUE THERAPY WITH LEVOFLOXACIN AND
BISMUTH AFTER FAILURE OF A HELICOBACTER PYLORI
ERADICATION TREATMENT
J.P. Gisbert1,2,*, P. Sol s-Munoz3, M. Romano4, A. Gravina5, A. Lucendo6,
J. Molina-Infante7, B. Velayos8, M. Herranz9, J. Barrio10, I. Modolell11,
J. Gomez12, F. Del Castillo13, J. Dom nguez14, A. Federico4, M. Martorano5,
T. Angueira6, L. Fernandez-Salazar8, A. Miranda4, A.C. Mar n1,2,
A.G. McNicholl1,2
1
Gastroenterology Unit, Hospital Universitario de La Princesa and IP,
2
CIBERehd, 3Gastroenterology Unit, Hospital de Madrid Norte San Chinarro,
Madrid, Spain, 4UO di Epatogastroenterologia ed Endoscopia Digestiva, AOU,
Napoli, 5UOC di Endoscopia Digestiva, Ospedale PO della Immacolata, Sapri,
Italy, 6Gastroenterology Unit, Hospital General de Tomelloso, Ciudad Real,
7
Gastroenterology Unit, Hospital San Pedro de Alcantara, Caceres,
8
Gastroenterology Unit, Hospital Clnico, Valladolid, 9Gastroenterology Unit,
Hospital N. Sra. Sonsoles, Avila, 10Gastroenterology Unit, Hospital Ro Hortega,
Valladolid, 11Gastroenterology Unit, Consorci Sanitari de Terrassa, Barcelona,
12
Gastroenterology Unit, Hospital Gregorio Maranon, Madrid, 13Gastroenterology
Unit, Hospital Don Benito, Badajoz, 14Gastroenterology Unit, Hospital Alcala la
Real, Jaen, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: The most commonly used second-line regimens for H. pylori
eradication are bismuth-containing quadruple therapy and levofloxacin-contain-
ing triple therapy, both offering suboptimal results. Combining bismuth and
levofloxacin in the same regimen may be an option as rescue regimen.
AIMS & METHODS: To evaluate the efficacy and tolerability of a second-line
quadruple regimen containing levofloxacin and bismuth in patients whose pre-
vious H. pylori eradication treatment failed.
Design: Prospective multicenter study. Patients: Patients in whom a standard
triple therapy (PPI, clarithromycin, and amoxicillin) or a non-bismuth quadruple
therapy (PPI, clarithromycin, amoxicillin and metronidazole, either sequential or
United European Gastroenterology Journal 2(5S)
concomitant) had failed. Intervention: Esomeprazole (40 mg b.i.d.), bismuth (240
mg b.i.d.), levofloxacin (500 mg o.d.), and amoxicillin (1 g b.i.d.) for 14 days.
Outcome: Eradication was confirmed using the 13C-urea-breath test 4-8 weeks
after therapy. Compliance/tolerance: Compliance was determined through ques-
tioning and recovery of empty medication envelopes. Incidence of adverse effects
was evaluated by means of a questionnaire.
RESULTS: 78 patients were consecutively included. Mean age 4616 years, 64%
women, 14% peptic ulcer. Previous failed therapy included: standard clarithro-
mycin triple therapy (57 patients), sequential (12), and concomitant (9). One
patient did not return after treatment. 92% took all medications correctly. Per-
protocol and intention-to-treat eradication rates were 89.5% (95%CI 82-97%)
and 87.2% (95%CI 79-95%). Cure rates (per-protocol) were similar when com-
pared depending on the diagnosis (peptic ulcer 100% vs. functional/uninvesti-
gated dyspepsia 88%) and previous treatment (standard triple therapy 89% vs.
sequential 83% vs. concomitant 100%). Adverse effects were reported in 60% of
patients (95%CI 49-72%), most commonly nausea (27%), metallic taste (26%),
diarrhoea (23%), abdominal pain (22%), asthenia (17%), and vomiting (6.4%).
In 2 cases, the adverse effects (nausea) were classified as severe (one patient
discontinued the treatment), but none of them was serious.
CONCLUSION: 14-day bismuth-and levofloxacin-containing quadruple therapy
is an effective (
previous standard triple therapy or non-bismuth quadruple (sequential or con-
comitant) therapy has failed, providing a simple and probably more effective
alternative than bismuth-quadruple or levofloxacin-triple standard regimens.
Disclosure of Interest: None declared
P0513 NON-BISMUTH QUADRUPLE CONCOMITANT THERAPIES IN
THE ERADICATION OF HELICOBACTER PYLORI: STANDARD
VS. OPTIMIZED (14 DAYS, HIGH-DOSE PPI) REGIMENS IN
CLINICAL PRACTICE
A.G. Mcnicholl1,*, J. Molina-Infante2, F. Bermejo3, Y. Harb4, I. Modolell5,
R. Anton6, J. Alcedo4, A. Perez-Aisa7, M. Barenys8, J. Barrio9, A. Huerta10,
J. Ortuno11, M. Fernandez-Bermejo2, L. Rodrigo12, N. Fernandez-Moreno7,
A. Tomas13, L. Pozzati14, M. Herranz15, P. Almela16, P. Canelles17, A.B. Vega8,
A. Cosme18, V. Andreu8, L. Ferrer-Barcelo17, J.M. Huguet-Malaves17,
A. Algaba3, A.C. Marin1, J.P. Gisbert1
1
H. La Princesa and IP, CIBERehd, Madrid, 2H. San Pedro Alcantara, Caceres,
3
Hospital, Fuenlabrada, 4Barbastro, Huesca, 5Consorci Sanitari, Terrassa,
6
Clinico, Valencia, 7Agencia Sanitaria Costa del Sol, Malaga, 8Hospital,
Viladecans, 9Rio Hortega, Valladolid, 10Sanchinarro, Madrid, 11La Fe, Valencia,
12
Central de Asturias, Oviedo, 13Sant Camil, Sant Pere de Ribes, 14Hospital,
Merida, 15Nuestra Sra de Sonsoles, Avila, 16Hospital, Castellon, 17General,
Valencia, 18Hospital, Donostia, Spain
Contact E-mail Address: adrian.mcn@gmail.com
INTRODUCTION: Non-bismuth quadruple concomitant regimen is increas-
ingly used as first-line H. pylori eradication treatment.
AIMS & METHODS: To evaluate the efficacy and tolerability of the standard
and optimized concomitant regimens.
Design: Prospective multicenter study. Patients: Consecutive H. pylori-infected
patients. Treatment: In a first phase, patients received a standard concomitant
therapy (CONC10): omeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg
and metronidazole 500 mg for 10 days b.i.d. In a second phase, patients received
the same regimen but with esomeprazole 40 mg b.i.d. and lasting 14 days
(CONC14). Outcome: Eradication confirmed with 13C-urea breath test 4-8
weeks after therapy. Compliance/tolerance: Compliance and adverse events
were determined through questioning and recovery of empty medication
envelopes.
RESULTS: 827 consecutive patients were included (mean age 48 years, 46%
males, 21% peptic ulcer): 356 in CONC10 and 471 in CONC14. Compliance
with treatment was 94% and 95% respectively (non-statistically significant dif-
ferences). Per-protocol eradication rates with CONC10 and CONC14 were
86%(95%CI 83-91%) and 93%(91-96%) (p50.01). Respective intention-to-
treat cure rates were 86%(83-90%) and 91%(90-92%) (p50.01). Adverse effects
(mostly mild) were reported in 32% of patients in CONC10 and in 44% in
CONC14 (p50.05), the most common being metallic taste, diarrhoea,
nausea and abdominal pain.
CONCLUSION: An optimized (fourteen-day and high-dose esomeprazole) non-
bismuth quadruple concomitant regimen for the eradication of H. pylori is
more effective than the standard one, and achieves over 90% cure rate.
Although the incidence of adverse events is higher with the optimized treatment,
these are mostly mild, and do not negatively impact the compliance.
Disclosure of Interest: None declared
P0514 SECOND-LINE RESCUE THERAPY WITH MOXIFLOXACIN
AFTER FAILURE OF TREATMENT TO ERADICATE
HELICOBACTER PYLORI INFECTION
J.P. Gisbert1, M. Romano2, J. Molina-Infante3, A.J. Lucendo4, E. Medina5,
I. Modolell6, M. Rodriguez-Tellez7, B.J. Gomez8, J. Barrio9, M. Perona10,
J. Ortuno11, I. Arino12, J.E. Dominguez-Munoz13, A. Perez-Aisa14, F. Bermejo15,
J.L. Dominguez16, P. Almela17, J. Gomez18, J. Millastre19, E. Martin-
Noguerol20, A.G. Gravina21, A.C. Marin1, A.G. Mcnicholl1,* on behalf of
Spanish H. pylori Study Group
1
H. La Princesa and IP, CIBERehd, Madrid, Spain, 2AUO, Napoles, Italy, 3H.
San Pedro Alcantara, Caceres, 4Hospital General, Tomelloso, 5Hospital General,
Valencia, 6Consorci Sanitari, Terrassa, 7Virgen Macarena, 8Quiron Sagrado
Corazon, sevilla, 9Rio Hortega, Valladolid, 10Quiron, Madrid, 11La Fe, Valencia,
12
Lozano Blesa, Zaragoza, 13Clinico, Santiago deCompostela, 14Agencia Sanitaria
United European Gastroenterology Journal 2(5S) A275
Costa del Sol, Malaga, 15Hospital, Fuenlabrada, 16Alto Guadalquivir, Jaen, 5- Labenz J, Ruhl GH, Bertrams J, et al. Medium- or high-dose omeprazole plus
17
Hospital, Castellon, 18Gregorio Maranon, Madrid, 19Miguel Servet, Zaragoza, amoxicillin eradicates Helicobacter pylori in gastric ulcer disease. Am J
20
Carmen y Severo Ochoa, Asturias, Spain, 21PO "Immacolata", Sapri, Italy Gastroenterol 1994; 89: 726-730.
Contact E-mail Address: adrian.mcn@gmail.com Disclosure of Interest: None declared

INTRODUCTION: Second-line bismuth-containing quadruple therapy is com-

plex and frequently induces adverse effects. A triple rescue regimen containing P0516 SECOND-LINE REGIMENS EFFICACY AGAINST
levofloxacin is an alternative for H. pylori eradication. However, resistance to HELICOBACTER PYLORI INFECTION AFTER STANDARD TRIPLE
quinolones is rapidly increasing and may jeopardize its future efficacy. THERAPY WITH PPI, AMOXICILLIN & CLARITHROMYCIN: META-
Moxifloxacin, a new generation quinolone, may be less affected by quinolone ANALYSES
resistance than levofloxacin. A.C. Mar n1,2, A.G. McNicholl1,2, J.P. Gisbert1,2,*
AIMS & METHODS: To evaluate the efficacy and tolerability of a second-line 1
Gasttroenterology Unit, Hospital de La Princesa and IP, 2CIBERehd, Madrid,
triple regimen containing moxifloxacin in patients whose previous H. pylori era- Spain
dication treatment failed. Contact E-mail Address: aliciacmarin@gmail.com
Design: Prospective multicenter study. Patients: Patients after failure of either:
- standard triple therapy (PPI, clarithromycin, and amoxicillin) INTRODUCTION: Helicobacter pylori infection is usually treated with a proton
- non-bismuth quadruple therapy (PPI, clarithromycin, amoxicillin and metroni- pump inhibitor (PPI), amoxicillin and clarithromycin, but it fails in  20% of
dazole, either sequential or concomitant) patients.
Intervention: Moxifloxacin (400 mg o.d.), amoxicillin (1 g b.i.d.), and esomepra- AIMS & METHODS: Aim: To estimate, by a systematic review and meta-ana-
zole (40 mg b.i.d.) for 14 days. Outcome: Eradication was confirmed using the lyses, the most effective rescue treatments after the failure of a first-line therapy
13C-UBT 4-8 weeks after therapy. Compliance/tolerance: Compliance was deter- with PPI, amoxicillin and clarithromycin in H. pylori eradication. Methods:
mined through questioning and recovery of empty medication envelopes. Selection of studies: Meta-analyses were performed with randomized clinical
Incidence of adverse effects was evaluated by means of a questionnaire. trials (RCT) that assessed the efficacy of second-line regimens; the generic inverse
RESULTS: 250 patients were consecutively included. Mean age 4815 years, variance was applied on prospective and retrospective studies. Inclusion criteria:
58% women, 11% peptic ulcer. Previous failed therapy included: standard Studies treating H. pylori-positive patients after clarithromycin-amoxicillin-PPI
triple therapy (179 patients), sequential (27), and concomitant (44). Four patients failure. Exclusion criteria: Second-line treatment based on the antibiotic sensitiv-
did not return after treatment. 97% of patients took all medications correctly. ity, or if the confirmation of eradication was made only by serology, PCR or
Per-protocol and intention-to-treat eradication rates were 85.7% (95%CI 81- polyclonal stool antigen test. Search strategy: Bibliographical searches were per-
90%) and 82.4 (95%CI 77-87%). Cure rates were similar when compared formed in PubMed, CINAHL, Cochrane Library, ClinicalTrials.gov, and several
depending on the diagnosis (peptic ulcer 77% vs. functional/uninvestigated dys- international congresses, up to April 2014. Data synthesis: Intention to treat
pepsia 82%) and previous treatment (standard triple therapy 83% vs. sequential eradication rate.
89% vs. concomitant 77%). In the multivariate analysis, age was the only vari- RESULTS: The efficacies of the second-line treatments are shown in the table
able associated with eradication success (OR 0.957; 95%CI 0.93-0.98). attached. A meta-analysis comparing the triple therapy with levofloxacin-amox-
Adverse effects were reported in 25% of patients (95%CI 20-30%), most com- icillin-PPI against the quadruple bismuth-metronidazole-tetracycline-PPI regi-
monly diarrhoea (9.6%), abdominal pain (9.6%), nausea (9.2%), metallic taste men showed a non-statistically significant tendency towards better results with
(4.5%), asthenia (4.5%), and vomiting (2.5%). In 13 cases, the adverse effects levofloxacin (OR 1.62; 95% C. I. 0.84-3.14; p 0.15; I2 75%; 7 studies;
were classified as intense, but none of them was severe. 1,158 patients).
CONCLUSION: 14-day moxifloxacin-containing therapy is an effective (480%)
and safe second-line strategy in patients whose previous standard triple therapy SECOND-LINE
or non-bismuth quadruple (sequential or concomitant) therapy has failed, pro- TREATMENT E. R. N. S. N. P. 95% C. I. I2
viding a simple alternative to bismuth quadruple or levofloxacin triple regimens.
Disclosure of Interest: None declared Levofloxacin Amoxicillin
PPI
P0515 THE ROLE OF A DUAL THERAPY CONTAINING HIGH-DOSE -Overall 75% 21 2,919 70 - 80% 88%
PPI IN ERADICATION IN PATIENTS WITH HELICOBACTER -7 day treatment 69% 11 632 64 - 74% 53%
PYLORI POSITIVE DYSPEPSIA -10 day treatment 83% 11 1,946 77 - 89% 89%
A.T. Ince1,*, M. Tozlu1, B. Baysal1, H. Senturk1, S. Arc2, A. Ozden3 -10 days with L(500 mg/24h) 87% 7 373 81 - 94% 77%
1 _
Gastroenterology, 2Pathology, Bezmialem Vakf University, Istanbul, A(1 g/12h)PPI
3
Gastroenterology, Ankara University Medical Faculty, Ankara, Turkey *Removing 1 outlier study 92% 6 273 89 95% 0%
Contact E-mail Address: dralince@gmail.com
-14 day treatment 74% 3 341 70 78% 96%
INTRODUCTION: H. pylori eradication rates vary by society and usually do *Removing 1 outlier study 86% 2 151 81 92% 0%
not exceed 80%. Some publications have reported that this rate was even higher Bismuth Metronidazole
with dual therapies containing high-dose proton-pump inhibitors. H. pylori era- Tetracycline PPI
dication is recommended in patients with dyspepsia. The objective of the present
study is to determine eradication rates with dual therapy containing high dose - Overall 77% 43 3,685 74 - 81% 86%
omeprazole in H. pylori-positive patients with dyspepsia. -7 day treatment 75% 31 2,345 71 - 80% 84%
AIMS & METHODS: The patients were treated orally with either dual (n:74, -10 day treatment 77% 2 142 60 - 93% 76%
omeprazole 20mg q.i.d and amoxicillin 1g b.i.d) or triple therapy (n:116, ome- -14 day treatment 81% 15 1,187 76 - 86% 83%
prazole 20mg b.i.d and amoxicillin 1g b.i.d and clarithromycin 500mg b.i.d) for
14 days. HpSA test was requested 3 months later. The results were evaluated Metronidazole Amoxicillin
statistically, p values 50.05 were considered significant. PPI
RESULTS: The study included 190 patients (808,1109, p40.05). The mean age - Overall 88% 24 1,642 85 - 91% 75%
was 35.611 years (p50.001). The mean duration of dyspeptic symptoms was -7 day treatment 75% 24 1,160 85 - 91% 75%
28.233.7 months (median:18, range:3338). Bloating was more frequent in the -7 days with M(250 mg/12h) 92% 12 751 89 - 95% 48%
triple therapy group (p50.01) while epigastric pain/burning and early satiation A(750 mg/12h)PPI
did not differ significantly between the groups (p40.05). Alcohol and smoking,
endoscopic findings and H. pylori rates with pathological examinations were not -10 day treatment 84% 4 314 77 - 91% 69%
significantly different between groups whereas there was a significant difference -14 day treatment 81% 2 127 75 - 88% 0%
in HpFast tests (p50.01). When examined with HpSA tests 3 months after the Amoxicillin PPI (14 days all
treatment, eradication rate was 81.1% in the dual therapy group versus 63.8% in the studies were done in
the triple therapy group (p 0.011). Dual therapy was more economic compared Japan)
to triple therapy (144USDvs.107USD,p50.001). - Overall 82% 5 200 69 - 95% 87%
CONCLUSION: Dual therapy in patients with dyspepsia was more successful,
cost-effective and is less risky in terms of side effects compared to standard triple -14 day with A (500 mg/6h) 93% 3 106 88 - 98% 3%
therapy. PPI(10 mg/6h)
REFERENCES -14 day with A (1 g/12h) PPI 66% 2 94 51 - 81% 58%
1-Lacy BE, Talley NJ, Locke GR 3rd, et al. Review article: current treatment (20 mg/12h)
options and management of functional dyspepsia. Aliment Pharmacol Ther 2012;
36: 3-15.
2-Tack J, Talley NJ, Camilleri M, et al. Functional gastroduodenal disorders. E. R.: eradication rate; N. S.: Number of studies; N. P.: number of patients.
Gastroenterology 2006; 130: 1466-1479. CONCLUSION: The most effective second-line treatments, after a clarithromy-
3-Malfertheiner P, Sipponen P, Naumann M, et al. Helicobacter pylori eradica- cin-amoxicillin-PPI failure, are the metronidazole-amoxicillin-PPI or a 10 day
tion has the potential to prevent gastric cancer: A state-of-the-art critique. Am J levofloxacin-amoxicillin-PPI therapy. More high quality trials, performed out-
Gastroenterol 2005; 100: 21002115. side Japan, are needed to verify the efficacy of the 14 day dual therapy with
4- Villoria A, Garcia P, Calvet X, et al. Meta-analysis: high-dose proton pump amoxicillin-PPI.
inhibitors vs. standard dose in triple therapy for Helicobacter pylori eradication. Disclosure of Interest: A. Mar n: None declared, A. McNicholl: None declared, J.
Aliment Pharmacol Ther 2008; 28: 868-877. Gisbert Other: Dr. P. Gisbert has served as a speaker, a consultant and advisory
member for, and has received research funding from MSD and Abbvie.
A276
P0517 SEVEN-DAY NON-BISMUTH CONCOMITANT QUADRUPLE
THERAPY IS SUFFICIENT IN ACHIEVING A GRADE A REPORT
CARD FOR FIRST-LINE ANTI-HELICOBACTER PYLORI THERAPY:
A PILOT STUDY
C.-M. Liang1,*, W.-C. Tai1, S.-K. Chuah1, K.-L. Wu1, Y.-C. Chiu1
1
Division of Hepato-gastroenterology, Department of Internal Medicine,
Kaohsiung Chang Gung Memorial Hospital and Chang Gung University,
Kaohsiung, Taiwan, Province of China
Contact E-mail Address: gimy54861439@gmail.com
INTRODUCTION: The eradication rate of the standard triple therapy has gen-
erally declined to unacceptable levels (i.e., 80% or less) recently because the
increasing incidence of clarithromycin-resistant strains of Helicobacter pylori
(H. pylori). 10-day concomitant therapy (non-bismuth concomitant quadruple
therapy) can achieve a promising success rate of 90-94% in the presence of
clarithromycin resistance. This therapy is superior to standard triple therapy
for H pylori eradication and less complex as this regimen does not involve chan-
ging drugs halfway through.
AIMS & METHODS: This study is to assess the efficacy of 7-day concomitant
therapy and to investigate the host and bacterial factors influencing the treatment
outcomes of all eradication therapies. One hundred and eighty consecutive H.
pylori-infected patients are randomly assigned to a 7-day non-bismuth quadruple
therapy (EACM group, Esomeprezole 40 mg bid., amoxicillin 1 g bid., clarithro-
mycin 500 mg bid., and metronidazole 500 mg bid. for 7 days) or a 7-day
standard triple therapy (EAC group, Esomeprezole 40 mg bid., amoxicillin
1mg bid., clarithromycin 500 mg bid., and for 7 days). Patients are asked to
return at the 2nd week to assess drug compliance and adverse events.
Repeated endoscopy with rapid urease test, histological examination and culture
is performed at the 8th week after the end of anti- H. pylori therapy. If patients
refuse follow-up endoscopy, urea breath tests are conducted to assess H. pylori
status. Additionally, antibiotic susceptibility of H. pylori will be examined.
Finally, the rates of eradication, adverse events and compliance will be compared
between groups by chi-square test, and the host and bacterial factors influencing
each efficacy of the regimen are assessed by multivariate analysis.
RESULTS: Our results demonstrated that the eradication rates for EACM ther-
apy and EAC standard triple therapy in intention-to-treat analysis were 86.7%
vs. 72.2%, P 0.016 and 95.1% vs. 79.2%, P 0.002) in the per-protocol ana-
lysis. Drug compliances were 100% in both groups although more adverse events
were reported in the EACM group (35.3% vs. 18.3%, P 0014). Clarithromycin
resistance was the only independent predictors of treatment failure in multivari-
ate analysis. In the subgroup analysis according to antibiotics susceptibility, none
of the patients with clarythromycin resistant strains and 33.3% with metronida-
zole resistant strains were eradicated in the EAC group while 75% of those with
resistant strains were eradicated in the EACM group.
CONCLUSION: This study suggests that a 7-day non-bismuth concomitant
quadruple therapy is sufficient in achieving a grade A report card for first-line
anti-H. pylori therapy. Clarithromycin resistance was the factor responsible for
eradication failures.
REFERENCES
1. Graham DY and Fischbach L. Helicobacter pylori treatment in the era of
increasing antibiotic resistance. Gut 2010; 59: 1143-1153.
2. Wu DC, Hsu PI, Wu JY, et al. Sequential and concomitant therapy with four
drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol
Hepatol 2010; 8: 36-41.
Disclosure of Interest: None declared
P0518 EMPIRICAL RESCUE THERAPY AFTER H. PYLORI
TREATMENT FAILURE. A 15-YEAR SINGLE CENTER STUDY OF
1,000 PATIENTS
D. Burgos Santamar a1,*, A.G. McNicholl1, J.L. Gisbert1, S. Marcos1,
M. Fernandez-Bermejo2, J. Molina-Infante2, J.P. Gisbert1
1
Hospital Universitario de La Princesa, IP, CIBEREHD, Madrid, 2Hospital San
Pedro de Alcantara, Caceres, Spain
Contact E-mail Address: diegoburgossantamaria@gmail.com
INTRODUCTION: The most commonly used empirical therapies for H. pylori
eradication fail up to 20-30% on first line, and even more in rescue therapies.
This is mainly due to increasing antibiotic resistances and poor compliance.
Therefore it is necessary to evaluate the efficacy and safety of the overall eradi-
cating strategy, including multiple and consecutive lines of treatment.
AIMS & METHODS: To evaluate the efficacy of different rescue therapies
empirically prescribed during 15 years to 1,000 patients in whom at least one
eradication regimen had failed to cure H. pylori infection.
Design: Retrospective single-center study. Patients: 1,000 consecutive patients
who had failed at least one eradication therapy (1998-2013). Intervention: The
most common eradication treatments were: 1) PPI-Amoxicillin-Levofloxacin
(PPI-A-L), 2) Ranitidine bismuth citrate-Tetracycline-Metronidazole (Rcb-T-
M), 3) Classic Quadruple therapy (PPI-Bismuth-Tetracycline-Metronidazole)
(PPI-B-T-M), 4) Esomeprazole-Moxifloxacin-Amoxicillin (E-Mox-A), 5) PPI-
Amoxicillin-Rifabutin (PPI-A-Rif). Rifabutin was prescribed only as 4th line,
and the other treatments were used both as 2nd and 3rd line. As antibiotic
susceptibility was unknown, rescue regimens were prescribed empirically.
Rescue regimens were prescribed without retreating with the same drugs.
Outcome: Eradication was defined as a negative 13C-urea breath test 4-8 weeks
after completing therapy. Modified intention-to-treat analysis was used, con-
sidering patients with poor compliance, but not those who were lost during the
follow-up.
RESULTS: Overall eradication rates of H. pylori with 2nd, 3rd and 4th lines of
rescue therapies were 74.6%, 71.1% and 50% respectively, with a cumulative
United European Gastroenterology Journal 2(5S)
eradication rate after consecutive administration of 4 treatments of 99.2%.
Compliance with 2nd, 3rd and 4th line regimens was 95.6%, 93% and 93.5%
respectively, with an overall compliance of 95.1%. The efficacy and adverse
effects of treatments were 83.5% and 24.2% with E-Mox-A, 77.8% and 24%
with PPI-L-A, 68.9% and 21.5% with PPI-B-T-M, 66% and 33.3% with Rcb-T-
M, and 62% and 37.9% with PPI-A-Rif. The highest rate of eradication was
achieved with E-Moxi-A (83%) as a 2nd line treatment, regardless of the first-line
regimen prescribed.
CONCLUSION: H. pylori eradication rates may reach 99% without performing
bacterial culture by using a rescue strategy of 4 consecutive empirical treatments.
The best rescue strategy to eradicate H. pylori is the consecutive administration
of quinolones (2nd line), PPI-B-T-M (3rd line) and PPI-A-Rif (4th line).
Disclosure of Interest: None declared
P0519 LETS TRY QUINTUPLE THERAPY AS A RESCUE ERADICATION
REGIMEN FOR REFRACTORY H. PYLORI INFECTION
F. Mansour-Ghanaei1,*, A. Shafaghi1, F. Joukar1, M. Naghipour2
1
Gastrointestinal and Liver Diseases Research Cente, 2Epidemiology, GUILAN
UNIVERSITY OF MEDICAL SCIENCES, Rasht, Iran, Islamic Republic Of
Contact E-mail Address: ghanaie@yahoo.com
INTRODUCTION:
To compare the efficacy, tolerability and side effect profiles of two quintuple
regimens for helicobacter pylori (H. pylori) eradication in patients who failed the
first line quadruple therapy.
AIMS & METHODS: Between April 2011 and March 2012, a total of 208
patients with dyspepsia who failed H. pylori eradication using the standard quad-
ruple therapy with BOAC (Bismuth subcitrate, Omeprazole, Amoxicillin,
Clarithromycin) or BOAM (Bismuth subcitrate, Omeprazole, Amoxicillin,
Metronidazole) were recruited for this study. The patients were randomized
into two equal groups using random block method. Patients in BOACT group
were treated by omeprzole 20 mg, combined with bismuth subcitrate 240 mg, and
three antibiotics clarithromycin 500 mg, amoxicillin 1000 mg and tinidazole 500
mg all twice daily for seven days. Patients in the BOTMO group were given
omeprazole 20 mg and bismuth subcitrate 240 mg along with tetracycline 500
mg and ofloxacin 200 mg in the same manner as in BOACT group. The eradica-
tion was confirmed at 12 weeks after end of therapy by C14 urea breath test.
Patients compliance and drugs side effects were evaluated at the end of treat-
ment. The success rates were calculated separating by intention-to-treat (ITT)
and per-protocol (PP) analyses.
RESULTS: A total number of 208 patients were included in the study and 205
patients completed the treatment course. The intention-to-treat and per-protocol
eradication rates were 75.5% and 76% in the BOACT group and 86.5% and
86.7% in the BOTMO group, respectively. The eradication rates of the BOTMO
group was significantly higher than BOACT group (p 0.04). Side effects were
reported from 33.2% of the patients which were mild and did not necessitate
interfere with therapy although 3 patients (2 patient in BOACT group and 1
patient in BOTMO group were excluded from the study due to severe drug side
effects.
CONCLUSION: Quintuple therapy with BOTMO could be an alternative
second-line rescue therapy for Iranian patients who have failed one previous
standard treatment for H. pylori eradication, but its efficacy needs to be con-
firmed in other populations before we can generalized our findings, considering
regional antimicrobial resistance. Considering the short length of treatment in
our study, further studies to assess the effects of quintuple therapies by BOTMO
regimen with periods longer than 7 days is recommend
Disclosure of Interest: None declared
P0520 HELICOBACTER PYLORI ERADICATION RATES AND PLASMA
PANTOPRAZOLE LEVELS IN TYPE 2 DIABETIC AND
NONDIABETIC PATIENTS
F. Sapmaz1,*, I.H. Kalkan1, I. Suslu2, S. Guliter1
1
Gastroenterology, Krkkale University Faculty of Medicine, Krkkale,
2
Pharmeceutics, Hacettepe University Faculty of Medicine, Ankara, Turkey
Contact E-mail Address: ferda-sapmaz@hotmail.com
INTRODUCTION: The eradication rate of Helicobacter pylori has been
reported as being lower in patients with type 2diabetes mellitus (DM) than in
those without DM.
AIMS & METHODS: The first aim of this study was to compare the efficacy of a
bismuth-based quadruple regimen as first-line therapy for Helicobacter pylori
(HP) eradication in diabetic and non-diabetic patients. The second aim of the
study was to compare plasma Pantoprazol levels in these patient groups during
H. pylori eradication treatment.
Forty consecutive type 2 DM and 40 non-diabetic na ve H. pylori infected patients
were enrolled in this study. All patients received Pantoprazole (40 mg b.i.d.),
bismuth citrate (120 mg q.i.d.), tetracycline (500 mg q.i.d.), and metronidazole
(500 mg t.i.d.) for 14 days as the eradication regimen. We used Square-Wave
Voltammetry method to determine plasma Pantoprazole levels in both groups.
RESULTS: The overall compliance rates among the diabetic patients and control
group were 90.0% (36/40) and 92.5% (37/40), respectively. The per-protocol HP
eradication rates (63.9% vs 89.2%, p 0.01), Intention-to-treatment HP eradica-
tion rates (60% vs 87.5%, p50.001) and Plasma Pantoprazole levels (0.25mgmL-1
vs. 0.34 mgmL-1, p 0.005) were significantly lower in diabetic patients.
CONCLUSION: Our study showed that diabetic patients had lower plasma
Pantoprazole levels which led to lower H. pylori eradication rates with a bismuth
and Pantoprazole including regimen. Clinical and pharmacokinetic investigations
are required to improve plasma proton pump inhibitor levels in diabetic patients
for satisfactory H. pylori eradication rates.
United European Gastroenterology Journal 2(5S) A277
Disclosure of Interest: None declared RESULTS: Twenty-two GS patients (mean  SD 40 9 years, BMI 223) and
22 CD patients were enrolled. Total Kcal were 1767 501 Vs 1544 539 in GS
and CD respectively, with no difference in % contribution of CHO, fats and
MONDAY, OCTOBER 20, 2014 9:0017:00 proteins to total calories. The proportion of macro-nutrients in the diet that was
SMALL INTESTINAL I POSTER EXHIBITION HALL XL_____________________ correct according to the LARN recommendations was 54%, 59% and 32% in
GS and 18%, 41% and 5% in CD for CHO, proteins and fats, respectively.
P0521 CAUSE-SPECIFIC MORTALITY IN PEOPLE WITH COELIAC Comparison of selected nutrient composition in GS Vs CD patients and Vs
DISEASE COMPARED TO THE GENERAL POPULATION: A LARN are reported in the table.
COMPETING-RISK ANALYSIS
A. Abdul Sultan1,*, C. Crooks1, T. Card1, L. Tata1, K. Fleming1, J. West1 Nutrients GS CD GS Vs LARN %x
1
University of Nottingham, Nottingham, United Kingdom
Contact E-mail Address: alyshah.sultan@hotmail.com PUFA, % TEV 4.62.2 3.41.2* - 50
INTRODUCTION: Quantifying excess cause specific mortality among people Fibres, g 20.024.9 11.96.5 -86
with coeliac disease (CD) compared to the general population accounting for Alcohol, g 2.34.4 4.08.9 NA
competing risks (which takes into account that patients may die due to other Vitamin B12, mg 3.91.8 1.01.6* -14
causes before dying from the cause of death of interest) will allow accurate Vitamin D, mg 2.21.2 1.50.9* -100
information to be given on prognosis and risks of adverse outcomes.
AIMS & METHODS: This study quantifies the excess cause specific mortality Folates, mg 324.5381.5 131.774.7* -73
among people with CD by 10 year of diagnosis compared to the general popula- Magnesium, mg 146.7101.4 44.664.4* -77
tion while accounting for competing risks. We identified from the Clinical Iron, mg 9.05.4 5.42.7* -68
Practice Research Datalink (CPRD), all patients with CD for whom linkage to Selenium, mg 39.016.3 10.416.0* -55
Office of National Statistics (ONS) data to determine cause of death if it occurred
was available. We selected controls by frequency matching from the registered
GP population within 10 year age bands. We calculated the adjusted cumulative
incidence (including adjustment for competing risks) for different causes of death CONCLUSION: Patients spontaneously adhering to a GFD for perceived GS
up to 10 years from diagnosis. We also calculated the excess cumulative incidence have, despite no dietetic instruction, a more balanced intake of macro- and
(eCI) for each cause of death compared to controls. micro-nutrients in comparison with CD patients. This phenomenon may be the
RESULTS: Of the 5,310 patients with CD, 352 died within the study period. The result of a behavioural attitude towards healthy food more pronounced in GS
overall mortality rateamong CD patients was 124 per 10,000 person-years com- than in CD patients, although LARN recommendations are not met for most
pared to 111/10,000 in controls. By 10 years after CD diagnosis, the cumulative nutrients.
incidence of death (Table 1) from cardiovascular related deaths was slightly lower Disclosure of Interest: None declared
compared to those without CD diagnosis (CD 0.16% versus Controls 0.26%)
with a corresponding eCI of 0.1% (95% CI -0.14 to -0.06). Overall there was no
difference in the cumulative incidence of respiratory, digestive or cancer related P0523 SPLEEN DIAMETER/RDW AS A NOVEL INDICATOR FOR
death among cases and controls. However, CD patients had 0.1% excess risk CELIAC DISEASE
(95%CI;0.01-0.16) of deaths death from non-Hodgkins lymphoma or D. V. Balaban1,*, A.M. Lungu1, A. Popp2, B. Macadon1, S. Bucurica1,
leukaemia. R. Costache1, P. Nut;a1, F. Ionit;a-Radu1, M. Jinga1,2
Table 1: Cumulative incidence and excess risk by 10 years after diagnosis 1
Gastroenterology Clinic, "Dr Carol Davila" Central Military Emergency
adjusted for competing risks, gender, age and social class University Hospital, 2"Carol Davila" University of Medicine and Pharmacy,
Bucharest, Romania
Cause of death With CD Without CD Excess 95% CI Contact E-mail Address: vbalaban@yahoo.com

Cardiovascular overall 0.16 0.26 -0.10 -0.14 -0.06 INTRODUCTION: Red cell distribution width (RDW) has been shown in pre-
vious studies to be a sensitive predictor for coeliac disease (CD), but it lacks
Ischemic heart disease 0.10 0.15 -0.05 -0.08 -0.16 specificity. Splenic hypotrophy is also noted frequently in celiac patients. Our aim
Respiratory overall 0.07 0.07 0.00 -0.02 0.03 was to evaluate if spleen size/RDW can be used as an indicator for celiac disease.
Neoplasm overall 0.78 0.72 0.06 -0.11 0.23 AIMS & METHODS: We evaluated 32 patients with small bowel disease (12
Non-hodgkins/leukemia 0.13 0.04 0.08 0.01 0.16 newly diagnosed CD patients and 20 patients with Crohns disease, IBD-CD) and
32 age-matched patients with irritable bowel syndrome (IBS), admitted to our
Digestive overall 0.15 0.11 0.05 -0.03 0.13 clinic over a one-year period. We evaluated the differences in spleen diameter,
RDW and their ratio among the three groups.
RESULTS: Of the 32 patients with small bowel disease, 11 were males, with a
CONCLUSION: Overall, people with CD have no major excess risk of cancer, mean age of 38.34 years. Mean RDW was significantly higher in the CD and
digestive, cardiovascular or respiratory related mortality compared to the general IBD-CD groups than the IBS group (14.49 and 16.73 vs. 13.51, p 0.0099),
population over the 10 year period following initial diagnosis. In addition they whereas mean spleen size was lowest in the CD patients (84.08, 107.85 and
have only a very small excess risk of dying of haematological malignancy. These 112.62 mm respectively). The mean spleen diameter/RDW was 5.82 in the CD
findings should be reassuring to both patients with CD and clinicians managing group, 6.65 in the IBD-CD group and 8.34 in the IBS group (p 0.0001). A ratio
their care. under 6 had a sensitivity of 75% and a specificity of 88.46% in detecting CD.
Disclosure of Interest: None declared CONCLUSION: Spleen diameter/RDW is a simple, widely available score,
which can be used to select patients for futher diagnostic tests. This should be
repeated in larger patient cohorts.
P0522 NUTRIENTS INTAKE IN NON CELIAC PATIENTS ON GLUTEN Disclosure of Interest: None declared
FREE DIET BECAUSE OF PERCEIVED GLUTEN SENSITIVITY:
COMPARISON WITH CELIAC PATIENTS AND WITH NATIONAL
NUTRITIONAL GUIDELINES P0524 CELIAC DISEASE AND DRUG-BASED THERAPIES: INQUIRY
B. Zanini1,*, M. Marullo1, A. Ferraresi1, F. Caselani1, C. Ricci1, F. Lanzarotto1, INTO PATIENTS DEMANDS
A. Lanzini1 F. Branchi1,2,*, C. Tomba1,2, M.T. Bardella1, L. Roncoroni1, M. Locatelli1,2,
1
Department of Clinical and Experimental Sciences, UNIVERSITY AND F. Somalvico1, D. Conte1,2, L. Elli1
1
SPEDALI CIVILI OF BRESCIA, Brescia, Italy Center for the Prevention and Diagnosis of Celiac Disease Gastroenterology and
Contact E-mail Address: b_zanini@tin.it endoscopy Unit, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico,
2
Universita` degli Studi di Milano, Milano, Italy
INTRODUCTION: Non celiac and non wheat allergic patients that sponta- Contact E-mail Address: lucelli@yahoo.com
neously adhere to gluten free diet (GFD) because of adverse gastrointestinal
and extra-intestinal reactions to gluten containing food are frequently encoun- INTRODUCTION: The gluten free diet (GFD) is the only available therapy for
tered in clinical practice and are commonly referred to as gluten sensitive (GS) patients with celiac disease (CD). Medical research is actively focused on the
patients. In most cases GS patients do not seek dietician advice on GFD, and no search for drug-based solutions as an alternative to GFD, which requires life-
information is available on the nutritional adequacy of their self-made diet. long, strict adherence.
AIMS & METHODS: We carried out a prospective clinical study to assess AIMS & METHODS: We aimed at evaluating the actual need for other-than-
macro- and micro-nutrients of GFD in GS patients compared with that of a GFD therapies perceived by CD patients, along with the impact of GFD itself on
cohort of patients with celiac disease (CD) matched according to gender and their life.
age (range /-4 years), and with the recommendations of the Italian nutritional During the 2012 meeting of the Lombardy section of the Italian CD Patients
guidelines (LARN 2012). Patients in the 2 study cohorts were asked to fill in a Association, adult CD subjects on GFD were invited to fill in a questionnaire
standardized 7-day food diary. Data from diaries were analyzed with Microdiet investigating their clinical profile in relation to GFD compliance, health status
software (Downlee systems, ltd. UK) that returns very detailed information on and quality of life as well as their opinion on GFD, alternative therapies and
diet composition. Nutritional characteristics included: total Kcal, proportion of research priorities.
total energy values of CHO, free sugars, proteins, fats, SFA and PUFA, and total RESULTS: 372 patients (76 M, mean age at diagnosis and at entry 29.7  16.9
amounts of fibres, vitamins A, C, D, B12, folates, sodium, calcium, iron, zinc, and 41.7  13.9 years, respectively) completed the questionnaire. 94% patients
selenium, magnesium and alcohol. For statistical analysis Fishers exact test and reported strict adherence to GFD. Patients reported a significant improvement in
Wilcoxon matched paires test were used as appropriate. health status and quality of life after the diagnosis of CD was made and GFD
was started (p50.001), with a greater improvement of health status than quality
A278
of life (82% vs 56%, p50.001). GFD was favourably considered and accepted by
88% patients, but a demand for alternative therapies was reported by 65%
patients. Subjects expressing the need for a drug-based therapy showed a signifi-
cantly lower increase of quality of life on GFD (p 0.002), but no differences
were observed in health status changes. The preferred option for an alternative
therapy was the on demand assumption of drugs, i.e. enzymes (145 subjects), G. I. Longarini1,*, E. Sugai1, H. Hwang1, F. Nachman1, A. Cabanne1,
followed by a vaccine-based strategy (111 subjects). Almost two thirds of the
cohort stated they would accept to be enrolled in ad hoc designed clinical trials.
CONCLUSION: GFD is favourably accepted and followed by most CD
patients, with significant health status improvement. Nevertheless, a considerable
proportion of patients pronounce themselves in favour of the development of
alternative drugs, although a chronic drug therapy is not considered a likely
opportunity.
REFERENCES
1. Schuppan D, Junker Y and Barisani D. Celiac disease: from pathogenesis to
novel therapies. Gastroenterology 2009; 137: 1912-1933.
2. Aziz I, Evans KE, Papageorgiou V, et al. Are patients with celiac disease
seeking alternative therapies to a gluten-free diet? J Gastrointestin Liver Dis
2011; 20: 27-31.
3. Mukherjee R, Kelly CP and Schuppan D. Nondietary therapies for celiac
disease. Gastrointest Endosc Clin N Am 2012; 22: 811-831.
Disclosure of Interest: None declared
P0525 IMPAIRED BONE MICROSTRUCTURE IMPROVES AFTER ONE-
YEAR ON GLUTEN-FREE DIET. A PROSPECTIVE LONGITUDINAL
STUDY IN WOMEN WITH ACTIVE CELIAC DISEASE
G. I. Longarini1,1,*, M.B. Zanchetta2, A.F. Costa1, V. Longobardi2,
M.P. Temprano1, H. Vazquez1, S. Niveloni1, E. Smecuol1, M.L. Moreno1,
H. Hwang1, R. Mazure1, A. Gonzalez1, E. Maurino1, J.C. Bai1
1
Medicine, Hospital Udaondo, 2IDIM, Buenos Aires, Argentina
Contact E-mail Address: mbzanchetta@idim.com.ar
INTRODUCTION: We have recently identified a significant deterioration of
trabecular and cortical microarchitecture in peripheral bones of patients with
undiagnosed celiac disease (CD) by using high resolution-peripheral quantitative
computed tomography (HR-pQCT). Such finding may underlie bone fragility
and lead to fractures in these patients. Up to now, the effect of the gluten-free
diet (GFD) on microstructural parameters of peripheral bones has not been
assessed.
AIMS & METHODS: Aim: To explore one-year changes of bone microstructure
associated with the GFD in a prospective cohort of premenopausal women with
newly diagnosed CD.
Materials: We prospectively enrolled 31 consecutive females with newly diag-
nosed CD. Up to now, 25 patients have been reassessed one-year after diagnosis.
Clinical and biochemical status, CD specific serology, assessment of the degree of
compliance with the GFD, bone densitometry and microstructural determina-
tions (HR-pQCT) were performed at both time points. HR-pQCT bone volu-
metric and structural measurements were determined at the distal non-dominant
radius and tibia. Parameters of patients were also compared with those of 22
healthy women of similar age and body mass index.
RESULTS: Compared with the baseline z-score, the one-year bone mineral den-
sity measured by dual energy x-ray absorptiometry (DXA) improved signifi-
cantly at the distal radius (meanSD) (-1.941.27 vs. -1.431.06; p50.02) but
not at the lumbar spine level. The microstructure of the trabecular compartment
in the distal radius was significantly improved (trabecular/bone volume fraction,
trabecular density and trabecular thickness: p50.0001) at the one-year time
point. At the level of tibia, treatment was associated with significant increment
of the total volumetric density (p50.01), cortical density (p50.002), trabecular
density (p50.0001), trabecular/bone volume fraction (p50.0001) and trabecular
thickness (p50.002). In contrast, the cortical thickness decreased significantly in
both sites (p50.001). Compared to the control group there were no statistically
significant differences in most trabecular parameters measured by HR-pQCT.
CONCLUSION: This is the first study exploring the effect of a one-year GFD on
microstructural parameters measured by HR-pQCT in patients with newly diag-
nosed CD. Our study shows that trabecular parameters impaired at the time of
diagnosis improved significantly by treatment reaching values comparable to
those in healthy controls. We postulate that bone microarchitecture improvement
underlie the decreased risk of fractures observed after treatment with a GFD.
Disclosure of Interest: G. Longarini: None declared, M. Zanchetta: None
declared, A. Costa: None declared, V. Longobardi: None declared, M.
Temprano: None declared, H. Vazquez: None declared, S. Niveloni: None
declared, E. Smecuol Financial support for research from: Astra Zeneca,
Lecture fee(s) from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, M.
Moreno: None declared, H. Hwang: None declared, R. Mazure: None declared,
A. Gonzalez: None declared, E. Maurino: None declared, J. Bai: None declared
United European Gastroenterology Journal 2(5S)
P0526 HOW DOES SPECIFIC SEROLOGY MATCH WITH ESPHGAN
SEROLOGIC GUIDELINES FOR DIAGNOSIS OF CELIAC DISEASE
IN A PROSPECTIVE COHORT OF ADULTS WITH HIGH PRETEST
PROBABILITY?
H. Vazquez1, M.L. Moreno1, A.F. Costa1, M. I. Pinto1, S. Niveloni1,
E. Smecuol1, R. Mazure1, E. Maurino1, J.C. Bai1
1
Medicine, Hospital Udaondo, Buenos Aires, Argentina
Contact E-mail Address: emiliasugai@yahoo.com
INTRODUCTION: Intestinal biopsy is considered mandatory for the diagnosis
of celiac disease (CD). This has been recently challenged by several studies and
the 2012 ESPGHAN guideline proposing an appropriate clinical and serological
algorithm that could be used to reduce the need for duodenal biopsy. This
provocative strategy has been confirmed by some studies but rejected by
others. However, all these studies were performed on the basis of retrospective
analyses of biased populations. Prospective evaluation of patients in whom diag-
nosis was based on histological grounds is important to clarify this controversy.
AIMS & METHODS: 1-To review the performance of serology tests in a pro-
spective and consecutive series of adult patients with high pretest probability for
CD; 2- to compare performance of serologic tests with the ESPGHAN serologic
algorithm; and 3- to establish the best serologic algorithm for diagnosing CD
using antibody tests detecting different antigens.
We performed a post hoc analysis of data from all patients enrolled in a previous
prospective study (WJG 2010; 16: 3144) where consecutive adults suspected of
intestinal disorders (high pretest population) were enrolled. Diagnosis of CD was
based on histology (Marshs stages 3a) in all patients irrespective of serology.
CD-related serology consisted of seven different assays but we only report the
performance of tissue transglutaminase (tTG) IgA, deamidated gliadin peptides
(DGP) IgG and the combination of both (INOVA Diag. Inc.). Serologic perfor-
mance was compared with the ESPGHAN serologic criterion (cut-off 410 times
the upper limit of normal -ULN-), the best cut-off (area under the ROC) and the
cut-off suggested by the manufacturer.
RESULTS: Sixty-three of 161 patients (39%) had histological criteria for CD.
According to the ESPGHAN criterion, IgA tTG sensitivity was 22% with 100%
positive predictive value (PPV). The best cut-off value (34 AU/mL) would detect
93.6% of patients with 100% of PPV. Finally, the manufacturer cut-off (20 AU/
mL) had 95.2% sensitivity and 97.9% PPV. The ESPGHAN criterion used for
IgG DGP was 3.2% sensitive with a PPV of 100%. The best cut-off (was similar
to that of the manufacturer: 20AU/mL) was 95.2% sensitive and had 100% PPV.
Any test was positive (420AU/mL) in all patients and both were concomitantly
positive in 90.5% of cases with100% of PPV.
CONCLUSION: This prospective study indicates that, under particular clinical
circumstances, a serologic strategy can be used to avoid duodenal biopsy in the
diagnosis of adult patients with CD. The need for biopsy could be avoided in a
minority of patients by using the ESPGHAN serologic criterion. Our results
suggest that the best serologic strategy for a high pretest population seems to
be the association of tTG IgA and DGP IgG. In such context, biopsy could be
avoided in more than 90% of the cases when both tests are positive.
Disclosure of Interest: G. Longarini: None declared, E. Sugai: None declared, H.
Hwang: None declared, F. Nachman: None declared, A. Cabanne: None
declared, H. Vazquez: None declared, M. Moreno: None declared, A. Costa:
None declared, M. Pinto: None declared, S. Niveloni: None declared, E.
Smecuol Financial support for research from: Astra Zeneca, Lecture fee(s)
from: Astra Zeneca; Takeda, Consultancy for: Astra Zeneca, R. Mazure: None
declared, E. Maurino: None declared, J. Bai: None declared
P0527 HIGH RATES OF PRIOR CELIAC DISEASE OVERDIAGNOSIS
AMONG PATIENTS REFERRING TO AN ITALIAN TERTIARY
CARE CENTER
G. Ianiro1,*, G. Bruno1, S. Bibbo`1, S. De Martino1, V. Arena2, A. Gasbarrini1,
G. Cammarota1
1
Dept of Internal Medicine, Division of Gastroenterology, 2Histopathology Unit,
CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: Celiac disease (CD) was formerly considered a rare condi-
tion and frequently underdiagnosed. Interest in CD has grown in recent years,
not only among gastroenterologists but also among general practitioners and
patients. Furthermore, focus of media on gluten-free diet (GFD) is increasingly
spreading worldwide. Therefore many patients are labeled as celiacs and start a
GFD even without completing the correct diagnostic process.
AIMS & METHODS: Our aim is to assess the impact of overdiagnosis in an
Italian tertiary referral center for CD. We reviewed the clinical history of all
patients referring to our Centre from October 2012 to December 2013. We
included only patients at their first examination. We questioned diagnoses for
the following reasons: EMA/TTG absence or negativity; duodenal biopsy not
performed or unclear; DQ2/DQ8 negativity. Following data of patients with a
doubtful diagnosis were extracted: people who have diagnosed CD (physicians or
patients); reasons for diagnosis (symptoms, DQ2/DQ8, specific antibodies, duo-
denal biopsy), gluten consumption status. Number of patients undergoing a
proper diagnostic process was determined, as well as of patients with a prior
undebatable diagnosis. Diagnosis was revaluated by repetition of serology and
by second-reading of duodenal tissue slides by an experienced pathologist. DQ2/
DQ8 was searched in pertinent cases.
RESULTS: Over the study period, 293 patients attended our Centre, of whom
150 for the first time. Of them, 47 (31.3%) presented with an undebatable diag-
nosis of CD, and 37 (24.7%) were newly diagnosed because of EMA/TTG posi-
tivity associated with duodenal Marsh lesions. In 15 patients (10%) referring for
United European Gastroenterology Journal 2(5S)
family history of CD, gastrointestinal symptoms or anemia, CD was excluded by
serology and histology assessment. The remaining 51 patients (34%) came for a
revaluation of previously diagnosed CD. Forty-five of them (88%) were on a
GFD at the time of the examination. Thirty-five patients (68.6%) were diagnosed
of CD by their trusted doctor (gastroenterologist, gynaecologist, dermatologist
or general practitioner), while the remaining 16 (31.4%) believed to be affected of
CD on their own. Motivations for prior CD diagnosis were often multiple for
each patient: serologic positivity (9 AGA, 5 EMA, 2 TTG) in 16 cases, histolo-
gical features in 19 cases, DQ2/DQ8 positivity in 20 cases, amelioration of symp-
toms after GFD in 16 cases. Reasons for questioning previous diagnosis were
also multiple for each patient: EMA/TTG absence or negativity in 45 cases; lack
of duodenal biopsy in 20 cases; unclear histology in 24 cases; DQ2/DQ8 nega-
tivity in 2 cases. Diagnosis of CD was rejected in 78.4% of doubtful cases
(n 40), being confirmed in only 19.6% (n 10) of them. In one patient, diag-
nosis is still ongoing.
CONCLUSION: Our retrospective study shows that a considerable number of
patients referring to an Italian tertiary care center experience previous misdiag-
nosis and/or overdiagnosis of CD. Such behavior may lead to both a diagnostic
delay of other diseases and a remarkable waste of economic resources (tax
exemptions, gluten-free food vouchers, diagnostic exams), with damage for
both patients and health services. Greater accuracy in the application of the
adequate diagnostic process and a higher adherence to guidelines are needed to
minimize misdiagnosis of CD.
Disclosure of Interest: G. Ianiro: nothing to declare, G. Bruno: nothing to
declare, S. Bibbo`: nothing to declare, S. De Martino: nothing to declare, V.
Arena: nothing to declare, A. Gasbarrini: nothing to declare, G. Cammarota:
nothing to declare
P0528 GLUTEN AVOIDANCE BEFORE A DEFINITE DIAGNOSIS IS
MORE COMMON AMONG NON-CELIAC SUBJECTS THAN
CELIAC ONES
G. Ianiro1,*, G. Bruno1, S. Bibbo`1, S. De Martino1, V. Arena2, A. Gasbarrini1,
G. Cammarota1
1
Dept of Internal Medicine, Division of Gastroenterology, 2Histopathology Unit,
CATHOLIC UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: Gluten is known to trigger not only celiac disease, but also
other conditions, such as non-celiac gluten sensitivity (NCGS) and wheat allergy,
recently grouped together as gluten-related disorders. Gluten has recently 1
shown to cause depression in subjects with NCGS. Furthermore, gluten is able
to cause gastrointestinal (GI) symptoms and to alter bowel barrier functions in
patients with diarrhea-predominant irritable bowel syndrome (IBS-D). Gluten-
free claims are increasingly spreading on the Web and other media, and many
subjects start a gluten-free diet (GFD) without any prior medical consultation.
Such a behavior may lead to a considerable waste of resources and to diagnostic
delay both in celiac and in non-celiac subjects.
AIMS & METHODS: Our aim was to assess the impact of gluten avoidance
before a definite diagnosis in both patients with and without celiac disease. We
reviewed the clinical history of all patients referring to our CD outpatient clinic
from October 2012 to December 2013. We included only patients without a
definite diagnosis of CD at their first examination at our Centre. Patients were
grouped according to their gluten consumption status at the time of examination.
Gluten was reintroduced for at least 2 months before any diagnostic assessment
in all subjects already on GFD. The following data were extracted from patients
on GFD at the time of examination: gender, age, reasons for gluten avoidance
without definite diagnosis (GI/extraintestinal symptoms, DQ2/DQ8, specific
antibodies, duodenal biopsy), proposer of GFD (physicians or the patient
itself). All patients underwent blood dosage of EMA, TTG and total IgA
levels, as well as upper endoscopy with duodenal biopsy. In all patients CD
was diagnosed because of EMA and TTG positivity associated with Marsh-
type intestinal lesions. Correlation between gluten avoidance and further diag-
nosis of CD was assessed by Chi-square test.
RESULTS: Over the study period, a total amount of 293 patients attended our
Centre, of whom 150 (M 41, F 109 mean age 39 y) for the first time. Ninety-two
patients came without a definite diagnosis of CD. Of them, 32 (34.8%) were on
GFD at the time of examination, and 60 (66.2%) were not. Reasons for GFD
without definite diagnosis were: GI symptoms (12 cases), extraintestinal symp-
toms (7 cases), DQ2/DQ8 positivity (9 cases), antibody positivity (6 cases), his-
tological features (9 cases). Sixteen patients started a GFD on their own (41%),
and 23 upon medical advice (58%). Gender did not influence gluten consumption
status (p 0.8376). Respectively, CD was diagnosed in 21.9% (7/32) of patients
on GFD and 71.8% (43/60) of patients on a gluten-containing diet at the time of
first examination (P50.0001).
CONCLUSION: Our study shows that gluten avoidance before a clear definition
of diagnosis is more common among subjects in whom CD is ruled out at a later
stage than ones diagnosed of CD afterwards. The increasing interest of physi-
cians and patients in gluten-related diseases, and unmotivated gluten-free claims
may explain such reasons. Also symptom burden and gluten influence on mental
component of patients may play a role in this phenomenon. However, the retro-
spective nature of our study represents a limitation in data analysis. Further,
prospective trials are warranted to clarify this issue.
Disclosure of Interest: G. Ianiro: nothing to declare, G. Bruno: nothing to
declare, S. Bibbo`: nothing to declare, S. De Martino: nothing to declare, V.
Arena: nothing to declare, A. Gasbarrini: nothing to declare, G. Cammarota:
nothing to declare
A279
P0529 IS VISCERAL ADIPOSE TISSUE A RISK FACTOR FOR SMALL
BOWEL ANGIOECTAISA?
A. Yamada1,*, R. Niikura1, Y. Kobayashi1, H. Suzuki1, H. Watabe1, S. Yoshida2,
Y. Hirata1, K. Koike1
1
Department of Gastroenterology, Graduate School of Medicine, 2Department of
Endoscopy and Endoscopic Surgery, The University of Tokyo, Tokyo, Japan
INTRODUCTION: Small bowel angioectasia (SBA) is one of the major bleeding
sources of obscure gastrointestinal bleeding (OGIB). Little is known about etiol-
ogy of SBA. Visceral adipose tissue (VAT) expresses some bioactive molecules
including vascular endothelial growth factor (VEGF), which is implicated in
normal or pathological vessel formation. In the present study, we investigated
VAT in association with the risk of small bowel angioectasia.
AIMS & METHODS: We retrospectively investigated 198 consecutive patients
(male: female; 117: 81, mean age 65.8  12.8 years) who underwent capsule
endoscopy (CE) and CT for investigation of overt and occult OGIB at the
University of Tokyo Hospital between January 2009 and September 2013.
VAT and subcutaneous adipose tissue (SAT) were measured by CT, and medical
history of concomitant disease and body mass index were obtained from their
medical records. Logistic regression analyses were used to evaluate associations.
RESULTS: Out of 198 OGIB patients, CE found SBA in 18 patients (9.1%).
Compared with patients without SBA, those with SBA had signiEcantly higher
VAT (96  76.0 cm2, vs. 63.4  51.5 cm2, p 0.016) and higher prevalence of
liver cirrhosis (11(61%) vs. 41(23%), p 0.0011). Prevalences of SBA progres-
sively increased according to VAT; 7.2% in patients with VAT less than 100 cm2,
whereas 12.5% in those between 100 cm2 and 150 cm2, 21.4% more than 150 cm2
(p 0.058 by trend test), respectively. Multivariate analysis showed that VAT
(odds ratio for each 10 cm2 increment, 1.1; 95% confidence interval (CI), 1.01-
1.19; p 0.025), liver cirrhosis (odds ratio, 5.5; 95% CI, 1.98-16.6; p 0.0011)
were related to significant risk factors of SBA.
CONCLUSION: In addition to liver cirrhosis, visceral adipose tissue is one of
the risk factors for small bowel angioectasia.
Disclosure of Interest: None declared
P0530 EVALUATION OF GASTRO-INTESTINAL LESIONS IN
PATIENTS UNDERGOING ORAL ANTICOAGULANT THERAPY BY
CAPSULE ENDOSCOPY
C. Marmo1,*, M.E. Riccioni1, R. Cianci2, G. Costamagna1
Digestive Endoscopy Unit, 2Institute of Internal Medicine, Catholic University of
Rome, "A. Gemelli" Hospital, Italy, Rome, Italy
Contact E-mail Address: clelia.marmo@alice.it
INTRODUCTION: Small bowel bleeding is still poorly studied in patients with
long-term anticoagulation therapy. Capsule endoscopy (CE) is the first-line
method for evaluation of bleeding in patient after negative upper endoscopy
and colonoscopy.
AIMS & METHODS: In this retrospective study, we had investigated the types
and frequency of small bowel GI bleeding lesions in patients undergoing oral
anticoagulant therapy, by CE. Of a total of 1085 CE obtained between January
2003 and June 2013, 679 were performed in patients with obscure gastrointestinal
bleeding. Of these 96 were obtained in patients undergoing oral anticoagulant
therapy, 55 males and 41 females, mean age 70.6 years (range 23-87 years). At
the time of evaluation by capsule endoscopy, the mean level of haemoglobin was
8.3 g/dl for males (normal values 14-18 g/dl) and 6.7 g/dl for females (normal
values 12-16 g/dl). The mean number of blood units used for transfusions was
5.7 per patient (range 2-20). All patients underwent upper and lower gastro-intest-
inal endoscopy, prior to capsule endoscopy (CE). If upper and lower examinations
were negative, CE was performed. The following data were recorded in the data
base: patient age, gender, indication for the examination, medical and surgical
history, bleeding history (including type of bleeding, total number of transfusions,
hospitalizations), number and type of prior diagnostic testing, and details of the
capsule examination.
RESULTS: In the series of patients undergoing oral anticoagulant therapy: 35/96
(36.4%) patients had negative examination; 22/96 (22.9%) had small-bowel
angiodysplasias, small bowel erosions 21/96 (21.8%), small bowel ulcerations
5/96 pts (5.2%), neoplasia 4/96 (4.1%). In the series of patients with OGIB
without anticoagulant therapy: 102/583 (17.4%) had angiodysplasias, small
bowel erosions 48/583 (8.2%), small bowel ulcerations 25/583 (4.2%), neoplasia
44/583 (7.5%)
CONCLUSION: Small bowel angiodysplasias remain the main cause of occult
GI bleeding. In our series, patients undergoing oral anticoagulant therapy had
high prevalence of small bowel angiodysplasias (36.4% for anticoagulant group
and 17.4% for control group). Furthermore in the anticoagulant group we have
seen a major occurrence of erosions (21.8% VS 8.2%).
Disclosure of Interest: None declared
P0531 FREQUENCY AND RISK FACTORS FOR REBLEEDING EVENTS
IN PATIENTS WITH SMALL BOWEL ANGIOECTASIA
E. Sakai1,*, H. Endo1, S. Umezawa1, A. Fuyuki1, S. Uchiyama1, H. Ohkubo1,
T. Higurashi1, T. Nonaka1, A. Nakajima1
1
Gastroenterology, Yokohama City University School of Medicine, Yokohama,
Japan
Contact E-mail Address: eiji525@yokohama-cu.ac.jp
INTRODUCTION: Small bowel angioectasia is reported as the most common
cause of bleeding in patients with obscure gastrointestinal bleeding (OGIB).
Although the safety and efficacy of endoscopic treatment have been demon-
strated, rebleeding rates are relatively high. To establish therapeutic and
A280
follow-up guidelines, we investigated the long-term outcomes and clinical pre-
dictors of rebleeding in patients with small bowel angioectasia.
AIMS & METHODS: A total of 68 patients were retrospectively included in this
study. All the patients had undergone CE examination, and subsequent control
of bleeding, where needed, was accomplished by endoscopic argon plasma coa-
gulation. Based on the follow-up data, the rebleeding rate was compared between
patients who had/had not undergone endoscopic treatment. Multivariate analysis
was performed using a Cox proportional hazard regression model to identify the
predictors of rebleeding. Rebleeding was defined as evidence of recurrent visible
gastrointestinal bleeding (hematochezia or melena) with recent negative upper
and lower endoscopic examinations and/or a reccurent drop of the hemoglobin
level by more than 2 g/dl from the baseline. We defined the OGIB as controlled if
there was no further overt bleeding within 6 months and the hemoglobin level
had not fallen below 10 g/dl by the time of the final examination.
RESULTS: The overall rebleeding rate over a median follow-up duration of 30.5
months (interquartile range 16.547.0) was 33.8% (23/68 cases). The cumulative
risk of rebleeding tended to be lower in the patients who had undergone endo-
scopic treatment than in those who had not undergone endoscopic treatment,
however, the difference did not reach statistical significance (P 0.14). In the
majority of patients with rebleeding (18/23, 78.3%), the bleeding was controlled
with additional endoscopic treatment by the end of the follow-up period.
Multiple regression analysis identified multiple lesions (3) (OR 3.82; 95% CI
1.3011.3, P 0.02) as the only significant independent predictor of rebleeding.
CONCLUSION: In conclusion, patients with small bowel angioectasia show
relatively high rebleeding rates. Although a single session of endoscopic treat-
ment was not sufficient to control future rebleeding, in most cases, rebleeding
could be controlled with repeated endoscopic treatment and/or iron replacement
therapy. Careful follow-up is needed for patients with multiple lesions, which was
identified as a significant risk factor for rebleeding.
Disclosure of Interest: None declared
P0532 GENE EXPRESSION LEVELS OF ANGIOGENIC FACTORS IN
SMALL BOWEL ANGIODYSPLASIA
G. Holleran1,*, B. Hall1, S. Smith1, D. McNamara1
1
Department of Clinical Medicine, Trinity College Dublin, Tallaght, Ireland
Contact E-mail Address: grainneholleran@gmail.com
INTRODUCTION: Angiodysplasias are known to account for 50% of small
bowel bleeding sources, but diagnosis and effective treatment of these lesions is
limited by a poor understanding of the pathophysiology of the condition. By
measuring serum angiogenic factors in patients with small bowel angiodysplasias
(SBA), we have already identified abnormalities in the angiopoietin pathway;
with elevated levels of Ang2 and decreased levels of Ang1, associated with the
condition. To determine the significance of these findings we need to determine
whether these factors and their receptors are specifically located in SBA tissue.
AIMS & METHODS: The aim of this study was to measure gene expression levels
of various angiogenic factors and receptors in SBA tissue compared to adjacent
normal tissue and to normal SB tissue in controls. Following informed consent,
patients aged 18-80 years of age undergoing double balloon enteroscopy for a
variety of small bowel disorders at Tallaght hospital were invited to participate.
From patients with SBA, one standard biopsy was taken from a single angiodys-
plasia lesion, and a further biopsy was taken from macroscopically adjacent normal
mucosa. In controls, a single small bowel mucosal biopsy was taken at random.
Biopsy samples were immediately placed in RNAlater solution and stored in a fridge
overnight before being stored at -80oC for batch analysis. Using a standard techni-
que, RNA was isolated and a reverse transcription reaction was performed on each
sample using the Fermantas first strand cDNA synthesis kit (Thermo Scientific).
The resulting cDNA was used in quantitative PCR reactions to determine the
relative expression of Ang1, Ang2, Tie2, VEGF and TNF. Relative gene expression
was calculated using the comparative cycle threshold (CT) method and was normal-
ised to the control gene GAPDH. Statistical analysis was performed using SPSS
version 20. Fold differences of each gene were expressed as a mean and compared
between groups, with a p value of 50.05 considered significant.
RESULTS: In total, 20 biopsy samples were collected; including 9 from angio-
dysplasia mucosa, 7 from adjacent normal mucosa, and 4 from normal mucosa in
controls. Detectable levels of genes encoding Ang1, Ang2, Tie2, TNF and VEGF
were found in all biopsy samples. There were significantly higher levels of Ang1
and its receptor Tie2 in angiodysplasia tissue compared to adjacent normal
mucosa and to controls, with mean fold differences of 1.77 vs 0.82 and 0.81
for Ang1 (p 0.049), and 1.66 vs 0.76 and 0.52 for Tie2 (p 0.02) respectively.
Levels of Ang2 appeared higher in angiodysplasias than both adjacent mucosa
and controls, however; this was only statistically significant between the angio-
dysplasias and their adjacent mucosa (p 0.04). There were no differences in
levels of TNF or VEGF expression between any of the samples.
Ang 1 Ang 2 Tie2 TNF VEGF
Control 0.8175 0.5625 0.76 0.79 1.1
Angiodysplasia 1.7667 0.7333 1.66 0.82 1.1367
Patient normal tissue 0.8129 0.3957 0.9714 0.8057 1.4057
p value 50.05 0.04 0.02 0.46 0.42
CONCLUSION: Expression of levels of genes encoding Ang1 and Ang2 and
their receptor Tie2 are higher in the mucosa overlying small bowel angiodyspla-
sias than unaffected mucosa. This further strengthens the identification of the
angiopoietin pathway as a key factor in the pathophysiology of SBA formation.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0533 WHAT IS THE LONG-TERM SAFETY OF A NEGATIVE CAPSULE
ENDOSCOPY IN PATIENTS WITH OBSCURE GASTROINTESTINAL
BLEEDING?
I. Ribeiro1,*, R. Pinho1, A. Rodrigues1, T. Pais1, C. Fernandes1, J. Silva1,
A. Ponte1, S. Leite1, J. Carvalho1
1
Centro Hospitalar Vila Nova Gaia, Vila Nova Gaia, Portugal
Contact E-mail Address: iolandacribeiro@gmail.com
INTRODUCTION: Although capsule endoscopy (CE) is the investigation of
choice in obscure GI bleeding (OGIB), the clinical outcomes of a negative capsule
remain contradictory according to different studies.
AIMS & METHODS: The aim of the study was to compare the long-term out-
come of patients with OGIB after a negative and a positive CE and identify risk
factors for rebleeding.
Methods: Retrospective study of 173 patients who underwent CE for OGIB, from
2005 to 2013; patients with a follow-up time 56 months were excluded. CE with no
lesions or with lesions P0 (petechial lesions; mucosal congestion) or P1 (isolated ero-
sions; small angiodysplasias) were considered negative. Rebleeding was defined as a
documented fall in hemoglobin of 2 g/dL from baseline, evidence of melena or hema-
tochezia, and the need for blood transfusion, at least 30 days after the index bleed.
We evaluated the demographic characteristics, type of OGIB (overt vs occult),
medication, rebleeding rate after a negative and a positive CE, type of treatment
(endoscopic/surgical) performed in patients with positive CE and the influence on
rebleeding. Statistical tests: t-student, 2.
RESULTS: The mean age was 61.7 years; 67% of patients underwent CE
because of occult GIB; 54.3% of CE were negative; the mean follow-up time
was 27 months ( 23.4) and the overall rebleeding rate was 22.5%. The rebleed-
ing rate after a negative CE was significantly lower than after a positive CE (16%
vs 30.4%, p 0.024). Patients who rebleed needed more transfusions of red blood
cells (mean 6.0) prior to CE when compared with those who did not rebleed
(mean 1.2, p50.001). Age, sex, anticoagulants or anti-agregants did not influ-
ence the rebeeding rate.
Almost 50% of patients with a positive study underwent endoscopic (56.4% -
argon plasma coagulation) or surgical treatment (28.2%), with significantly
lower rebleeding rate than patients who did not undergo any treatment (23.1%
vs 37.5%, p 50.02).
CONCLUSION: Conclusions: A negative CE study in patients with OGIB is
associated with a low rate of recurrent bleeding in the long term (16%). It is
reasonable to take an expectant approach with these patients, thus avoiding the
need for unnecessary additional investigations. The endoscopic/surgical treat-
ment decreases the rebeeding rate after a positive CE.
Disclosure of Interest: None declared
P0534 SMALL BOWEL CAPSULE ENDOSCOPY IN ELDERLY
PATIENTS. INDICATIONS AND FINDINGS
N. Viazis1, K. Katopodi1,*, M. Chanias1, E. Anastasopoulos1, G. Kechagias1,
K. Markoglou1, M. Mela1, E. Keimali1, D.G. Karamanolis1
1
Department of Gastroenterology, EVANGELISMOS HOSPITAL, Athens,
Greece
Contact E-mail Address: nikos.viazis@gmail.com
INTRODUCTION: Given the aging of the European population a growing
number of elderly patients need to be subjected to small bowel capsule endo-
scopy. In our study we aimed to determine the indications and findings of
patients aged 4 80 years old subjected to small bowel capsule endoscopy in
our Department, in comparison to those aged 5 80 years old.
AIMS & METHODS: From March 2003 till August 2013, 3410 patients have been
subjected to small bowel capsule endosopy (Given imaging) in our Department.
Among them, 131 were 4 80 years old. We analyzed the indications and findings of
these patients in comparison to the rest of the patients subjected to the test.
RESULTS: Among the 131 patients aged 4 80 years old, the 106 (80.9%) have
been subjected to small bowel capsule endoscopy because of obscure gastroin-
testinal bleeding. The corresponding percentage for patients aged 5 80 years old
was 60.2%. The remaining patients have been subjected to the test because of
suspected Crohns disease (n 9, 6.8%), chronic diarrhea (n 9, 6.8%) and
abdominal pain (n 7, 5.3%). The corresponding figures for those patients
aged 5 80 years old were 21.7%, 3.7% and 4.3% respectively. The findings of
the test in both age groups in cases of obscure gastrointestinal bleeding are
presented in table 1. No patient aged 4 80 years old had any complication
due to the small bowel capsule endoscopy investigation.
Table 1. Findings of small bowel capsule endoscopy
Patients 4 80 years old Patients 5 80 years old
Angiodysplasias 86.3% 59.2%
Apthoid ulcers 0.9% 13.0%
Ulcerations 5.4% 12.0%
Polyps 2,7% 9.9%
Tumors 4,6% 5.8%
CONCLUSION: Small bowel capsule endoscopy in elderly patients is mainly
done for the investigation of obscure gastrointestinal bleeding. The test appears
to be safe in these cases and angiodysplasias are detected more frequently than in
younger patients.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0535 NON ANEMICS WITH EROSIVE GASTRITIS MORE
FREQUENTLY PRESENT SMALL BOWEL ULCERATIVE LESIONS
P. Tsibouris1, P. Apostolopoulos1, C. Kalantzis1, E. Houda1, K. Dimopoulos1,
C. Beltsidou1, E. Vlachou1,*, G. Alexandrakis1
1
GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece
INTRODUCTION: Although erosive gastritis can cause iron deficiency anemia,
its presence cannot prevent small bowel evaluation with capsule endoscopy.
AIMS & METHODS: Aim: To define the risk to find small bowel ulcerative
lesions and anemia in patients with erosive gastritis.
Methods: 1010 patients undergone small bowel capsule endoscopy, gastroscopy
and colonoscopy were evaluated. 537 were evaluated for iron deficiency anemia
or recent obscure bleeding, 324 for diarrhea, 60 for unexplained abdominal pain
and 89 for other causes. 176 patients excluded from the analysis, as they pre-
sented either inflammatory bowel disease or celiac disease and 81 because they
presented a gastric or a duodenal ulcer, leaving a study population of 753
patients (mean age 6416 years, 421 men, 159 active smokers). Erosive gastritis
was present in 132 (mean age 6515 years, 77 men, 32 active smokers). Stat: X2,
logistic regression analysis.
RESULTS: 50 (38%) patients with erosive gastritis and 161 (26%) without pre-
sented small bowel erosions (p 0.006). 27 (48%) patients with erosive gastritis
consuming aspirin or NSAIDs and 50 (33%) NSAIDs consumers without erosive
gastritis presented small bowel erosions (p 0.04). 13 (41%) patients with erosive
gastritis on clopidogrel and 23 (29%) clopidogrel consumers without erosive
gastritis presented small bowel erosions (p 0.26). Among patients not on anti-
platelets, 10 (23%) with erosive gastritis and 88 (23%) without presented small
bowel erosions (p 0.97). Among anemics, 19 (42%) patients with erosive gas-
tritis consuming aspirin or NSAIDs and 44 (34%) NSAIDs consumers without
erosive gastritis presented small bowel erosions (p 0.04). 12 (30%) patients with
erosive gastritis on clopidogrel and 18 (28%) clopidogrel consumers without
erosive gastritis presented small bowel erosions (p 0.26). No patient with ero-
sive gastritis not consuming antiplatelets and 40 (20%) without erosive gastritis
presented small bowel erosions (p 0.048). In logistic regression analysis old age,
erosive gastritis, AF and use of aspirin were related with increased risk for small
bowel ulcerative lesions and diabetes with reduced risk.
CONCLUSION: Non anemics with erosive gastritis are at risk for small bowel
erosions, especially if they consume aspirin or NSAIDs, because small bowel
mucosa is possibly more vulnerable to noxious stimula. On the other hand,
among anemics erosive gastritis was related with less small bowel ulcerative
lesions among no antiplatelet consumers. Possibly because erosive gastritis is
an independent cause of iron deficiency anemia.
Disclosure of Interest: None declared
P0536 PATIENTS WITH ATRIAL FIBRILLATION ON CLOPIDOGREL
ARE AT HIGH RISK TO DEVELOP SMALL BOWEL ULCERATIVE
LESIONS AND ANEMIA
P. Tsibouris1,1, P. Apostolopoulos1, I. Koumoutsos1, C. Kalantzis1, E. Chounta1,
K. Dimopoulos1, C. Beltsidou1, G. Alexandrakis1,*
1
GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece
INTRODUCTION: Patients with atrial fibrillation are usually on antiplatelet
treatment or anticoagualants.
AIMS & METHODS: Aim: To define the risk to find small bowel ulcerative
lesions and anemia in patients with atrial fibrillation on antiplatelet or antic-
oagulant treatment.
Methods: 1010 patients undergone small bowel capsule endoscopy, gastroscopy
and colonoscopy were evaluated. 537 were evaluated for iron deficiency anemia
or recent obscure bleeding, 324 for diarrhea, 60 for unexplained abdominal pain
and 89 for other causes. 176 patients excluded from the analysis, as they pre-
sented either inflammatory bowel disease or celiac disease, leaving a study popu-
lation of 834 patients (mean age 6416 years, 476 men, 176 active smokers).
Atrial fibrillation (AF) presented 78 patients (mean age 767 years, 41 men, 8
active smokers). Stat: X2, logistic regression analysis.
RESULTS: 246 (29%) patients presented small bowel ulcerative lesions; 164
(31%) anemic and 78 (26%) non-anemic (p 0.19). 33 (42%) AF patients and
213 (28%) without AF presented small bowel ulcerative lesions. Small bowel
ulcerative lesions were present in 14 (48%) AF aspirin/NSAID users, 13 (42%)
AF clopidegrel consumers and 6 (33%) AF patients not receiving antiplatelets. In
addition they were present in 132 (38%) aspirin/NSAID users without AF
(p 0.31), 23 (29%) clopidogrel consumers without AF (p 0.02) and 109
(23%) patients without AF not receiving antiplatelets (p 0.33). Thus small
bowel ulcerative lesions were more common among aspirin users without AF
(p 0.001), but not those with AF (p 0.41). Moreover there was no difference
between aspirin and clopidogrel (AF: p 0.62; no AF: p 0.14). Among anemics
small bowel ulcerative lesions were present in 14 (56%) AF aspirin/NSAID users,
14 (47%) AF clopidegrel consumers and 2 (17%) AF patients not receiving anti-
platelets. In addition they were present in 67 (37%) aspirin/NSAID users without
AF (p 0.08), 17 (27%) clopidogrel consumers without AF (p 0.02) and 109
(22%) patients without AF not receiving antiplatelets (p 0.33). Thus small bowel
ulcerative lesions were more common among aspirin users with (p 0.02) and
without AF (p 0.0006). Moreover there was no difference between aspirin and
clopidogrel (AF: p 0.49; no AF: p 0.13). In logistic regression analysis old age,
erosive gastritis, AF and use of aspirin were related with increased risk for small
bowel ulcerative lesions and diabetes with reduced risk.
CONCLUSION: Small bowel ulcerative lesions are more common among
aspirin users. Clopidogrel is generally safer, nevertheless both presence of
anemia and small bowel ulcerative lesions are more common among patients
with atrial fibrillation, possibly because small bowel mucosa is more vulnerable
to develop inflammatory lesions in this patient group.
A281
Disclosure of Interest: None declared
P0537 REDUCTION OF NSAID-INDUCED SMALL INTESTINAL
DAMAGE IN RHEUMATOID ARTHRITIS PATIENTS RECEIVING
SULFASALAZINE
A. Balabanceva1, S. Tkach2,*
Crimea Medical University, Simferopol, Russian Federation, 2National Medical
1
Univercity, Kyiv, Ukraine
INTRODUCTION: Recent studies have demonstrated that nonsteroidal anti-
inflammatory drugs (NSAIDs) often cause damage to the small intestine, and
NSAID-induced enteropathy is mediated by different inflammatory cytokines.
Sulfasalazine is being widely used in patients with rheumatoid arthritis (RA), and
this drug have the potential to induce mucosal healing in patients with intestinal
diseases such as inflammatory bowel diseases.
AIMS & METHODS: To evaluate the preventive effect of sulfasalazine against
small intestinal damage due to chronic NSAID use in RA patients. Between
March 2009 and June 2011, capsule endoscopy was performed in 51 consecutive
RA patients who received NSAIDs for more than 3 months with or without
sulfasalazine therapy over a period of 3 months. The findings were scored as
follows according to the method described by Graham et al. (Clin Gastroenterol
Hepatol. 2005): 0, normal; 1, red spots; 2, 1 to 4 erosions; 3, 44 erosions; and 4,
large erosions/ulcers. Scores of 3 and 4 indicated severe damage. The relationship
between the use of sulfasalazine therapy and risk of severe damage (score 3 or 4)
or severest damage (score 4) were assessed using multiple logistic regression.
RESULTS: Comparative data were analyzed for 47 patients, and 4 patients were
excluded because the entire small bowel could not be visualized in these patients.
Of the 25 patients who did not receive sulfasalazine therapy, 12 (48%) had severe
damage (score of 3 [n 8] or 4 [n 4]). On the other hand, of the 26 patients
receiving sulfasalazine therapy, 5 (19.2%) had severe damage (score of 3 [n 3]
or 4 [n 2]). On stratifying the patients by sulfasalazine therapy, we obtained a
crude odds ratio (OR) of 0.26 for severe damage with a 95% confidence interval
(CI) of 0.10 to 0.66, and of 0.38 for severest damage with a 95% CI of 0.17 to
0.88. This effect of sulfasalazine therapy on NSAID-induced enteropathy
remained robust to adjustment for age, gender, history of peptic ulcers, disease
activity score-28 (a disease activity index for RA), use of selective cyclooxygen-
ase-2 inhibitors or steroids, blood hemoglobin concentration, and all these vari-
ables, with the adjusted ORs for severe damage ranging from 0.19 to 0.25 and
those for severest damage ranging from 0.30 to 0.40.
CONCLUSION: Sulfasalazine therapy may protect against NSAID-induced
small intestinal damage in RA patients and may be effective in the treatment
of NSAID-induced enteropathy.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
NUTRITION I POSTER EXHIBITION HALL XL_____________________
P0538 IS THE TRADITIONAL DIET DISAPPEARING AT THE SAME
TIME AS THE PREVALENCE OF OBESITY IS INCREASING IN
ITALY? EVALUATION OF EATING HABITS IN A GROUP OF
ITALIAN OBESE FEMALE PATIENTS
A. Guida1,*, A. Frascari1, E. Canducci1, B. Ravani1, G. Bersani2, A. Rossi2,
R. Arena1, A. Maimone1, V. Alvisi3, G. Ricci1
1
Medical Sciences, University of Ferrara, Ferrara, 2Digestive Endoscopy Service,
3
Internal Medicine, Malaesta Novello Hospital, Cesena, Italy
Contact E-mail Address: ada.guida@student.unife.it
INTRODUCTION: The nutrition transition from traditional to Western dietary
patterns could account for the dramatic rise in the prevalence of obesity in Italy
(1).
AIMS & METHODS: We describe the dietary patterns in a group of obese
Italian female patients. A retrospective survey was conducted on the records of
113 obese (BMI 40.27.0 kg/m2) female inpatients aged 19-60 y (mean 40.5 y).
Anthropometric measurements and dietary patterns were obtained from the
records. Dietary habits were recorded by detailed questioning and computed
database determined the nutrient intakes. The recommended dietary allowances
(RDAs) for the Italian population were used as the reference range. The sample
was also divided, according to age, into three groups (19-35y, 36-45y, 46-60y).
Statistical analysis was performed by PASW 18.0.
RESULTS: The table shows the variations, as percentages, of the nutrient
intakes over or below the RDAs. The values are expressed as 50th (25th, 75th)
percentile. Animal protein intakes averaged 266% over the RDAs in the whole
sample, with median variations from 241 to 278% among the age groups. The
intake rates of total carbohydrates (CHO) were minimally higher on average (15-
19%) than the RDAs. The simple CHO intake averaged 67-90% over RDAs.
The !-6/!-3 fatty acid ratio was about 100% over the RDA, without significant
differences among age groups. Moreover the intakes of !-6 fatty acids was 64%
over the RDA, but in the younger group the variation rate from the RDA was
significantly higher (72%, p50.05) than in the older group (50%). Nutrients with
protective effects, such as PUFA and !-3 fatty acids, averaged 35-48% and 11-
19% below RDAs, respectively.
A282 United European Gastroenterology Journal 2(5S)

P0540 THE RELATIONSHIP BETWEEN OSTEOPOROSIS AND LEPTIN

Nutrient intakes RDAs (g) all (113) 19-35 y (37) 36-45 y (36) 46-60 y (40) IN OBESE FEMALES
D. Neagoe1,*, G. ianosi2, A. amzolini1, A. farmazon3, M. popescu4,
Protein 64 (59, 66) 100 (71, 132) 95 (75, 108) 119 (70, 166) 112 (80, 130) A. turculeanu5, C. deliu3, T. ciurea1
1
Animal Protein 74 (55, 100) 266 (171, 349) 241 (171, 316) 248 (164, 385) 278 (214, 354) internal medicine, 2surgical, university of medicine and pharmacy, 3internal med-
Fat 136 (112, 165) 129 (88, 175) 151 (113, 175) 129 (85, 195) 118 (80, 162) icine, emercency hospital no.1, 4endocrinology, 5laboratory, university of medicine
PUFA 10 (7, 13) -44 (-57, -23) -35 (-53, -15) -35 (-57, -19) -48 (-59, -31) and pharmacy, craiova, Romania
!-3 1.2 (1.1, 1.3) -16 (-34, 11) -11 (-28, 44) -19 (-43, 8) -18 (-34, 9)
!-6 4.8 (4.6, 5.3) 64 (27, 123) 72 (42, 164) 74 (27, 126) 50 (23, 90) INTRODUCTION: The pathogenesis of decreased bone mineral density (BMD)
!-6/!-3 4 100 (66, 123) 89 (49, 119) 102 (69, 133) 102 (67, 123) in NAFLD is unclear. Hyperleptinemia, hormone mainly secreted by white adi-
pose tissue, is associated with inflammatory process, suppress bone formation
Total CHO 363 (347, 380) 19 (2, 40) 19 (-2, 42) 31 (9, 51) 15 (-2, 28)
and increase bone resorbtion. Aim of our study was to correlate leptin level with
Simple CHO 69 (66, 72) 84 (27, 146) 90 (32, 142) 84 (14, 166) 67 (33, 117)
decreased BMD in obese females.
AIMS & METHODS: We included obese females in postmenopausal period for
at least 1 year: 54 with NAFLD and 56 without NAFLD, age, waist circumfer-
CONCLUSION: We observed that the highest variation rates were not found for ence (WC) and body mass index (BMI) matched. Exclusion criteria: diabetes
total carbohydrates or simple carbohydrates, as could be expected, but for fat mellitus, chronic use of corticosteroids, supplementation with calcium products,
and protein, and especially for animal protein. Moreover the excessive consump- secondary obesity due endocrine diseases, renal disease, alcohol intake, smoking,
tion !-6 fatty acid, with unbalanced !-6/!-3 fatty acid ratio, could show a previous fractures. Blood samples were collected in both groups for lipid profile,
tendency to change the traditional Italian diet towards Western eating habits. hepatic enzymes and leptin (references values 4.9-24ng/ml). Lumbar BMD was
However there was no significant difference between younger and older people. measured by DEXA and abdominal ultrasonography was performed by the same
REFERENCES physician and steatosis was graded using a semi-quantitative scale of 1 (mild) to 3
1. Inelmen EM, Toffanello ED, Enzi G, et al. Differences in dietary patterns (severe).
between older and younger obese and overweight outpatients. J Nutr Health RESULTS: In NAFLD group mean age was 49.5 years, BMI 32,53 and WC
Aging 2008; 12: 3. 995cm, in second group mean age was 51,3 years, BMI 30,33 and WC 975,
Disclosure of Interest: None declared without statistic significance between the two groups. In NAFLD group 24
females had mild steatosis, 18 had moderate and 12 had severe steatosis. No
evidence of steatosis in group B. Leptin level was 8.7ng/ml1.2 in group B
P0539 CAN INTERVENTION ON LIFESTYLE HAVE AN IMPACT ON and 15.2ng/ml5.1 in NAFLD group, with significance statistic differences
CARDIORESPIRATORY FITNESS IN THE NON-OPERABLE between the two groups. In NAFLD group we found 9 patients with normal T
SEVERELY OBESE PATIENT? score, 21 patients with osteopenia and 24 with osteoporosis. In group B we found
D.A. L. Hoff1,*, F. Wammer2, A. Haberberger3 15 patients with normal T score, 25 with osteopenia and 16 with osteoporosis.
1
Dept.of Medicine, Div. of Gastorenterology and Hepatology, 2Dept.of Medicine, BMD was lower in NAFLD women than these without NAFLD and osteoporo-
Div. of Pulmonary diseases, Aalesund Hospital, Aalesund, 3Centre of achievement sis in NAFLD group seemed to be associated a more severe liver disease. In
and rehabilitation, Muritunet, Valldal, Norway NAFLD group the highest levels of serum leptin were found in moderate or
Contact E-mail Address: dagalhoff@gmail.com severe steatosis with osteoporosis and we found a positive correlation with
BMI and WC (p 0.000 and p 0.002). In the other group, leptin level had
INTRODUCTION: Severe obesity (BMI 4 40 kg/m2 or 35 kg/m2 and complica- no significant differences in relationship with BMI, WC or decreased BMD.
tions) is associated with higher frequency of comorbidities such as respiratory CONCLUSION: In our study, leptin level was correlated with osteoporosis in
failure and higher premature mortality compared to less obese patients. Diet NAFLD group. In obeses females without NAFLD, leptin level was similar
change, physical exercise and lifestyle modifications are the only therapeutic despite the presence or absence of osteoporosis.
options for a substantial proportion of patients. The literature on cardiorespira- Disclosure of Interest: None declared
tory fitness in these patients is sparse.
AIMS & METHODS: To examine whether or not a systematic rehabilitation
program providing lifestyle intervention has a significant positive impact on P0541 ENDOSCOPIC REMOVAL OF GASTRIC BANDS A HEAVY
cardiorespiratory fitness in the non-operable severely obese patients. ISSUE
Forty non-operable severely obese patients (F 29, M 11, mean age 44 y, range 23- D. Branquinho1,*, D. Gomes1, N. Almeida1, C. Sofia1
62 y) were consecutively enrolled in a rehabilitation program. In total 33 patients 1
Gastroenterology, Coimbra University Hospital (CHUC), Coimbra, Portugal
stayed in the program 12 months after enrolment, but 6 of them did not complete Contact E-mail Address: diogofbranquinho@yahoo.com
all tests due to acute illness. Eligible for enrolment was patients in groups of 12-
15, in all 4 groups. The first stay lasted 4 weeks, the consecutive stays 2 weeks INTRODUCTION: One of the most popular methods in bariatric surgery is the
every 6 months. At each stay a team of nurses, physician, dietician, psychologist gastric band. However, its migration into the gastric lumen has frequently been
and physical activity therapist provided education and physical exercise to each described as a long-term complication. There is no consensus on how to handle
patient individually or to patients assembled as a group, including matched such cases, but its removal through endoscopy is increasingly being documented
patients conversations. At enrolment patients were classified as respiratory as a safe and effective alternative. The authors present a Gastroenterology
healthy or as having chronic respiratory illness. Furthermore at the beginning department 5-year experience.
of each stay body weight, peak oxygen uptake (VO2peak) and functional residual AIMS & METHODS: To describe our experience in a relatively novel endo-
capacity % (FRC %) were registered and body mass index (BMI) calculated. The scopic technique useful to handle a common bariatric surgey complication.
test was performed on a treadmill programmed in a standard fashion regarding Review of clinical files and endoscopic imaging.
velocity and inclination. All tested patients reached anaerobic threshold RESULTS: A total of eight procedures were undertaken in morbidly obese
(VO2peak). female patients (average age: 38.7 years old). Median time between initial surgery
Mean  standard deviation are reported at inclusion and one year after inclu- and band removal was about 6931.9 months. Clinical manifestation was weight
sion. FRC% is regarded normal above 80 %. increase in 5 patients and upper abdominal pain in the remaining three. All cases
RESULTS: We report on cardiorespiratory fitness in 27 patients (F 19, M 8, were diagnosed through upper digestive endoscopy.
mean age 45 y, range 23-62) 12 months beyond baseline. Ten patients were During such procedures, a 0.035 inch guidewire and a Soehendra lithotripter
respiratory healthy and 17 had respiratory illnesses; asthma (N 4), chronic were used to cut through the band, which was then pulled with a polypectomy
obstructive lung disease (N 1) and obstructive sleep apnoea syndrome snare. Extraction of the cutaneous port was done by the assisting surgeon.
(N 12). Body weight: 125.5  21.7 kg vs 120.1  23.1 kg, p 0.004. BMI: Average duration of the procedure was about 30 minutes.
42.1  3.9 kg/m2 vs 40.6  5.2 kg/m2, p 0.016. FRC%:76.9  12.1 % vs A peritoneal leak was the only major complication, due to the passage of air from
80.4  13.8 %, p 0.069. VO2peak during exercise: 22.7  3.0 ml*kg-1min-1 vs the stomach lumen to the peritoneum through the band internal canal.
24.0  4.5 ml*kg-1min-1, p 0.032. CONCLUSION: Considering the high number of gastric band procedures under-
CONCLUSION: We found a significant improvement in cardiorespiratory fit- taken in the last few years, its intra-gastric migration will be a common clinical
ness in a group of 27 non-operable severely obese patients that participated in a issue. This endoscopic approach, although technically demanding, is a safe and
systematic rehabilitation program for one year. Our results should be verified in effective alternative, thereby avoiding morbidity associated with a major surgical
larger scale studies. This would also make it possible to stratify patients accord- intervention.
ing to respiratory health. Disclosure of Interest: None declared
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0543 FIRST REPORTS OF THE NEW SPATZ 3 ADJUSTABLE
BALLOON SYSTEM
E. Machytka1,*, Z. Kowalczyk2, S. Al Awadhi3, M. Al Falasi3, J. Mason4,
L. Bene5, S. El Asala6, V. Puig-Divi7, M. Buzga1, J. Brooks8
1
Faculty of Medicine, UNIVERSITY OF OSTRAVA, Ostrava, Czech Republic,
2
Bariatric clinic Pulsmed, Lodz, Poland, 3Rashid Hospital, Dubai, United Arab
Emirates, 4National Obesity Surgery Center, Manchester, United Kingdom,
5
Rozsakert Medical Center, Budapest, Hungary, 6Alain Hospital, Dubai, United
Arab Emirates, 7Opcion Medical Clinic, Barcelona, Spain, 8Spatz FGIA, Great
Neck, United States
Contact E-mail Address: machytka@obezita-balon.cz
INTRODUCTION: The original Spatz Adjustable Balloon System for weight
loss was introduced in 2010. It was the first intragastric balloon approved for
1 year implantation with the added feature of balloon volume adjustability. This
enabled changes to balloon volume during the course of the 1 year implantation
period. It contained a rigid catheter and metal chain that caused duodenal migra-
tion. The new Spatz 3 intragastric balloon device, CE Mark approval in 2012, has
a soft catheter to simplify the procedure and decrease complications. In addition,
reports of volume adjustments using a mean 177 ml yields additional 1.7 kg/
month wt loss. It has been suggested that adjusting with larger volumes will yield
better results. We report our experience with the Spatz 3 device in 7 centers.
AIMS & METHODS: To determine the difference between the reported results
of the original Spatz Adjustable balloon System and the new Spatz3 Adjustable
balloon System with respect to ease of use, complications, weight loss results and
the effect of larger volume adjustments. 158 patients with mean BMI 40.1; mean
weight 109 kg; mean age 37; were implanted with the Spatz3 device. Mean
balloon volume was 473 ml (400-600). Adjustments were made for intolerance
or weight loss plateau.
RESULTS: All endoscopists felt that the Spatz 3 device was easier to use than the
original Spatz adjustable balloon system device. Mean wt loss at 12 weeks was
12.5 kg with an 11.7% wt loss and 28.8 % EWL (% excess wt loss). At 24 weeks
mean wt loss was 16,2 kg; 16.7% wt loss, and 35,3 % EWL. 94 patients reached 9
months with a reported mean wt loss of 23.2 kg; 20.4 % weight loss; and 44.9 %
EWL. And 48 patients after 12 months with mean wt loss of 24.1 kg; 20.6 %
weight loss; and 48.1 % EWL. There were 49 balloon volume adjustments: 11
downward adjustments of 100 cc alleviated early intolerance, with added mean
wt loss of 15.3 kg after the adjustment; 38 upward adjustments (mean 327 ml;
range 150-500) at a mean month 4,1 yielded additional mean wt loss of 8.7kg
after the adjustment. 7 balloons were extracted; early intolerance and refusal to
adjust volume downward (4); gastric ulcer (2); deflation (1).
CONCLUSION: The Spatz 3 adjustable balloon is easier and less complicated
than the original Spatz device. Complications associated with the original cathe-
ter have not been seen in the Spatz 3 device. Larger volume adjustments yield
greater weight loss results.
Disclosure of Interest: E. Machytka: None declared, Z. Kowalczyk: None
declared, S. Al Awadhi: None declared, M. Al Falasi: None declared, J.
Mason: None declared, L. Bene: None declared, S. El Asala: None declared,
V. Puig-Divi: None declared, M. Buzga: None declared, J. Brooks Shareholder
of: Spatz FGIA
P0544 WEIGHT MAINTENANCE 2 YEARS AFTER EXTRACTION OF
THE SPATZ ADJUSTABLE BALLOON
E. Machytka1,*, L. Bene2, G. Lopez-Nava3, M. Buzga1
1
Faculty of Medicine, UNIVERSITY OF OSTRAVA, Ostrava, Czech Republic,
2
Rozsakert Medical Center, Budapest, Hungary, 3Hospital Sanchinarro, Madrid,
Spain
Contact E-mail Address: machytka@obezita-balon.cz
INTRODUCTION: The Spatz Adjustable Balloon System was developed to
provide an adjustable intragastric balloon approved for 1 year implantation.
Weight loss results 4 20 kg/year have been reported in the literature. The ques-
tion is whether treatment with an intragastric balloon also leads to better weight
loss maintenance after balloon removal. A prospective study on the BIB balloon
has reported maintenance of 4 10% weight loss in 25% of patients for up to 2.5
years after BIB balloon removal.
AIMS & METHODS: 79 patients from 3 centers who were implanted with the
Spatz Adjustable Balloon for 1 year were contacted and asked to provide their
weight 1 year and 2 years post balloon extraction. Net weight changes were
recorded, and % weight loss was calculated based on weight prior to balloon
implantation. Net weight loss 4 10% was considered successful weight
maintenance.
RESULTS: 70 of the 79 patients contacted (88.6%) were responsive in providing
their weight data. The groups data at the original implantation was as follows: mean
weight 120.3 kg (80-180); mean BMI 38.8 (30-65). At the time of balloon extraction
(12 months) the groups mean weight loss was 24 kg with a 23.8% weight loss. All of
the 70 patients had reached at least 12 months post Spatz balloon extraction. Fifty
three of the seventy (75.7%) retained at least 10% weight loss at 1 year post balloon
extraction. 34 of the 70 patients had reached 2 years post extraction, and 26 (76.4%)
retained at least 10% weight loss. The groups mean weight change was 6.7 kg at 1
year and 3.4 kg at 2 years after balloon extraction.
CONCLUSION: The maintenance of 4 10% Weight loss at 1 year and 2 years
after Spatz Adjustable Balloon extraction has been retrospectively documented in
75.7% and 76.4% of patients, respectively. This study is limited by its retro-
spective review and the small numbers in year 2 and requires prospective
review to confirm these findings. Nonetheless, it suggests a long term benefit
to longer implantation time and/or adjustable balloon function and warrants
further study.
Disclosure of Interest: None declared
A283
P0545 SACCHAROMYCES BOULARDII ADMINISTRATION CHANGES
GUT MICROBIOTA AND REDUCES HEPATIC STEATOSIS, LOW
GRADE INFLAMMATION AND FAT MASS IN OBESE AND TYPE 2
DIABETIC DB/DB MICE
L. Geurts1,*, A. Everard1, S. Matamoros1, N. Delzenne1, P.D. Cani1
1
Louvain Drug Research Institute, Walloon Excellence in Life sciences and
BIOtechnology (WELBIO), Metabolism and Nutrition Research Group,
Universite catholique de Louvain, Brussels, Belgium
Contact E-mail Address: patrice.cani@uclouvain.be
INTRODUCTION: Obesity and type 2 diabetes are associated with an altered
gut microbiota and inflammation. Growing evidence suggest that the gut micro-
biota is involved in the regulation of energy homeostasis. We and others have
shown that gut microbiota modulation using prebiotics constitute an interesting
target in the physiopathology of obesity.
AIMS & METHODS: So far, probiotic yeast have not been investigated in this
context. The aim of this study is to evaluate the role of the most studied probiotic
yeast (i.e., Saccharomyces boulardii Biocodex) on obesity and associated meta-
bolic disorders. S. boulardii was administrated daily by oral gavage to leptin-
resistant obese and type 2 diabetic mice (db/db) for 4 weeks.
RESULTS: We found that S. boulardii treated mice exhibited reduced body
weight, hepatic steatosis, fat mass and both hepatic and systemic inflammation.
These effects were associated with local effects in the intestine, such as an
increased caecum weight and caecum tissue weight. Importantly, we also found
that S. boulardii induced dramatic changes in gut microbial communities at the
phylum, family and genus levels. We also found that microbial changes in
response to S. boulardii were correlated with host metabolism response.
CONCLUSION: In conclusion, our study demonstrated that S. boulardii acts as
a beneficial probiotic treatment in the context of obesity and type 2 diabetes.
Disclosure of Interest: L. Geurts: None declared, A. Everard: None declared, S.
Matamoros: None declared, N. Delzenne: None declared, P. Cani Financial
support for research from: Biocodex
P0546 CORRELATION BETWEEN DIET AND NON-ALCOHOLIC
FATTY LIVER DISEASE: INVESTIGATION OF A COHORT OF
ITALIAN PATIENTS
L. Abenavoli1,*, M. Pellegrini2, M. Busacchi2, G. Marchesini3, E. Bugianesi4,
A. Barchetti2, S. Bellentani5
1
Health Sciences, University Magna Graecia of Catanzaro, Catanzaro,
2
Diagnostic, Clinical and Public Health, University of Modena and Reggio Emilia,
Modena, 3Clinical Dietetics, Alma Mater Studiorum University of Bologna,
Bologna, 4Division of Gastro-Hepatology, University of Torino, Torino, 5Centro
studi Fegato, Azienda USL Modena, Carpi, Italy
Contact E-mail Address: l.abenavoli@unicz.it
INTRODUCTION: The Western diet is characterized by a high-energy intake,
saturated fats and refined sugars. Excess calorie intake, associated with reduced
physical activity, leads to obesity, type 2 diabetes mellitus, cardiovascular disease
and non-alcoholic fatty liver disease (NAFLD).
AIMS & METHODS: Within the FP7 - European FLIP (Fatty Liver Inhibition
Program) program we tried to investigate the role of diet in NAFLD, in a large
cohort of patients from three different Italian Centers (Modena, Bologna and
Turin). We used the EPIC questionnaire to investigate energy intake (Ei) and
intake of food in a well-characterized series of 163 NAFLD patients.
Anthropometric measurements, blood tests, insulin resistance, liver ultrasound
(Hamagouchi score) and liver stiffness were analysed. Nutrient intakes were
compared with Italian reference values.
RESULTS: The daily intake of simple sugars (18.4% vs. a reference intake
515%), saturated fats (12% vs. 510%) and the ratio between animal pro-
teins/vegetal protein in the diet (68% vs. 550%) was higher than recommended,
whereas the fiber intake was lower (19g vs. 25g). In the patients, a significant
direct correlation (p50.005) was observed between BMI, waist circumference,
insulin resistance, transient elastography values, Hamagouchi score, and lipid
intake.
CONCLUSION: The dietary intakes of NAFLD patients are systematically
different from the recommended daily intakes for the Italian population. In
particular the higher-than-recommended intake of simple sugars might be one
of the possible causes of NAFLD (Supported by FLIP Project, (FP7/20072013)
under grant agreement no. HEALTH-F2-2009-241762).
REFERENCES
1. Ratziu V, et al. A position statement on NAFLD/NASH based on the EASL
2009 special conference. J Hepatol 2010; 53: 372-384.
2. Abenavoli L, et al. Transient elastography in non-alcoholic fatty liver disease.
Ann Hepatol 2012; 11: 172-178.
3. Centis E, et al. Stage of change and motivation to healthier lifestyle in non-
alcoholic fatty liver disease. J Hepatol 2013; 58: 771-777.
Disclosure of Interest: None declared
P0547 FOOD INTOLERANCE AND OBESITY: NEW STRATEGY IN THE
TREATMENT OF OBESITY
M. Rotter1,*
1
Dietology, UKRAINIAN RESEARCH INSTITUTE OF NUTRITION, Kyiv,
Ukraine
Contact E-mail Address: rottermaria@mail.ru
INTRODUCTION: Challenges associated with the treatment of obesity still
remain high, in spite of efforts made by professionals combating the public
health issue. A low-calorie diet, which is considered as the most effective
A284
treatment, is hard for many patients to incorporate due to the discomfort
brought by hunger. An effective treatment should focus on increasing the quality
of a patients life, by creating a treatment that reduces symptoms associated with
obesity, while allowing patients to not experience hunger during the treatment
period.
AIMS & METHODS: The aim of the study was to compare the difference in
effectiveness between the traditional low-calorie diet and the elimination diet. A
Survey was completed by 60 patients, 30 women and 30 men, with the average
age 37.6  4.7 years. In addition to routine methods of investigation, all patients
were analyzed on food intolerance using the FED- test, which is based on the
immunetermistometrical principle, a new term we used to describe the conduc-
tivity and viscosity change in the blood after making contact with certain food
extract. The FED- test uses 96 different food extractions to evaluate food intol-
erance. To evaluate the improvement of a patients condition, questionnaires were
used before and after the treatment to receive any complaints patients had
throughout the treatment period. Information about complaints was assessed
on a Harington scale of a unit from 1 (no symptoms) to 0.1 (maximum symp-
tom). Patients were divided into 3 equal groups - overweight, and 1 or 2 class
obesity. Each group was divided into two subgroups. Patients in the (A) sub-
group were on a low-calorie diet: 1200-1600 Kcal, depending on the age, sex, and
physical activity. Patients of the (B) sub-group were on the individual eucalorie
(with normal energetic value) elimination diet, based on the results from the
FED- testing.
RESULTS: 1. The influence that the type of diet had on weight reduction.
Among the first two groups with overweight patients, greater weight loss was
observed in those patients who adhered to the elimination diet. The difference in
BMI accounted for 0.776  0.222 kg \ m2 in the group A and 1.788  0.449 kg/
m2 in the group B. In obese patients, the following similar results were observed:
in the elimination diet weight loss was 3.764 kg \ m2 and 4.065 kg \ m2 in in
patients with class 1 and 2 obesity accordingly. In low-calorie diet, BMI reduc-
tion was 1.291 kg \ m2 and 2.280 kg \ m2 in patients with class 1 and 2 obesity
accordingly.
2. Improvements in patients condition. On the elimination diet improvement of
the patients condition amounted to 0.292 in the obese group, and 0.222 in the
overweight group. In groups in which patients followed the low-calorie diet, no
significant dynamics in the state of the patients were observed: 0.046 in a group
of obese patients and 0.034 patients in the overweight group.
CONCLUSION: Under the influence of elimination diet BMI reduction was
significantly better in patients with 1 and 2 class obesity compared to the
dynamics of BMI on the standard low-calorie diet (p 0.0037). Between
groups of patients who were overweight, no significant differences were found
(p 0.087).
The patients quality of life after 6 months of treatment differed significantly in
subgroups of those treated with the elimination diet, compared to the subgroups
of those that received the standard low-calorie diet treatment (p 0.004).
Disclosure of Interest: None declared
P0548 ARGON PLASMA FULGURATION TO TREAT WEIGHT REGAIN
AFTER BARIATRIC SURGERY
R.J. Fittipaldi-Fernandez1,*, C.F. Diestel2,3
1
Digestive Endoscopy, Endogastro Med Service, 2Nutrition Division, UNI-RIO Rio
de Janeiro University, 3Nutrition Division, Endogastro Med Service, Rio de
Janeiro, Brazil
Contact E-mail Address: ricfittipaldi@hotmail.com
INTRODUCTION: The weight regain is a problem after bariatric surgery and
occurs, in part, by dilatation of the gastro-jejunal anastomosis, which causes a
faster gastric emptying and increased food intake.
AIMS & METHODS: Objective: To evaluate the efficacy of endoscopic fulgura-
tion of the anastomosis and of the gastric stump using argon plasma (APF)
aiming to reduce the diameter thereof.
Methods: We analyzed 32 patients. 30 of them underwent at least 02 sessions of
FPA. Two patients underwent only one session due to an immediate reduction of
the anastomosis to a diameter smaller than 10 mm after the first session, wich is
the procedure target. The coagulation was held at the anastomosis and in gastric
stump. 80 w power was used in the 1st session, and 70w power FPA in the
following, with an Agon flow of 2L/min. The objective is to obtain an anasto-
mosis with a diameter less than or equal to 10 mm. Data were analyzed with
descriptive statistics, students t test and Spearman correlation.
RESULTS: Of the 32 patients, 87.5 % were women (n 28). The mean regained
weight in relation to the maximum weight lost (Nadir) after bariatric surgery was
46.9 % (14 to 76.9). The mean duration of treatment was 170 days (56-338).
There was a significant reduction in body mass index (BMI) at the end of the
analysis (32.424.45 kg/m2) compared to the initial mean BMI (mean
BMI 37.054.76 kg/m2) (p 5 0.0001). The average loss of the regained
weight was 66.92% (22.08-211.11). The average weight loss in Kg was 12.73
(6.3-25.5). There was significant correlation between the reduction in the BMI
and the highest number of sessions of FPA (p 0.0003) and between the longer
duration of the treatment (p 0.0212). The analyzed patients remain in
treatment.
CONCLUSION: The FPA has demonstrated great efficacy in the treatment of
weight regain after bariatric surgery of gastric bypass in Roux-Y.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0549 ANALYSIS OF 1973 PATIENTS SUBMITTED TO ENDOSCOPIC
TREATMENT OF EXCESS WEIGHT WITH AN INTRAGASTRIC
BALLOON
R.J. Fittipaldi-Fernandez1,*, C.F. Diestel2,3, B. Sander4, A.F. Teixeira5,
M. Galvao Neto6
1
Digestive Endoscopy, 2Nutrition Division, Endogastro Med Service, 3Nutrition
Division, UNI-RIO Rio de Janeiro University, Rio de Janeiro, 4Digestive
Endoscopy, Clnica Sander, Belo Horizonte, 5Digestive Endoscopy, Gastros Bahia,
Feira de Santana, 6Digestive Endoscopy, Gastro Obeso Center, Sao Paulo, Brazil
Contact E-mail Address: ricfittipaldi@hotmail.com
INTRODUCTION: Endoscopic methods, especially the intragastric balloon
(IGB), have been shown to be effective for the treatment of excess weight.
AIMS & METHODS: OBJECTIVE: To assess the efficacy and complications of
excess weight treatment with an IGB in patients seen at the Endogastro Med
Service clinic, Gastro Obeso Center and Sander clinic.
METHODS: A total of 1973 patients were analyzed. An Allergan IGB (BIB)
with a volume of 600 to 700 ml was used. The patients had a minimum initial
body mass index (BMI) of 27 kg/m2 and were followed up by a multidisciplinary
team consisting of a nutritionist, a doctor and a psychologist. For statistical
analysis, the patients were divided into groups according to sex and degree of
excess weight (overweight and grade I, II and III obesity). Data were analyzed
using descriptive statistical methods, the Student t-test, and analysis of variance
followed by the Tukey post-test. The level of significance was set at p50.05.
RESULTS: 107 patients were excluded from the analysis: 70 (3.55%) due to early
IGB removal, 13 (0.66%) due to absence of weight loss, 14 (0.71%) due to weight
gain, and 10 (0.51%) due to incomplete data. The incidence of fungus was 0.2%
(n 4) and the incidence of leakage was 0.25% (n 5), pregnancy was 0.1%
(n 2); Wernick Korsakoff syndrome due to excessive vomiting was 0.05%
(n 1), gastric perforation and upper digestive bleeding was 0.05% each
(n 1). Of the 1866 remaining patients, 1402 were women and 464 were men.
Mean age was 37.32 years. The patients showed a significant weight loss, with a
significantly lower final BMI (mean: 28.934.71 kg/m2; range: 18.98-57.38) than
the initial BMI (mean: 36.475.61 kg/m2; range: 27-74.74) (p50.0001). Mean
BMI reduction was 7.553.49 kg/m2 (range: 0.36-29.79). Mean percent weight
loss was 20.437.82% and mean percent excess weight loss (EWL) was
73.4836.71% (range: 2.22-431.1). Percent EWL was higher in the overweight
group, followed by obesities grades I, II and III sequentially (p50.0001). Percent
EWL was also higher in women than in men (p50.0001).
CONCLUSION: Endoscopic treatment of excess weight with an IGB has been
established as an excellent therapeutic option for patients of both genders with
overweight or different degrees of obesity.
Disclosure of Interest: None declared
P0550 PREDICTIVE RISK FACTORS FOR SUCCESS OF BARIATRIC
THERAPY WITH BIOENTERICS INTRAGASTRIC BALLOON
R. Cerqueira1, M. Correia1,*, M.C. Manso2
1
Gastroenterology, Centro Hospitalar entre Douro e Vouga, Santa Maria Feira,
Santa Maria Feira, 2Biostatistics - Requimte-up, University Fernando Pessoa,
Porto, Portugal
Contact E-mail Address: rute.cerqueira@chedv.min-saude.pt
INTRODUCTION: In obese patients, a large amount of data shows that bar-
iatric therapy with Bioenterics intragastric balloon (BIB) results in weight loss in
some patients. However there is a paucity of data about predictive risk factors for
BIB success.
AIMS & METHODS: The aim of this study was to determine the effectiveness of
this device on weight loss and predictive risk factors for BIB success. A prospec-
tive study with 147 patients [(75.5% females, mean age 40 (11.9)] submitted to
BIB insertion, which was removed after 41.4 (12.7) weeks. Anthropometric and
laboratory parameters were assessed when BIB was positioned and when BIB
was removed. BIB success was defined as weight loss  50% of the weight excess
(pre BIB weight calculated weight to lower the BMI to 24.9).
RESULTS: At baseline, mean weight was 97.2 Kg ( 16.1), mean body mass
index (BMI) was 36.5 (5.9) kg/m2, 19 (12.9 %) patients had type II Diabetes
Mellitus and mean insulin resistance (HOMA-IR) was 2.9 ( 2). With BIB
intervention, mean weight and mean BMI decreased, respectively, to 83.5 (
16.9), p5 0.001 and 31.4 (6.3), p50.001. Regarding laboratory parameters,
cholesterol, triglycerides and HOMA-IR were significantly reduced (p50.05).
There was no significant improvement in TGP, G-GT, HDL cholesterol and
ferritin. BIB success was observed in 57 (38.8%) patients. Predictive risk factors
for BIB success were mean pre-operative weight, 92.8 (13) vs 99.7 ( 16.9)kg,
p 0.011 and mean pre-operative BMI, 35 (3.5) vs 37.5 (6.9), p 0.007; a
trend was observed for baseline HOMA-IR, 2.7 (2.3) vs 3 (1.7), p 0.056.
CONCLUSION: BIB therapy achieves significant weight loss and significantly
improves laboratory parameters of the metabolic syndrome in obese patients.
BIB success is associated with baseline weight and baseline BMI further empha-
sizing that the endoscopic technic has major impact in mild obese, those that are
not surgical candidates.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0551 PREOPERATIVE ENDOSCOPY IN ASYMPTOMATIC
BARIATRIC PATIENTS IS IT STILL WORTH IT?
S.R. Fernandes1,*, L. Meireles1, L.A. Correia1, L.C. Ribeiro1, J. Velosa1
1
Gastrenterologia e Hepatologia, Hospital Santa Maria - Centro Hospitalar Lisboa
Norte, Lisboa, Portugal
Contact E-mail Address: Samuelrmfernandes@gmail.com
INTRODUCTION: Obesity represents a major public health problem associated
with increased risk of diabetes, cardiovascular and cerebrovascular disease and
cancer. Surgery has shown to be an effective long term treatment. Preoperative
endoscopy (POE) is recommended by the current "guidelines", but evidence
supporting this recommendation in asymptomatic patients is scarce.
AIMS & METHODS: We sought to determine whether endoscopic findings
justify routine POE before bariatric surgery. Obese (BMI4 30 kg/m2) and mor-
bidly obese (BMI4 35 kg/m2) patients undergoing endoscopy in our institution
were retrospectively selected. Endoscopic and histological findings and their
impact on surgical strategy were assessed.
RESULTS: Of 557 patients (78.3 % female, mean age 46.911.5 years), 43.3 %
had a normal endoscopy. Esophageal, gastric and duodenal disease were present
in 22.6 %, 44.2 % and 11.0 % respectively. The most frequent esophageal find-
ings were hiatus hernias (17.2 %) and esophagitis (8.0 %, 97.5 % Class A and B
of Los Angeles). Gastric changes included erosive (18.3%) and non-erosive gas-
tritis (19.7%), polyps (4.8%) and ulcers (1.6%, all Forrest III). Bulbitis (10.4%),
ulcers (0.5%) and polyps (0.2%) composed most common duodenal findings.
From a total of 218 gastric biopsies 46.3% revealed the presence of
Helicobacter pylori (Hp) bacilli. In 3 patients Barretts esophagus was diagnosed
(without dysplasia) and in 2 gastric low grade MALT lymphoma (which
regressed after eradication of Hp).
CONCLUSION: Our findings were of little relevance and did not alter the
operative strategy. Given the high prevalence of Hp, which has been associated
with higher postoperative complications, its screening by non-invasive methods
prior to surgery may be a less expensive alternative. This study suggests that EPO
might be dispensable in asymptomatic bariatric patients.
Disclosure of Interest: None declared
P0552 MODIFIED PROBIOTIC ESCHERICHIA COLI NISSLE
INCREASES COLONIC SHORT CHAIN FATTY ACIDS AND FECAL
BIFIDOBACTERIA AND LACTOBACILLI COUNT IN RATS
A.K. Singh1,*, S. Pandey1, A.S. Parihar1, N.K. Gattupalli1
1 Vitamin B12, mg
Biochemistry, The Maharaja Sayajirao University of Baroda, Vadodara, India
Contact E-mail Address: singhashish1186@gmail.com
INTRODUCTION: Short Chain Fatty Acids (SCFAs) are considered as one of
the most important metabolite produced by commensal organism in the gut.
Dietary consumption of complex carbohydrates such as inulin, fructo-oligosac-
charides and sodium gluconate are known to increase SCFAs in the colon.
However, they limit in their efficacy if not consumed daily. E. coli represents a
major commensal population the human colon. E. coli expresses an apo- form of
membrane bound enzyme, glucose dehydrogenase, which converts glucose to
gluconic acid. However, it is unable to synthesize the cofactor, PQQ
(Pyrroloquinoline quinone). E. coli produces gluconic acid when PQQ is supplied
in the medium.
AIMS & METHODS: We hypothesized that, recombinant probiotic E. coli
Nissle 1917 (EcN) expressing PQQ synthesis genes is able to synthesize large
amount gluconic acid in the intestine and subsequently increased production of
SCFAs.
pqqABCDE gene cluster was cloned and expressed in EcN. Rats were fed with
starch containing diet along with recombinant probiotic EcN for 60 days.
RESULTS: Recombinant EcN expressing pqqABCDE gene cluster produces high
amounts of gluconic acid in M9 minimal medium supplemented with glucose
under laboratory conditions. Weekly treatment of recombinant EcN producing
gluconic acid results in increased production of gluconic acid in the colon.
Additionally, SCFAs (Butyrate and Acetate) concentration was also found to
be elevated by approximately 3 fold and 1.6 fold respectively. mRNA profile of
colon showed increased expression of mucin and intestinal trefoil factor genes in
treated rats. The treated rats also had increased fecal Bifidobacteria and lactoba-
cilli number.
CONCLUSION: The present study suggest that engineered probiotic could be a
potent nutritional supplement against intestinal dysbiosis and other related
pathologies.
REFERENCES
Kameue C, et al. Dietary sodium gluconate protects rats from large bowel cancer
by stimulating butyrate production. J Nutrition 2004; 134: 940-944.
Rucker R, Chowanadisai W and Nakano M. Potential physiological importance
of pyrroloquinoline quinone. Alternative Med Review 2009; 14.
Biagi G, et al. Effect of gluconic acid on piglet growth performance, intestinal
microflora, and intestinal wall morphology. J Animal Sci 2006; 84: 370-378.
Asano T, et al. Effects of gluconic acid on human faecal bacteria. Microbiol Ecol
Health Dis 1994; 7: 247-256.
Sonnenborn U and Schulze J. The non-pathogenic Escherichia coli strain Nissle
1917 features of a versatile probiotic. Microb Ecol Health Dis 2009; 21: 122-158.
Disclosure of Interest: None declared
A285
P0553 NUTRIENT INTAKES AT THE TIME OF DIAGNOSIS IN
PATIENTS WITH HIV INFECTION: COMPARISON WITH
NATIONAL NUTRITIONAL GUIDELINES AND WITH A COHORT
OF HEALTHY SUBJECTS
B. Zanini1,*, R. Bosio1, N. Brianese1, A. Ferraresi1, A. Arrighi1, E. Quiros-
Roldan1, F. Castelli1, A. Lanzini2
1
Department of Clinical and Experimental Sciences, 2UNIVERSITY AND
SPEDALI CIVILI OF BRESCIA, Brescia, Italy
Contact E-mail Address: b_zanini@tin.it
INTRODUCTION: Assessment of nutrient intake is an important key element in
healthcare of HIV patients because nutritional status is a determinant of HIV
outcomes and of many co-morbidities including gastrointestinal problems, osteo-
porosis, cardiovascular diseases, diabetes and other metabolic changes (1,2).
Little is known about nutritional adequacy among HIV patients at the time of
diagnosis and prior to pharmacological treatment.
AIMS & METHODS: We carried out a prospective clinical study to assess
macro- and micro-nutrient components of diet in a cohort of HIV patients at
the time of diagnosis, and to compare them with Italian recommended levels of
nutrient intake (LARN 2012) and with those of a cohort of healthy subjects,
matched with HIV cohort according to gender and age (range  4 years).
Patients in the two cohorts were instructed to fill in a standardized 7-day food
diary. Data from diaries were analyzed with Microdiet software (Downlee
system, ltd. UK) and nutritional characteristics studied were: total Kcal, propor-
tion of total energy value of CHO, free sugars, proteins, fats, SFA and PUFA,
and total amounts of fibre, vitamins A, B12, C, and D, folates, sodium, calcium,
iron, zinc. For statistical analysis Fishers exact test and Wilcoxon matched pairs
test were used as appropriate.
RESULTS: 22 HIV patients signed informed consent, 21 returned the diary and
14 were at present analyzed. Eleven were male, age 42 1 year (mean  SD),
BMI 23.8 3.3 Kg/m2 with 4 patients in overweight class, 1 in grade 1 obesity
class and 9 in normal BMI class. Comparison of selected nutrient composition
with LARN and with healthy subjects are reported in the table.
Nutrients HIV patients Healthy subjects HIV Vs LARNx %
CHO, % TEV 48.26.9 40.05.6* - 21
Fats, %TEV 33.26.0 37.03.4* 36
Proteins, %TEV 16.32.2 16.62.6 79
3.71.4 2.50.8* -21
Vitamin D, mg 2.51.8 3.41.6 -100
Folates, mg 191.644.6 140.349.8* -100
Calcium, mg 508.9133.0 771.0253.9 -100
Iron, mg 7.01.4 9.72.3* -100
Zinc, mg 8.41.5 8.82.1 -79
CONCLUSION: Daily intake is inadequate in HIV patients at time of diagnosis
for most macro- and micro- nutrients, but is closer to LARN recommendations
than in healthy subjects. Nutritional counseling must be provided in HIV na ve
patients in order to improve their nutritional status and to contribute to preven-
tion of gastrointestinal and metabolic co-morbidities.
REFERENCES
Hendricks KM, et al. Am J Clin Nutr 2008; 88: 1584-1592.
2) Giudici KV et al. Sao Paulo Med J 2013; 131: 145-152.
Disclosure of Interest: None declared
P0554 SUPPLEMENTATION WITH A PROBIOTIC MILK DRINK DOES
NOT ALTER GUT MICROBIOTA COMPOSITION IN PATIENTS
WITH METABOLIC SYNDROME
B. Leber1,*, N. Tripolt2, S. Trajanoski3, C. Hogenauer4, H. Sourij2,
V. Stadlbauer4
1
Transplantation Surgery, 2Endocrinology and Metabolism, 3Center for medical
Research - Bioinformatics, 4Gastroenterology and Hepatology, Medical University
of Graz, Austria, Graz, Austria
Contact E-mail Address: bettina.leber@medunigraz.at
INTRODUCTION: Metabolic syndrome (MetS) is associated with disturbances
in gut microbiota including changes in the Bacteroidetes/Firmicutes ratio. In
animal models, modulation in the composition of gut microbiota through sup-
plementation with probiotics is possible. It is not known to date if this is also
possible in humans.
AIMS & METHODS: We therefore aimed to study whether supplementation
with a probiotic milk drink containing Lactobacillus casei Shirota (LcS) is able to
modulate gut microbiota composition in patients with MetS. In a single-center,
prospective, randomized-controlled pilot study, 28 subjects with MetS received
either LcS (YAKULT light 3 bottles a day, 65 ml each, containing LcS at a
concentration of 108/ml) for 12 weeks (LcS group; n 13) or received standard
medical therapy (n 15). 6 healthy subjects served as controls. Stool samples
were collected at baseline and after 3 months. Gut microbiota composition was
characterized using 454 pyrosequencing of the amplicon libraries from V1 to V3
hypervariable regions of 16S rRNA genes. Generated sequencing data was ana-
lyzed with Quantitative Insights Into Microbial Ecology (QIIME version 1.7.0)
pipeline in stool samples.
RESULTS: No significant differences in Unifrac distances or Bray-Curtis dis-
tances between samples from the same patients in two time points were found
A286
(p 0.70 and 0 0.48, respectively). The Bacteroidetes/Firmicutes ratio was not
different compared to healthy controls and was not influenced by probiotic
supplementation (Controls: 0.783; LcS baseline: 0.961; LcS 3 months: 1.007;
Standard baseline: 0.921; Standard 3 months: 0.995). Diversity (using Shannon
index) and richness of gut microbiota in MetS showed similar distribution com-
pared to healthy controls and was not influenced by probiotic supplementation.
LcS was only detectable in 1 individual of the treatment group after 3 months of
supplementation with LcS.
CONCLUSION: In our study no difference in gut microbiota composition was
found between healthy subjects and patients with MetS. The supplementation of
LcS did not change gut microbiota composition, so we conclude that the micro-
biota variations occurring in the treatment group were not larger than the nor-
mally expected variations during this time period. This is in accordance with our
previous findings that supplementation with LcS did not influence clinical and
biochemical parameters of glucose metabolism, inflammation and innate immune
response.
Disclosure of Interest: None declared
P0555 QUANTIFICATION OF IN VIVO COLONIC SHORT CHAIN
FATTY ACID PRODUCTION FROM INULIN
E. Boets1,*, E. Houben1, S. Gomand2, J. Delcour2, K. Verbeke1
1
Translational Research for Gastrointestinal Disorders, Leuven Food Science and
Nutrition Research Centre, 2Laboratory of Food Chemistry and Biochemistry,
Leuven Food Science and Nutrition Research Centre, KU Leuven, Leuven, Belgium
Contact E-mail Address: eef.boets@med.kuleuven.be
INTRODUCTION: Short chain fatty acids (SCFA; acetic (Ac), propionic (Pr)
and butyric (Bu) acid) are produced during bacterial fermentation of undigested
carbohydrates in the colon. In this study, we determined the bioavailability of
each SCFA and applied a stable-isotope dilution method to quantify the colonic
production of SCFA after consumption of inulin.
AIMS & METHODS: Six healthy subjects (3F/3M; 297y) each performed 4
test days with minimal 1 week interval. On the first 3 test days they received
either 400mg 13C-Ac or 340mg 13C-Pr or 990mg 13C-Bu in a pH-dependent colon
delivery capsule with a standard breakfast. After collection of a basal blood
sample, they received a primed constant infusion of 2H-labelled SCFA
(Ac:20mmol/kg.h; Pr:2mmol/kg.h; Bu:1mmol/kg.h) for 12h. On the 4th test day,
the SCFA production from inulin fermentation was quantified. The subjects
received 15g of inulin (Raftilin HP, Beneo-Orafti) with a standard breakfast
and an infusion with 13C-SCFA (Ac:12mmol/kg.h; Pr:1.2mmol/kg.h;
Bu:0.6mmol/kg.h) for 12h. Additional blood samples were collected at regular
times during the day. Plasma total SCFA concentrations, 13C- and 2H-SCFA
enrichments were measured using gas chromatography (GC), GC combustion
isotope ratio mass spectrometry (IRMS) and GC pyrolysis IRMS, respectively.
The bioavailability index (F) of the respective SCFA was calculated from the area
under the curve (AUC) of the 13C-SCFA concentration time curve (F AUC x
Cl x 100/administered dose). The clearance rate (Cl) was determined using the
2
H-SCFA infusion (Cl infusion rate (i)/steady state (SS) 2H-SCFA concentra-
tion). SCFA turnover was calculated using stable-isotope dilution. The infusion
with 13C-SCFA results in a constant 13C-SCFA enrichment in the blood. After
fermentation of inulin in the colon, SCFA enter the blood and dilute the 13C-
SCFA resulting in a decrease of 13C-SCFA enrichment. The total turnover (T) of
the SCFA at each time was calculated as follows: T i x [(Tracer enrichment/
Plasma enrichment)-1]. The turnover at SS was subtracted from the total turn-
over to obtain the exogenous SCFA turnover. The AUC was calculated to yield
total SCFA appearance in plasma. Finally, the bioavailability index and SCFA
plasma concentrations were used to quantify the SCFA produced in the colon.
Results are expressed as medians and interquartile ranges.
RESULTS: The bioavailability index of Ac, Pr and Bu were 37 [30-57]%, 21 [17-
25]% and 4 [3.5-9]%, respectively. SS turnover of Ac, Pr and Bu were 13 [8-16],
0.23 [0.19-0.31] and 0.26 [0.15-0.34] mmol/kg.min, respectively. The total amount
of Ac in plasma was 661 [512-991] mmol/kg; corresponding to a production of 112
[88-194] mmol of Ac in the colon within 12h after inulin ingestion. The AUC of
Pr and Bu were 14 [9-22] and 13 [10-15] mmol/kg, respectively. Twelve hours after
inulin ingestion a total of 0.9 [0.6-1] and 0.7 [0.6-1] mmol of Pr and Bu appeared
in the circulation. The colonic produced Pr and Bu levels were 4 [2-6] and 19 [11-
24] mmol, respectively.
CONCLUSION: In conclusion, inulin is mainly fermented into acetate followed
by butyrate and propionate. Stable isotope technology allows to quantify in vivo
SCFA production from carbohydrate fermentation and will facilitate the evalua-
tion of health benefits attributed to SCFA.
Disclosure of Interest: None declared
P0556 ABDOMINAL HEMODYNAMIC IN PATIENTS WITH
MALNUTRITION AND HEREDITARY CONNECTIVE TISSUE
DISORDERS
G. Nechayeva1, M. Livzan1, E. Lialiukova1,*
1
Omsk state medical academy, Omsk, Russian Federation
INTRODUCTION: The aim of the research is to study the peculiarities of
abdominal hemodynamic in patients with malnutrition and hereditary connective
tissue disorders.
AIMS & METHODS: To study mechanisms of malnutrition at the patients with
hereditary connective tissue disorders.
121 patients with hereditary connective tissue disorders were included in the
research (The revised Ghent nosology for the Marfan syndrome, 2010). The
control group was represented by 40 healthy subjects to be comparable by sex
and age. The assessment of malnutrition and ultrasonic dopplerography of the
abdominal vessels (vena portae, arteria hepatica communis, arteria mesenterial
United European Gastroenterology Journal 2(5S)
superior and arteria splenica) were performed for the patients. The investigation
was undertaken with fasting after feeding test, with the ultrasound scanner
Sonoace-8000 (Medison, South Korea).
RESULTS: The signs of malnutrition in patients with hereditary connective
tissue disorders have been revealed in 70,9% of cases. The degree of malnutrition
has been correlated with the expression of hemodynamic disturbances (r -0,55;
o50,001).
By estimating the abdominal blood flow in persons with hereditary connective
tissue disorders more lower volume rates of a blood flow were recorded: along
vena portae - 1853,0 [1688,0-2297,0] ml/min., in the group of comparison -2149,0
[1827,0-2400,0] ml/min (o50,05); along arteria mesenterial superior - 988,0
[837,0-1272,0] ml /min, in the group of comparison - 1136,5 [992,0-1465,0] ml/
min (o50,05); along the vessels of a celiac trunk: arteria hepatica communis -
480,5 [425,0-587,0] ml/min, in the group of comparison - 591,5 [536,0-689,0] ml/
min. (o50,001) and splenic arteries - 600,0 [452,0-709,0] ml/min, in the group of
comparison - 700,0 [591,0-795,0] ml/min (o50,01). After meal the persons with
hereditary connective tissue disorders had fewer high-speed indicators gain and it
didnt exceed 30% from the initial indicators (o50,001).
The data of the abdominal blood flow were correlated with some central hemo-
dynamic changes (minute volume of circulation): at the vena portae (r 0.55, o
50,05), at the arteria hepatica communis (r 0.60, o 50,05), at the splenic
artery (r 0.77 o 50,05); by the extent of vegetative sympathetic influences on
a vascular tonus: at the arteria hepatica communis (r -0,48, o50,05), at the
splenic artery (r -0,27, o50,05), at the arteria mesenterial superior (r -0,36, o
50,05); by splanchnoptosis degree: at the portal vein (r -0,210; o50,05), at the
arteria hepatica communis (r -0,38; o50,05), at the arteria mesenterial superior
(r -0,86; o50,05).
CONCLUSION: The signs of malnutrition in patients with hereditary connective
tissue disorders have been revealed in 70.9% of cases. The degree of malnutrition
has been correlated with the expression of systemic connecting tissue involve-
ment. The postprandial period abdominal blood flow has been characterized by
the low values of volume rate at the vessels of the celiac trunk, arteria mesenterial
superior, and portal vein. Some disturbances of a cardiac hemodynamic, preva-
lence of sympathetic influences on vascular tonus, splanchnoptosis presence may
be considered to be the main causes of blood flow decreasing.
Disclosure of Interest: None declared
P0557 OPTIMIZATION OF DIAGNOSIS AND TREATMENT OF
NUTRITIONAL INSUFFICIENCY IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE
A.A. Iakovlev1,*, T.S. Kazaryan1
1
gastroenterology, ROSTOV ON DON STATE MEDICAL UNIVERSITY,
Rostov on Don, Russian Federation
Contact E-mail Address: gastroklinika@yandex.ru
INTRODUCTION: Development of nutritional deficiency (ND) due to the loss
of nutrients, water and electrolytes with frequent stools, nutrients malabsorption,
anorexia and increased catabolism is typical for patients with IBD relapse. To
determine the frequency and structure of ND in patients with IBD relapse and to
evaluate the therapeutic effect of nutritional support (NS) of nutritive mixtures
during the course of therapy.
AIMS & METHODS: Two-phase three step study with prospective monitoring
in patients with IBD was conducted during 3 years in the period from 2010 to
2012. The first phase was carried out using a one-time screening scales MUST
and NRS, further in phase 2, the NS structure was refined. 520 patients with IBD
were examined: 410 with ulcerative colitis (UC) and 110 with Crohns disease
(CD).
RESULTS: The 1st, 2d and 3d degree of ND was detected in 111 (27.1%), 96
(23.4%) and 42 (10.2%) patients with UC, respectively. 2d and 3d degree of ND
was recorded in 48 (43.6%) and 29 (26.4%) cases in patients with CD, respec-
tively. At the second stage of the study, 80 patients with UC were randomized
into two major groups, depending on the degree of NN, were divided into groups
A (2d degree of ND) and B (3d degree of ND). On basic therapy, patients of the
Ist group received a diet with a high amount of protein (HAPD) and increased
calorage (2500 kcal / day), while to the patients of the IId group in addition to the
basic therapy, nutritional mixtures: peptamen and modulen IBD (Nestle) in the
amount of 1/3 of the daily calorage were prescribed. Efficacy of treatment was
evaluated on the 3 d, 4th, 12th week. At the third stage of the study, during 3
years, the long-term results were studied using index of the relapse frequency
(IRF). Pick of the IRF was in the 1st group and by the end of the study it was 15
(75%) and 17 (85%) cases, respectively. In the second group IRF was signifi-
cantly lower: 9 (45%) and 12 (60%) (p 50,05).
CONCLUSION: In patients with UC and CD relapse ND of the 1st and 3d
degree was recorded an average of 20.3% and 35%, respectively. Use of NS
provides a low rate UC relapse, and thus stable remission of the disease.
Disclosure of Interest: None declared
P0558 TEDUGLUTIDE FOR PATIENTS WITH SHORT BOWEL
SYNDROME-INTESTINAL FAILURE. A SINGLE CENTER
EXPERIENCE
A. Ukleja1, A. Alvarez1,*, K. Alvarez2, L. Lara1
1
Gastroenterology, CLEVELAND CLINIC FLORIDA, Weston, United States,
2
Nutrition, Licda Nutricion Clnica & Bariatrica, Guatemala City, Guatemala
Contact E-mail Address: uklejaa@ccf.org
INTRODUCTION: Teduglutide (TG) is a novel agent recently approved for the
treatment of parenteral support (PS) dependent patients with short bowel syn-
drome (SBS). PS dependence is a major concern for patients with SBS because of
PS caries a risk of serious complications and affects quality of life. In phase III
United European Gastroenterology Journal 2(5S)
trial, TG use lead to significant reduction in PS volume in SBS patients. Limited
data is available regarding clinical results outside the research protocols.
AIMS & METHODS: Aims: To evaluate short and long-term outcomes of SBS
patients receiving TG and assess patients interest in TG therapy. Methods:
Retrospective medical chart review was conducted. 19 pts. with SBS were identi-
fied. Demographics, length of small bowel, primary diagnosis, past surgical his-
tory, PS (TPN/IV fluids) volume and duration, TG dose and related
complications were collected. SBS patients who received TG from 04/2013 to
03/2014 were included in the final analysis.
RESULTS: 6 of 19 SBS pts. received TG (Females 4, Males 2); Race: Caucasian
4, Hispanic 1, African-American 1. Mean age: 45.8 yrs. (range 26-71). Cause of
SBS: vascular 3, RYGB/strangulation 1, surgical resections 2. SB length: range
30-120 cm. Colon in continuity 4, stoma 3 (ileostomy 2, colostomy 1). TPN
duration: range 114 years. PS volume/week 1-8 Liters. Duration of TG ther-
apy:1-12 months. Complications: bowel obstruction (SBO) 1, stoma swelling 2,
bloating 4 (subsided). TG discontinuation 1 (SBO*), TG dose reduction 1 (stoma
swelling). PS discontinued 4. Volume reduction in 6/6 pts. Gain or stable weight
in all while on TG. No biliary/pancreatic complications, TG injection aversion
were seen. Reason for no TG therapy in 13 pts.: No TG candidates 4 (recent
cancer 2, post surgery 512 months 1, massive small bowel dilation 1), no insur-
ance approval 1, no interest in TG therapy 8. Characteristics of SBS patients who
received TG therapy.
SB PS PS PS
length Colon Duration Volume Reduction PS TG duration
Pts. Age Sex (cm) present (years) (Week) 420% Stopped (months)
1 52 F 90 N 1.5 8L Y N 1 identify any correlation between peristomal infection and patient characteristics.
2 29 F 30 Y 14 7.2L Y Y 12
3 26 F 70 Y 5 6.4L Y Y 9 community prospectively over a 4-year period.
4 36 M 50 Y 2 7.5L Y Y 6 Patients aged 16 and over who have had percutaneous endoscopic gastrostomies
5 61 F 120 N 2 1L Y Y 5 placed at Derriford hospital, Plymouth, UK during years 2008 to 2012 were
6 71 M 90 Y 2 7L Y N 4 (TG stopped*)
CONCLUSION: From our eligible SBS patients only 6/14 (43.8%) received TG
and 4 50% of them expressed no interest in TG therapy. Three PS/nutrient
dependent patients with colon in continuity and one with end-stoma discontin-
ued PS completely with TG therapy. All patients had 420% reduction in PS
volume while on TG. All had significant reduction in stoma/stool output. TG
was well tolerated. Further studies with a larger sample size are needed in SBS
patients to assess clinical benefits of TG and address patient decision process
regarding this therapy.
Disclosure of Interest: A. Ukleja Consultancy for: NPS, A. Alvarez: None
declared, K. Alvarez: None declared, L. Lara: None declared
P0559 BEDSIDE ELECTROMAGNETIC GUIDED PLACEMENT OF
NASOJEJUNAL FEEDING TUBES IN PATIENTS AFTER
PANCREATODUODENECTOMY: PROSPECTIVE SINGLE-CENTER
PILOT STUDY
A. Gerritsen1,*, A.C. Duflou2, M. Ramali2, O.R. Busch1, D.J. Gouma1,
L.M. Mathus-Vliegen2, M.G. Besselink1
1
Department of Surgery, 2Department of Gastroenterology, Academic Medical
Center, Amsterdam, Netherlands
Contact E-mail Address: a.gerritsen@amc.nl
INTRODUCTION: Early oral feeding is now considered the routine feeding
strategy after pancreatoduodenectomy. Some 35-45% of patients will develop
delayed gastric emptying postoperatively and consequently require nasojejunal
tube feeding. Endoscopic placement of a nasojejunal feeding tube by gastroen-
terologists is relatively labour-intensive and a cumbersome procedure for
patients. Bedside electromagnetic (EM) guided placement using the Cortrak
Enteral Access System by nurses has been found to be a simple, safe and cost-
effective strategy in several patient categories. To date, however, an altered anat-
omy of the upper gastrointestinal tract is seen as a relative contraindication for
EM-guided tube placement.
AIMS & METHODS: The aim of this study was to determine the success rate of
bedside EM-guided placement of nasojejunal feeding tubes in patients after
pancreatoduodenectomy.
We performed a prospective single-center pilot study in all patients requiring a
nasojejunal feeding tube after pancreatoduodenectomy between July 2012 and
March 2014. EM-guided nasojejunal tubes were placed by two specialized nurses
with extensive experience with the technique. EM-guided placement was not
performed in patients with upper gastrointestinal stenosis or oesophageal varices
or when it was not possible for logistical reasons. Primary endpoint was the
success rate of primary tube placement confirmed on plain abdominal x-ray
(AXR). Success was defined as the tip of the tube positioned in the efferent
jejunal limb.
RESULTS: In our study period, 55 of 126 (44%) patients who underwent pan-
creatoduodenectomy required a nasojejunal feeding tube. In 36 patients the tube
was placed under EM-guidance at a median of 8 (6-11) days after pancreatoduo-
denectomy. Initial tube placement was successful according to the nurse in 25
(69%) patients and on AXR in 21 (58%) patients. Median procedure time was 25
(15-35) minutes. 22 (61%) patients underwent 50 replacement procedures after
previously failed placement attempts (n 31) or after luxation or blockage of the
tube (n 19). 36 replacements were performed endoscopically, with a success rate
of 67%, and 14 under EM-guidance, with a success rate of 71%. No tube
(re)placement related complications occurred. There was no learning curve
effect when comparing the first 10 with the subsequent 26 procedures concerning
A287
success rate, but median procedure time decreased from 33 (18-45) to 20 (15-30)
minutes.
CONCLUSION: Bedside EM-guided placement of nasojejunal tubes after pan-
creatoduodenectomy was successful in 58% of patients, which seems acceptable
given the potential benefits for the patient. Based on these findings we have
included patients after pancreatoduodenectomy in an ongoing randomized multi-
center trial focussing on the magnitude of benefits of EM-guided placement, such
as reduced patient discomfort and costs as compared to endoscopy.
Disclosure of Interest: None declared
P0560 PROSPECTIVE STUDY OF PERISTOMAL INFECTIONS AFTER
PERCUTANEOUS ENDOSCOPIC GASTROSTOMY OVER A FOUR-
YEAR PERIOD
C.R. Chimakurthi1,*, S. Lewis1, N. Pitts2, V. Chudleigh3
1
Gastroenterology, 2Endoscopy, 3Remedial Services, Plymouth Hospitals NHS
Trust, Plymouth, United Kingdom
Contact E-mail Address: cchimakurthi@nhs.net
INTRODUCTION: Incidence of peristomal infections following percutaneous
endoscopic gastrotomy in the community is not well known. Data on subsequent
site infections and the organisms responsible is limited. Despite the use of pro-
phylactic antibiotics, the incidence of peristomal infections is significant and
result in substantial morbidity in patients with PEGs.
AIMS & METHODS: We aim to evaluate the prevalence of peristomal infection
in our local community over a four year period after their PEG placement. Other
objectives were to characterise the microbiology from wound site swabs and to
Our study also looked at incidence of subsequent peristomal infection rates in the
included in the study period. Patients with venting gastrostomies and those
who had their gastrostomies placed while undergoing treatment for Head &
Neck cancer were not included in this study. All patients had their PEGs
placed according to British Society of Gastroenterology guidelines with pre-pro-
cedure prophylactic antibiotics. Community enteral feed dieticians followed all
patients at clinically appropriate intervals in the community following discharge
from hospital. They recorded incidence of infections and various other complica-
tions over the four-year period. Endoscopy reports, clinical case records, and
microbiological investigation results were also reviewed. Excel and Stata 10 were
used for data collection and analysis.
RESULTS: 341 patients underwent percutaneous endoscopic gastrostomy
during the study period. 110 patients (31%) needed treatment for an insertion
site infection. The median time from PEG insertion to first wound site infection
was 85 days (14, 363). Mixed skin commensals (42.7%) followed by
Staphylococcus aureus (29%) were most frequently isolated from gastrostomy
wound site swab. Only one patient had Methicillin resistant staphylococcus
aureus isolated. The spectrum of organisms for subsequent peristomal infection
was similar to those causing the first infection. The majority of infections
resolved with appropriate treatment. Indications for PEG insertion, age, sex
and residence did not correlate with peristomal infection. Two patients needed
replacement with new PEG tubes in view of infection. Both of them needed their
PEG tubes replaced thrice further. No specific organisms were associated with
the removal and replacement of PEG tubes.
CONCLUSION: Our rates of peristomal infection are similar to previous stu-
dies1. Although staphylococcus aureus was frequently isolated from insertion
site, the prevalence of MRSA was much lower in our cohort2. The time from
PEG insertion to initial infection was also much longer2.
REFERENCES
1. Zopf Y, Konturek P, et al. Local infection after placement of percutaneous
endoscopic gastrostomy tubes: a prospective study evaluating risk factors. Can J
Gastroenterol 2008; 22: 987-991.
2. Duarte H, Santos C, et al. Peristomal infection after percutaneous endoscopic
gastrostomy: a 7-year surveillance of 297 patients. Arq Gastroenterol 2012; 49:
255-258.
Disclosure of Interest: None declared
P0561 RESTORATION OF BOWEL CONTINUITY CAN REDUCE THE
RISK OF CHRONIC CHOLESTASIS IN PATIENTS WITH A SHORT
BOWEL
F. Adaba1,*, C. Vaizey1, S. Gabe1, J. Warusavitarne1, J. Nightingale1
1
St Marks Hospital, Harrow, United Kingdom, London, United Kingdom
Contact E-mail Address: f.adaba@nhs.net
INTRODUCTION: Patients with a short bowel and on home parenteral nutri-
tion (HPN) have an increased risk of chronic cholestasis. This is may be due to
recurrent sepsis, reduced bile flow with biliary stasis or associated with HPN.
Restoration of bowel continuity can result in HPN requirements being reduced
or stopped. This study aims to determine the effect of restoration of bowel
continuity on the risk of chronic cholestasis (CC).
AIMS & METHODS: A retrospective review of patients with short bowel due to
mesenteric infarction from 2000-2010. Chronic cholestasis (CC) was defined as
two of bilirubin, alkaline phosphatase and gamma-glutamyl transferase being 1.5
times the upper limit of normal for more than 6 months.
RESULTS: Number of patients with data on liver functions was 101 (55 females,
median age 54 years). Fifteen (54%) of 28 patients with a jejunostomy had CC
while 4 (25%) of 16 patients who had a primary anastomosis and 11(19%) of 57
patients who had a delayed anastomosis had CC. Univariate analysis showed
restoration of bowel continuity reduced the risk of chronic cholestasis
A288
(p 0.002). Of 11 patients with delayed anastomosis and CC, 3 had resolution of
CC, 3 patients died and 5 had continuing CC.
CONCLUSION: Restoration of bowel continuity can reduce the risk of chronic
cholestasis in patients with a short bowel.
Disclosure of Interest: None declared
MONDAY, OCTOBER 20, 2014 9:0017:00
THE IMMUNE SYSTEM: A DRIVING FORCE IN DIGESTIVE HEALTH AND DISEASE
I POSTER EXHIBITION HALL XL_____________________
P0562 FACTORS RELATED TO LYMPH NODE METASTASIS AMONG
ADDITIONAL SURGICAL RESECTION AFTER NON-CURATIVE
ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC
CANCER
N. Kawata1,*, N. Kakushima1, T. Sugino2, M. Tanaka1, K. Takizawa1,
M. Yoshida1, Y. Kishida1, K. Imai1, K. Hotta1, H. Matsubayashi1, H. Ono1
1
Endoscopy, 2Pathology, Shizuoka Cancer Center, Nagaizumi-cho, Japan
Contact E-mail Address: n.kawata@scchr.jp
INTRODUCTION: Indication of endoscopic resection for early gastric cancer
(EGC) has been determined by the analysis of node-negative cancer using a large
database of surgically resected EGC patients. Pathological assessment of tumor
depth and lymphovascular infiltration among surgically resected specimens are
likely to be underestimated compared to that of endoscopically resected speci-
mens because the section interval is thick (five and two millimeters, respectively).
The aim of this study was to clarify the related factors for lymph node metastasis
(LNM) among additional gastrectomy in EGC patients who were judged as
having a non-curative endoscopic submucosal dissection (ESD).
AIMS & METHODS: Clinical and pathological records of 455 patients who
underwent gastrectomy with lymph node dissection for a non-curative ESD
during September 2002 to December 2013 were retrospectively studied.
Patients with (1) multiple synchronous or metachronous non-curative lesions,
(2) recurrent lesions, (3) histological special type, (4) remnant stomach and (5)
insufficient pathological data of preceding ESD were excluded. Main histological
type (differentiated-type (D-type) or undifferentiated-type (UD-type)), lesion dia-
meter (2cm or 2cm5), tumor depth (mucosa (pT1a) or submucosa (pT1b)),
lymphovascular infiltration, vertical tumor margin (VM) and ulcerative finding
(UL) were examined.
RESULTS: A total of 359 patients (male/female: 287/72) with a median age of 70
year were enrolled. Additional gastrectomy was performed a median of 70 days
after ESD. Main histologic type were D-type/UD-type 301/58, lesion diameter
were 2cm/2cm5 109/250, tumor depth pT1a/pT1b 82/277, lymphovascular
infiltration was positive in 177, VM positive or indefinite was observed in 76,
and UL was positive in 91 patients. LNM was found in 32 patients (9%).
Univariate analysis revealed that tumor depth (OR: 4.8, 95%CI: 1.1-20.4) and
lymphovascular infiltration (OR: 11.7, 95%CI: 3.5-39.1) were significant related
factors for LNM. Multivariate analysis revealed that lymphovascular inflitration
was an independent related factor for LNM (OR: 9.78, 95%CI: 2.76-34.59).
LNM was found in 29 patients (16.4%) among 177 patients with positive lym-
phovascular infiltration. In contrast, LNM was found only 3 patients (1.6%)
among 182 patients with negative lymphovascular infiltration.
CONCLUSION: Lymphovascular inflitration was an independent related factor
for LNM among additional gastrectomy after non-curative ESD. Detailed search
of lymphovascular infiltration is the most important factor in the pathological
evaluation of endoscopically resected specimens.
Disclosure of Interest: None declared
P0563 METFORMIN INHIBITS NUCLEAR FACTOR KAPPAB
SIGNALING AND ENDOPLASMIC RETICULUM STRESS IN
GASTRIC EPITHELIAL CELLS, AND AMELIORATED ETHANOL
INDUCED GASTRITIS IN MICE
Y. Choi1,*, S.-J. Koh1, J.W. Kim1, B.G. Kim1, K.L. Lee1
1
Internal medicine, Seoul National University Boramae Hospital, Seoul, Korea,
Republic Of
Contact E-mail Address: spoon0820@naver.com
INTRODUCTION: Metformin has been recently reported to provide anti-
inflammatory or antitumor activity in colitic and colitic tumor animal models
through inhibition of nuclear factor kappaB (NF-B) signaling. There is no
evidence of metformin induced attenuation of gastric mucosal inflammation by
alcohol.
AIMS & METHODS: The aim of this study is to investigate the effect of met-
formin on NF-B signaling and endoplasmic reticulum (ER) stress in human
gastric epithelial cells in vitro and on ethanol-induced acute murine gastritis
in vivo. Human gastric epithelial MKN-45 cell lines were pretreated with met-
formin and then stimulated with tumor necrosis factor- (TNF-). Interleukin-8
(IL-8) expression was determined by real-time RT-PCR. NF-B DNA-binding
activity in the nuclear extracts was assessed by electrophoretic mobility shift
assay (EMSA). The molecular marker of ER stress, including CHOP and
XBP1 was evaluated using PCR. In the ethanol-induced acute gastritis model,
mice were given absolute ethanol (50 mg/kg, 250 mg/kg) by oral gavage with or
without metformin. Using the extracted gastric tissue, macroscopic assessment,
histological evaluation and immunohistochemical staining for phospho-IB
kinase (IKK) was performed.
RESULTS: Metformin significantly inhibited the upregulated expression of IL-8
in MKN-45 cells stimulated with TNF- in a dose dependent manner.
Pretreatment of MKN-45 cells with metformin decreased activity of NF-B in
TNF-  -stimulated cells. CHOP and XBP1 mRNA expression was enhanced in
the presence of TNF-, and it was dampened by pretreatment of metformin.
United European Gastroenterology Journal 2(5S)
Administration of metformin significantly attenuated the severity of ethanol-
induced acute murine gastritis, as assessed by macroscopic and histological eva-
luation of gastric mucosal damage.
CONCLUSION: These results indicate that metformin inhibits NF-B activation
and ER stress in gastric epithelial cells and that it ameliorates experimental
murine gastritis. These results suggest that metformin is a potential gastropro-
tective agent.
REFERENCES
Kim JM, Kim SH, Ko SH, et al. The guggulsterone derivative GG-52 inhibits
NF--B signaling in gastric epithelial cells and ameliorates ethanol-induced gas-
tric mucosal lesions in mice. Am J Physiol Gastrointest Liver Physiol 2013; 304:
G193G202.
Koh S-J, Kim JM, Kim I-K, et al. Metformin inhibits NF-B signaling in intest-
inal epithelial cells, and ameliorates murine colitis and colitis-associated colon
cancer. J Gastroenterol Hepatol 2014; 29: 502-510.
Ma TY, Iwamoto GK, Hoa NT, et al. TNF-alpha-induced increase in intestinal
epithelial tight junction permeability requires NF-kappa B activation. Am J
Physiol Gastrointest Liver Physiol 2004; 286: G36776.
Ardite E, Panes J, Miranda M, et al. Effects of steroid treatment on activation of
nuclear factor kappaB in patients with inflammatory bowel disease. Br J
Pharmacol 1998; 124: 431433.
Li SN, Wang X, Zeng QT, et al. Metformin inhibits nuclear factor kappaB
activation and decreases serum high-sensitivity C-reactive protein level in experi-
mental atherogenesis of rabbits. Heart Vessels 2009; 24: 446453.
Disclosure of Interest: None declared
P0564 RESTING-STATE FMRI IN PATIENTS WITH NON-SPECIFIC
DIGESTIVE TRACT DISEASES
G. Piotrowicz1,*, K. Skrobisz-Balandowska2, P. Naumczyk3, A. Sabisz4,
K. Markiet2, G. Rydzewska5, E. Szurowska2
1
Department of Gastrology, Self-Dependent Health Care Unit of Ministry of
Interior, 22nd Department of Radiology, Medical University of Gdansk, 3Institute
of Psychology, Department of Social Science, 4Institute of Experimental Physics,
University of Gdansk, Gdansk, 5Department of Gastronenterology, Central Clinical
Hospital of the Ministry of Interior in Warsaw, Warsaw, Poland
Contact E-mail Address: piotrowicz.grazyna@interia.eu
INTRODUCTION: The purpose of the study was to assess the differences in
brain activity during resting-state fMRI (rs-fMRI) in patients with non-specific
digestive tract diseases (Functional Dyspepsia-FD, Inflammatory Bowel
Diseases-IBD and Irritable Bowel Syndrome-IBS) in comparison to healthy
group.
AIMS & METHODS: Twelve patients (FD, IBS, IBD) and eleven in control
group were included into the study.
The functional and anatomical images were acquired with a 3T Achieva TX
Scanner (Philips Healthcare) with the use of the 8-channel head coil. To evaluate
and exclude subjects with brain pathology standard T1 and T2 sequences were
applied. No contrast agent was administered. For functional imaging a T2*
Gradient Echo-Planar Imaging sequence was used. The rs-fMRI analyses were
performed with the use of the standard preprocessing. Afterwards an
Independent Component Analysis was applied resulting in maps of the Default
Mode Network for each of the participants. Those were further compared across
the groups. The following psychological tests were applied: STAI, EAS, EPQ-R,
CISS, BPCQ.
RESULTS: Compared to patients with non-specific digestive tract diseases the
healthy controls DMN comprised additional areas in right hemisphere involving
the Medial Frontal Gyrus and Cingulate Gyrus. The DMN network of the
patients involved additional area in the medial frontal area. See table for detailed
stereotactic coordinates and Z-scores.
Table 1 Significant additional brain regions of the Default Mode Network of the
healthy controls compared with patients with non-specific digestive disorders
No. of
Anatomical region x y z Z voxels
healthy 4 patients Medial Frontal Gyrus 0 66 9 4.16 9
Cingulate Gyrus 12 24 30 4.25 5
Cingulate Gyrus -9 0 36 4.08 6
patients 4 healthy Superior Frontal Gyrus -15 63 6 4.06 8
Results of the 2nd level between-group analysis, p50.05 FDR corrected, x, y, z
are MNI coordinates of the most significant center of the activation within the
activated cluster. Z Z-value, BA Brodmann
CONCLUSION: Our study showed that the DMNs of the patients and the control
altered in the involvement of the medial structures of the prefrontal cortex (Medial
Frontal Gyrus and Superior Frontal Gyrus) as well as the dorsal anterior cingu-
lated cortex (the Cingulate Gyrus). Combined with the psychological results, the
rs-fMRI indicates differences regarding emotional self-control. Further studies are
required to establish clinical significance of those findings.
REFERENCES
1. Mayer EA, Naliboff BD and Craig AD. Neuroimaging of the brain-gut axis:
from basic understanding to treatment of functional GI disorders.
Gastronenterology 2006.
2. Mayer EA, Aziz Q, Coen S, et al. Brain imaging approaches to the study of
Functional gi disorders: A rome working team report. Neurogastroenterol Motil
2009 June.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0565 MEDIUM-TERM EFFICACY OF SACRAL NERVE STIMULATION
FOR IRRITABLE BOWEL SYNDROME
J. Fassov1,2,*, L. Lundby2, S. Laurberg2, S. Buntzen2, K. Krogh1
1
Neurogastroenterology Unit, Department of Gastroenterology and Hepatology,
2
Department of Surgery P, Aarhus University Hospital, Aarhus, Denmark
Contact E-mail Address: janfas@rm.dk
INTRODUCTION: In a recent randomized, controlled, crossover study we con-
cluded that sacral nerve stimulation (SNS) is an effective treatment for severe
IBS.1
AIMS & METHODS: In the present study, we aimed at evaluating the medium-
term results of SNS in the same group of patients.
Our criteria for permanent SNS were at least 30% reduction in IBS-specific
symptom score (GSRS-IBS questionnaire) during the percutaneous nerve evalua-
tion (PNE) test. Primary endpoint was change in the IBS-specific symptom score.
Secondary endpoint was change in the IBS-specific quality of life score.
RESULTS: Forty-three selected patients with severe diarrhoea predominant or
mixed IBS underwent a PNE test at our tertiary centre. Among these, 31 (76%,
as 2 tests were inconclusive) qualified for permanent SNS and 26 (60%) were
actually implanted. Of patients receiving permanent SNS 22 (85%) were eligible
for the present study. At follow-up after median 42 months (range; 12-60) the
median IBS-specific symptom score (26; range 13 to 64) remained significantly
lower than at baseline (62, range 45 to 80) (P50.0001). The effect was observed
in all IBS symptom clusters. Also, the median IBS-specific quality of life score
remained significantly improved at follow-up (52, range 26 to 162) compared to
baseline (134, range 82 to 180) (p 0.0001). The effect was observed in all IBS
quality of life domains. Therapeutic success was maintained in 18 patients (82%)
of whom 5 had had the stimulator for 5 years.
CONCLUSION: The positive effect of SNS for selected patients with severe IBS
is maintained at medium-term (1-5 years) follow-up.
REFERENCES
1. Fassov J, Lundby L, Buntzen S, et al. A randomised, controlled, crossover
study of sacral nerve stimulation for irritable bowel syndrome. Ann Surg. Epub
ahead of print February 2014.
Disclosure of Interest: J. Fassov: None declared, L. Lundby Lecture fee(s) from:
Medtronic Inc, S. Laurberg Other: Previously member of Medtronic Incs medical
advisory board, S. Buntzen Lecture fee(s) from: Medtronic Inc, K. Krogh: None
declared
P0567 PREVALENCE AND SEVERITY OF IRRITABLE BOWEL
SYNDROME IN MORBID OBESITY
A.S. Schneck1, D. Pishvaie1, R. Anty1, R. Dainese1, M. Vivinus1, X. Hebuterne1,
J. Gugenheim1, A. Tran1, A. Iannelli1, P. Thierry1,*
1
CHU Nice, Universite de Nice Sophia Antipolis, Nice, France
Contact E-mail Address: piche.t@chu-nice.fr
INTRODUCTION: The relationship between irritable bowel syndrome (IBS)
and obesity has been poorly investigated. Only few recent reports have suggested
an interesting correlation between obesity and IBS (1,2).
AIMS & METHODS: We aimed to determine the prevalence and severity of IBS
and associated co-morbidities in a prospective cohort of obese patients. Ninety
morbid obese patients (BMI 40.94.3 kg/m2) were included prospectively before
gastric bypass. The diagnosis of IBS and each subtype (predominance of con-
stipation, diarrhea, alternant or undetermined) was performed according to the
Rome III criteria using a Bristol scale for stool consistency. Patients were also
asked for IBS related co-morbidities including chronic fatigue, migraine, low
back pain, gastroesophageal reflux (GER), genitourinary problems and dyspep-
sia. Patients had to complete a set of questionnaires at the same time to assess the
severity of IBS (IBS Severity Score), gastroesophageal reflux (Reflux Qol), psy-
chological factors including anxiety and depression scale (HAD), fatigue (Fatigue
Impact Scale), and quality of life (SF-12).
RESULTS: Among 90 obese patients, 26 of them (28.8%) fulfilled the Rome III
criteria for IBS (IBS-D, n 11, IBS-C, n 9, IBS-A, n 1, IBS-U n 5). Obese
patients with or without IBS were similar in age (41.713.1 vs 41.512.0 years
p 0.9), sex (69% vs 65% of females, p 0.3) and BMI (40.93.9 vs 41.1 kg/m2
p 0.8). Obese patients with IBS reported significantly higher prevalence of
GER (84% vs 25.9%, p50.001), migraines (75 % vs 25% p 0.01), low back
pain (80% vs 57% p 0.03), genitourinary problems (19% vs 5% p 0.03),
chronic fatigue (80% vs 43% p 0.001) and dyspepsia (69% vs 32%
p 0.001). Obese patients with IBS had significant higher score of fatigue
(3335 vs 6339, p 0.0009), anxiety (7.03.3 vs 10.43.8 p 0.0001), depres-
sion (4.93.4 vs 6.84.1 p 0.03), severity of IBS (5855 vs 165100
p 0.0001), and poorer quality of life (39.14.736.05.4, p 0.01) than
those without IBS. Obese patients having both IBS and GER had significant
higher IBS severity scores than those without GER (171.4106 vs 9542,
p 0.05). BMI did not correlated with IBS severity whatever the presence of
Rome III criteria. In a logistic regression model including BMI, anxiety, depres-
sion, fatigue and GER score, only anxiety was significantly and independently
associated with the presence of IBS (RR 1.25 CI 95% 1.1-1.51).
CONCLUSION: A relatively high 28.8% prevalence of IBS was found in obese
patients. The severity of IBS was not correlated with BMI. However, anxiety was
independently associated with IBS in obese patients suggesting that psychological
factors are key features of IBS whatever the presence of obesity.
REFERENCES
1. Delgado-Aros S, et al. Am J Gastroenterol 2004.
2. Talley NJ, et al. Neurogastroenterol Motil 2004.
Disclosure of Interest: None declared
A289
P0568 CHRONIC INTESTINAL PSEUDO-OBSTRUCTION (CIPO): A
MULTI-LEVEL NEUROMUSCULAR-BASED DIAGNOSTIC
APPROACH
R. DAngelo1, R. Rinaldi1, V. Stanghellini2, L. Pironi2, R.F. Cogliandro2,
E. Ruggeri2, G. Cenacchi3, V. Donadio3, R. Liguori3, V. Carelli3, R. Lodi3,
C. Tonon3, R. De Giorgio2,* on behalf of CIPO Bologna Group
1
Int Med Aging Nephrol, S. Orsola-Malpighi Hospital, Bologna, Italy, 2Med Surg
Sci, 3Biom NeuroMot Sci, Univ of Bologna, Bologna, Italy
Contact E-mail Address: rdangelo81@libero.it
INTRODUCTION: Chronic intestinal pseudo-obstruction (CIPO) is a failure of
gut motility leading to recurrent episodes of intestinal sub-occlusion with no
demonstrable mechanical reason. CIPO diagnosis and management is often
very difficult because of the lack of standardized approach in relation to under-
lying causes.
AIMS & METHODS: We report our approach to diagnosis of CIPO patients
with the aim to identify possible underlying neurological causes by using a multi-
level investigation. Forty-nine CIPO patients (M: 15; age range: 19-63 yrs; F: 34;
age range: 16-61 yrs) performed first-level exams including laboratory tests, neu-
rological assessment and electromyography. Three patients did not comply to the
diagnostic protocol and were excluded. Second-level examinations included
muscle/skin biopsy and/or biochemical/molecular assays based on previous
results. MR imaging and spectroscopy were performed if mitochondrial encepha-
lomyopathy was suspected. Biochemical/molecular tests included thymidine
phosphorylase activity and a-galactosidase enzyme assay as well as gene analysis
of mitochondrial disorders; transthyretin or enteric smooth muscle actin genes
were also performed. Full-thickness gut biopsies were obtained only in cases
undergoing either elective or emergency surgery (because of intestinal sub-
occlusion).
RESULTS: At the end of the complete diagnostic work up 46 out of 49 patients
(94%) were thoroughly investigated. Three groups of CIPO patients were identi-
fied: A) n 11 had mitochondrial diseases; specifically n 6 had mitochondrial
encephalomyopathy proved by genetic analysis (4 MNGIE, 1 MERRF, 1 POLG)
and other n 5 had a likely mitochondrial encephalomyopathy, although not yet
confirmed by genetic analysis; B) n 21 had a neuromuscular non-mitochondrial
diseases; specifically n 16 had neuropathy, in particular n 3 polyneuropathy
(1 associated with lymphoma, 1 Hu-related autoantibody, 1 idiopathic poly-
neuropathy), n 12 small fiber neuropathy demonstrated by skin biopsy, n 1
enteric neuropathy; finally, n 5 had myopathy, in particular n 1 myofibrillar
myopathy and n 4 an undefined myopathy; C) n 14 had an idiopathic CIPO
with no underlying neurological causes including abnormalities of the intrinsic or
extrinsic innervation of the gut, as indicated by full thickness analysis and/or
intestinal manometry.
CONCLUSION: After an accurate neurological evaluation and tests, only a
third of CIPO are actually idiopathic. Mitochondrial disorders should be
always sought in patients with CIPO, while skin biopsy is suggested as an aid
to unravel a small fiber disorder, a peripheral neuropathy affecting also the
autonomic nerve component. Taken together our data suggest that a thorough
neurological evaluation and tests represent an important part in the management
of patients with CIPO.
Disclosure of Interest: None declared
P0569 THE SAME DAY SPLIT CLINIC A PRESCRIPTION FOR
EFFICIENCY IN THE GASTROENTEROLOGY OUTPATIENT
CLINIC
M.F. Jaboli1,*, M. Grimes1, H. Palmer1, C. Clayman1, T. Rayne1, C. Durcan1,
I. Mason1, O. Epstein1
1
Gastroenterology, Royal Free Hospital, London, United Kingdom
INTRODUCTION: Worldwide, healthcare providers are striving to balance
escalating costs with the patients expectation of efficient access to specialist
opinion, rapid investigation and treatment. Over the past 65 years, the NHS
gastroenterology outpatient journey has remained unchanged. Patients are
assessed at the first visit, followed by one or more hospital visits for gastrointest-
inal investigations and a return hospital attendance for final assessment. The
same day split clinic has been designed, wherever possible, to condense the jour-
ney from months to hours.
AIMS & METHODS: Over a period of three months, each gastroenterology
referral letter was previewed in advance of the outpatient appointment. Each
patient was triaged as solution or complex. For the solution cohort,
investigations were predicted and scheduled for the same day as the outpatient
attendance. Patients were asked to attend the clinic starved and told to expect one
or more same day gastrointestinal investigations. On the appointment day,
solution patients attended the same day split clinic for: 1) an initial specialist
assessment, 2) scheduled investigation(s), 3) a return to the specialist clinic for a
summative assessment & management plan.
RESULTS: Of 174 referrals, 95 patients were triaged from the referral letter as
Solution patients, and 81 attended the split clinic (7 did not arrive, 4 post-
poned, 3 direct to surveillance colonoscopy). In those who attended, 46 same day
tests were performed (14 upper endoscopies, 11 sigmoidoscopies, 5 barium swal-
lows, 6 Eso Capsule endoscopies, 5 ultrasound scans, 1 electrogastrogram, 2 CT
abdomen and 2 CT colonoscopy). Twenty-seven patients (34%) were discharged,
and twenty-two (27 %) were discharged after a single follow up telephone con-
sultation. Overall, 49 patients designated as Solution patients (60%) required
only a single hospital visit. Sixteen patients (17%) were re-designated as
Complex requiring further tests and 3 (3%) were referred elsewhere. Overall,
95 (46 same day tests and 49 return to follow up clinic in old system) return
hospital visits were avoided. The visits were reduced by 40% and the follow up
appointments were down by 60%.
A290 United European Gastroenterology Journal 2(5S)
CONCLUSION: Analytical triage of GP referral letters allows identification & time-international normalized ratio (PT-INR), levels of fibrin/fibrinogen degra-
triage of most solution patients. This facilitates pre-emptive investigation plan- dation products (FDP), C-reactive protein (CRP), DIC scores based on JAAM
ning and scheduling which, in turn, supports a same day split clinic designed to criteria were measured on days 0,3, and 7 to evaluate therapeutic results.
condense months of investigation and follow up into a few hours. The well Furthermore, DIC resolution rate were assessed 3 and 7 days after the start of
planned same day split clinic meets the patients expectation for an efficient DIC treatment.
journey and a quick diagnosis. The inconvenience of numerous hospital atten- RESULTS: Before treatment, DIC scores based on JAAM criteria were 50.95
dances is minimized, whilst appointment capacity is freed up. in the rTM group, and 5.91.3 in the control group (p50.05), respectively.
Disclosure of Interest: None declared However, there were no significant differences between two groups regarding
age, sex, and causative disease of DIC. The duration of rTM administration
was 3.61.44 days (range 1 to 7 days). As shown in the table, significant intra-
P0570 DEVELOPING A EUROPEAN CLINICAL RESEARCH NETWORK group improvement was observed in all parameters except for FDP in both
FOR PAEDIATRIC GASTROENTEROLOGY, HEPATOLOGY AND groups. However, there were no significant inter-group differences in comparison
NUTRITION of all parameters. Result from the repeated measures analysis of variance, sig-
N. Croft1,*, V. Tailor1, L.de Ridder2, S. Hussey3 on behalf of PEDDCReN nificant improvements were seen in the DIC scores in the rTM treated group
Steering Group (p 0.001).
1
Centre for Digestive Diseases, Blizard Institute, Queen Mary University of
London, London, United Kingdom, 2Erasmus MC, Rotterdam, Netherlands, Day0 Day3 Day7
3
University College Dublin, Dublin, Ireland
4
Contact E-mail Address: n.m.croft@qmul.ac.uk Platelet count (10 /mL) rTM 11.16.5 10.54.7 17.99.0*
INTRODUCTION: Paediatric European Digestive Diseases Clinical Research control 10.66.9 8.45.7 14.98.7**
Network (PEDDCReN) was established in April 2013. The need for this initiative PT-INR rTM 1.390.32 1.180.16** 1.210.22**
was identified by ENPR-EMA (The European Network of Paediatric Research control 1.430.32 1.220.3** 1.20.19**
at the European Medicines Agency). The Project is supported by LINKS funding FDP (mg/ml) rTM 32.319.4 19.824.5 17.613.7
from the UEG (United European Gastroenterology) and is led by the British,
Irish and Dutch Societies of Gastroenterology in collaboration with ESPGHAN control 37.434.1 24.914.5 22.213.0
and ENPR-EMA. CRP (mg/dL) rTM 14.18.8 9.75.4* 6.65.6**
AIMS & METHODS: The aim of PEDDCReN is to support the development of control 14.57.6 12.26.1 7.55.2**
large studies in paediatric patients in the speciality of Gastroenterology, DIC score rTM 50.95 3.11.8** 2.01.7**
Hepatology and Nutrition (GHN).
We report the preliminary results of an online survey as a first step of control 5.91.3 4.51.9** 3.22.3**
PEDDCReN, identifying investigators resources, expertise and interest in stu- DIC resolution rate (%) rTM 48 68
dies in this area in the UK, Ireland and the Netherlands. control 28.6 50
The survey was designed by the steering group of PEDDCReN and utilised the
web based system REDCap. It takes 5 minutes to complete with 1 respondent per Data are shown with MeanSD *p50.05 vs Day0, **p50.01 vs. Day0
hospital. To date the survey has had responses from paediatric gastroenterolo-
gists in the UK, Ireland and the Netherlands as members of BSG, BSPGHAN,
Irish and Dutch Gastroenterology Societies. As a result of PEDDCReN promo- CONCLUSION: These results suggest that rTM would be the useful medicine
tions in UEG & ESPGHAN newsletters one centre from Italy, Germany, Serbia for treatment DIC in the gastroenterology field.
and Poland has also responded. Disclosure of Interest: None declared
RESULTS: After six months 25 units (including 53 investigators) had replied
representing childrens services with a median of 211 beds (range 15-800). 10 were
stand alone childrens hospitals, 11 were childrens hospitals co-located with P0572 THE EFFECT OF ACUTE SLIGHTLY INCREASED INTRA
adult hospitals, 2 were smaller childrens units in adult hospitals and one was ABDOMINAL PRESSURE ON INTESTINAL PERMEABILITY AND
a neonatal unit. 76% of responding units had neonatal ICUs on site with almost OXIDATIVE STRESS IN A RAT MODEL
all of these carrying out neonatal surgery. All wished to be part of PEDDCReN Y. Leng1,*, G. Yao1
and were happy for contact details to be passed on to both industry and non- 1
Intensive care unit, Peking University Third Hospital, Beijing, China, Beijing,
industry investigators. The survey identified each units interest in recruiting into China
a range of GI and liver diseases (eg 88% wished to recruit for IBD studies Contact E-mail Address: lengyuxin1980@126.com
whereas only 24% for infant diarrhoea). Less than 33% would also recruit to
liver studies including infective hepatitis. Of the respondents 60% have been a INTRODUCTION: The harm of Intra-abdominal hypertension (IAH) on criti-
principle investigator (in their hospital) and 40% had been chief investigators for cally ill patients has gained great attention. However, there are still 60% under-
their country. 68% were willing to take on phase I or II studies but only 36% had IAH patients in critical care units, whose intra abdominal pressure (IAP) runs
done any in the last 3 years. 64% had a clinical research facility available on site slightly higher, at 5 to 7 mmHg. Among the frequently IAH-affected organ
and 68% have access to research nurses. Sites were also asked whether they systems, the intestine is initially influenced. Nevertheless, the adverse effect of
currently followed up any patients with rare GI or liver diseases such as con- transient exposure to slightly raised IAPs on intestinal mucosa remains unclear.
genital enteropathy (12/25), congenital transport defect (7/25), polyposis syn- AIMS & METHODS: To study the acute effects of different grade nitrogen
dromes (17/25), chronic intestinal pseudo-obstruction (15/25). pneumoperitoneum on colon mucosa, male Sprague- Dawley rats were assigned
CONCLUSION: This shows the ability of PEDDCReN to identify interest, to six groups with different IAPs (baseline, 4mmHg, 8mmHg, 12mmHg,
expertise and resources in 3 countries. This will shortly be extended to the rest 16mmHg, 20mmHg, n 6 per group). During the 90 minutes exposure, we
of Europe. The potential for investigators and industry to utilise this network to dynamically monitored the heart rate and noninvasive hemodynamic paramaters.
support the development of large scale clinical trials and rare diseases studies After decompression slowly, the arterial blood gas analyses were conducted.
within this speciality is a major benefit. Then the structural injury to the colon mucosa was confirmed by light micro-
Disclosure of Interest: None declared scopy. The colon permeability was revealed by expression and localization of
tight junction proteins (claudin 5 and occludin), combined with the absorption of
fluorescein isothiocyanate dextran (FD-4, with another proportion of rats, n 6
P0571 THE EFFICACY OF RECOMBINANT HUMAN SOLUBLE per group). The pro-oxidantantioxidant balance of the colon was determined by
THROMBOMODULIN IN PATIENTS WITH SEPSIS AND the levels of malondialdehyde (MDA), glutathione peroxidase (GSH-Px), cata-
DISSEMINATED INTRAVASCULAR COAGULATION IN THE lase (CAT) and serum super oxide dismutase (SOD).
GASTROENTEROLOGY FIELD RESULTS: IAPs greater than 12 mmHg significantly disturbed the colonic integ-
T. Ito1,*, A. Nagahara1, T. Osada1, J. Kato1, H. Ueyama1, H. Saito1, rity, expression of tight junction protein, mucosal permeability to FD-4 and the
S. Watanabe1 pro-oxidantantioxidant balance. Interestingly, slight elevation of IAPs not
1
gastroenterology, Juntendo University, Tokyo, Japan reaching the level of IAH also showed a similar undesirable effect. In 8mmHg
Contact E-mail Address: tmitou@juntendo.ac.jp group, mild hyponatremia, hypocalcemia and hypoxemia occurred, accompanied
with the reduction of blood pressure and abdominal perfusion pressure. Whats
INTRODUCTION: Inpatients with digestive disease often have coexisting ser- more, mild microscopically inflammatory infiltration and increase of MDA were
ious infections. Some of them result in disseminated intravascular coagulation also detected in under-IAH groups. 8mmHg-IAP markedly inhibited the expres-
(DIC). Recently, recombinant human soluble thrombomodulin (rTM) was sion of claudin 5 and occludin, though no significant differences were found in
approved and has been used in clinical practice for DIC treatment in Japan. permeability to FD-4 between control and 8mmHg groups.
However, there are few studies to evaluate the efficacy of rTM for DIC in the CONCLUSION: Acute exposure to slightly raised IAPs may bring adverse
gastroenterology field. The purpose of this study is to make a comparison effects on intestinal permeability and pro-oxidantantioxidant balance.
between rTM-treated patients and patients treated other agents, and to evaluate Accordingly, we concluded that for critically ill patients, IAPs should be mon-
the efficacy of rTM. itored dynamically and intervened as soon as possible to avoid the intestinal
AIMS & METHODS: The purpose of this study is to make a comparison mucosal injury and the subsequent gut- derived sepsis.
between rTM-treated patients and patients treated other agents, and to evaluate REFERENCES
the efficacy of rTM. Fifty-three inpatients at our department with sepsis-induced 1. Cheng J, Wei Z, Liu X, et al. The role of intestinal mucosa injury induced by
DIC between January 2009 and February 2014 were retrospectively analyzed. intra-abdominal hypertension in the development of abdominal compartment
The patients were classified into the rTM treatment group (n 25), and conven- syndrome and multiple organ dysfunction syndrome. Crit Care 2013; 17: R283.
tional treatment group (rTM was not used) as the control group (n 28). 2. Gong G, Wang P, Ding W, et al. Microscopic and ultrastructural changes of
Diagnosis of DIC was made according to the criteria of acute DIC of the the intestine in abdominal compartment syndrome. J Invest Surg 2009; 22: 362-
Japan Association of Acute Medicine (JAAM). Platelet count, prothrombin 367.
United European Gastroenterology Journal 2(5S)
3. Malbrain ML, Cheatham ML, Kirkpatrick A, et al. Results from the interna-
tional conference of experts on intra-abdominal hypertension and abdominal
compartment syndrome: I. Definitions. Intensive Care Med 2006; 32: 1722-1732.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 9:0017:00
POSTER PLUS VIDEO II POSTER EXHIBITION HALL XL_____________________
P0573 USE OF A NOVEL SELF-EXPANDING METAL STENT TO
ALLOW FOR ENDOSCOPIC DRAINAGE AND NECROSECTOMY
OF PANCREATIC FLUID COLLECTIONS
M.T. Huggett1,*, K.W. Oppong1, S.P. Pereira2, V. Mitra1, R.M. Charnley3,
M.K. Nayar1
1
Department of Gastroenterology, Freeman Hospital, Newcastle upon Tyne, United
Kingdom, 2University College Hospital, London, United States, 3Department of
HPB surgery, Freeman Hospital, Newcastle upon Tyne, United Kingdom
Contact E-mail Address: matthewhuggett@doctors.net.uk
INTRODUCTION: Post-inflammatory peri-pancreatic fluid collections are fre-
quent sequelae of severe acute pancreatitis. Collections are at risk of suppurative
infection complicated by pancreatic necrosis. Over the last decade there has been
an increasing emphasis on minimally invasive drainage procedures, including
EUS-guided cyst-gastrostomy, and these approaches seem to be associated
with lower morbidity and mortality. Access to the necrosis cavity has however
been severely limited by having to maintain the tract with small diameter plastic
stents. Recently, a novel flanged fully covered self-expanding metal stent
(FCSEMS; NAGI stent, Taewoong Medical, Korea) has been developed to
allow for better drainage of infected necrosis and easier endoscopic access into
the cavity. Setting: A non-randomised prospective multicentre phase II study to
determine the safety and efficacy of FCSEMS endoscopic cyst- gastrostomy in
the management of complex/infected pancreatic fluid collections.
AIMS & METHODS: Patients were included if they had evidence of a pancreatic
fluid collection which was deemed to be amenable for EUS- guided drainage after
discussion at a HPB multidisciplinary meeting. Patients selected for EUS-guided
drainage had cross sectional imaging (MR or CT) performed within 2 weeks of
the procedure and then an EUS assessment was made of the necrotic component.
The collection was punctured using a cystotome and the FCSEMS inserted over a
guidewire with fluoroscopic control. Repeat procedures were performed as
necessary.
RESULTS: A total of 11 patients (8 male, 3 female) were included in the study.
Median age was 57.3 years. The aetiology of the collection was gallstones in 6
patients, idiopathic in 3, ischaemic in 1 and drug-induced in 1. Ten patients had
evidence of at least 30% necrosis within the collection. Mean diameter of the
collection was 15cm and EUS-guided puncture was initially performed in all
patients. The tract was dilated with a balloon in 6 patients. Stent insertion was
either with a 20mm (7 patients) or 30mm (4 patients) length FCSEMS. Ten
patients underwent endoscopic necrosectomy, with a median of 3 procedures
(range 1-10). Significant reduction in the size of collection was achieved in all
patients. Adverse events included stent migration in 3 (2 spontaneously and 1
during necrosectomy). Two patients died of complications of severe acute
pancreatitis.
CONCLUSION: FCSEMS insertion is feasible and safe for drainage of pancrea-
tic fluid collections. It allows repeated through the stent necrosectomy proce-
dures and appears to be a major advance in the management of infected
pancreatic necrosis.
Disclosure of Interest: None declared
P0574 LUCKY LOOP: A VARIANT OF AN ENDOLOOP CLIP P0576 DEVELOPMENT
WOUND CLOSURE TECHNIQUE AFTER COLONIC DEFIANT
POLYP REMOVAL
E. Rosa-Rizzotto1,*, C. Lucchini1, F. De Lazzari1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital, Padua,
Italy
INTRODUCTION: This report describes a variant of an iatrogenic wound clo-
sure technique after endoscopic mucosal
resection (EMR) or endoscopic submucosal dissection (ESD). After removal of
defiant polyps without signs of perforation or important bleeding, iatrogenic
wounds are generally not closed as second intention healing is expected. In the
past patients were often hospitalized after those procedures for 2-3 days, but
when discharged a 6.5% prevalence of delayed bleeding persists(1). The com-
bined technique of endoloop plus clip or clip alone to close iatrogenic wounds or
perforations during operative endoscopies is a well established practice. Clips
plus endoloop technique have been coined King Closure(2) or clutching rose
stems techniques(3).
AIMS & METHODS: We propose a tobacco-pouch suture technique for
wounds that are a maximum of 4 cm diameter, anchoring a single endoloop
with 5-6 long type clips cirumferencially to the wound edge perimeter and closing
the loop using a single double channel endoscope. A hemoclip short type is
placed over the plastic tube that tightens the loop to fix the suture at the end
of the procedure.
Sixteen (8 ESD and 12 EMR) patients underwent endoscopic removal of polyps
425 mm 5 40 mm between June and December 2013. All the iatrogenic wounds
were closed with the technique described in the video. The mean time to perform
the procedure was 8 min (range 6-13 min). High definition endoscopes PCF-
H180AL and GF-H180J (OLYMPUS, Tokyo, Japan) with an external artificial
second channel, a 30 mm diameter endoloop (PolyLoop, OLYMPUS, Tokyo,
Japan) and Clips HX-610-090L and HX-610-135S (EZ-Clip, OLYMPUS,
Tokyo, Japan) were used. Carbon dioxide insufflation was used during all of
A291
the procedures. The patients were examined three, seven and thirty days after the
procedure.
RESULTS: All the patients were discharged 2 hours after the endoscopic proce-
dure was completed and none had any post procedural complications (fever,
delayed bleeding, perforation or abdominal pain).
CONCLUSION: These results demonstrate that when this closure is utilized
patients can be safely discharged from the hospital 2-3 hours after endoscopic
removal of a polyp. The technique is quick, (it was coined Lucky Loop in
honor of Luky Luke the fast solitary gunslinger cartoon character created by
Maurice De Bevere) easy and economic and can be also used in cases of large
gastrointestinal perforations or in patients that cant stop double or triple anti-
platelet therapy.
REFERENCES
1 Hong SP. Clin Endosc 2012; 45: 282-284.
2 Ryska O, et al. Gastroent Hepatol 2011; 65: 207210.
3 Samarasena JB, et al. Endoscopy 2012; 44: E424-E425.
Disclosure of Interest: None declared
P0575 PERFORMANCE CHARACTERISTICS OF COLORECTAL FULL
SPECTRUM ENDOSCOPY (FUSE) PROSPECTIVE, PARALLEL,
RANDOMIZED STUDY
H. Neumann1,*, G.E. Tontini1,2, M. Vieth3, C. Gunther1, M. Grauer1,4,
M.F. Neurath1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany, 2IRCCS
Policlinico San Donato, San Donato Milanese, Italy, 3Klinikum Bayreuth,
Bayreuth, 4Klinikum Neumarkt, Neumarkt, Germany
INTRODUCTION: Full Spectrum Endoscopy (FUSE) provides a 330 field of
view, thereby potentially allowing the endoscopists to see more anatomy in com-
parison to standard forward viewing endoscopes (FVE). Recent data has already
shown that FUSE is feasible to significantly reduce adenoma miss rates.
AIMS & METHODS: The aim of this prospective, parallel, randomized study
was to assess the performance characteristics of FUSE in comparison to FVE.
Patients were randomly assigned to undergo colonoscopy with FUSE (Group A)
or FVE (Group B) after a previous sample size calculation. Performance char-
acteristics including time to cecum, withdrawal time, total examination time,
medication, patient and endoscopists satisfaction, and polyp detection rates
were recorded.
RESULTS: 57 patients were included (male 52%; mean age 56 years, Range 21
88 years). Time to cecum (minutes, mean  SD) was 4.05  0.6 minutes for
FUSE and 5.48  0.6 for FVE (P 50.05). Withdrawal times were 12  4.4
minutes and 15  4.5 minutes for FUSE and FVE, respectively. Total examina-
tion time was 16.5  4.4 minutes in the FUSE group and 20.1  4.5 minutes in
the FVE group. Sedation was less required in the FUSE group as compared to
FVE (mean propofol dosage, 170 mg vs. 230 mg). Significantly more patients
needed analgesia in the FVE group (meperidine; p 0.01). Patient and endosco-
pists satisfaction were high throughout the cases and not different between both
groups. Per patient polyp detection rates were 37% and 18% for FUSE and
FVE, respectively.
CONCLUSION: Advancement times of the scope to the cecum and withdrawal
times were faster with the FUSE scope as compared to standard FVE.
Satisfaction rates of patients and endoscopists were similar in both groups
while patients needed more sedation and analgesia in the FVE group.
Although more polyps were found in the FUSE group the study was not powered
to compare adenoma detection rates between both groups.
Disclosure of Interest: None declared
AND VALIDATION OF A SIMPLE
CLASSIFICATION SYSTEM FOR IN VIVO DIAGNOSIS OF
COLORECTAL POLYPS USING VIRTUAL CHROMOENDOSCOPY
THE VISIBLE STUDY
H. Neumann1,*, C. Gunther1, L.C. Fry2, M. Vieth3, G.E. Tontini1,4,
M. Grauer1,5, M.F. Neurath1, K. Monkemuller2
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, Germany,
2
University of Alabama at Birmingham, Birmingham, United States, 3Klinikum
Bayreuth, Bayreuth, Germany, 4IRCCS Policlinico San Donato, San Donato
Milanese, Italy, 5Klinikum Neumarkt, Neumarkt, Germany
INTRODUCTION: Although the diagnostic performance of virtual chromoen-
doscopy (VCE) has already been reported, validated classification systems allow-
ing both experienced and inexperienced endoscopists to apply VCE have not
been established.
AIMS & METHODS: To develop and validate a simple classification system for
differentiating hyperplasic and adenomatous colorectal lesions by using VCE.
In the first phase, the capacity of experienced endoscopists to predict the histol-
ogy of colorectal polyps was assessed. In the second phase, a simplified classifi-
cation was developed allowing histologic prediction. Thirdly, the validity of the
classification was evaluated among inexperienced raters, including medical stu-
dents and GI fellows. Last, a pilot clinical evaluation was performed during real-
time colonoscopy. The study was performed in a multicenter, international
setting.
RESULTS: A simple classification system for differentiating hyperplasic and
adenomatous colorectal lesions by using VCE was developed and validated.
Diagnosis was made in 78% to 89% (mean 82.5%) of polyps with high confi-
dence. Sensitivity and specificity ranged from 95% to 98% and 78% to 100%,
respectively. During real-time colonoscopy, diagnosis was made with high-con-
fidence in 84% of polyps with sensitivity of 91%, specificity of 85%, and accu-
racy of 93%. Positive and negative predictive values were 93% and 93%,
respectively.
A292 United European Gastroenterology Journal 2(5S)
CONCLUSION: We developed and validated for the first time a simple classi- percentage of polyps for which pCLE correctly differentiated between non-ade-
fication system for differentiating hyperplasic and adenomatous colorectal nomatous, adenomatous and carcinomatous polyps.
lesions by using VCE during real-time colonoscopy. RESULTS: The overall diagnostic accuracy of real time pCLE for colorectal
Disclosure of Interest: None declared polyps was 75% and was not different between the endoscopists (74% vs.
76%, p 0.81). Accuracy remained stable when comparing the first 25 proce-
dures with the last 25 procedures of both endoscopists (respectively 76% vs.
P0577 THE OBSERVATION OF SECOND-GENERATION AUTO- 72%, p 0.75 and 76% vs. 76%, p 1.00). According to the size of the
FLUORESCENCE IMAGING (AFI) HELPS EASILY TO DETECT OF polyps, accuracy was non-significantly different (67% for 68 polyps 5 mm,
FLAT COLON NEOPLASIA FOR NON-EXPERT ENDOSCOPISTS 86% for 21 polyps 10 mm and 89% for 18 polyps 410 mm; p 0.08).
S. Saito1,*, D. Ide1, H. Inomata1, T.R. Ohya1, N. Tamai1, T. Kato1, Sensitivity for detecting neoplasia in polyps 5 mm was 65% (59% for right
M. Ikegami2, H. Tajiri3 sided polyps and 73% for left sided polyps).
1
Endoscopy, 2Dept. of Pathology, 3Division of Gastroenterology and Hepatology, CONCLUSION: The diagnostic accuracy of two endoscopists starting to use real
Dept. of Internal Medicine, THE JIKEI UNIVERSITY SCHOOL OF time pCLE for colorectal polyps was 75% and remained stable during the first 50
MEDICINE, Tokyo, Japan procedures. Sensitivity for detecting neoplasia in small polyps was below the
Contact E-mail Address: ssaito@jikei.ac.jp required 90% and suggests that real-time pCLE cannot be used to guide
follow-up decisions and that histologic evaluation of removed polyps is still
INTRODUCTION: We reported about the features of observation for colon required.
polyps by using the AFI system 1). Namely, hyperplastic lesion is shown as Disclosure of Interest: None declared
dark green color similar to surrounding mucosa. In contrast, most of the neo-
plastic lesion is changed to magenta color at the localized tumor area. And also,
this strength of change is suggested to correlate with the histological grading. In P0579 NOVEL COMPUTER-AIDED DIAGNOSIS SYSTEM FOR
this study, we examined the benefits of using this system to detect the colon COLORECTAL LESIONS USING ENDOCYTOSCOPY
neoplasia for beginner endoscopists. Y. Mori1,*, S.-E. Kudo1, K. Wakamura1, M. Misawa1, Y. Ogawa1,
AIMS & METHODS: Two studies were used to clarify for the usefulness by M. Kutsukawa1, T. Kudo1, T. Hayashi1, H. Miyachi1, F. Ishida1, S. Hamatani1,
second-generation AFI observation. One method used four pictures (white light H. Inoue1
conventional image (WHL), indigo carmine dye sprayed image (CE), NBI and 1
Digestive Disease Center, SHOWA UNIVERSITY NORTHERN YOKOHAMA
AFI). Another method used short movies, which recorded WHL and AFI within HOSPITAL, Yokohama, Japan
about one minute, respectively. At first study, twenty-four cases (flat type intra- Contact E-mail Address: ibusiginjp@hotmail.com
mucosal lesion 22 cases and depressed submucosal invasive cancer; 2 cases) were
retrospectively reviewed. In contrast, thirty cases (sessile serrated (SS) lesion; 12 INTRODUCTION: Endocytoscopy (EC) enables observation of nuclei at 450-
cases, intramucosal (IM) lesion; 13 cases and submucosal invasive cancer (SM); 5 fold magnification during gastrointestinal endoscopy, thus allowing precise pre-
cases) were reviewed at second study. These pictures and videos were shown to a diction of lesion pathology, however it requires training and experience.[1,2]
group of 5 beginner endoscopists (non-experienced for using AFI system) and a AIMS & METHODS: The aim of the present study was to develop and evaluate
group of 4 expert endoscopists (experienced more than 1000 cases). The used a computer-aided diagnosis (CAD) system for EC imaging of colorectal lesions.
scope is CF: FH260AZI with second generation Lucera Elite system (Olympus The proposed CAD system comprised image acquisition, nuclear segmentation,
Medical Systems, Tokyo, Japan). feature extraction, and classification into three pathological groups (non-neo-
RESULTS: At first study, the visualization score was defined as follows: the plastic, adenoma, and cancer). The classification algorithm was programmed
worst visualization was scored as 0 and the best as 10. And to evaluate the based on six features of nuclei that were significantly relevant to pathological
visualization of colon neoplasia, we calculated the average visual analog scale classification by multivariate analysis: area (p 0.009), standard deviation of
(VAS) scores for each groups. The mean AFI visualization score; 8.9 was sig- area (P50.001), circularity (P50.001), circularity of the top 20 nuclei
nificantly higher than that of WHL; 6.5, CE; 8.2 and NBI; 7.1 by non-experi- (P50.001), shortest diameter (P50.001), and longest diameter (P50.001). To
enced group. And there was difference in average visualization scores between validate this CAD system, we conducted a pilot study using test sets of EC
AFI; 7.5 and another modalities (WHL; 4.8, CE; 7.2 and NBI; 5.8) by experi- images from 176 small colorectal polyps (132 neoplastic lesions and 44 non-
enced group. At second study, the strength changing to the magenta color from neoplastic lesions, all 10mm). The performance of the CAD system for predic-
dark green with excitation light was evaluated by 10-point VAS. In non-experi- tion of neoplastic change was compared with diagnoses by two expert endosco-
enced group, the score of SS lesion, IM lesion and SM lesion were 2.3, 5.2 and pists and two trainee endoscopists. The average time for diagnosis and intra-
7.8, respectively. In contrast SS lesion, IM lesion and SM lesion were 2.4, 5.7 and observer agreement (using 20 EC images at a 4-week interval) were also measured
7.8 in experienced group, respectively. It was shown almost same as VAS scores and compared among the three groups.
between non-experienced and experienced as result. RESULTS: The CAD system automatically output the pathological prediction
CONCLUSION: AFI provided significantly better visualization to detect and of all subject images immediately on their input. The CAD system provided a
differentiate non-neoplastic lesion and neoplastic lesion for beginner endosco- sensitivity of 92.0% and an accuracy of 89.2% which were comparable with those
pists. It suggested that it is not difficult to diagnose the indication of endoscopic provided by the experts (p 0.868 and 0.256, respectively) and significantly
treatment for neoplastic changes within intramucosal layer using AFI system for higher than those provided by the trainees (P50.001 and 0.002, respectively).
non-experienced endoscopist. It was also expected to detect flat elevated lesion The CAD system achieved a feasible specificity of 79.5%, which was not signifi-
more easily by non-experienced endoscopists. cantly different from that achieved by the experts and trainees (p 0.081 and
REFERENCES 0.728, respectively). The CAD system also enabled instant diagnosis which took
1) Saito S, Aihara H, Tajri H, et al. Autofluorescence imaging makes it easy to only 0.3 seconds for each lesion with perfect reproducibility (Kappa 1). (See
differentiate neoplastic lesions from non-neoplastic lesions in the colon. In: New Table)
challenges in gastrointestinal endoscopy. Tokyo: Springer Inc., 2008, pp. 330-337.
Disclosure of Interest: None declared Computer-aided P value P value
diagnosis (CAD vs (CAD vs
(CAD) Experts Trainees experts) trainees)
P0578 THE ACCURACY OF REAL-TIME PROBE BASED CONFOCAL
LASER ENDOMICROSCOPY FOR DIFFERENTIATION OF Sensitivitiy, % 92.0 92.7 81.8 0.868 50.001
COLORECTAL POLYPS DURING COLONOSCOPY Specificity, % 79.5 91.0 75.6 0.081 0.728
T.D. Belderbos1,*, M.G. van Oijen1, L.M. Moons1, P.D. Siersema1 Accuracy, % 89.2 92.3 80.4 0.256 0.002
1
Gastroenterology and Hepatology, University Medical Center Utrecht, Utrecht, Time for diagno- 0.3 4.5 16.0 50.001 50.001
Netherlands sis, seconds
Contact E-mail Address: t.d.g.belderbos@umcutrecht.nl Intra-observer Almost perfect Substantial Substantial NA NA
agreement (Kappa 1) (Kappa 0.79) (Kappa 0.71)
INTRODUCTION: Reliable real-time differentiation between neoplastic and
non-neoplastic colorectal polyps during colonoscopy may guide treatment deci-
sions and reduce the need for post hoc histologic evaluation of resected polyps. In
the hands of experts, probe based confocal laser endomicroscopy (pCLE) has CONCLUSION: This fully automated CAD system provides excellent sensitivity
been suggested to be a highly accurate technique for this. Previous studies have and accuracy with acceptable specificity, ultra-rapidness, and perfect objectivity.
shown a short learning curve for offline interpretation of pCLE images of color- Thus, it can be a powerful tool for decision support during screening
ectal polyps. It is however not known whether colonoscopists starting to use this colonoscopy.(This study was registered as UMIN000012797 and supported by
technique can also accurately differentiate colorectal polyps during routine colo- JSPS KAKENHI Grant Number 25860564.)
noscopy by using real time pCLE to directly evaluate images. REFERENCES
AIMS & METHODS: The primary aim was to determine the diagnostic accu- 1. Mori Y, et al. Comprehensive diagnostic ability of endocytoscopy compared
racy of real-time pCLE for the differentiation of colorectal polyps during the first with biopsy for colorectal neoplasms: a prospective randomized noninferiority
50 pCLE cases of two endoscopists routinely performing colonoscopy. The sec- trial. Endoscopy 2013; 45: 98-105.
ondary aim was to compare the sensitivity for diagnosing neoplasia small polyps 2. Kudo S, et al. Diagnosis of colorectal lesions with a novel endocytoscopic
(5 mm) in this study with a sensitivity threshold of 90% that is required for classification a pilot study. Endoscopy 2011; 43: 869-875.
selective polypectomy or resect and discard strategies. We included patients of Disclosure of Interest: None declared
45 years or older undergoing colonoscopy for screening, surveillance or diagnos-
tic work-up between August 2012 and April 2014. After a training to obtain and
interpret pCLE images two senior endoscopists performed 50 pCLE procedures
each. Intravenous fluorescein was used as contrast agent. All polyps were
resected endoscopically and histologic diagnosis by an expert pathologist was
used as reference. Primary outcome was the diagnostic accuracy, defined as the
United European Gastroenterology Journal 2(5S)
P0580 TRANS-ANAL SUBMUCOSAL ENDOSCOPIC RESECTION
(TASER): A NEW ENDO-SURGICAL APPROACH TO THE
RESECTION OF BENIGN GIANT RECTAL LESIONS
Z.P. Tsiamoulos1,*, J. Warusavitarne2, T. Elliott1, B.P. Saunders1
1
Wolfson Unit for Endoscopy, 2Department of Colorectal Surgery, St Marks
Hospital/Academic Institute, London, United Kingdom
INTRODUCTION: Trans-anal surgical (TEMS/TAMIS) and advanced endo-
scopic resection (ESD, P-EMR) procedures have the potential to provide com-
plete and successful eradication of giant rectal polyps. Both approaches however
have limitations in terms of practicality and safety. We describe a new endo-
surgery technique called Trans-Anal Submucosal Endoscopic Resection
(TASER) which combines the advantages of both the endoscopic and transanal
surgical approach.
AIMS & METHODS: The GelPoint Path trans-anal access port allows simulta-
neous passage of an endoscope and two laparoscopic retractors. Working with
the endoscopic image the laparoscopic retractors (Johen 33mm forceps) allow
dynamic tissue retraction to facilitate endoscopic dissection (Flush knife BT) or
snare placement (Olympus snare master/spiral snare). All procedures were per-
formed under general anesthesia and with patients in the lithotomy position.
RESULTS: Eleven patients (mean age 55 years, 3 male/8 female) underwent
TASER for 11 lesions, distributed from the lower rectum to the recto-sigmoid
junction and with a median size of 85mm, range 40-180mm. Polyp morphology
was (3/11 flat (Paris 2a), 4/11 sessile (Paris 1s) and 4/11 mixed type (Paris 2a1s).
In all cases a circumferential mucosal incision was made and histology confirmed
free lateral margins in all cases. 10/11 rectal polyps were adenomatous and one
had a small focus of moderate differentiated adenocarcinoma (incomplete local
excision).
Complete endoscopic excision in a single session was achieved in 10/11 cases
(91%). Median completion time of the procedure was 215min, range 120-
480min. Tissue retraction was used in every case and resection was completed
by ESD alone (4/11), ESD EMR (4/11) ESD EMR trans-anal surgical
excision (3/11). Intra-procedural bleeding occurred in 8 cases, controlled with
hemostatic clips and Coagrasper (Olympus); surgical suturing was required in
one case (1/8). Prophylactic clips (2/11) and surgical sutures (1/11) were placed to
treat deep muscle injury. There were no perforations and no delayed bleeding
episodes. Patients were discharged the day following TASER in all cases.
Surveillance at 3-6 months revealed no recurrence in 6 cases, whereas in four
cases the follow up procedure is still pending. The malignant polyp case was
referred to surgery with a good clinical outcome (T3, N0, M0).
CONCLUSION: TASER appears to be a safe and efficient approach providing
an optimal platform for resection of large rectal lesions. In our experience it
provides the optimal platform for the minimally-invasive management of these
high risk lesions.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 9:0017:00
LIVER & BILIARY II POSTER EXHIBITION HALL XL_____________________
P0581 EVALUATION OF FERRITIN 41000 CUTOFF POINT TO
DIAGNOSE LIVER IRON OVERLOAD
A. Castiella1,*, E. Zapata1, I. Urreta2, L. Zubiaurre1, A. Iribarren1,
J.M. Alustiza3, E. Salvador3, A. azkune4, E. zubillaga4, L. Rincon5, J.
I. Emparanza2 on behalf of Burnia Group
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro, 2clinical epide-
miology, Donostia hospital, 3Radiology, Osatek Donostia, 4Internal Medicine,
Donostia hospital, Donostia, 5GASTROENTEROLOGY, Bidasoa Hospital, Irun,
Spain
Contact E-mail Address: agustincastiella@yahoo.es
INTRODUCTION: Ferritin41000 has been associated with high grade fibrosis
in hemochromatosis and in liver iron overload disorders.
AIMS & METHODS: To establish the nosologic characteristics of ferritin
41000 ng/ml to diagnose high liver iron overload (hepatic iron index4 1.9)
(HIO) and for the diagnosis of significant iron overload in liver (4 60 micromol
Fe/g) (SIO).
Cohort of consecutive patients studied by MRI for quantification of liver iron
concentration (LIC). Variables: age, sex, ferritin and LIC. We calculate the mean
and standard deviation for quantitative variables and absolute and relative fre-
quencies for qualitative variables.
The relationship between ferritin and LIC is analyzed using a simple linear
regression model.
To establish the nosological characteristics of ferritin we calculated the sensitivity
(S), specificity (Sp), positive predictive value (PPV) and negative (NPV) with
their 95% CI.
RESULTS: Total number of patients was 538 (449 men), with a mean age of 53.6
(SD 13.4). Mean ferritin value was 804.5 (SD 655.2). 56 patients (10.4%) had
HIO and 125 (23.2%) had (SIO). Mean LIC in patients with ferritin4 1000 was
55.9 micromol Fe /g. The PPV for HIO is 27.1% (19.9 to 35.8) and NPV of
94.3% (91.6 to 96.1). With our prevalence of 10.4%, the expected results by
chance alone would have been: PPV 10.7% (5 to 21.5) and NPV 89.6 (86.6
to 92), close to the values obtained with ferritin 4 1000. To diagnose SIO, PPV
of ferritin 41000 is 50% (41.1 to 58.9) and NPV of 84.3% (80.5 to 87.5). In this
case, the expected results by chance would have been: PPV 24.6% (17.7 to 33.1)
and NPV 77.1% (72.9 to 80.9).
CONCLUSION: Ferritin4 1000 has a low value for the diagnosis of HIO or for
SIO.
Disclosure of Interest: None declared
A293
P0582 DIAGNOSTIC ALGORITHM FOR HIGH LIVER IRON
OVERLOAD. WHEN IS MRI INDICATED?
A. Castiella1,*, E. Zapata1, I. Urreta2, J.M. ALUSTIZA3, L. ZUBIAURRE1,
E. Salvador3, G. Letamendi4, B. Arrizabalaga5, U. Mendarte6, P. Otazua7,
L. Rincon8, M.D. de Juan9, J. I. Emparanza2 on behalf of Burnia Group
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro, 2clinical epide-
miology, DONOSTIA HOSPITAL, 3radiology, osatek donostia, DONOSTIA,
4
hematology, Galdakao Hospital, galdakao, 5radiology, Cruces Hospital,
Baracaldo, 6GASTROENTEROLOGY, DONOSTIA HOSPITAL, DONOSTIA,
7
GASTROENTEROLOGY, mondragon hospital, mondragon,
8
GASTROENTEROLOGY, Bidasoa Hospital, irun, 9immunology, DONOSTIA
HOSPITAL, DONOSTIA, Spain
Contact E-mail Address: agustincastiella@yahoo.es
INTRODUCTION: HIO is considered if the Hepatic iron index4 1.9 (estimated
by MRI).
AIMS & METHODS: To develop and validate a diagnostic algorithm for high
iron overload (HIO) based on laboratory and genetic variables.
We collected a retrospective cohort with all consecutive patients between 2001-2008
studied by Magnetic Resonance Imaging (MRI) to determine liver iron concentra-
tion (LIC). This cohort served as the derivation set. We analyzed all variables using
univariate statistics with the MRI acting as the gold standard. We studied the best
combination of the diagnostics variables to build the algorithm.
We validated the algorithm in a prospective cohort, collecting all patients
referred to our hospital for study of iron metabolism alteration since 2009
onwards. We estimate the sensibility, specificity and predictive values with
95% CI.
RESULTS: Retrospective cohort: 242 patients (198 men/44 women), mean age
52,4 (SD 13.3). Thirty six of them had HIO. Nearly half of the patients (117/
242 48.4%) had both Transferrin saturation index (TSI) and Ferritin elevated
and 28 (11.5%) were C282Y homozygous. The final algorithm was as follows:
We consider a patient as having HIO with the simultaneous occurrence of TSI
and Ferritin elevated and C282Y homozygosis. HIO is discarded if TSI or
Ferritin are within normal values. The rest should be studied by MRI.
Prospective cohort: 177 patients (148 men/29 women), mean age 56 (SD 13.9).
The nosological characteristics of the algorithm in this validation study are:
CONCLUSION: MRI is not necessary in 77% of the patients for HIO diagnosis.
MRI is indicated inpatients not C282Y homozygous with raised TSI and
Ferritin.
Disclosure of Interest: None declared
P0583 LIVER IRON CONCENTRATION (LIC) IN PATIENTS REFERRED
FOR HYPERFERRITINEMIA (HF) TO A SECONDARY HOSPITAL:
ANALYSIS OF THE DIFFERENT GROUPS ACCORDING TO HFE
MUTATIONS AND TRANSFERRIN SATURATION INDEX (TSI)
A. Castiella1,*, E. Zapata1, L. Zubiaurre1, A. Iribarren1, M.D. De Juan2,
J.M. ALUSTIZA3, P. OTAZUA4, F. MUGICA5, E. Elosegui5, A. Arriola5,
E. Utrilla6, J. I. Emparanza7
1
GASTROENTEROLOGY, MENDARO HOSPITAL, mendaro,
2
IMMUNOLOGY, DONOSTIA HOSPITAL, 3osatek radiology, osatek,
4
GASTROENTEROLOGY, MONDRAGON HOSPITAL,
5
GASTROENTEROLOGY, DONOSTIA HOSPITAL, DONOSTIA, 6internal
medicine, zarauz health center, zarauz, 7clinical epidemiology, DONOSTIA
HOSPITAL, DONOSTIA, Spain
Contact E-mail Address: agustincastiella@yahoo.es
INTRODUCTION: Olynyk et al (1) analyzed in Australia in 2009 the LIC by MRI
of 52 consecutive patients who were referred for HF to a tertiary hospital. They
described three different groups according to HFE mutations and TSI (A Group: no
predisposing mutations (PM) for Hereditary Hemochromatosis (HH) and TSI 4 45
%, B Group: PM for HH: C282Y/C282Y; C282Y/H63D, and TSI 4 45 %; C
Group: no PM for HH and normal TSI). They concluded that LIC in B Group was
significantly higher than in A and C groups. In the Basque Country, predisposing
mutations differ, with relevance of the H63D/H63D mutation (2).
AIMS & METHODS: To study the relevance of HFE mutations and TSI in
determining LIC of HF patients attending the outpatient clinic at a secondary
hospital.
Prospective study of 132 consecutive patients with HF. January to December
2010. In 120 HFE study was available. In 79 LIC was obtained by MR. In 71
patients values of HFE mutations, TSI, and LIC by MR were available. The LIC
was measured in mmol / g (normal  36 mmol /g) by MR (Alustiza et al method
(3)).
RESULTS: mean age: 55.68  14.26 (23-83), 55 men and 16 women (77.5 %,
22.5 %). The mean age for men was 53.07  13.61; 64.63  13.14 in women. The
mean LIC by MR in men was 35.66  36.85; 38.81  29.75 in women. Patients in
A Group: 21, 14 with normal LIC, 7 raised LIC; B Group: 19-H63D/H63D;
C282Y/H63D-, 11 normal LIC, 8 raised LIC; C Group: 31 patients, 23 normal
LIC, 8 raised LIC. The mean LIC in A Group: 38.80  45.18 (5-210), B group:
48.96  37.51 (15-160), C group: 28.12  18.85 (5-75). We compared the LIC
mean values of the 3 groups using ANOVA, with no significant differences.
CONCLUSION: In our study, the LIC in different groups of patients referred
for HF to a secondary hospital, with different predisposition to HH (PM, raised
TSI), are similar. The different HFE mutations and TSI values do not appear to
be relevant in the LIC of these patients.
REFERENCES
(1). Olynyk, et al. Clin Gastroenterol Hepatol 2009; 7: 359-362.
(2). Castiella, et al. J Gastroenterol Hepatol 2010; 25: 1295-1298.
(3). Alustiza, et al. Radiology 2004; 230: 479-484.
Disclosure of Interest: None declared
A294
P0584 GLUCAGON-LIKE PEPTIDE-1 (GLP-1) ANALOGUE,
LIRAGLUTIDE, INHIBITS OXIDATIVE STRESS AND
INFLAMMATORY RESPONSE IN THE LIVER OF RATS WITH DIET
INDUCED NON-ALCOHOLIC FATTY LIVER DISEASE
H.T. Gao1, L.S. Xu1,*, Z.G. Zeng1, L.C. Guan1, W.P. Deng1
1
Guangdong General Hospital, Guangzhou, China
INTRODUCTION: Liraglutide, a glucagon-like peptide-1 (GLP-1) analogue,
has been demonstrated to reduce hepatic steatosis. However, the mechanisms
of the lipid-lowering effect of liraglutide in the liver remains unclear. The aim
of the present study was to investigate the beneficial effect of liraglutide on diet
induced non-alcoholic fatty liver disease (NAFLD) and the underlying mechan-
isms in rats.
AIMS & METHODS: NAFLD was induced by in Sprague-Dawley rats by
feeding a high fat and high cholesterol (HFHC) diet. Liraglutide (0.6 mg/kg
body weight/day) was injected intraperatoneally to the rats subjected to HFHC
diet 4 weeks before sacrificing. Body and liver weight, fasting blood glucose
(FBG), fasting insulin, serum aminotransferase (ALT) and lipid accumulation
in the liver were determined. Markers of oxidative stress, such as malondialde-
hyde (MDA), free fatty acid (FFAs), superoxide dismutase (SOD), and pro-
inflammatory cytokine tumor necrosis factor-a (TNF-a) were detected with
RIA or ELISA kits. Serum and hepatic adiponectin were measured. The expres-
sion of JNK-1 and phosphorylated JNK1 were examined with Western blot.
RESULTS: Liraglutide improved insulin resistance, decreased hepatic steatosis
and reversed liver dysfunction. The hepatic levels of MDA, FFAs, TNF-a were
significantly decreased. While, the SOD and adiponectin levels in the liver were
significantly elevated by liraglutide treatment. Administration of liraglutide also
inhibited the expression of JNK-1 and phosphorylated JNK-1.
CONCLUSION: Liraglutide exerted anti-oxidative and anti-inflammatory
effects in the liver and consequently reverse hepatic steatosis and insulin resis-
tance. Such effects might be mediated by the elevation of adiponectin levels and
the inactivation of JNK1.
Disclosure of Interest: None declared
P0585 SHORT CHAIN C6-CERAMIDE LIPOSOMAL UPTAKE AFFECTS
INFLAMMATION, PROLIFERATION, FIBROSIS AND OXIDATIVE
STRESS IN MCD-INDUCED NASH IN VIVO
F. Zanieri1, L. Longato2,*, S. Omenetti1, S. Galastri1, S. Madiai1, T. V. Luong2,
T. Fox3, S.S. S. Velandy3, M. Kester3, M. Pinzani2, K. Rombouts2
1
Department of Experimental and Clinical Medicine and Center of Excellence for
the study at molecular and clinical level of chronic, degenerative and neoplastic
diseases to develop novel therapies DENOthe, University of Florence, Florence,
Italy, 2Division of Medicine, University College of London, Institute for Liver &
Digestive Health, Royal Free, London, United Kingdom, 3Department of
Pharmacology, Penn State University College of Medicine, Hershey, United States
Contact E-mail Address: k.rombouts@ucl.ac.uk
INTRODUCTION: Ceramides are members of the sphingolipid family and are
an integral part of the lipid bilayer of cell membranes. Ceramides exert biological
effects through cellular proliferation, differentiation and cell death. The role of
changes in endogenous ceramides to the pathogenesis of NAFLD to NASH is
sparse. In this study the effect of exogenous liposomes containing short chain C6-
Ceramide (Lip-C6) was evaluated in a NASH model and in vitro in primary
human Hepatic Stellate Cells (hHSC) as possible Lip-C6 target.
AIMS & METHODS: NASH was induced by feeding mice for 9 weeks a methio-
nine-and choline-deficient (MCD) diet, or control diet (CD), followed by a single
tail-vein injection of Lip-C6. The effect of Lip-C6-treatment was investigated by
measuring ALT/AST, histology, Q-PCR and protein analysis. Possible changes
in hepatic ceramide magnitude/species specificity and sphingosines were mea-
sured by employing untargeted LC-MS/MS lipidomics. The effect of Lip-C6
on primary hHSC proliferation, cytotoxicity and signaling pathways was
investigated.
RESULTS: MCD-Lip-C6 treatment did not exacerbate MCD-induced NASH
when analyzing ALT/AST, steatosis, lobular inflammation, ballooning, apopto-
sis and fibrosis. Protein analysis showed that Lip-C6-treatment affects the endo-
genous antioxidant system KEAP1-Nrf2-NQO1 in MCD-fed mice. MCD-fed
mice showed a reduction in p-JNK, cleaved caspase-3/PARP, the mRNA stabi-
lizing protein ELAV1/HuR and its downstream target phosphorylated p62 when
compared to CD-fed mice which were not affected by Lip-C6-treatment.
Exogenous liposomal short chain ceramide C6 treatment does not affect inflam-
mation markers TNFalpha and NFKB signalling pathway. A strong phosphor-
ylation of AMPK was induced in Lip-C6-treated MCD-fed indicating a
stimulation of energy producing catabolic pathways. Of particular note, Lip-
C6-treatment reverses the significant decreases in phosphatidylcholines (PC)
and phosphatidylethanolamines (PE) species and rearranges the significant
increases in specific sphingolipid species in MCD-fed mice. Moreover, Lip-C6-
Rhodamine was taken up by primary hHSC and Lip-C6-treatment inhibits pro-
liferation and cytotoxicity in a concentration-dependent manner.
CONCLUSION: These results demonstrate that a single injection of short chain
C6-ceramide liposomes does not exacerbate inflammation, apoptosis, prolifera-
tion and oxidative stress in MCD-induced NASH, possibly by restoring changes
in membrane lipid content induced by NASH.
Disclosure of Interest: F. Zanieri: no conflict of interest to declare, L. Longato: no
conflict of interest to declare, S. Omenetti: no conflict of interest to declare, S.
Galastri: no conflict of interest to declare, S. Madiai: no conflict of interest to
declare, T. V. Luong: no conflict of interest to declare, T. Fox: no conflict of
interest to declare, S. S. S. Velandy: no conflict of interest to declare, M. Kester
Directorship(s) for: Penn State Research Foundation has licensed ceramide
nanotechnology to Keystone Nano, Inc. (PA, USA) and M. K. is cofounder
United European Gastroenterology Journal 2(5S)
and Chief Medical Officer of Keystone Nano, M. Pinzani: no conflict of interest
to declare, K. Rombouts: no conflict of interest to declare
P0586 APOC3 ( 455T4C) POLYMORPHISM CONFERS
SUSCEPTIBILITY TO NONALCOHOLIC FATTY LIVER DISEASE
IN A HAN CHINESE POPULATION
M. Li1,*, S. Zhang1, X. Liao1, K. Chao1, J. Yao1, B. Zhong1
1
Division of Gastroenterology, The First Affiliated Hospital, Sun Yat-sen
University, Guangzhou, China
Contact E-mail Address: sophiazhong@medmail.com.cn
INTRODUCTION: Genetic variation in apolipoprotein C3 (APOC3) was
reported to be associated with nonalcoholic fatty liver disease (NAFLD), but
its role in Chinese population is not well understood.
AIMS & METHODS: To investigate the association between the apolipoprotein
C3 (APOC3, -455T4C) polymorphism and nonalcoholic fatty liver disease
(NAFLD), we recruited 300 NAFLD patients and 300 healthy controls to a
cohort representing Han Chinese at The First Affiliated Hospital, Sun Yat-sen
University, from January to December 2012. Polymerase chain reaction-restric-
tion fragment length polymorphism (PCR-RFLP) and DNA sequencing were
used to genotype the APOC3 (-455T4C) variants.
RESULTS: After adjusting for age, gender, and BMI, TC and CC genotypes
were found to increase the susceptibility to NAFLD compared to that of the TT
genotype, with odds ratios (ORs) of 1.94 (95% CI, 1.26-2.98) and 3.01 (95% CI,
1.76-5.16), respectively. Further stratification analysis indicated that the CC
genotype was more susceptible to insulin resistance (IR) than the TT genotype,
with OR of 2.59 (95% CI, 1.26-5.30). The CC genotype also was associated with
a much higher risk of hypertension, hypertriglyceridemia, and low levels of high-
density lipoprotein cholesterol (P50.05). No association was found between the
APOC3 (-455T4C) polymorphism and body-mass index, level of fasting plasma
glucose, serum uric acid, total cholesterol, and low-density lipoprotein choles-
terol (P40.05).
CONCLUSION: APOC3 (-455T4C) genetic variation is involved in the suscept-
ibility to develop NAFLD, IR, and some metabolic syndrome disorders in the
Han Chinese population.
Disclosure of Interest: None declared
P0587 SERUM ADIPOKINES IN PATIENTS WITH NON ALCOHOLIC
FATTY LIVER DISEASE, IS THERE A ROLE FOR PREDICTING
THE SEVERITY OF LIVER DISEASE?
M.A. Amin1,*, K. Al-Ashmawi1, O. Shaker2, S. Mussa1
1
internal medicine, 2biochemistry, Cairo University, Cairo, Egypt
Contact E-mail Address: monasleman@hotmail.com
INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) is considered to
be among the most common liver diseases world-wide. NAFLD encompasses a
broad spectrum of pathological conditions ranging from simple steatosis (SS) to
steatohepatitis (NASH), fibrosis and finally even cirrhosis. Adiponectin (A) has
been associated with inhibition of fibrogenesis and liver protection while leptin
(L) contributes to fibrogenesis in various chronic liver diseases, notably in
NASH.
AIMS & METHODS: To determine the validity of serum adipokines including
leptin, adiponectin, and A/L ratio to act as a potential markers for NAFLD and
to discriminate NASH from SS.
Patients and methods: Eighty four patients who have bright liver on abdominal
ultrasonography and 28 healthy individuals served as control group. Serum
Leptin and Adiponectin were estimated by ELISA technique. Liver biopsy was
done for 46 patients and according to histopathological examination they were
divided into 21 patients with SS and 25 patients with NASH.
RESULTS: The serum concentration of adiponectin was significantly lower in
NASH than SS group (P 50.001). There was no significant difference between
serum concentration of leptin in both groups (p 0.4). A/L ratio in NASH group
was significantly lower than SS group (P 50.001). Adiponectin was negatively
correlated with BMI, total cholesterol and LDL-C in both groups. A/L ratio in
NASH group was significantly positively correlated with adiponectin (P50.001)
while it was significantly negatively correlated with leptin (P50.001). In SS
group A/L ratio was significantly negatively correlated with leptin (r -0.863,
P50.001).
CONCLUSION: In patients with NAFLD, the serum adiponectin and A/L ratio
can discriminate simple steatosis from NASH and predict the severity of liver
injury.
Disclosure of Interest: None declared
P0588 MYOSIN LIGHT CHAIN KINASE INVOLVED IN INTESTINAL
BARRIER FUNCTION CHANGE OF MICE WITH NAFLD
Y. Zhang1,*, J. Li1 on behalf of 1, Y. Chi2 on behalf of 2, Y. Liu1 on behalf of 1
1
Gastroenterology Department, 2Institution of Clinical Molecular Biology, Peking
University Peoples Hospital, Beijing, China
Contact E-mail Address: medicalyuan@foxmail.com
INTRODUCTION: Myosin Light Chain Kinase (MLCK) plays a central role in
the mechanisms of barrier dysfunction, and some studies showed nonalcoholic
fatty liver disease (NAFLD) had intestinal barrier function change. The present
study aimed to identify whether MLCK was involved in the pathogenesis of
nonalcoholic fatty liver disease (NAFLD).
AIMS & METHODS: The NAFLD mice model was established by giving high-
fat diet (HFD) and NASH was induced by lipopolysaccharide (LPS) administra-
tion. Mice received MLCK inhibitor ML-7 by intraperitoneal injection. The level
United European Gastroenterology Journal 2(5S)
of ALT, AST was assessed. The degree of liver steatosis was observed by HE
stain. Intestinal mucosal tight junction was observed by electron microscope, and
the occludin protein was stained by immunofluorescence.
RESULTS: MLCK expression increased in NAFLD and NASH groups vs con-
trol group. ALT and AST elevated in the NAFLD and NASH group, which
could be reduced by MLCK inhibitor ML-7 (Table.1, *P50.05 vs NAFLD
group, ** P50.05 vs NASH group). The liver pathology showed no significant
change after ML-7 administration. The intestinal tight junctions occludin protein
were seemed to be ameliorated by ML-7,but there were no significant difference.
U/L Control NAFLD NAFLDML-7 NASH NASHML-7
ALT 20.330.843 20.002.014 13.800.663 31.703.208* 18.801.597**
AST 46.672.704 44.002.075 37.602.349 117.612.23* 73.105.382**
CONCLUSION: MLCK inhibitor ML-7 could protect liver function via improv-
ing the intestinal barrier of NAFLD mice.
REFERENCES
1. Miele L, Valenza V, La Torre G, et al. Increased intestinal permeability and
tight junction alterations in nonalcoholic fatty liver disease. Hepatology 2009; 49:
1877-1887.
2. Wang N, Yu H, Ma J, et al. Evidence for tight junction protein disruption in
intestinal mucosa of malignant obstructive jaundice patients. Scand J
Gastroenterol 2010; 45: 191-199.
Disclosure of Interest: None declared
P0589 EPITHELIAL MYOSIN LIGHT CHAIN KINASE-DEPENDENT
BARRIER DYSFUNCTION INVOLVED IN INTESTINAL BARRIER
FUNCTION CHANGE OF MICE WITH NAFLD
Y. Zhang1,*, J. Li1 on behalf of 1, Y. Chi2 on behalf of 2, Y. Liu1 on behalf of 1
1
Gastroenterology Department, 2Institution of Clinical Molecular Biology, Peking
University Peoples Hospital, Beijing, China
Contact E-mail Address: medicalyuan@foxmail.com
INTRODUCTION: Myosin Light Chain Kinase (MLCK) plays a central role in
the mechanisms of barrier dysfunction, and a lot of studies showed the intestinal
barrier permeability increased in nonalcoholic fatty liver disease (NAFLD).
AIMS & METHODS: The research aimed to identify whether MLCK was a
regulator in the intestinal barrier permeability change of nonalcoholic fatty liver
disease (NAFLD). The NAFLD mice model was established by giving high-fat
diet (HFD) and NASH was induced by lipopolysaccharide (LPS) administration.
Mice received MLCK inhibitor ML-7 by intraperitoneal injection. The intestinal
mucosal tight junction was observed by electron microscope, and the LPS con-
centration of portal vein was detectedd by ELISA.
RESULTS:
MLCK expression increased significantli in fatty liver (NAFLD) and NASH,
which could be blocked by ML-7. The intestinal epithelial tight junction of
NASH were broader compared with control group, which could be improved
by MLCK inhibitor ML-7 (Table 1). The LPS in portal vein of NASH mice was
higher, suggesting the intestinal barrier permeability dysfunction. After MLCK
was blocked by ML-7, the LPS in portal vein decreased significantly.
nm Control NAFLD NAFLDML-7 NASH NASHML-7
TJ 14.900.329 19.801.197* 19.200.997* 26.61.200* 14.900.666#
Table 1: The tight junction of intestinal epithelial of different groups.
CONCLUSION: The intestinal barrier function was restored by specifically
inhibiting MLCK, suggesting that MLCK activity was responsible for the
change of barrier function in NAFLD.
REFERENCES
1. Al-Sadi R, Guo S, Ye D, et al. TNF- modulation of intestinal epithelial tight
junction barrier is regulated by ERK1/2 activation of Elk-1. Am J Pathol 2013;
183: 1871-1884.
2. Al-Sadi R, Guo S, Ye D, et al. Mechanism of IL-1beta modulation of intest-
inal epithelial barrier involves p38 kinase and activating transcription factor-2
activation. J Immunol 2013; 190: 6596-6606.
Disclosure of Interest: None declared
P0590 ABACAVIR AND DIDANOSINE ENHANCE ACETAMINOPHEN-
INDUCED HEPATOTOXICITY THROUGH GSH DEPLETION
A. Blas-Garc a1,2,*, V.M. V ctor2,3, M. Polo1,2, H.A. Funes1, A. Mart -Rodrigo1, toxicity induced by other stimuli such as other antiretroviral drugs, co-infections
N. Apostolova3,4, J. V. Esplugues1,2
1
Pharmacology, Universidad de Valencia-CIBERehd, 2FISABIO-Hospital
Universitario Dr. Peset, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: ana.blas@uv.es
INTRODUCTION: Liver disease is a leading cause of mortality among HIV-
infected patients and has been related in some cases to combined Antiretroviral
Therapy (cART). Little is known about the acute effects of nucleoside/nucleotide
reverse transcriptase inhibitors (NRTI) on hepatic cells, although the purine
analogue abacavir (ABC) has been reported to induce an acute mitotoxic effect
in vitro. Since acetaminophen (APAP), a well-known hepatotoxic drug, is com-
monly prescribed to HIV-infected patients and also interferes with mitochondria,
A295
we hypothesised that its combination with antiretrovirals can specifically exacer-
bate the hepatotoxic effects of the latter drugs.
AIMS & METHODS: To analyse the acute mitochondrial effects of clinically
relevant concentrations of the purine analogues ABC and didanosine (ddI), to
assess their impact on mitochondrial function and the viability of hepatic cells,
and to explore potential synergisms with APAP and other hepatotoxic drugs.
Several parameters of mitochondrial function (oxygen consumption, mitochon-
drial membrane potential - m-, reactive oxygen species ROS- production,
intracellular ATP levels, GSH levels) and cellular viability were assessed in
non-HIV-infected Hep3B and hepatocyte-like HepaRG cells treated (1-48h)
with the purine analogues ABC and ddI. Further experiments were performed
in the presence of sub-damaging concentrations of different hepatotoxic stimuli
(APAP, the antiretroviral drugs ritonavir and nevirapine, and ethanol). Data
were reported as mean/-SEM, and their statistical significance versus vehicle
was analyzed by one-way ANOVA. Correlations were analysed using
Spearmans correlation coefficient.
RESULTS: Clinical concentrations of purine analogues produced an immediate
and significant decrease in mitochondrial function, evident in a concentration-
dependent inhibition of O2 consumption, increased ROS production, and a
reduction of  m and intracellular ATP levels. This mitochondrial dysfunction
did not compromise cell survival, as the aforementioned parameters returned to
previous values after 24h treatment. However, co-administration of these drugs
with APAP concentrations below those considered toxic in hepatic cellular
models exacerbated the deleterious effects of both treatments on mitochondrial
function and cellular viability, thus decreasing intracellular GSH concentrations.
Such effect was not observed with the other hepatotoxic stimuli evaluated.
Interestingly, a significant positive correlation was detected between GSH
levels and cell viability.
CONCLUSION: The combination of ABC or ddI with low concentrations of
APAP significantly effects GSH concentrations in a way that increases the risk of
APAP-mediated liver injury. Our findings are of considerable relevance given
that APAP is currently prescribed to patients taking NRTI and that HIV infec-
tion itself has been reported to undermine intracellular GSH levels.
Disclosure of Interest: None declared
P0591 THE NON-NUCLEOSIDE REVERSE TRANSCRIPTASE
INHIBITOR EFAVIRENZ MODIFIES THE INFLAMMATORY
RESPONSE OF HEPATIC CELLS
A. Blas-Garc a1,2,*, F. Alegre1,2, D. Ortiz-Masia2, L. Milian-Medina1,
N. Apostolova3,4, J. V. Esplugues1,2
1
FISABIO-Hospital Universitario Dr. Peset, 2Pharmacology, Universidad de
Valencia-CIBERehd, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: ana.blas@uv.es
INTRODUCTION: Efavirenz (EFV) is the most widely used drug in the treat-
ment of HIV-infection, but has recently been associated with oxidative stress,
mitochondrial dysfunction and endoplasmic reticulum stress in hepatocytes. As
mitochondrial damage and ER-stress are frequently related to inflammatory
disease, we have evaluated the effects of EFV on the cytokine/chemokine expres-
sion pattern of hepatic cells. In addition, we have explored the possible involve-
ment of the redox-sensitive transcription factor nuclear factor-kappaB (NF-kB)
and NLRP3 inflammasome, both of which trigger signalling pathways implicated
in hepatic inflammation and liver injury.
AIMS & METHODS: Non-HIV-infected Hep3B cells were treated with clini-
cally-employed concentrations of EFV (10 and 25mM). Inflammation-related
gene expression was studied with Real time PCR. Activation of NF-kB was
confirmed by Western blot. An electrophoretic mobility shift assay (EMSA)
was carried out to determine the binding of NF-kB to promoters of some of
the genes whose expression was found to be up-regulated. Chemokine secretion
was evaluated in culture supernatant samples using an immunoassay kit. Data
(n3) were analysed with one-way ANOVA followed by a Newman-Keuls test.
*p50.05, **p50.01, ***p50.001 (vs control).
RESULTS: EFV induced mRNA expression of the inflammatory mediators
TNF, IL-6, PAI-1, TXNIP and NLP3 in a significant and concentration-depen-
dent manner. Furthermore, EFV reduced IkBa protein levels, thus increasing
NF-kB translocation to the nucleus. The EMSA assay demonstrated that
trans-activation of PAI-1 was mediated by interaction of NF-kB with a consen-
sus sequence located within the PAI-1 promoter. Nevertheless, EFV also signifi-
cantly reduced the production and secretion of IL-8 and IP-10, chemokines
involved in the progression of liver injury.
CONCLUSION: Due to its inhibitory effects on mitochondrial function, EFV
promotes a pro-inflammatory response through NF-kB- and NLRP3-dependent
pathways. Interestingly, EFV also reduced the secretion of IL-8 and IP-10, thus
playing a dual role in regulating the inflammatory response. In the context of
lifelong use of EFV, these effects could accumulate and exacerbate the liver
(hepatitis B and/or C) or co-morbidities associated with HIV infection.
Disclosure of Interest: None declared
A296
P0592 LIVER FUNCTION AND ELASTICITY MONITORING DURING
RHEUMATOID ARTHRITIS DISEASE MODIFYING TREATMENT
A.A. Popov1,*, E.G. Martemyanova2
1
Internal Medicine Dept.#2, URAL STATE MEDICAL UNIVERSITY,
2
Preobrazhenskaya Clinic, Ekaterinburg, Russian Federation
Contact E-mail Address: art_popov@mail.ru
INTRODUCTION: Rheumatoid arthritis (RA) requires early intervention with
disease modifying drugs (DMARDs) in order to prevent disease progression and
disability [1]. Liver safety issues may delay or limit DMARDs administration [2].
AIMS & METHODS: Aim: to assess liver function tests and liver elasticity
during first year of RA DMARDs treatment in everyday clinical practice.
Methods: 20 consecutive rheumatologists out-patients (16 females) aged from 26
to 56 (mean 47.7) were enrolled in a prospective cohort study. All had newly
diagnosed established seropositive RA according to ACR/EULAR 2010 criteria.
Viral hepatitides being preliminarily excluded, anthropometry, serum ALT, AST,
GGTP, bilirubine levels, were registered as safety measures by 2, 4, 12, 24, 36, 48
week. Liver ultrasound elastography (FibroScan, Echosens, France) was per-
formed twice: at enrollment and end of study visit. RA disease activity was
assessed by DAS28 index by 12, 24, 26 and 48 week. All patients were adminis-
tered oral methotrexate 10-25 mg weekly or leflunomide 20 mg daily as
DMARDs. Ibuprophen up to 1200 mg per 24 hours was allowed as on
demand rescue treatment. Rescue medication consumption was registered by
tablets count. All patients received advices on smoking cessation, diet optimiza-
tion, physical exercises and daily activies adjusted to body mass index and
comorbidities.
ra w n
RESULTS: All patients had comorbidities by DMARDs initiation. The most
frequent were arterial hypertension (11 pts.), dyslipidemia (20 pts.), obesity (5
d
pts.), high fasting glucose (7 pts.), type 2 diabetes mellitus (5 pts.). In 13 subjects
only 1 subject.
i t h
metabolic syndrome (MS) was diagnosed. Non-alcocholic steatohepatitis
W
(NASH) was diagnosed in 8 patients, while normal liver elasticity was found in
DMARDs administration during 1 year resulted in DAS28 20% reduction in all
subjects, 50% DAS28 reduction was registered in 16 subjects, and 70% response
was found in 7 subjects. Liver elasticity has increased in 1 person with Type 2
diabetes mellitus. There had been 7 liver test worsening episodes during 1 year
study. All liver test increases were seen in obese subjects with glucose metabolism
disorders. No difference between methotrexate and leflunomide groups was
found.
CONCLUSION: NASH had been frequent in RA patients before DMARDs
were started. All liver test abnormalities during DMARDs administration were
likely to be NASH related. The data support the hypothesis that conventional
RA treatment is safe and does not cause liver lesions.
REFERENCES
1. Smolen JS, Landewe R, Breedveld FC, et al. EULAR recommendations for
the management of rheumatoid arthritis with synthetic and biological disease-
modifying antirheumatic drugs: 2013 update. Ann Rheum Dis 2014; 73: 492-509.
2. Curtis JR., Beukelman R, Onofrei A, et al. Elevated liver enzyme tests among
patients with rheumatoid arthritis or psoriatic arthritis treated with methotrexate
and/or leflunomide. Ann Rheum Dis 2010; 69: 43-47.
Disclosure of Interest: None declared
P0593 OSTEOPOROSIS AND BONE FRACTURES IN ALCOHOLIC
LIVER DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
C.S. Bang1, D.J. Kim1, G.H. Baik1, S.H. Park1, H.S. Kim1, E.J. Kim1,*,
K.T. Suk1
1 1
Department of Internal Medicine, Hallym University College of Medicine,
Chuncheon, South Korea, Chuncheon, Korea, Republic Of
Contact E-mail Address: cloudslove@naver.com
INTRODUCTION: Excessive alcohol consumption is an well-established risk
factor for osteoporosis and bone fractures. However, moderate amount of alco-
hol ingestion is known to be associated with higher bone mineral density (BMD).
Osteodystrophy is a frequently overlooked complication in patients with chronic
liver disease, which could result in serious outcome. However, the exact preva-
lence or mechanism of osteodystrophy in patients with alcoholic liver diseases
(ALD) have not been described.
AIMS & METHODS: The aim of this study was to evaluate the current evidence
on osteoporosis and bone fractures in ALD. Case-control or cohort studies were
identified from databases (Pubmed, EM-BASE, and the Cochrane Library). The
searching keywords were alcoholic liver diseases, osteoporosis, or bone frac-
tures using Boolean operators. The prevalence of any fractures or osteoporosis,
and BMD score were extracted and analyzed using risk ratios (RRs) and stan-
dardized mean difference (SMD). A random effect model was applied based on
Higgins I2 tests. Publication bias was evaluated using a funnel plot, Eggers test,
trim and fill, and the rank correlation test.
RESULTS: In total, 16 studies performed between 1986 and 2011 were identified
and analyzed. Overall, ALD showed an RR of 1.944 (95% CI: 1.354-2.791, P 5
0.001) for the development of bone fractures. However, ALD showed an RR of
0.849 (95% CI: 0.523-1.38, P 0.509) for the development of osteoporosis. BMD
was not statistically different between ALD and control group, although lower
trend in patients with ALD (SMD in femur BMD: -0.192, 95% CI: -0.48-0.096,
P 0.191) (SMD in spine BMD: -0.429, 95% CI: -0.925-0.067, P 0.09).
Subgroup analysis showed consistent results. Publication bias was only detected
in the analysis of bone fractures.
CONCLUSION: Current publications indicate significant association between
bone fractures and ALD, however insignificant association between osteoporosis
and ALD. Due to the qualitative and quantitative heterogeneity among studies,
further researches using homogenous population with common validated
United European Gastroenterology Journal 2(5S)
measurement of BMD and risk factors are needed to elucidate the mechanism
of bone fractures in ALD.
Disclosure of Interest: None declared
P0594 IS SQSTM1/P62 A DEFENCE AGAINST EFV-INDUCED
HEPATOTOXICITY?
F. Alegre1,2,*, A. Blas-Garc a1,2, M. Polo1,2, H.A. Funes2, N. Apostolova3,4, J.
V. Esplugues1,2
1
FISABIO-Hospital Universitario Dr. Peset, 2Pharmacology, Universidad de
Valencia-CIBERehd, 3CIBERehd, Valencia, 4Facultad de Ciencias de la Salud,
Universidad Jaime I, Castellon de la Plana, Spain
Contact E-mail Address: fernando.alegre@uv.es
INTRODUCTION: Sequestome 1/p62 is a multifunctional protein known to be
involved in autophagy, during which it acts as a substrate carrier and becomes
degraded. It has also been reported that p62 plays important roles in other
cellular events, including oxidative stress responses, proteostasis, inflammation
and cell survival, while, interestingly, it is implicated in several liver diseases, such
as non-alcoholic steatohepatitis. The non-nucleoside reverse transcriptase inhi-
bitor Efavirenz (EFV) is widely employed in combined antiretroviral therapy to
treat HIV1 infection, and, though generally considered safe, has been associated
with hepatotoxic events. Although the underlying mechanisms of the deleterious
hepatic effects of EFV are still unclear, evidence points to altered lipid metabo-
lism, mitochondrial dysfunction/mitophagy and endoplasmic reticulum stress in
human hepatocytes.
AIMS & METHODS: To analyse the implication of p62 in EFV-induced toxicity
in hepatocytes. The human hepatoma line Hep3B and cells lacking functional
mitochondria (Hep3B rho-zero obtained through pharmacological interruption
of mtDNA replication) were exposed to clinically relevant concentrations (10 and
25M) of EFV for 4, 8, 24 and 48h. Key experiments were carried out with
pharmacological inducers of oxidative stress (rotenone) or endoplasmic reticu-
lum stress (thapsigargin). Quantitative PCR was performed to analyse p62 gene
expression. Western Blot was employed to measure LC3 II (a marker of autop-
hagy induction) and p62 protein levels and translocation to the nucleus of the
transcription factors NF-kB and Nrf2, which have been reported to regulate p62
expression and to be involved in ER/oxidative stress and autophagy.
RESULTS: EFV clearly enhanced the protein expression of LC3 II
(Microtubule-associated protein 1A/1B-light chain 3), but no reduction of p62
levels was observed. Conversely, both mRNA and protein expression of p62 were
increased in EFV-treated cells in a concentration- and time-dependent manner.
Western blot studies demonstrated that EFV promoted translocation of NF-B,
but not of Nrf2, to the nucleus. Moreover, the increase in p62 protein level
triggered by EFV in wild type hepatocytes was less pronounced in rho-zero
cells and completely absent in rotenone.
CONCLUSION: Despite inducing autophagy, clinical concentrations of EFV
increase p62 expression, an effect that maybe related to NF-kB translocation
to the nucleus. The results obtained in rho-0 cells suggest that overexpression
of p62 is a defence mechanism against the mitochondrial and ER dysfunction
triggered by EFV.
Disclosure of Interest: None declared
P0595 THE INCIDENCE RATE OF ALCOHOLIC FATTY LIVER
RELATED TO ALCOHOL CONSUMPTION: A 4-YEAR
RETROSPECTIVE COHORT STUDY
M.Y. Lee1,*, Y.K. Cho2, K.B. Bang2, D.S. Lee2, J.H. Yu2, H.A. Lee2, E.H. Park2,
C. I. Sohn2
Sungkyunkwan University Kangbuk Samsung Hospital, Seoul, Korea, Republic
Of, 2Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital,
Seoul, Korea, Republic Of
Contact E-mail Address: choyk2004.cho@samsung.com
INTRODUCTION: Alcohol consumption is one of the most well-known
common causes of fatty liver. There is a lack of studies on incidence rate of
alcoholic fatty liver related to alcohol consumption. We conducted a retrospec-
tive cohort study design to examine the relationship between alcohol consump-
tion and alcoholic fatty liver among healthy Koreans.
AIMS & METHODS: A healthy cohort of 29,281 individuals, who had partici-
pated in a medical health check-up program in 2008, was followed up until 2012.
Alcoholic fatty liver was diagnosed and defined based on both ultrasonographic
finding and serum AST/ALT ratio  2. Alcohol consumption was divided into
four groups (non-drinker, 520g/d in Female & 540g/d in Male, 20-40g/d in F &
40-60g/d in M, 440g/d in F & 460g/d in M). Cox proportional hazard model
was used to determine if alcoholic fatty liver was associated with baseline alcohol
consumption level.
RESULTS: During 100,233 person-years of follow-up, 4,889 cases of alcoholic
fatty liver was diagnosed between 2009 and 2012. After adjusted for sex, age,
interaction effect between sex and alcohol consumption level, the Hazard ratios
(HRs) for incidence rates of alcoholic fatty liver increased according to the base-
line alcohol consumption levels (HR: 0.926, 95% CI 0.827-1.038, HR: 3.257,
95%CI 2.323-4.565, HR: 3.728, 95%CI 2.238-6.213), compared to the non-
drinker.
CONCLUSION: Alcoholic consumption was associated with an increased rate
of alcoholic fatty liver. In female, incidence of alcoholic fatty liver was higher
than the male. In addition, obesity was independent risk factors for incidence of
alcoholic fatty liver.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0596 UNIVERSAL SCREENING FOR ALCOHOL MISUSE IN ACUTE
MEDICAL ADMISSIONS IS ACHIEVABLE AND IDENTIFIES
PATIENTS AT HIGH RISK OF LIVER DISEASE
P. Meredith1, P. Schmidt2, S. Atkins3, P. Greengross4, G. Westwood5,
R. Aspinall6,*
1
TEAMS Centre, 2Acute Medicine, 3Alcohol Specialist Nursing Service,
Portsmouth Hospitals NHS Trust, Portsmouth, 4Primary Care & Public Health,
Imperial College Healthcare NHS Trust, London, 5Faculty of Health Sciences,
University of Southampton, 6Gastroenterology & Hepatology, Portsmouth
Hospitals NHS Trust, Portsmouth, United Kingdom
Contact E-mail Address: r.j.aspinall@doctors.org.uk
INTRODUCTION: Many people who die from Alcohol Related Liver Disease
(ARLD) have a history of recurrent hospital admissions. These episodes may
represent missed opportunities for intervention. Universal screening of medical
patients has been advised but little is known of the feasibility of this or its
efficiency at detecting high risk cases. In 2011, we introduced a 7-day Alcohol
Specialist Nursing Service (ASNS) coupled with universal screening of medical
patients using a novel electronic data capture system. We now present our data
on the feasibility of unselected screening and the resulting alcohol profiles of over
28,000 medical admissions in a major acute hospital serving a catchment popula-
tion of 650,000.
AIMS & METHODS: From July 2011 to December 2012, all admissions via the
Acute Medical Unit (AMU) were screened using the VitalPAC clinical observa-
tion system with a VitalPAC Alcohol Assesment Score (VPAAS) based on the
Paddington Alcohol Test. At-risk patients (VPAAS of 6 or more) were referred
to the ASNS and an Alcohol Use Disorders Identification Test (AUDIT) per-
formed. Data analysis was performed on patient demographics, unit consump-
tion, diagnosis, mortality and previous Emergency Department (ED) attendances
and admissions.
RESULTS: There were 29,361 admissions of whom 28,098 (96%) completed
VPAAS alcohol screening. Mean AMU population age was 67.4 years, 52.3%
female. Of 1,123 high risk cases, 770 were seen by the ASNS and 636 defined as
dependent (AUDIT 420). Compared to the general AMU cohort, the at-risk
group had more ED attendances (7.8 vs 2.9) and hospital admissions (4.8 vs 3.1)
in the previous 3 years and a lower age of death (58.3 vs 81.5). Dependent women
had fewer recurrent attendances and admissions than men but had a higher
mortality rate and lower age of death (52.2 vs 62.4). The maximum AUDIT
score of 40 was recorded in 41% of cases seen by the ASNS and this subgroup
had a mean age of death of 52.7 with 6.2 admissions and 10.8 ED attendances
previously. The most frequent primary diagnoses in those with a VPAAS of 6
were liver disease, mental health disorders and GI bleeding.
CONCLUSION: Our analysis of over 28,000 admissions demonstrates that
screening of all medical patients for alcohol misuse is achievable. We successfully
identified a cohort of high risk patients with recurrent admissions and ED atten-
dances, high unit consumption and an elevated risk of liver disease and early
death. This cohort can be targeted with interventions to reduce the burden of
alcohol related harm.
Disclosure of Interest: P. Meredith: None declared, P. Schmidt Consultancy for:
Unpaid research advisor to The Learning Clinic, who created & licenced
VitalPAC, S. Atkins: None declared, P. Greengross Consultancy for: Part-time
Medical Director of The Learning Clinic, who created & licenced VitalPAC, G.
Westwood: None declared, R. Aspinall: None declared
P0597 CHEMOPROPHYLAXIS IN PORTUGUESE MILITARY
PERSONNEL. SHALL MEFLOQUINE BE CONSIDERED A SAFE
DRUG FOR THE LIVER?
T. Meira1,2,*, D. Fernandes1, L. Lopes2
1
Operational Health, Portuguese Navy Medical Center, 2Healthcare Department,
Portuguese Frigate D. Francisco de Almeida, Lisbon, Portugal
Contact E-mail Address: tania_meira@hotmail.com
INTRODUCTION: Mefloquine is a drug administered in the chemoprophylaxis
of malaria (Plasmodium falcipurum). The arising migration to malaria endemic
areas has contributed to the increase of mefloquine prescription. This drug has a
low potential hepatotoxicity induction, with only two reported cases of acute
hepatitis.
AIMS & METHODS: Observational and analytical study. The military person-
nel who took part in NATO Operation Ocean Shield, on board Portuguese Navy
Frigate D. Francisco de Almeida in 2011, having port visits of malaria endemic
regions, such as Djibouti, were suggested to perform chemoprophylaxis (meflo-
quine 250mg / week), starting a week before entering Djibouti territorial waters
and finishing 12 weeks after departure. A survey was conducted on the 11th week
of prophylaxis, in order to assess the degree of adherence and adverse effects.
Serum analyses before and after the mission were cumulatively conducted at the
home port.
RESULTS: 85 military personnel participated in this study, showing no disease
or chronic medication, reduced alcohol consumption, no remarkable pre-deploy-
ment blood analysis issues and that had completed the full course of chemopro-
phylaxis. 75% of the side effects were the gastroenterological related (29% upper
abdominal pain, 24% diarrhea, 22% heartburn). Two weeks after the end of the
deployment, analytical blood analysis of the military personnel revealed liver
enzymes changes in 14% of the cases (mean values: AST 67 IU/ L, ALT 82
IU/L, gamma GT 98 IU/L, alkaline phosphatase174 UI/L). There were no
changes in bilirubin values. Six weeks after chemoprophylaxis, an analytical
reassessment was performed revealing that changes only persisted in two indivi-
duals, in who the presence of hepatic steatosis was found, on completion of
further ecographic investigation.
A297
CONCLUSION: Whereas a significant proportion of individuals had an increase
in liver enzymes levels, the theoretical potential for liver injury is not to be
discharged when planning prophylaxis, particularly when in synergy with other
factors such as medication, alcohol consumption, and liver disease.
Disclosure of Interest: None declared
P0598 IS ALCOHOLIC FATTY LIVER DISEASE ASSOCIATED WITH
THE METABOLIC SYNDROME?
Y.K. Cho1,*, K.B. Bang1, D.S. Lee 1, D. I. Park1, W.K. Jeon1, B. I. Kim1, C.
I. Sohn1, J.H. Park1
1
Internal Medicine, Sungkyunkwan University Kangbuk Samsung Hospital, Seoul,
Korea, Republic Of
Contact E-mail Address: choyk2004.cho@samsung.com
INTRODUCTION: Accumulating evidence supports an association between
nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS).
However, there still are not enough studies to date showing association between
alcoholic fatty liver disease (AFLD) and metabolic abnormalities.
AIMS & METHODS: We conducted this study to investigate whether AFLD is
associated with the MetS and its components. A total of 52303 subjects (63.1%
men, and 36.9% women) were included in this cross-sectional study. The pre-
sence of fatty liver was assessed using standard ultrasound criteria. The term
significant alcohol consumption was defined as weekly alcohol consumption
exceeding 210 g in men and 140 g in women for the previous 2 years. The
presence of metabolic abnormalities were compared according to the fatty liver
status and its etiology. Logistic regression model was performed to assess the
odds ratios (ORs)
RESULTS: The prevalence of NAFLD and AFLD was 29.1% and 4.6%, respec-
tively. The MetS was more prevalent in AFLD (31%) and NAFLD (23.2%) than
in control group (3.6%, p50.001). All metabolic components of AFLD group,
including waist circumference, blood pressure, serum triglyceride, high density
lipoprotein, and fasting blood glucose were statistically worse or more severe
than those of NAFLD group (P50.001). After adjusting for other multiple
covariates, the ORs (95% confidence interval [CI]) for MetS was higher in the
AFLD (3.86; 3.44-4.34) than NAFLD group (2.89; 2.68-3.12).
CONCLUSION: MetS and its components are associated with both NAFLD
and AFLD. However, AFLD has a higher risk of MetS than NAFLD. Further
prospective studies are needed to investigate the effects of AFLD on the devel-
opment of MetS.
Disclosure of Interest: None declared
P0599 THE BETA-BLOCKERS HAVE A BENEFICIAL OR A HARMFUL
EFFECT IN PATIENTS WITH CIRRHOSIS AND PORTAL
HYPERTENSION?
C. Sfarti1,*, A. Trifan1, A.-M. Singeap1, C. Cojocariu1, O. Chiriac1, C. Stanciu1
1
Institute of Gastroenterology and Hepatology, UNIVERSITY OF MEDICINE
AND PHARMACY IASI, Iasi, Romania
INTRODUCTION: The possible harmful effect of non-selective beta-blockers
for the treatment of portal hypertensive-related complications (esophageal
varices and advanced ascites) in patients with cirrhosis has been suggested by
few recent studies.
AIMS & METHODS: Thus, the aim of the study was to determine the risk of
mortality in patients with cirrhosis and portal hypertension taking non-selective
beta-blocker therapy for the prevention of variceal hemorrhage.
We performed a retrospective analysis of 3215 patients admitted with cirrhosis
and portal hypertension to Institute of Gastroenterology and Hepatology Iasi
from 2009-2013. There were considered two groups: patients with varices only
(1436 cases) and those with both varices and ascites (1779 cases) (Table).
RESULTS: The primary outcome measure for this study was the in-hospital
mortality by any cause. Overall, the mortality was 102/1851 (5.51%) for the
patients in treatment with beta-blockers and significantly higher for patients
not taking beta-blockers 189/1364 (13.85%) (p 5 0.01).
When we assessed the correlation between the beta-blockers use and mortality in
each sub cohort we obtained similar results (Table); In the sub cohort with
varices only, the mortality was 4.62% (40/864) for the patients taking beta-block-
ers and 11.19% (64/572) in the group without treatment (p50.05). In the sub
cohort with varices and ascites the mortality was 6.28% (62/987) for the patients
taking beta-blockers and 15.78 (125/792) in the group without treatment
(p50.01)
We evaluated several parameters for correlation with the in-hospital mortality.
Multivariable regression analysis revealed that Child-Pugh score was associated
with increased mortality, while the use of beta-blockers was associated with
reduced mortality. The other parameters which were evaluated (hemoglobin,
platelets, bilirubin, INR, creatinine) didnt influenced significantly the mortality.
Beta-blockers therapy
Yes No P-value
Varices only N 864 N 572
Mortality 4.62% 11.19% 50.05
Varices and ascites N 987 N 792
Mortality 6.28% 15.78% 50.01
All patients 1851 1364
Overall mortality 5.51% 13.85% 50.01
A298
CONCLUSION: In a very large cohort of cirrhotic patients with portal hyper-
tension, the mortality was significantly lower in patients treated with non-selec-
tive beta-blockers than in those not taking beta-blockers. These data confirm that
the use of non-selective beta-blockers provides a significant survival benefit in
patients with cirrhosis and portal hypertension. Thus, we recommend the use of
non-selective beta-blockers in patients with portal hypertension and its
complications.
Disclosure of Interest: None declared
P0600 EVALUATION OF THE RELATIONSHIP BETWEEN THE
CHRONIC LIVER DISEASE QUESTIONNAIRE AND THE EQ-5D
INDEX IN HEPATIC ENCEPHALOPATHY PATIENTS TREATED
WITH RIFAXIMIN-A
E. Berni1,*, C.A. Bannister2, C.D. Poole3, P. Conway4, K. Nanuwa4, C.J. Currie2
1
Global Epidemiology, Pharmatelligence, 2Cochrane Institute of Primary Care &
Public Health, 3School of Medicine, Cardiff University, Cardiff, 4Norgine,
Uxbridge, United Kingdom
Contact E-mail Address: ellen.berni@pharmatelligence.co.uk
INTRODUCTION: Estimation of health-related utility is a vital component of
the evaluation of the relative cost-effectiveness of healthcare interventions. The
correlation between different measures of quality of life and health-related utility
in hepatic encephalopathy (HE) has not been explored.
AIMS & METHODS: The aim of this study was to characterize for the first time
the relationship between scores for the Chronic Liver Disease Questionnaire
(CLDQ) and health-related utility as measured by the EQ-5D index in patients
with HE. Data were available from a phase three trial of rifaximin- in patients
with recurrent HE. CLDQ and SF-36 scores were recorded at monthly visits. EQ-
5D scores were derived from the SF-36 using a recognized mapping technique.
Generalized, linear, mixed modelling methods were used to examine for any
association in order to allow for repeated measures.
RESULTS: 202 of the 299 trial patients, with 920 corresponding observations,
were included in this analysis, having excluded those with missing values at base-
line. The average age of the cohort was 57 years, and 133 (66%) were males, with
an average baseline MELD score of 13.8 units. The average time since diagnosis
of HE was 23 months. The model had an r-squared value of 0.827, indicating a
strong relationship between EQ-5D index and CLDQ. The model equation was
EQ-5D -0.010 0.136*CLDQ. Other potential covariates, such as age and sex,
were tested but were not significant (at 0.05).
CONCLUSION: This is the first time that a direct association between the EQ-
5D index and the CLDQ score has been reported. The r-squared value of this
association suggests that liver-related morbidity may explain the majority of
differences in health-related utility in these subjects.
Disclosure of Interest: E. Berni Consultancy for: Norgine, C. Bannister
Consultancy for: Norgine, C. Poole Consultancy for: Norgine, P. Conway
Other: Employee of Norgine, K. Nanuwa Other: Employee of Norgine, C.
Currie Consultancy for: Norgine
P0601 OUTCOMES OF SECONDARY PROPHYLAXIS FOR GASTRIC
VARICEAL BLEED WITH BETA BLOCKER AFTER GASTRIC
VARICEAL OBTURATION FOR GASTRIC VARICEAL BLEEDING
G. Muzzaffar1,*, S.M. Gill1, M. Malik1 on behalf of Gastroenterology,
Maroof International Hospital, Islamabad
1
Gastroenterology, Maroof International Hospital, Islamabad, Pakistan
INTRODUCTION: Gastric variceal obturation therapy using Histoacryl for the
gastric variceal bleeding is the most appropriate treatment. However, the second-
ary prophylactic efficacy of beta blocker after gastric variccal obturation therapy
has not been established. We wanted to evaluate the secondary prophylactic
efficacy of beta blocker after gastric variceal obturation therapy. We conducted
this study from January 2011 to January 2014.
AIMS & METHODS: We enrolled 100 consecutive patients, with gastric variceal
bleeding who received gastric variceal obturation therapy using Histoacryl.
Gastric variceal obturation therapy was continued until gastric variceal eradica-
tion. Among these 100 patients 48 patients underwent only gastric variceal
obturation therapy (Group I) and 52 patients along with gasstric variceal obtura-
tion therapy did receive beta blocker therapy (Group II). We gave Carvedalolo
12.5 to 25 mg daily doses. In all patients, the desired heart rate was achieved. The
rate of rebleeding free overall survival was observed in two groups by Kaplan-
Meyer analysis.
RESULTS: This is ongoing study, we are reporting the interim results. The mean
follow-up period was 24 months. During follow-up period, rebleeding occurred
in 10 patients (20%) in group 1 and 20 patients (40%) in group 11 respectively.15
patients died in group 1 and 25 patients in group 11 over 2 years period, which
was statistically significant at p 0.05. The mean rebleeding free survival times
were 70 and 40.months, respectively, and were statistically significant (p 0.05).
The mean overall survival time were 60 versus 40 months, respectively, and were
significant differences between two groups (p 0.001).
CONCLUSION: The beta blocker adding therapy after gastric variceal obtura-
tion therapy using Histoacryl for first gastric variceal bleeding could decrease
rebleeding and mortality, as compared with gastric variceal obturation therapy
alone. Further prospective large-scale studies are needed to confirm or refute our
observation.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0602 SPLEEN STIFFNESS AS A PREDICTOR OF DECOMPENSATION
IN LIVER CIRRHOSIS
H. Stefanescu1,*, B. Procopet1,2, A. Bugariu3, A. Horhat3, C. Radu2, M. Tantau2
1
Hepatology Department, Regional Institute of Gastroenterology and Hepatology,
2
3rd Medical Clinic, 3University of Medicine and Pharmacy, Cluj-Napoca,
Romania
Contact E-mail Address: drhstefanescu@gmail.com
INTRODUCTION: Noninvasive assessment of chronic liver disease is of major
importance. Spleen stiffness measurement (SSM) was proposed as a surrogate
noninvasive marker for prediction of large esophageal varices (LEV) or clinically
significant portal hypertension (CSPH). It was recently hypothesised that SSM
may predict clinical decompensation (CD) during follow up in cirrhotic patients.
AIMS & METHODS: The aim of this study was to evaluate SSM as a predictor
of decompensation in patients with cirrhosis.
Fifty-two consecutive compensated cirrhotic patients due to viral (HCV and/or
HBV) or alcoholic aetiology were included. They were mainly men (27; 52%)
with a mean age of 55.9 years. 25 patients (48%) had large (grade 2 and 3)
oesophageal varices at inclusion. All patients underwent liver and spleen stiffness
measurement at baseline as previously described, abdominal ultrasound and liver
function was assessed by usual biochemical tests. Modified SSM (mSSM) was
also calculated from each spleen elastogram using an alternate calculation algo-
rithm so that an extension of the scale (up to 150 kPa) could be obtained. Clinical
decompensation was defined as the occurrence of one of the following: variceal
bleeding, development of ascites, hepatic encephalopathy (HE), jaundice (total
bilirubin 4 3 mg/dl), infection, spontaneous bacterial peritonitis (SBP), hepato-
renal syndrome (HRS), hepatocellular carcinoma (HCC) or death or liver
transplantation.
RESULTS: During the median follow-up period of 13 months (range 4-28), 23
patients (44%) decompensated. Most frequent cause of CD was ascites (7
patients, 30.4%), followed by infection/SBP (6 patients, 26.1%), variceal bleed-
ing (4 patients, 17.4%), HE and HCC (3 patients, 13.05% in each group). 14
patients (26.4%) had more than one episode of decompensation and 3 (5.6%)
died during the follow-up.
In multivariate analysis baseline values of mSSM (HR 1.085; p 0.01), albu-
min (HR 0.17; p 0.02) and total bilirubin (HR 1.642; p 0.05) were the
only variables associated with CD in the follow-up, overcoming LSM, SSM
and MELD.
CONCLUSION: Although conducted in a small heterogeneous population of
cirrhotic patients for a limited period of time, the findings of this study supports
the conclusion that modified SS measurement by transient elastography together
with simple biological parameters (Albumin and Bilirubin) may have an impor-
tant clinical relevance by selecting patients with high risk of decompensation.
Disclosure of Interest: None declared
P0603 SMALL BOWEL CAPSULE ENDOSCOPY AS A TOOL TO
DIAGNOSE PORTAL HYPERTENSIVE ENTEROPATHY IN
CIRRHOTICS: THE EDINBURGH EXPERIENCE
K.J. Dabos1,*, A. Koulaouzidis1, P.C. Hayes2, J.N. Plevris1
1
Gastroenterology, 2Hepatology, Royal Infirmary of Edinburgh, Edinburgh, United
Kingdom
Contact E-mail Address: konstantinos.dabos@nhslothian.scot.nhs.uk
INTRODUCTION: Portal hypertensive enteropathy (PHE) remains difficult to
diagnose in patients with cirrhosis and portal hypertension. Small bowel capsule
endoscopy (SBCE) would be ideal in this situation but it is rarely performed
AIMS & METHODS: We aimed to determine the prevalence of PHE using
SBCE in a cirrhotic patient population from our centre
Methods. This was a retrospective study using the SBCE data base of our unit.
We searched through 1,477 patients that had SBCE between 2005 and 2013.
Patients with cirrhosis who underwent SBCE were identified, data retrieved
and abstracted. The Fischers exact test or the chi square test were used to
compare between groups. A two-tailed P value of 50.05 was considered statis-
tically significant.
RESULTS: We identified 53 patients with cirrhosis who underwent SCBE. We
used PillCamSB (GivenImaging Ltd, Israel) system on 36 patients and the
MiroCam capsule (IntroMedic Co, Korea) on 17 patients. Thirty patients
were referred for iron deficiency anaemia, 15 for obscure gastrointestinal bleed-
ing and 4 for other indications. Four data sets were not available for review at the
time of the study, leaving 49 patients to be reviewed. Mean age was 61.1914.54
years (M/F 27/22). The most common aetiology for cirrhosis in our patients
was alcoholic liver disease (15 patients) followed by NAFLD (9 patients) and
hepatitis C (7 patients). Thirty three patients had evidence of portal hypertensive
gastropathy (PHG) and 17 patients had evidence of oesophageal varices. In total,
29 patients had SCBE evidence of PHE (67%). 28/29 (96.5%) of patients with
PHE had also evidence of PHG. 13/17 (76.4%) patients with oesophageal varices
had also evidence of PHE. Mean gastric transit time was 54  9 minutes and
mean small bowel transit time was 204  64 minutes. There were no statistically
significant differences between the mean gastric transit times in cirrhotic patients
with and without PHE (p 0.235) or the small bowel transit time (p 0.49). Our
mean follow up was 58.0  13.7 months. Twenty patients died during the follow
up period. There was no correlation between the presence of PHE and aetiology
of liver disease (p 0.4261) or subsequent death (p 0.2145).
CONCLUSION: The prevalence of PHE in our study was 67%. SBCE is a useful
tool in evaluating PHE in cirrhotic patients irrespective of aetiology.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0604
HPS
(n14)
Parameter XSD (Range)
CSV (mL) 75,9620,68 (54,4-116,96)
MAP (mm Hg) 88,438,94 (76,66-100)
CI 3,311,32 (2,05-6,26)
SVR 2421,46878,65 (979,01-3900,43)
NT-proBNP (pg/mL) 1264,642188,45 (88,78-6052,5)
PRA (mg/ml/h) 4,415,85 (0,1-16,8)
NA (nmol/L) 5,974,18 (1,46-11,51)
P0604 THE SENSITIVITY AND SPECIFICITY OF INHIBITORY
CONTROL TEST IN THE DIAGNOSIS OF MINIMAL HEPATIC
ENCEPHALOPATHY: A META-ANALYSIS
M.T. T. Panlilio1,*, A.Q. Taguba1, M.E. VIllamayor1, J.P. Ong1
1
Section of Gastroenterology, University of the Philippines Manila-Philippine
General Hospital, Manila, Philippines
Contact E-mail Address: mttpanlilio@gmail.com
INTRODUCTION: Minimal hepatic encephalopathy (MHE) is a complication
of liver cirrhosis that does not show symptoms of overt hepatic encephalopathy
(OHE). This state reflects alterations in cognitive function, but clinically exhibit a
normal mental status examination. Patients with MHE have been shown to have
higher rates of automobile accidents, it predicts the development of OHE, and is
associated with poor survival.
Diagnosis of MHE is difficult, as the absence of clinical evidence of encephalo-
pathy is key to its diagnosis. Neuropsychological testing, specifically the
Psychometric Hepatic Encephalopathy Score (PHES), is accepted as a reference
standard in the diagnosis of MHE. Newer computer-assisted techniques, such as
the Inhibitory Control Test (ICT), have been studied to improve the detection of
MHE. ICT is a simple computer-based test, consisting of presentation of several
letters at 500-millisecond intervals. The ease of performing the test in the out-
patient setting may make it a good test for detecting MHE.
AIMS & METHODS: This study aims to determine the sensitivity and specificity
of Inhibitory Control Test in diagnosing minimal hepatic encephalopathy.
COCHRANE and MEDLINE were searched for articles published between
January 2003 to October 2013. Studies that compared ICT with psychometric
tests in cirrhotics were included. Data analysis was performed using the validated
application Meta-Disc version 1.4 (Universidad Complutense, Madrid, Spain). The
DerSimonian-Laird random effects method was used to produce summary estimates
of sensitivity, specificity, likelihood ratios (LR), and diagnostic odds ratio (DOR).
RESULTS: The search strategy identified 133 studies. Based on pre-stated cri-
teria, three studies were included in the final review. There were 235 patients with
liver cirrhosis and a matched control group that underwent both psychometric
testing and ICT. Pooled data showed that the ICT had a sensitivity of 88%
(I2 0%), specificity of 72% (I2 69.2%), and DOR was 21.2 (95% CI: 8.08
55.24). A symmetrical sROC depicted an area under the receiver operator curve
(AUC) of 0.89 (standard error 0.03).
CONCLUSION: Inhibitory Control Test is a good tool to exclude cirrhotic
patients without minimal hepatic encephalopathy. It is effective in discriminating
patients with MHE from those without MHE and therefore has potential as a
screening test. However, more high-quality studies are needed to establish test
accurarcy.
REFERENCES
Stinton LM and Jayakumar S. Minimal hepatic encephalopathy. Can J
Gastroenterol 2013; 27: 572-574.
Hisamuddin K, et al. Is the ICT as accurate as standard psychometric testing for
diagnosing hepatic encephalopathy? Nat Clin Pract Gastroenterol Hepatol 2008;
5: 132-133.
Bajaj JS, et al. Inhibitory control test for the diagnosis of MHE. Gastroenterol
2008; 135: 15911600.
Bajaj JS, et al. Inhibitory Control Test Is a Simple Method to Diagnose MHE
and Predict Development of OHE. American J Gastroenterol 2007: 754-760.
Sharma P, et al. Inhibitory control test, critical flicker frequency, and psycho-
metric tests in the diagnosis of MHE in cirrhosis. Saudi J Gastroenterol 2013; 19:
4044.
Disclosure of Interest: None declared
P0605 SYSTEMIC HEMODYNAMICS IN PATIENTS WITH ALCOHOLIC
LIVER CIRRHOSIS AND HEPATOPULMONARY SYNDROME OR
PORTOPULMONARY HYPERTENSION
N. Ljubicic1,*, D. Zekanovic1, T. Pavic1, M. Nikolic1, I. Budimir1, A. Biscanin1
1
Division of Gastroenterology, Department of Internal Medicine, Sestre milosrd-
nice University Hospital, University of Zagreb School of Medicine and University
of Zagreb School of Dental Medicine, ZAGREB, Croatia
Contact E-mail Address: neven.ljubicic@kbcsm.hr
INTRODUCTION: There is a lack in knowledge about the correlation of sys-
temic circulation parameters and the degree of liver failure with respect to the
presence of hepatopulmonary syndrome (HPS) and portopulmonary hyperten-
sion (PPH).
AIMS & METHODS: The aim of this study was to evaluate the changes in the
systemic circulation by using non-invasive diagnostic approach in the patients
A299
PPH Other
(n14) (n42)
XSD (Range) XSD (Range)
8420,94 (61-116,74) 86,6918,81(46,78-132,2)
83,384,39 (78,33-90) 93,87,5 (78,33-110)
3,520,92 (2,7-4,10) 3,690,89 (1,97-5,74)
1992,76420,35 (1595,28-2321,15) 2129,18533,9 (1347,72-3865,03)
1323,392028,7 (127,52-5849,1) 607,931149,73 (11,31-5849,1)
12,6620,26 (0,6-57,6) 6,2111,28 (0,1-57,6)
586,291532,21 (0,3-4061) 149,90759,51 (0,3- 4061)
fulfilling the criteria for HPS and PPS. The study sample included 70 patients
with alcoholic liver cirrhosis;22 patients with grade A, 24 patients with grade B,
and 24 patients with grade C according to the Child-Pugh clinical score. Systemic
circulation measurements included: heart rate (HR), mean arterial pressure
(MAP), cardiac index (CI), systemic vascular resistance (SVRI) and cardiac
stroke volume (CSV)1. Neurohumoral parameters included: NT-proBNP, nora-
drenalin (NA) and plasma renin activity (PRA). HPS was diagnosed if the pre-
sence of impaired arterial oxygenation (PaO2580mmHg and alveolar-arterial
oxygen gradient 15mmHg; for patients older than 64 years PaO270 mmHg,
and A-a gradient 20 mmHg) and pulmonary vascular abnormalities were
found. PPH was characterized by increased mean pulmonary artery pressure
425 mmHg at rest and if the diameter of the main pulmonary artery is 29
mm with concomitant segmental arteryto-bronchus ratio 4 1:1 at least in three
out of four pulmonary lobes, or the ratio of the main pulmonary artery diameter
to the aortic diameter 41.
RESULTS: HPS and PPH were found in 28 (40%) patients. Patients with HPS
were mostly patients from group B (57.2%) and C (42.8%) with respect to the
degree of liver failure, while all patients with PPH were patients with advanced
liver failure. When correlating systemic hemodynamic and neurohumoral para-
meters in relation to the presence of HPS and PPS no significant difference was
found. (Table 1).
CONCLUSION: The combined application of the Doppler and contrast echo-
cardiography is a simple, non-invasive and reproducible method that enables the
diagnosis of both HPS and PPH. Systemic hemodynamic parameters remained
unchanged among patients with HPS and PPS.
REFERENCES
1. Zekanovic D, LJubicic N, Boban M, et al. Doppler ultrasound of hepatic and
system hemodynamics in patients with alcoholic liver cirrhosis. Dig Dis Sci 2010;
55: 458-466.
Disclosure of Interest: None declared
P0606 DO COAGULATION AND PLATELET FUNCTION DISORDERS
INFLUENCE THE PREVALENCE OF VARICEAL BLEEDING IN
PATIENTS WITH LIVER CIRRHOSIS?
P. Rogalski1,*, E. Wroblewski1, M. Rogalska-Plonska2, A. Swidnicka-
Siergiejko1, A.A. Baniukiewicz1, A. Dabrowski1
1
Department of Gastroenterology and Internal Medicine, 2Department of Infectious
Diseases and Hepatology, Medical University of Bialystok, Bialystok, Poland
INTRODUCTION: Bleeding from gastro-esophageal varices is a life-threatening
condition and occurs in approximately one third of patients with liver cirrhosis
during their lifetime. On the other hand patients with history of variceal bleeding
have 70% risk of recurrent bleeding within the next year since the first episode.
Coagulation disorders in patients with liver cirrhosis are complex, and their role
in variceal bleeding remains unclear. Previous studies have shown that the results
of standard laboratory tests such as prothrombin time (PT) and activated partial
thromboplastin time (APTT) provide a narrow measure of procoagulant system
only and do not predict bleeding in cirrhotic patients. Thromboelastometry has
been used for decades for intraoperative transfusion guidance and it can show
defects in multiple components of hemostasis. Multiplate impedance platelet
aggregometry (IPA) allows rapid evaluation of platelet aggregation in whole
blood.
AIMS & METHODS: The aim of our study was to compare the character of
coagulation disorders in patients with liver cirrhosis and a history of variceal
bleeding with non-bleeding cirrhotic patients. We compared standard laboratory
clotting tests, thromboleastometry (ROTEM thromboelastometer) and IPA
parameters of cirrhotic patients with medium-large varices who have never
bled (non-bleeding group) with patients with a history of variceal bleeding at
least 3 weeks before (bleeding group). The following thromboelastometry para-
meters were measured: clotting time (CT), clot formation time (CFT), maximum
clot firmness (MCF) and the clot amplitude at 5, 10 and 15 minutes in three tests
with specific activators to evaluate the extrinsic (EXTEM) and intrinsic
(INTEM) systems, and the clotting factors alone after platelet inactivation
(FIBTEM). In addition, IPA was performed with ADP as an activator and
aggregation was quantified as area under the curve (AUO).
RESULTS: Blood was sampled from 44 patients (23- non-bleeding group, 21-
bleeding group). Baseline characteristics of the bleeding and non-bleeding groups
were comparable apart from a more prolonged PT in the bleeding group [15,8
(14,1 - 17,3) vs 14,3 (13,5-16,0), p 0.045]. The severity of liver disease according
to ChildPough score was comparable in both groups [8,00 points (8,0-10,0)
non-bleeding group vs 9,0 (8,0-10,0) bleeding group, p 0.889]; 5 patients
class A, 23 patients - class B, 16 patients - class C. In FIBTEM there was
significantly lower amplitude at 15 minutes in the bleeding group compared
with non-bleeding group [12.0 (9,5-14,5) vs 15.0 (11,0-19,0), p 0.049]. The
A300
other results of thromboelastometry and aggregometry parameters did not differ
significantly between both groups, which suggest a compensatory role of platelets
in EXTEM and INTEM tests. The compensatory role of platelets is also sup-
ported by the results of IPA in which we demonstrated higher value of AUO in
bleeding group in comparsion with non-bleeding group [273.0 (99,0-557,0) vs
189.00 (132,0-640,0), NS].
CONCLUSION: Despite prolonged PT in bleeding group, the patients with liver
cirrhosis with and without history of variceal bleeding have similar efficiency of
blood clotting, which may suggest compensatory role of platelets in these
patients.
Disclosure of Interest: None declared
P0607 REAL WORLD EXPERIENCE OF RIFAXIMIN FOR HEPATIC
ENCEPHALOPATHY - EFFECTIVE MAINTENANCE OF
REMISSION AND REDUCTION OF HOSPITAL ADMISSIONS IN A
LARGE SECONDARY CARE PATIENT COHORT
H. Preedy1, A. Fowell1, R. Aspinall1,*
1
Gastroenterology & Hepatology, Portsmouth Hospitals NHS Trust, Portsmouth,
United Kingdom
Contact E-mail Address: r.j.aspinall@doctors.org.uk
INTRODUCTION: Rifaximin has been shown to maintain remission of chronic
hepatic encephalopathy (HE) and reduce hospital admissions (Bass et al 2010).
However, the literature mainly reflects tertiary centres and could include referral
bias. Therefore, we examined the real world utility of rifaximin in a large mainly those with ascites/edema. Some studies demonstrate that Maastricht
secondary care acute hospital, serving a population of 650,000.
AIMS & METHODS: All patients with cirrhosis and chronic HE who were
commenced on rifaximin between May 2010 and November 2012 were identified
from a departmental database and pharmacy records. Analysis included formal
review of casenotes, pathology, hospital admission statistics and calculation of
MELD, UKELD and Childs-Pugh scores. Data were analysed for the 6 months
prior to rifaximin usage and at 3, 6 and 12 months later.
RESULTS: The study population comprised 42 patients, 62% male, mean age 59
years. Cirrhosis aetiology was alcohol 55%, NASH 24%, autoimmune 10%,
HCV 5%, miscellaneous 6%. At initiation, 24% of patients were using alcohol
and 19% took quinolone secondary prophylaxis against spontaneous bacterial
peritonitis. Mean baseline prognostic scores were Childs-Pugh 9.4 (SD 2.1),
MELD 15.0 (SD 7.9), UKELD 51.2 (SD 5.1). Survival at 3, 6 and 12 months
post-rifaximin was 78%, 67% and 62% respectively. There was a significant
reduction in Childs-Pugh scores at 3 and 6 months (p50.01) but not 12
months and no significant change in MELD or UKELD. Comparing the 6
months pre/post rifaximin, hospitalisation days fell from 233 to 143, a mean of
5.6 per patient, representing a saving of E1,829 in healthcare tariff costs. The
number of admission episodes fell from 25 to 11.
CONCLUSION: In an unselected real world cohort of patients with chronic gender or etiology. MI detected malnourishment/malnutrition in 38% (n 19) of
hepatic encephalopathy, rifaximin was associated with fewer readmission spells
and a reduction in bed days with potential savings in healthcare utilisation costs.
The efficacy of rifaximin for the maintenance of remission in patients with
chronic HE can be demonstrated in a secondary care environment.
REFERENCES
Bass NM, Mullen KD, Sanyal A, et al. Rifaximin treatment in hepatic encepha-
lopathy. N Engl J Med 2010; 362: 1071-1081.
Disclosure of Interest: H. Preedy: None declared, A. Fowell: None declared, R.
Aspinall Consultancy for: RA has received consultancy fees from Norgine UK
P0608 NON-INVASIVE PORTAL HYPERTENSION AND
OESOPHAGEAL VARICES EVALUATION BY LIVER AND SPLEEN
TRANSIENT ELASTOGRAPHY IN PATIENTS WITH CHRONIC
LIVER DISEASE
R. Zykus1,*, L. Jonaitis1, V. Petrenkiene_1, I. Valantiene_1, L. Kupcinskas1,2
1
Gastroenterology, 2Institute of Digestive Diseases, Lihuanian University of Health
Sciences, Kaunas, Lithuania
Contact E-mail Address: rzykus@gmail.com
INTRODUCTION: Liver transient elastography (TE) can predict liver fibrosis
with high specificity and sensitivity. However, there is only limited data if TE
could predict clinically significant portal hypertension or presence of oesophageal
varices.
AIMS & METHODS: The aim of our study was to assess correlation between
liver and spleen transient elastography, hepatic venous pressure gradient (HVPG)
and presence of oesophageal varices. In this prospective study the correlations of
liver and spleen TE with HPVG and presence of oesophageal varices were
assessed in 78 chronic liver disease patients (50 patients had chronic hepatitis
C). Spleen TE was feasible in 72 of them. TE was measured at the same day
before HPVG measurement. Interquartile range/median 520% and success rate
460% were considered as good quality criteria during TE both for spleen and
liver investigations. Endoscopy was performed in one week period after TE was
done. Oesophageal varices were classified into 0 - III grades (according Baveno
consensus). Patients were categorised into those with and without oesophageal
varices. HPVG was measured using catheter occlusion technique by experienced
radiologist. Patients were classified in to 4 12mmHg (clinically significant
portal hypertension), and 512mmHg HPVG groups. Cut-off values were estab-
lished by ROC analysis.
RESULTS: Strong correlation of liver stiffness R 0.74 (p50.01) and moderate
correlation of spleen stiffness R 0.52 (p5 0.01) with HVPG were established.
To determine the patients with HVPG 4 12mmHg, liver TE cut-off value
18.5kPa had sensitivity 0.91 and specificity 0.74; spleen TE cut-off value 57.0
kPa had sensitivity 0.75 and specificity 0.77. Area under the ROC curve was 0.90
for liver TE and 0.83 for spleen TE.
United European Gastroenterology Journal 2(5S)
Strong correlation of liver stiffness R 0.61 (p50.01) and moderate correlation
of spleen stiffness R 0.48 (p5 0.01) with oesophageal varices grade were
established. To predict the presence of oesophageal varices liver TE cut-off
value 21.5kPa had sensitivity 0.86 and specificity 0.83; spleen TE cut-off value
57.0 kPa had sensitivity 0.73 and specificity 0.75. Area under the ROC curve was
0.86 for liver TE and 0.76 for spleen TE.
CONCLUSION: Liver transient elastography strongly correlates and spleen TE
moderately correlates with HVPG and oesophageal varices grade. Liver TE
accurately predicts significant portal hypertension and oesophageal varices in
patients with chronic liver disease and is more sensitive and specific than
spleen TE. Therefore liver transient elastography could be reproducible outpa-
tient screening tool for portal hypertension or oesophageal varices.
Disclosure of Interest: None declared
P0609 NUTRITIONAL EVALUATION OF THE CIRRHOTIC PATIENT
WITHOUT ASCITES: IS THERE A ROLE FOR ANTHROPOMETRIC
PARAMETERS?
S.M. D. Giestas1,*, A. Giestas1, C. Agostinho1, C. Sofia1
1
Centro Hospitalar e Universitario de Coimbra, Coimbra, Portugal
Contact E-mail Address: silviagiestas@gmail.com
INTRODUCTION: Malnutrition due to chronic liver disease is common and its
assessment is difficult. The anthropometric parameters, often used in clinical
practice, have limited use in the nutritional evaluation of cirrhotic patients
Nutritional Index (MI) is the best assessment in early stages of the disease,
however the best method of nutritional evaluation in cirrhotic patients remains
controversial.
AIMS & METHODS: Aim: To determinate the role for anthropometric para-
meters in the nutritional evaluation of cirrhotic patients without ascites and
compare it with the MI.
Patients and Methods: Prospective study of cirrhotic outpatients without ascites
(diagnosis based on histological evidence and/or high clinic/ biochemical /imagi-
ological suspicion). Exclusion criteria: enteric nutrition, amputation, malabsorp-
tion syndrome, chronic pancreatitis, inflammatory bowel disease, chronic kidney
disease, acquired immunodeficiency syndrome, neuromuscular diseases and
oncologic advanced disease. Included patients where classified according Child-
Pugh Score; weight (kg), height (cm) and body mass index (BMI) were evaluated;
and based in MI they were stratified in mild (40-3), moderate (43-6) and severe
(46) impaired nutritional status.
RESULTS: 50 cirrhotic patients were included in the study, 84% (n 42) had
alcoholic cirrhosis, the mean age was 58/-11.4 years and 60% were male
(n 30). Concerning cirrhosis severity: 88% (n 44) were Child-Pugh A and
12% (n 6) Child-Pugh B. 8% (n 4) had a BMI518.5%, regardless of age,
patients: 24% (n 12) mild and 14% (n 7) moderate impaired nutritional
status. In MI evaluation no statistically difference was found between etiology,
gender and age. No association between malnutrition and disease severity (Child-
Pugh Score) was found with both methods.
CONCLUSION: In this study anthropometric parameters underestimate malnu-
trition in cirrhotic patients when compared with the Maastricht Nutritional
Index, which detected malnutrition in early stages of hepatic disease.
Disclosure of Interest: None declared
P0610 EFFICACY OF TRANSJUGULAR INTRAHEPATIC
PORTOSYSTEMIC SHUNT FOR THE PREVENTION OF VARICEAL
REBLEEDING IN CIRRHOTIC PATIENTS WITH PORTAL VEIN
THROMBOSIS
P. Chen1, Y. Zhuge1,*
1
Gastroenterology, Affiliated Drum Tower Hospital of Nanjing University Medical
School, China, Nanjing,Jiangsu, China
Contact E-mail Address: 304293942@qq.com
INTRODUCTION: Although several studies have elucidated the beneficial
effects of TIPS on PVT in patients with cirrhosis[1, 2, 3] in short term, it is
regrettable that the long term effects of TIPS in cirrhotic patients with PVT is
not very clear, especially in patients with a history of oesophageal and gastric
varices bleeding, therefore the aim of this retrospective study was to evaluate the
feasibility, safety, and efficacy of TIPS for the prevention of variceal rebleeding
in cirrhotic patients with PVT.
AIMS & METHODS: Aim The aim of this study was to evaluate the efficacy of
TIPS for the prevention of variceal rebleeding in cirrhotic patients with PVT
retrospectively.
Methods Forty consecutive cirrhotic patients with a history of variceal bleeding
were referred for TIPS between August 2008 and December 2013. All patients
were diagnosed with non-malignant PVT, including 37 partial PVT and 3 portal
cavernoma. Patients were followed until last clinical evaluation, diagnosis of
hepatocellular carcinoma, liver transplantation, or death.
RESULTS: TIPS were successfully placed in 85% of patients (34/40), 86.5% (32/
37) in patients with partial PVT and 66.7% (2/3) with portal cavernoma, without
complication or TIPS-related mortality. Patients with successful TIPS were fol-
lowed up for a mean of 12.9 months (range1-37 months) and portosystemic
pressure gradient (PSG) was reduced from a mean 21.6 4.0 to 14.4 5.2mm
Hg after TIPS placement, the decreasing amplitude of PSG reached 29.4% 
5.0% from baseline. The 1- and 2-year cumulative variceal rebleeding rates were
11.8% and 48.5% in the success group and 16.7% and 37.5% in the failure
group, respectively (p 0.438). The only independent predictor for variceal
rebleeding in the success group was TIPS shunt flow velocity. The cumulative
rate of TIPS dysfunction at 1-and 2-year was 11.8% and 31.4%. Hepatic
United European Gastroenterology Journal 2(5S)
encephalopathy occurred in 44.1% (15/34) of patients, and all of them happened
within the first year after TIPS. The 1- and 2-year cumulative survival rates were
80.1% and 49.9% in the success group and 100% and 75.0% in the failure group,
respectively (p 0.471).
CONCLUSION: TIPS placement is safe, feasible and has a fairly high success
rate to prevent variceal rebleeding in cirrhotic patients with PVT. Moreover,
TIPS can highly decrease the risk of variceal rebleeding because of the reduction
of PSG, and the only independent predictor for variceal rebleeding was TIPS
shunt flow velocity. We suggest TIPS should be considered a viable treatment
option for cirrhotic patients with PVT, especially in patients with a high risk of
variceal rebleeding.
REFERENCES
1. Han G, et al. Transjugular intrahepatic portosystemic shunt for portal vein
thrombosis with symptomatic portal hypertension in liver cirrhosis. J Hepatol
2011; 54: 78-88.
2. Perarnau JM, et al. Feasibility and long-term evolution of TIPS in cirrhotic
patients with portal thrombosis. Eur J Gastroenterol Hepatol 2010; 22: 1093-
1098.
3. Luca A, et al. Short- and long-term effects of the transjugular intrahepatic
portosystemic shunt on portal vein thrombosis in patients with cirrhosis. Gut
2011; 60: 846-852.
Disclosure of Interest: None declared
P0611 CO-LOCALIZATION OF HBX AND COXIII PROMOTES HL-7702
CELL PROLIFERATION THROUGH CROSSTALK AND SYNERGY
OF COX-2 AND B-CATENIN SIGNAL PATHWAYS
B. Zheng1,*, X. Fang1, L. Zou2, D. Li1, Y. Huang1, Z. Chen1, L. Zhou3,
X. Wang1
1
Gastroenterology, 2Infection, Union Hospital of Fujian Medical University, 3 Lab
of Electron Microscopy, Fujian Medical University, Fuzhou, China
Contact E-mail Address: drzhengby@163.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is one of the most
common malignant diseases, and HBx leads to the development of HBV-asso-
ciated HCC. Our recent studies have revealed that HBx can interact with the
inner mitochondrial membrane protein, COXIII, by yeast two-hybrid system,
mating experiment and coimmunoprecipitation.
AIMS & METHODS: To futher explore the co-localizaiton of HBx and COXIII
in HL-7702 cell and to investigate the molecular mechanism of HBx in HL-7702
cell proliferation. A HL-7702 cell line stably expressing the HBx gene by lenti-
virus vectors were constructed. Confocal microscopy was utilized to assess the
interaction between HBx protein and COXIII. The functional relevance of HBx
proteinCOXIII interaction was investigated in cell cultures.
RESULTS: Our studies first demonstrated that HBx co-localized with the inner
mitochondrial protein, COXIII, in HL-7702 cells, causing the up-regulation of
COXIII protein expression as well as COX activity. HBx elevated the generation
of mitochondrial ROS and ROS was necessary for it to activate the expression of
COX-2. Moreover, HBx promoted cell proliferation through COX-2/-catenin
signaling pathways.
CONCLUSION: Collectively, the major finding of this study is that the co-
localization of HBx and COXIII leads to the changes of mitochondrial biogenesis
and morphology. Besides, COX-2 and -catenin signal pathways stimulated by
mitochondrial ROS have crosstalk and synergy in the oncogenesis of HBV-asso-
ciated HCC.
REFERENCES
1. Tian Y, Yang W, Song J, et al. Hepatitis B virus X protein-induced aberrant
epigenetic modifications contributing to human hepatocellular carcinoma patho-
genesis. Mol Cell Biol 2013; 33: 2810-2816.
2. Xu C, Zhou W, Wang Y, et al: Hepatitis B virus-induced hepatocellular
carcinoma. Cancer Lett 2013.
3. Wang XZ, Li D, Tao QM, et al. A novel hepatitis B virus X-interactive
protein: cytochrome C oxidase III. J Gastroenterol Hepatol 2006; 21: 711-715.
4. Li D, Wang XZ, Yu JP, et al. Cytochrome C oxidase III interacts with
hepatitis B virus X protein in vivo by yeast two-hybrid system. World J
Gastroenterol 2004; 10: 2805-2808.
Disclosure of Interest: None declared
P0612 RISK FACTORS ASSOCIATED WITH MORTALITY IN
HEPATITIS E RELATED ACUTE LIVER FAILURE DURING
PREGNANCY
S. Sharma1,*, A. Kumar1, P. Kar2, S. Agarwal3, S. Prasad1
1
Obstetrics and Gynaecology, 2Medicine, 3Biochemistry, Maulana Azad Medical
College, Delhi, India
Contact E-mail Address: sheetal02sharma@gmail.com
INTRODUCTION: HEV infection is fatal during pregnancy. The mortality rate
in pregnant women with ALF is 15-20%, which is associated with an altered
status of hormones and difference in immune response.
AIMS & METHODS: Aim of the study is to determine biochemical and hae-
motological factors associated with mortality in Hepatitis E related acute liver
failure during pregnancy. A total of 73 consecutive ALF pregnant patients with
HEV infection were recruited in the study during July 2008 to August 2013 and
patients were followed up until death or complete recovery. Patients with viral
co-infections and with history of pre-existing liver disease were excluded.
Biochemical and pathological parameters included detailed liver function tests
(AST, ALT, alkaline phosphatase and total serum bilirubin), total proteins,
prothrombin time and complete haemogram. All the cases were screened for
hepatitis virus markers by ELISA. ROC curve was drawn to predict cut-off
level of serum albumin in ALF pregnant patients.
A301
RESULTS: The mean maternal age and gestational at delivery were 25.32
3.62years and 29.534.62 weeks respectively. Forty six out of 73 (63.01%)
ALF pregnant patients were non survived and twenty seven out of 73
(36.98%) were survived. HEV was found to be the commonest cause of ALF
in pregnancy. It was found that in univariate logistic regression analysis AST,
ALP, bilirubin, prothrombin time, total protein and albumin were the statisti-
cally significant factors between survival and non-survival group. A multivariate
logistic regression analysis was performed using significant independent vari-
ables, and it was found that variables that independently predicted mortality
were serum alkaline phosphatase (OR 5.21, 95% CI 1.27-21.42; p50.05),
prothrombin time (OR 6.47, 95% CI 1.6924.77; p50.01), serum albumin
(OR 7.85, 95% CI 1.73-35.55; p 0.01) and serum total protein (OR 3.88;
95% CI 1.0114.94; p50.05). A receiver operating characteristic curve was
drawn for serum albumin. The area under the curve was 0.643. The serum
albumin level of 2.1g/dl was found to be the cut-off for ALF pregnancy patients
with 67% sensitivity and 63% specificity.
CONCLUSION: Serum albumin, serum total protein, serum alkaline phospha-
tase and prothrombin time were significant independent risk factors associated
with mortality in ALF pregnant patients.
Disclosure of Interest: None declared
P0613 FAVORABLE ANTIVIRAL EFFECT OF NUCLEOSIDE
ANALOGUES REDUCES HEPATOCELLULAR CARCINOMA
DEVELOPMENT IN HIGH RISK PATIENTS WITH CHRONIC
HEPATITIS B VIRUS INFECTION
A. Kawano1,*, S. Onohara2, H. Shigematsu1, K. Miki1, T. Maruyama1,
H. Nomura3, S. Shimoda2 on behalf of Fukuoka Study Group for the Treatment
of Liver Diseases
1
Department of Internal Medicine, Kitakyushu Municipal Medical Center,
Kitakyushu, 2Department of Medicine and Biosystemic Science, Graduate School
of Medical Sciences, Kyushu University, Fukuoka, 3The Center for Liver Disease,
Shin-Kokura Hospital, Kitakyushu, Japan
Contact E-mail Address: k-akira1971july@jcom.home.ne.jp
INTRODUCTION: Chronic hepatitis B virus (HBV) infection leads to cirrhosis
and hepatocellular carcinoma (HCC). Recently, HCC risk scales enable us to
estimate the risk of developing HBV related HCC (REACH-B score, Lancet
Oncol 2011;12:568). The objective of this study was to evaluate the on-treatment
predictive factors of nucleoside analogues (NAs) to reduce HBV related HCC
development for the high risk patients of chronic HBV infection in Japan, where
genotype C is the most prevalent.
AIMS & METHODS: This study was retrospective cohort study including the
patients treated with NAs for at least 12 months. The patients were applied into
REACH-B score and risk scores were generated based on sex, age, serum ALT
concentration, HBeAg status, and serum HBV DNA level. The favorable
responses of NAs were defined as each of these cases, (1)decrease in serum
ALT levels to within the normal range by 24 weeks, (2)decrease in HBV DNA
less than 4.0 log copies/mL by 24 weeks, (3) achievement of HBeAg seroconver-
sion or (4)decrease in HBsAg less than 100 IU/mL. We compared the incidence
of HCC between favorable responder and poor responder.
RESULTS: A total of 76 Japanese patients with nucleoside-na ve chronic HBV
infection were included. Thirty two patients were started with lamivudine, 44
patients were started with entecavir. Mean treatment duration was 1387 days
(range 374-4360). Mean pre-treatment HBV DNA and ALT levels were 7.14 log
copies/mL and 282 IU/L, respectively. The mean age was 50.011.9 years and 47
(61.8%) patients were male. Forty (52.6%) patients were HBeAg positive, 18
patients (23.7%) had clinical evidence of liver cirrhosis. Genotype C was the
most prevalent (43 of 48, 89.6%). Nine patients developed HCC during follow-
up. All 9 patients were from the group whose REACH-B scores were 11 points or
more (52 patients, defined as high risk patients, in this study). Of the high risk
patients, those who had achieved HBeAg seroconversion reduced HCC develop-
ment significantly (p 0.0478). The cumulative HCC incidence rates at 5-year
were 4.7% and 40.0% for the patients who achieved HBeAg seroconversion
(favorable responder) and those who did not (poor responder), respectively.
CONCLUSION: The high risk patients still have the risk of developing HCC.
NAs can reduce HCC development for the high risk patients with chronic HBV
infection (Hepatology 2013;58:98). From our study, favorable antiviral effect (for
example, achievement of HBeAg seroconversion) of NAs may reduce HCC
development in the high risk patients with chronic HBV infection.
Disclosure of Interest: None declared
P0614 PREVIOUS INTERFERON THERAPY DOES NOT LEAD TO A
BETTER VIROLOGICAL RESPONSE IN PATIENTS TREATED
WITH ENTECAVIR: A COHORT STUDY
C.M. Preda1,*, C. Baicus2, L. Tugui1, S. V. Olariu1, A. Andrei1, N. Grecu1,
M.M. Diculescu1
1
Gastroenterology and Hepatology, Institutul Clinic Fundeni, 2Internal Medicine,
N. Ghe. Lupu Hospital, Bucharest, Romania
Contact E-mail Address: preda_monicaa@yahoo.com
INTRODUCTION: Entecavir (ETV) is a potent inhibitor of HBV replication.
AIMS & METHODS: The aim of the study was to explore if previous interferon
(IFN) therapy might influence response to Entecavir in chronic hepatitis B.
A retrospective cohort study was performed, including all subjects who received
ETV for chronic hepatitis B, in the south-Eastern Romania. We assessed viral
response, HBeAg loss and seroconversion, HBsAg loss and seroconversion, bio-
chemical response. Comparison of categorical data was performed by c2-test or
Fishers exact were applicable.
A302
RESULTS: 533 patients were followed for a median period of 24 months. The
cohort was 64% male, 23% HBeAg-positive, 23% IFN-pretreated, 17%
Lamivudine-pretreated, 8% cirrhotics. At baseline, the median hepatitis B
virus DNA was 5.95 (interquartile range 1.08-9.97) log10 IU/ml. At week 48,
71% of the patients (32% HBeAg-positive; 82% HBeAg-negative) achieved a
virological response and 91% (78% HBeAg-positive; 95% HBeAg-negative) of
those with elevated baseline alanine aminotransferase showed a biochemical
response. Thirty-two per cent (39/123) of the HBeAg-positive patients lost
HBeAg and 23% (28/123) achieved seroconversion to anti-HBe. Positive predic-
tive factors for virologic response are: low score of fibrosis (p-0.006), low level of
HBV DNA (p-0.003). Negative predictive factors for virologic response are: HBe
antigen positive status (OR odds ratio 0.15, 95%CI confidence interval 0.07-
0.30; p-value50.001), prior IFN therapy. (OR 0.45, 95% CI 0.24-0.86; p-value
0.015). Baseline level of ALT, age, sex, previous Lamivudine therapy had no
impact on virologic response. Virological breaktrough was found in 0.8% of
patients. Seven patients (1.31%) showed clearance of hepatitis B surface antigen.
CONCLUSION: ETV maintained and even increased the high initial response
rate (from 71% to 90.6%). Low score of fibrosis, low level of HBV DNA, HBe
antigen negative status, absence of prior interferon therapy predict a good vir-
ologic response. Lamivudine-resistant patients usually respond well to ETV, but
15.62% are non-responders, suspect of Entecavir resistance.
REFERENCES
1. European Association for the Study of the Liver. EASL Clinical Practice
Guidelines: Management of chronic hepatitis B virus infection. J Hepatol 2012,
http://dx.doi.org/10.1016/j.jhep.2012.02.010
2. Caruntu FA, Streinu-Cercel A, Gheorghe LS, et al. Efficacy and safety of
peginterferon alpha-2a (40 kD) in Hbe Ag-positive chronic hepatitis B patients.
J Gastrointestin Liver Dis 2009; 18: 425-431.
3. Shouval D, Lai C-L, Chang T-T, et al. Three years of entecavir (ETV) re-
treatment of HbeAg-negative ETV patients who previously discontinued ETV
treatment: results from study ETV-901. Hepatology 2008; 48: 722A.
4. Gheorghe L, Csiki IE, Iacob S, et al. The prevalence and risk factors of
hepatitis B virus infection in Romania: a nationwide survey. Eur J
Gastroenterol Hepatol 2013; 25: 56-94.
5. Buti M, Morillas RM, Prieto M, et al. Efficacy and safety of entecavir in
clinical practice in treatment-naive Caucasian chronic hepatitis B patients. Eur
J Gastroenterol Hepatol 2012; 24: 535-542.
Disclosure of Interest: None declared
P0615 BENEFITS OF LONGER DURATION NUCLEOS(T)IDE
ANALOGUES THERAPY IN PATIENTS WITH CHRONIC
HEPATITIS B: A NATIONWIDE COHORT STUDY
C.-Y. Wu1,*, J.-T. Lin2, H.J. Ho2, T.-Y. Lee1, J.-C. Wu3
1
Division of Gastroenterology, Taichung Veterans General Hospital, Taichung,
2
School of Medicine, Fu Jen Catholic University, New Taipei City, 3School of
Medicine, National Yang-Ming University, Taipei, Taiwan, Province of China
Contact E-mail Address: dr.wu.taiwan@gmail.com
INTRODUCTION: Nucleos(t)ide analogues (NUCs) therapy reduced the risk of
hepatitis B virus (HBV) disease progression. However, whether NUCs long-term
therapy is more effective than short-term therapy remains controversial.
AIMS & METHODS: We conducted a nationwide cohort study based on
Taiwans National Health Insurance Research Database (NHIRD) between
October 1, 2003 and December 31, 2011. Among the CHB patients, we used
propensity scores to match 8,631 patients with NUCs therapy for at least 1.5
years (long-term therapy cohort) with 8,631 patients with NUCs therapy for at
least 90 days, but less than 1.5 years (short-term therapy cohort). Major out-
comes, including liver decompensation, hepatic failure, or overall mortality,
between the 1.5 and 3 years after date of starting NUCs therapy were analyzed.
Cumulative incidences and multivariable analyses were calculated after adjusting
for competing mortality.
RESULTS: Compared with short-term therapy cohort, long-term therapy cohort
had significantly lower risk of liver decompensation (1.05%; 95% confidence
interval [CI], 0.81-1.30% vs. 2.13%; 95%CI, 1.82-2.45%; P50.001), hepatic fail-
ure (0.35%; 95% CI, 0.21-0.49% vs. 0.63%; 95% CI, 0.46-0.80%; p 0.008), and
overall mortality (1.67%; 1.37-1.98% vs. 2.44%; 95% CI, 2.10-2.77%; P50.001).
After adjusting for competing mortality and other confounders, long-term ther-
apy was associated with a reduced risk of liver decompensation (adjusted hazard
ratio, aHR: 0.47; 95%CI, 0.36-0.62, P50.001), hepatic failure (aHR: 0.53;
95%CI, 0.33-0.86, p 0.01) and overall mortality (aHR: 0.67; 95% CI, 0.53-
0.84, p 0.001).
CONCLUSION: NUCs long-term therapy was associated with reduced risks of
liver decompensation, hepatic failure and overall mortality in CHB patients.
Disclosure of Interest: None declared
P0616 THE INACTIVE HBV-CARRIER PROFILE: THE LONG-TERM
OUTCOME
H. Zejly1,*, R. Afifi1, Y. Cherradi1, H. Benbrahim1, I. Benelbarhdadi1,
F.Z. Ajana1, W. Essamri1, A. Essaid ElFeydi1
1
Hepatogastroenterology (Medecine C), Ibn Sina Hospital, Rabat, Morocco
Contact E-mail Address: hindzejly@gmail.com
INTRODUCTION: The inactive HBV profile is one of the aspects of natural
history of chronic hepatitis B (HVB). We aimed to define epidemiological, clin-
ical and virological features of inactive HVB-carriers and to evaluate their long-
term outcome
AIMS & METHODS: Its a monocentric and descriptive study including 575
chronic HVB-carriers - over 18 years old- followed since 1998. The inactive HBV
profile was defined by normal serum aminotransferases, HBeAg-negative state
United European Gastroenterology Journal 2(5S)
and DNA levels 52000 IU/ml. We excluded patients with HIV and/or HCV co-
infection and alcohol consumers. HBV-reactivation was defined by an HVB
DNA load up to 2000 IU/ml. All clinical, biological and serological data were
collected. Serum HBV DNA levels were measured using real-time PCR quanti-
fication assays. Liver biopsy was indicated according to international
recommendations
RESULTS: Of 575 considered patients, the inactive HVB-carriers represented
49.7% (n 286). Mean age was 35.5 years old [18-63], male gender was promi-
nent (sex-ratio 1.93). Mean time of follow-up was 6 years [1- 15]. The most
probable ways of HVB transmission were unprotected sexual practices and
unsafe tooth-care (respectively 57 % and 34.5%). Ultrasonography found an
heterogeneous hepatic parenchyma in 12% and steatosis in 4%. Liver biopsy
was indicated in 6 patients: fibrosis was less than F2 according to Metavir
score. HVB-reactivation was reported in 2 patients (0.01%) which indicates anti-
viral treatement. Spontaneous HBsAg loss was achieved in 5 patients. No case of
hepatocellularcarcinoma was reported.
CONCLUSION: Our real-life experience confirms that the inactive HVB pro-
file is associated to less complications and better long-term outcome.
Disclosure of Interest: None declared
P0617 ANTIVIRAL EFFICACY OF ENTECAVIR VERSUS ENTECAVIR
PLUS ADEFOVIR FOR HEPATITIS B VIRUS RTA181V/T MUTANTS
ALONE
M.J. Oh1,*
1
Department of Internal Medicine, CHA Gumi Medical Center, CHA University
School of Medicine, Gumi, Korea, Republic Of
Contact E-mail Address: zenus1@hanmail.net
INTRODUCTION: Hepatitis B virus (HBV) rtA181V/T mutants developed by
long-term nucleos(t)ide analogues therapy are known to confer cross-resistance
for other nucleos(t)ide analogues, except entecavir (ETV). Although ETV has
primarily been used as rescue therapy for rtA181V/T mutants, some studies have
reported that rtA181V/T mutants could induce cross-resistance to ETV. In prac-
tice, a clinical investigation reported that rtA181V/T mutants might confer HBV
DNA persistence, and showed an association with incomplete response, despite
rescue therapy with ETV.
AIMS & METHODS: The aim of this study was to investigate antiviral efficacy
of ETV alone and in combination with adefovir (ADV) as rescue therapy for
HBV rtA181V/T mutants alone. A total of 30 patients who received ETV (1.0
mg/day) monotherapy or ETV plus ADV (10 mg/day) therapy over 48 weeks
against HBV rtA181V/T mutants only without other concomitant mutation
between April 2008 and October 2011 were enrolled. The subjects were divided
into the ETV group (n 16) and the ETV ADV group (n 14). Virological,
biochemical, and serological response after 48 weeks of rescue therapy were
investigated retrospectively.
RESULTS: No significant difference in baseline characteristics, including serum
HBV DNA levels (4.8  1.7 vs. 4.1  1.8log10IU/mL) and the rate of HBeAg
positivity (93.8 vs. 100%) was observed between the two groups (p40.05).
Virological response at 48 weeks showed complete virological response (serum
HBV DNA 5 20 IU/mL) (62.5 vs. 42.9%), partial virological response (6.3 vs.
28.6%), non-response (25.0 vs. 28.6%), and virological breakthrough (6.3 vs.
0%), respectively. No statistical significance was observed in virological response
(p 0.278). No significant difference in mean reduction of serum HBV DNA and
biochemical response rates was observed between both groups, respectively (4.3
 2.9 vs. 4.1  1.8log10IU/mL; p 0.294, 88.9 vs. 100%; p 1.000). In addition,
no significant difference in HBeAg loss or seroconversion was observed between
the two groups (26.7 vs. 28.6%; p 1.000).
CONCLUSION: As rescue therapy for HBV rtA181V/T mutants alone, ETV
monotherapy was clinically as effective as ETV plus ADV therapy.
REFERENCES
1. Villet S, Pichoud C, Billioud G, et al. Impact of hepatitis B virus rtA181V/T
mutants on hepatitis B treatment failure. J Hepatol 2008; 48: 747-755.
2. Warner N and Locarnini S. The antiviral drug selected hepatitis B virus
rtA181T/sW172* mutant has a dominant negative secretion defect and alters
the typical profile of viral rebound. Hepatology 2008; 48: 88-98.
Disclosure of Interest: None declared
P0618 HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B
PATIENTS UNDER ANTIVIRAL TREATMENT - RISK FACTORS
AND THE PERFORMANCE OF A VALIDATED PREDICTIVE RISK
SCORE
P. Magalhaes-Costa1,*, L. Lebre1, M. Bispo1, T. Bana1, P. Peixe1, C. Chagas1
1
Gastrenterology, Hospital Egas Moniz - Centro Hospitalar Lisboa Ocidental,
Lisboa, Portugal
Contact E-mail Address: pmagalhaescosta@gmail.com
INTRODUCTION: Antiviral therapy reduces but does not eliminate the risk of
hepatocellular carcinoma (HCC) in chronic hepatitis B patients with or without
cirrhosis. Retrospective or prospective observational cohort studies that provide
HCC data for patients mainly treated with tenofovir are lacking.
AIMS & METHODS: We performed a single-center retrospective cohort study
of 120 patients with chronic hepatitis B (age, 4714; 83 male), 20% (n 24) with
clinical cirrhosis, who were treated with tenofovir 300mg daily (n 85; 72%) or
entecavir 0.5/1mg daily (n 33; 28%) for at least 12 months. Patients co-infected
with hepatitis C virus or human imunodeficiency virus were excluded. Univariate
and multivariate analysis of risk factors associated with HCC development were
performed. Accuracy of a recent validated HCC-risk score (REACH-B) was
assessed.
United European Gastroenterology Journal 2(5S)
RESULTS: Our population was mainly caucasian (n 80; 67%) and african
(n 37; 31%). The most common serological profile was AgHBe negative
(n 82; 73%). 69 patients (60%) were treatment-na ve. Alcohol abuse was
reported in 14 patients (12%). The rates of biochemical, total and partial viro-
logical response were: 96.5%, 89.2% and 8.3%. The mean time under antiviral
therapy was 4119 months. After a 8254 months of follow-up, 9 patients
(7.6%) developed HCC. The 1 and 3-year cumulative incidence of HCC was
2.7% and 11.1%. Patients who developed HCC were older (p 5 0.001), alco-
holics (p 5 0.05), cirrhotic at baseline (p 5 0.05; OR 15.469; 95%CI: 3.454-
69.272) and displayed a higher REACH-B score at baseline (p 5 0.05). On an
univariate analysis, a REACH-B baseline score  8 predicted relatively well HCC
occurrence (p 0.071; OR 6.352; 95%CI: 0.754-53.486) however, a score  12
points predicted better (p 5 0.05; OR 10.595; 95%CI: 2.275-49.338). Gender,
ethnic origin, AgHBe status, baseline viremia, previous treatment and time under
antiviral therapy were not associated with HCC occurrence. Through logistic
regression, multivariate analysis identified as risk factors associated with HCC
occurrence: cirrhosis at baseline (p 0.016; OR 7.975; 95%CI: 1.464-43.432) and
REACH-B score baseline  12 (p 0.015; OR 7.603; 95%CI: 1.480-39.070). The
1 and 3-year cumulative incidence of HCC in patients with REACH-B score
baseline  8 was 7.4% and 16.8%, while a score  12 confered a risk of
12.6% and 42.7%, respectively. By Kaplan-Maier analysis, excluding alcohol
abusers, patients who scored  8 points in REACH-B had a significantly
higher risk of developing HCC (p 0.029) compared with those with 5 8
points. At baseline, the REACH-B score performed well, with a AUC of 0.811
(95%CI: 0.668-0.954). A cut-off score of  8 (at baseline) yielded 87.5% sensi-
tivity, 47.6% specificity, 11.5% positive predictive value (PPV) and 98% negative
predictive value (NPV).
CONCLUSION: Even with long periods under antiviral therapy, the occurrence
of hepatocellular carcinoma in patients with chronic hepatitis B remains a pro-
blem. In our cohort, HCC mostly occured in older ( 50 y/o) and alcohol con-
suming patients, probably with an underlying cirrhotic liver. The performance of
REACH-B score (with a cut-off  8) in non-alcoholic patients seems to perform
well in predicting the risk of developing HCC.
Disclosure of Interest: P. Magalhaes-Costa: None declared, L. Lebre: None
declared, M. Bispo: None declared, T. Bana: None declared, P. Peixe Lecture
fee(s) from: Gilead, Bristol-Myers Squibb, Roche and Bayer, Consultancy for:
Gilead, Bristol-Myers Squibb, Roche and Bayer, C. Chagas Lecture fee(s) from:
Abbvie
P0619 REACTIVATION OF HEPATITIS B VIRUS IN HBSAG-NEGATIVE
HBCAB-POSITIVE PATIENTS WITH PSORIASIS UNDERGOING
IMMUNOSUPPRESSIVE THERAPY
R. Granata1,*, N. Balato2, F. Ayala2, M. Guarino1, S. Labella2, F. Auriemma1,
I. Loperto1, N. Caporaso1, F. Morisco1
1
Department of Clinical Medicine and Surgery, Gastroenterology Unit,
2
Department of Clinical Medicine and Surgery, Dermatology Unit, University of
Naples "Federico II", Naples, Italy
Contact E-mail Address: filomena.morisco@unina.it
INTRODUCTION: Viral hepatitis reactivation has been widely reported in
patients undergoing immunosuppressive therapy; however, few data are available
on the risk of HBV reactivation in patients with psoriasis receiving immunosup-
pressive drugs.
AIMS & METHODS: We conducted a retrospective study to value the effect of
immunosuppressive therapy on HBV infection in psoriatic patients.
The study included all consecutive psoriatic patients who attended an Italian
tertiary referral hospital from 2008 to 2012. A total of 412 patients were con-
secutively enrolled. We evaluated: HBV markers, type of immunosuppressive
treatment and the occurrence of HBV reactivation. Reactivation was defined
as reappearance of HBsAg, increase in HBV-DNA at least 1 log in comparison
to basal level, in association with or without increase of aminotransferase levels.
The observational period ranged from the beginning of immunosuppressive
treatment to 6 months after the end of therapy.
RESULTS: A total of 225/412 (54.6%) patients with psoriasis and receiving
immunosuppressive therapy (cyclosporine or methotrexate, and/or biological
drugs, such as adalimumab, infliximab, etanercept, golimumab, ustekinumab)
were tested for markers of HBV infection. We identified 23/225 subjects
(10.2%) with isolated HBcAb positivity and 36/225 (16%) with HBcAb/
HBsAb positivity. No patient was HBsAg positive. No patient underwent pre-
emptive therapy with Lamivudine or other antiviral drugs. No patient showed
episodes of HBV reactivation.
CONCLUSION: In dermatological setting the immunosuppressive therapy, in
HBcAb and HBcAb/HBsAb patients, seems to be safe regardless to the type
of treatment schedule.
Disclosure of Interest: None declared
P0620 SPANISH MULTICENTRE STUDY PIBHE: PREVALENCE OF
HEPATITIS B VIRUS INFECTION AND IMMUNIZATION IN
HEMODIALYSIS PATIENTS
S. Aoufi Rabih1,* on behalf of Dialysis Virus Group of the Spanish Society of
Nephrology, R. Garc a Agudo2 on behalf of Dialysis Virus Group of the Spanish
Society of Nephrology, G. Barril Cuadrado3 on behalf of Dialysis Virus Group
of the Spanish Society of Nephrology, F. Perez Roldan1, P. Gonzalez Carro1 on
behalf of Dialysis Virus Group of the Spanish Society of Nephrology
1
Gastroenterology and Hepatology, 2Nephrology Department, La Mancha-Centro
Hospital, Alcazar de San Juan, Ciudad Real, 3Nephrology Department, La
Princesa Universitary Hospital, Madrid, Spain
Contact E-mail Address: samiaoufi@hotmail.com
A303
INTRODUCTION: The estimated prevalence for chronic hepatitis B virus
(HBV) infection is 0-10 % in hemodialysis patients, with wide variations geogra-
phically and between units in the same country. The estimated prevalence in
Spain was 3.1 % in 2003. Immunization in the vaccinated patients is 40-70 %
compared to 97% of the general population.
AIMS & METHODS: National multicenter cohort study, approved by the
Ethics and Clinical Investigation Committee of the coordinating center, con-
ducted between January 2013 and January 2014. The aim of this study was to
determine the prevalence of HBV in hemodialysis patients in Spain and their
situation regarding immunization. A case report form was sent to all the hemo-
dialysis units of Spain to collect information about the patients after informed
consent. The data were included in a central database.
RESULTS: One hundred and forty two hemodialysis units participated (104
hospitals, 38 satellite centers). Of the 13,845 patients included, 125 were HBV-
positive, resulting in a prevalence of 0.9%. A third of the centers had a HBV-
positive patient. The mean age was 66.6 (20-98) in the HBV-negative patients and
45.5 years old in HBV-positive patients (26-72).
In HBV-positive patients, 17.3 % were coinfected with hepatitis C and/or human
immunodeficiency viruses. 70 % of patients had positive antiHBe. 82% had a
viral load below 2,000 IU/ml. The AST and ALT levels were 18.3  10.5 IU / ml
and 14.5  9 IU / ml, respectively. 8.7 % had undergone a liver biopsy; 32% had
received antiviral treatment; 37.5 % were candidates for renal transplantation
and 65.2 % were followed for Gastroenterology.
In HBV-negative patients, 33.6 % had not been vaccinated; 14.2% had positive
anti-HBc. Fourteen different vaccination schedules were used. The immune
response stood at 66.4 %. The levels of anti-HBs after vaccination were 10-99
mIU/ml in 29.5 %, 100-999 mIU/ml in 23.9% and equal to or greater than 1000
mIU/ml in 8.4%. More than a half (56.7%) had received a vaccination course;
22.6 %, two cycles; 0.6%, three cycles; and 9.5%, an annual booster. The most
likely to achieve an immune response was achieved with four doses of 40 mcg of
adjuvanted vaccine (OR 4.9), for the same age and number of revaccination
cycles and boosters. Age and dose and adjuvant vaccine usage influenced the
immune response and the title of antiHBs reached (p 5 0.05). 81.1 % of
researchers agreed that the questionnaire had helped them to assess the manage-
ment of HBV infection that performed on their patients.
CONCLUSION: Prevalence of chronic HBV infection in hemodialysis in Spain
is low, and so are the rates of immunization against HBV. The vaccination
schedules are diverse and have been correlated with the immune response. It
would be necessary to formalize the most effective schedule in increasing immu-
nization in these patients.
Disclosure of Interest: None declared
P0621 REACTIVATION OF HBV INFECTION IN HBSAG NEGATIVE
ONCOHAEMATOLOGICAL PATIENTS TREATED WITH
CHEMOTHERAPY CONTAINING OR NOT RITUXIMAB
S. Camera1,*, M. Picardi2, N. Pugliese2, G. Maria1, A. Vitiello1, M. Raimondo2,
I. Loperto1, C. Nicola1, F. Pane2, F. Morisco1
1
Department of Clinical Medicine and Surgery, Gastroenterology Unit,
2
Department of Clinical Medicine and Surgery, Haematology Unit, University of
Naples "Federico II", Naples, Italy
INTRODUCTION: Routine prophylaxis for hepatitis B reactivation is recom-
mended for oncohaematological HBsAg subjects undergoing immunosuppres-
sive therapy, due the risk of reactivation. In particular, HBV reactivation occurs
more frequent in patients receiving Rituximab. Nonetheless,the incidence in
those receiving Rituximab-free therapy needs to be better investigated
AIMS & METHODS: This study evaluates the effects of chemotherapy with or
without Rituximab in patients HBsAg negative/HBcAb positive with Non-
Hodgkin Lymphoma (NHL) or Hodgkin Lymphoma (HL).
123 patients (21 with NHL and 102 with HL) were consecutively enrolled. We
evaluated HBV markers, treatment schedule and occurrence of HBV reactivation
(reappearance of HBsAg, increase in HBV-DNA at least 1 log in comparison to
basal level with or without increase of aminotransferase levels during therapy and
6 months after the end of therapy).
RESULTS: 46 patients (M/F 24/22, median age 49 yrs, range 21-74 yrs), 33 with
isolated HBcAb and 13 with HBcAb/HBsAb positivity, were observed. Six/46
were treated with therapeutic schedule containing Rituximab. Five/6 received
successfully preemptive therapy with Lamivudine. HBV reactivation was
observed in the only patient (HBcAb/HBsAb positive) treated with R-CHOP
without Lamivudine prophylaxis. None of the other 40 patients treated with
cytotoxic chemotherapy without Rituximab (ABVD-VEBEP) and without
receiving preemptive therapy, showed HBV reactivation.
CONCLUSION: HBV reactivation is mainly related to the type of therapy. Our
data revealed that patients with occult HBV infection receiving chemotherapy
with Rituximab, in absence of prophylactic therapy, may be at high risk of
reactivation. Otherwise, prophylaxis is not mandatory in patients HBcAb posi-
tive with or without HbsAb positivity undergoing Rituximab-free schedule. This
results suggest that preemptive therapy will be tailored to the cytotoxic che-
motherapeutic schedule.
Disclosure of Interest: None declared
A304
P0622 HEPATITIS B SEROLOGIC MARKERS AFTER 14 YEARS OF
UNIVERSAL NEW-BORN VACCINATION
S. Carvalhana1,2, R. Pinto3, J. Leitao4, A.P. Silva5, C. Alves6, M. Bourbon6,
A. Carvalho4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
metabolismo, FML, 3Hospital Prisional de S. Joao de Deus, Caxias, Lisbon,
4
Internal Medicine, CHUC, Coimbra, 5Gastroenterology, CHVNG, Vila Nova de
Gaia, 6INSA, Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: The burden of hepatitis B infection around the world is very
high. In Portugal, hepatitis B vaccination was part of the National Vaccination
Programme, with vaccination of all adolescents, since 1995, extended to all new-
borns in the year 2000. The aim of the present study was to evaluate how it
affected serological markers of hepatitis B in the general population and in high-
risk groups.
AIMS & METHODS: Prevalence of HBs Ag was evaluated in a sample of three
groups: adult general population (GP): 989 individuals, prison population (PP):
784, and drug-users (DU): 18305. Prevalence of HBsAg, HBsAb, HBcAb, and
ALT and AST serum levels were determined in the general population.
RESULTS: Prevalence of HBsAg was GP: 12/989(1.2%); PP: 32/784 (4.1%) and
DU: 927/18305 (5.0%). In the GP, the prevalence of HBsAg negative, HBsAb
positive with HBcAb negative (suggesting effective previous vaccination) was:
315/989 (31.8%), with mean age: 38.8 years. Furthermore two thirds of the
individuals aged less than 30 years had the latter pattern. Prevalence of
HBcAb positive was 107/989 (11%): in 29 (2.9%) cases isolated, and in 75
(7.5%) associating with HBsAb positive, the latter suggesting past infection.
CONCLUSION: Prevalence of HBs Ag was higher in the risk populations,
although no major differences were found. There is evidence of effective vaccina-
tion status in the younger population. Emphasis on continuing universal hepatitis
B programmes is of utmost importance.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0623 IL28B POLYMORPHISM CORRELATES WITH ACTIVE
HEPATITIS IN HBEAG-POSITIVE CHRONIC HEPATITIS B
PATIENTS
Y.K. Jung1,*, S.K. Shin2
1
Internal Medicine, Korea University Ansan Hospital, Gyenggi-do, 2Internal
Medicine, Gachon Gil Hospital, Incheon, Korea, Republic Of
Contact E-mail Address: 93cool@hanmail.net
INTRODUCTION: In recent studies, polymorphisms near the IL28B gene are
strongly associated with spontaneous and treatment-induced viral clearance in
chronic hepatitis C patients. However, the role of IL28B in the prediction of
treatment outcome in chronic hepatitis B (CHB) patients and association with
the natural course of CHB is currently debated. This study aimed to determine
the relationship between IL-28B polymorphisms and hepatitis activity in CHB.
AIMS & METHODS: 190 treatment-na ve CHB patients were identified and
IL28B related SNPs were determined by pyrosequencing method. Active hepa-
titis in patients without liver cirrhosis was defined as persistent ALT 4 2 x upper
limit of normal (ULN) for over 3 months or a peak ALT level 4 5x ULN. In
patients with liver cirrhosis, active hepatitis was defined as persistent ALT4
ULN for over 3 months.
RESULTS: 143 patients were enrolled and 41(38%) had active hepatitis.
rs12979860 CC and rs8099917 TT were 87%. and the two SNPs were found to
be in strong linkage disequilibrium (D 1.0, r2 0.9082). The IL28B SNP
rs12979860 minor allele T and rs8099917 minor allele G were correlated men for 12 (N 208) or 24 weeks (N 172). Key eligibility criteria included:
with active hepatitis in patients with HBeAg positve CHB (p 0.029). On the
contrary, in HBeAg negative CHB there was no relationship between IL28B
SNPs and active hepatitis.
CONCLUSION: We could find that host immune response related to IL28B
polymorphism considering viral factor like genotype plays an important role in
active hepatitis in HBeAg positive CHB patients.
Disclosure of Interest: None declared
P0624 TREATMENT OF HEPATITIS C IN PRISON IN FRANCE IN 2011-
2012: MORE PATIENTS TREATED IN FEWER MEDICAL
JAILHOUSE UNITS: RESULTS OF NATIONAL PRACTICE SURVEY
A.J. Remy1,* on behalf of UCSA DE FRANCE
1
hepatogastroenterology, centre hospitalier, perpignan, France
Contact E-mail Address: andre.remy@ch-perpignan.fr
INTRODUCTION: In France inmates health care was done by public hospitals
since 1994. Access to antiviral treatment was normally equal as people outside.
Treatment of hepatitis C was until 2011 dual therapy (peg-interferon and riba-
virin); in 2011, two direct antiviral agents (AAD), telaprevir INCIVO* and
boceprevir VICTRELIS*, were available in triple therapy. National 2005 study
of practices had demonstrated that at time of dual therapy, only 14 % of inmates
with hepatitis C were treated. Recent national health institute studies (PRI2DE
and PREVACAR) did not allow to answer the question of percentage of inmates
treated for hepatitis C. Did arrival of triple therapy increase or decrease patients
percentage treated in prison?
AIMS & METHODS: Our objective was to study in national survey, in retro-
spective vision (since compassionate use of AAD in January 2011) and prospec-
tive vision over 2011 and 2012, number of patients treated by dual therapy and
triple therapy in MJU. It was postal and/or mail survey.
United European Gastroenterology Journal 2(5S)
RESULTS: On December 31th 2013, 77 MJU over 182 participated and were
already analyzed: they took care of 38998 inmates; hepatitis screening was sys-
tematically proposed in 100 % of MJU; 30290 serology C were annually realized
in 2011 and 31580 in 2012; 2012 rate was 4.5 % positivity (677 patients).
Followed patients were 1579 in 2011 and 1717 in 2012; 49 % of MJU had regular
hepatology consultation (one per month to two per week) and 33 % regular
infectious diseases consultation; to evaluate liver fibrosis 227 FIBROSCAN*
and 511 FIBROTEST / FIBROMETRE were realized in 2012 but only 2 liver
biopsy. In 2011, 301 patients were treated (19 % of patients with serology C
positive) and in 2012, 497 patients (29 %). Triple therapy constituted 12 % of
treatment in 2011 and 39 % in 2012 (telaprevir 80/72 %, boceprevir 20/28 % in
2011/2012); 42 % of the MJU introduced no treatment in 2011 (77 % any triple
therapy) and 56 % in 2012 (66 % any triple therapy).
CONCLUSION: These results allowed following conclusions: 1/ frequent posi-
tive patients VHC in jailhouses, 2/ good screening and diagnosis and using widely
not invasive methods of fibrosis 3/ but very different practices for hepatitis
treatment between few MJU treating a lot of patients and a lot of MJU treating
none. Compared with national study of 2005, percentage of treated patients was
doubled but percentage of MJU involved decreases in 45 %. A score of care of
people infected by hepatitis C will be calculated from answers to items screening,
specialized consultation, treatments 2011 and treatments 2012.
REFERENCES
Coquelicot 2004. Jauffret-Roustide, et al. BMC Infect Dis 2009; 9-113.
Coquelicot 2011. Jauffret-Roustide, et al. BEH 2013; 39-40: 504-509.
Remy, et al. Presse Med 2005; 35: 1249-1254.
Meffre, et al. INVS, http://www.invs.sante.fr/publications/2006/prevalence_b_c/
vhb_france_2004.pdf
Prevacar. http://www.sante.gouv.fr/IMG/pdf/Enquete_PREVACAR_
-_Volet_offre_de_soins_-_VIH_hepatites_et_traitements_de_substitution_en_
milieu_carceral_octobre_2011.pdf
PRI2DE Michel, et al. BEH 39: 409-411.
Disclosure of Interest: A. J. Remy Financial support for research from: ROCHE
JANSSEN, Consultancy for: ROCHE JANSSEN
P0625 SAFETY COMPARISON OF 12- AND 24-WEEK TREATMENTS IN
HCV GENOTYPE 1-INFECTED PATIENTS WITH CIRRHOSIS:
RESULTS FROM TURQUOISE-II
H. Wedemeyer1,*, X. Forns2, A. Craxi3, N. Reau4, P. Kwo5, S. Bourgeois6,
M. Bennett7, S. Ryder8, D. Larrey9, D. Mutimer10, S. Lovell11, M. Abunimeh11,
M. Pedrosa11, R. Trinh11
1
Medizinische Hochschule Hannover, Hannover, Germany, 2Liver Unit, Hospital
Clinic, IDIBAPS, CIBEREHD, Barcelona, Spain, 3A. O. U Policlinico "P.
Giaccone" Dip. Di Gastroenterologia ed Epatologia D. B. M. I. S., Palermo, Italy,
4
University of Chicago Medical Center, Chicago, 5Indiana University, Indianapolis,
United States, 6ZNA Stuivenberg, Antwerpen, Belgium, 7Medical Associates
Research Group, San Diego, United States, 8Nottingham Digestive Diseases Centre
and Biomedical Research Unit, Nottingham, United Kingdom, 9CHU de
Montpellier, Hopital Saint Eloi, Montpellier, France, 10Queen Elizabeth Hospital
and NIHR Liver Biomedical Research Unit, Birmingham, United Kingdom,
11
AbbVie Inc., North Chicago, United States
INTRODUCTION: Interferon-containing protease inhibitor regimens have been
associated with a high rate of serious adverse events (AEs) in patients with
cirrhosis.1 We report the safety of the 3 direct-acting antiviral (3D) regimen of
ABT-450 (identified by AbbVie and Enanta) co-dosed with ritonavir (r), ombi-
tasvir (formerly ABT-267) and dasabuvir (formerly ABT-333) with ribavirin
(RBV) in the treatment of 380 HCV genotype 1-infected patients with cirrhosis.
AIMS & METHODS: Patients were randomized to receive the 3DRBV regi-
Child-Pugh A cirrhosis, platelet count 60.000 cells/mm3, serum albumin 2.8
g/dL, and total bilirubin 53 mg/dL. Treatment-emergent AEs from the time of
study drug administration until 30 days after last dose for all patients who
received 1 dose of study drug are reported.
RESULTS: The percentage of patients experiencing any AE, severe, or serious
AEs were similar in both arms. AEs were mostly mild or moderate in severity.
The most common AEs in the 12- and 24-wk arms respectively, were fatigue
(32.7% vs. 46.5%), headache (27.9% vs. 30.8%), and nausea (17.8% vs.
20.3%). Four (1.1%) patients experienced AEs consistent with hepatic decom-
pensation but were considered unrelated to study drugs. Five of 380 (1.3%)
patients experienced serious AEs that were assessed by the investigator to have
reasonable possibility of being related to the 3D regimen. All patients who mod-
ified RBV dose for any reason, 4 patients who received erythropoietin, and 2
patients who received a transfusion all achieved SVR12.
12-Wk 24-Wk
3DRBV 3DRBV
Treatment-Emergent AEs, n (%) (N 208) (N 172)
Any AE 191 (91.8) 156 (90.7)
Severe AE 14 (6.7) 13 (7.6)
Serious AE 13 (6.3) 8 (4.7)
AE Leading to Study Discontinuation 4 (1.9) 4 (2.3)
AE Leading to RBV Dose Reduction 17 (8.2) 22 (12.8)
Death 0a 0
a
One patient died due to non-treatment emergent AEs that began 80 days after
the last dose of study drug.
United European Gastroenterology Journal 2(5S)
CONCLUSION: The 3DRBV regimens were generally well tolerated, with no
clinically significant differences in safety profiles based on treatment duration.
AEs reported in this study of 380 patients with cirrhosis were generally consistent
with those demonstrated for the 3DRBV regimen in previous studies of patients
without cirrhosis.
REFERENCES
1. Hezode C, Fontaine H, Dorival C, et al. J Hepatol 2013; 59: 434-441.
Disclosure of Interest: H. Wedemeyer Financial support for research from:
Abbott, BMS, MSD, Novartis, Roche, Lecture fee(s) from: Abbott, AbbVie,
Achillion, BMS, Boehringer Ingelheim, Gilead, GSK, ITS, Janssen, Merck,
Novartis, Roche, Roche Diagnostics, Siemens, Transgene, Consultancy for:
Abbott, AbbVie, Achillion, BMS, Boehringer Ingelheim, Gilead, GSK, ITS,
Janssen, Merck, Novartis, Roche, Roche Diagnostics, Siemens, Transgene, X.
Forns Financial support for research from: Roche, MSD, Consultancy for:
Janssen, MSD, Gilead, AbbVie, A. Craxi: None declared, N. Reau: None
declared, P. Kwo Financial support for research from: AbbVie, Anadys,
Bristol Myers Squibb, Conatus, Gilead, Merck, Novartis, Roche, Vertex,
Consultancy for: AbbVie, Bristol Myers Squibb, Gilead, Johnson and
Johnson, Merck, Novartis, Vertex, Other: Gilead, Merck, Vertex, S. Bourgeois
Financial support for research from: Roche, Janssen, MSD, Consultancy for:
Gilead, AbbVie, Janssen, BMS, M. Bennett Shareholder of: AbbVie, S. Ryder
Financial support for research from: AbbVie, Consultancy for: Boehringer
Ingelheim, MSD, Conatus, Gilead, D. Larrey: None declared, D. Mutimer
Consultancy for: AbbVie, Gilead, Janssen, BMS, S. Lovell Shareholder of:
AbbVie, Other: AbbVie, M. Abunimeh Shareholder of: AbbVie, Other:
AbbVie, M. Pedrosa Shareholder of: AbbVie, Other: AbbVie, R. Trinh
Shareholder of: AbbVie, Other: AbbVie
P0626 STUDY ON IL28B SNP RS12979860 AND SNP RS8099917
GENOTYPING AND TREATMENT RESPONSE WITH PEGYLATED
INTERFERON AND RIBAVIRIN IN EGYPTIAN PATIENTS WITH
CHRONIC HEPATITIS C VIRUS INFECTION
M.A. Amin1,*, N. Algarem1, D. Sabri2, E. Qasem3, E. hasan4
1
internal medicine, 2biochemistry, Cairo University, 3internal medicine, 4pathology,
National liver institute, Cairo, Egypt
Contact E-mail Address: monasleman@hotmail.com
INTRODUCTION: Hepatitis C virus (HCV) infection is a common universal
problem especially in the Arab world. A single nucleotide polymorphism near the
IL28B gene on chromosome 19 coding for interferon-lambda-3 is associated with
an approximately 2-fold difference in SVR rates among patients of different
ethnicities.
AIMS & METHODS: The aim was to assess the value of IL28B SNP rs12979860
and SNP rs8099917 as a predictor of virological response to Pegylated interferon
plus ribavirin in treatment of Egyptian patients with chronic hepatitis C virus
infection. Our study included 604 HCV infected Egyptian patients with genotype
4. All patients received pegylated Interferon 2a and 2b plus ribavirin. We divided
our cases according to their response to treatment into two groups: group I (344
patients) responded to treatment and group II (260) non responder patients.
Analysis of both IL28 rs8099917 and IL28rs12979860 by real time PCR techni-
que were done to all patients.
RESULTS: TT genotype of IL28 rs8099917 was associated with a higher
response rate to treatment than other genotypes. TT genotype was present in
53.2% of responders Vs 17.7% of non responders (P50.001) while GG genotype
was present in 6.4% of responders Vs 37.7% of non responders (P50.001). T
allele was present in 73.4% of responders Vs 40 % in non responders while G
allele were present in 26.6% of respnders Vs 60% in non responders (P50.001).
The response rate was lower in patients with T allele compared to those with C
allele of IL28 rs12979860 and CC genotype were present in 47.4% of responders
Vs 5% of non responders and TT genotype were present in 6.1% of responders
Vs 33.1 % of non responders (P50.001). The C allele was present in 70.6% of
responders Vs 36% of non responders while T allele was present in 29.4% of
responders Vs 64% of non responders (P 5 0.001).
CONCLUSION: IL28B polymorphisms are strong predictors of virological
response in chronic hepatitis C with genotype 4 and analysis of IL-28B genotype
might be used to guide treatment for these patients.
Disclosure of Interest: None declared
P0627 IMPACT OF HEPATITIS C VIRUS ON ALLOGRAFT SURVIVAL
AFTER RENAL TRANSPLANTATION
P. Magalhaes-Costa1,*, L. Lebre1, D. Machado2, C. Chagas1
1 4
Gastrenterology, Hospital Egas Moniz - Centro Hospitalar Lisboa Ocidental,
2
Nephrology and Renal Transplantation, Hospital Santa Cruz, Lisboa, Portugal
Contact E-mail Address: pmagalhaescosta@gmail.com
INTRODUCTION: The long-term impact of hepatitis C virus (HCV) infection
on kidney allograft survival remains controversial. Some studies found a signifi-
cant deleterious effect of HCV infection on allograft survival and also higher
mortality in this group of patients.
AIMS & METHODS: In this retrospective, single-center study, we aimed to
compare the differences in kidney allograft survival over a long-term follow-up
period between non-infected vs infected patients. Study population (HCV
infected patients) was selected from a kidney transplant center database (1985 -
2013) and compared to a random sample extracted from the same database.
Groups were compared using Chi-square test, student-T test, Mann-Whitney
U test and survival methods (Kaplan-Meier) when appropriate. Statistical ana-
lyses were carried using SPSS 20.0 IBM@ (Chicago, IL, United States).
RESULTS: We identified 34 patients with HCV infection and the random
sample population was 80 patients. The mean follow-up period, for both
A305
groups, was 132 months (range: 67-290). There was no statistical differences
between groups regarding age, gender, ethnic origin, previous dialytic support
(or kind of dialytic support) or primary kidney disease. HCV infected patients
remained longer on dialysis waiting-time period (median: 60 months; P25/75: 48/
132) and were younger at transplantation timing (3712 y/o). Imunossupressive
regimens using calcineurin inhibitors (75% vs 40%; p 5 0.05) and azathioprine
(44% vs 16%; p5 0.05) were more frequently applied on HCV infected patients.
On the other hand, there was a significant lesser use of tacrolimus (28% vs 55%;
p 5 0.05). Regarding hospitalization (69% vs 65%), septic complications (35%
vs 43%), primary allograft disfunction (31% vs 26%), new-onset diabetes after
transplant (4% vs 13%) or malignancy, there were no significant differences
between groups. A higher frequency of major cardiovascular events was detected
on HCV infected group (32% vs 9%; p 5 0.05). The global rate of allograft loss
was significantly higher among HCV group (50% vs 20%; p 5 0.05). The 1, 5
and 10 year-allograft survival rate in HCV group was 94.1%, 78.1% and 66.9%;
for the sample group: 94.9%, 89.1% and 80.4%. Using a survival model
(Kaplan-Meier), there was no statistical difference (log rank test: p 0.154) in
allograft survival between HCV positive and negative patients. In order to isolate
the effect of HCV on allograft survival we used a Cox regression model, showing
that HCV infection, althought negatively impacted on allograft survival (HR:
1.657; IC95%: 0.817-3.364; p 0.162), that effect had no statistical significance.
CONCLUSION: Our findings suggest that, whilst HCV may play an ominous
effect on allograft survival of renal transplants, its global effect is minor. Hence,
in light of our findings, renal transplantation in HCV infected patients seem to
foretell similar allograft survival as that in general population.
Disclosure of Interest: P. Magalhaes-Costa: None declared, L. Lebre: None
declared, D. Machado: None declared, C. Chagas Lecture fee(s) from: Abbvie
P0628 ASSOCIATIONS OF REACTIVE OXYGEN SPECIES AND IRON
METABOLISMS WITH DEVELOPMENT OF HEPATOCELLULAR
CARCINOMA AFTER PEGYLATED INTERFERON THERAPY IN
JAPANESE PATIENTS WITH CHRONIC HEPATITIS C
S. Nanba1,*, F. Ikeda1, H. Seki1, K. Yamamoto1
1
Department of Gastroenterology and Hepatology, Okayama University Graduate
School of Medicine, Dentistry and Pharmaceutical Sciences, okayama, Japan
INTRODUCTION: Chronic hepatitis C (CHC) may induce reactive oxygen
species (ROS) and excessive iron deposition in the liver.
AIMS & METHODS: The present study was planned to clarify the impact of
surplus ROS and iron deposition on virological response to the therapy with
pegylated interferon plus ribavirin and development of hepatocellular carcinoma
(HCC) thereafter for CHC patients. A total of 210 CHC patients who received
combination therapy of pegylated interferon and ribavirin are enrolled. Liver
histology was evaluated for all the patients before the therapy. Hepatic ROS
was assessed with immunohistochemical staining of 8-hydroxy-2-deoxyguanosine
(8-OHdG). Hepatic iron deposition was assessed by Prussian blue staining.
Factors associated with hepatic 8-OHdG levels were analyzed by stepwise logistic
regression analysis. Proportional hazard models were utilized to identify patient
characteristics associated with HCC development after interferon therapy.
RESULTS: Severe hepatic iron deposition was significantly associated with high
level of 8OHdG in stepwise logistic regression analysis (p 50.0001). Interferon
therapy resulted in sustained virological responses (SVR) in 104 patients. Hepatic
8OHdG was significantly associated with SVR in univariate analysis for the
patients with HCV genotype 1, without statistical significance in multivariate
analysis. Hepatic iron deposition showed no significant associations with SVR
for the patients with HCV genotypes 1 or 2. During the follow-up after interferon
therapy (median period of 4.6 year), HCC development was observed in 14
patients (16%). Heavy alcohol drinking, low platelet counts, non-SVR and
high levels of hepatic 8OHdG had significant associations with HCC develop-
ment (p 0.0276, 0.0102, 0.0067, and 0.0003, respectively).
CONCLUSION: Hepatic 8OHdG level was useful in prediction of HCC devel-
opment after interferon therapy for CHC patients.
Disclosure of Interest: None declared
P0629 HCV AND HBV PREVALENCE IN THE POPULATION: LARGE
DISPARITY BETWEEN HEPATITIS C IN THE GENERAL
POPULATION, COMPARING WITH HIGH RISK GROUPS
S. Carvalhana1,2, R. Pinto3, J. Leitao4, A.P. Silva5, C. Alves6, M. Bourbon6,
A. Carvalho4, H. Cortez-Pinto1,2,*
1
Gastroenterology, Hospital de Santa Maria, CHLN, 2Unidade de nutricao e
metabolismo, FML, 3Hospital prisional de Sao joao de Deus, Caxias, Lisbon,
Internal medicine, CHUC, Coimbra, 5Gastroenterology, CHVNG, Vila Nova de
Gaia, 6INSA, Lisbon, Portugal
Contact E-mail Address: sofiacarvalhana@msn.com
INTRODUCTION: The burden of hepatitis B and C infections around the world
is high. With the upcoming very effective treatments for hepatitis C and the
rather effective treatments for hepatitis B, there is urge to identify these patients
and estimate their prevalence in each country.
AIMS & METHODS: Hepatitis B and C prevalence was evaluated in a sample of
three groups: adult general population (GP): 989 individuals, prison population
(PP): 784, and drug-users (DU): 19832. HBsAg, HBsAb, HBcAb, anti-HCV
(Cobas, Roche), ALT and AST were done. In the general population, anti-
HCV positive individuals were tested for HCV PCR.
RESULTS: Prevalence of Anti-HCV was: GP: 5/989 (0.5%); PP: 147/784
(18.8%) and DU: 11862/19839 (59.8%). Prevalence of HBsAg was GP: 12/
989(1.2%); PP: 32/784 (4.1%) and DU: 927/18305 (5.0%). Interestingly,
among individuals that were anti- HCV positive in the GP, only 20% were
HCV PCR positive. In Portugal, adult GP is estimated about 8 600 000
A306
individuals, PP are about 14 000, and DU are about 30 000. So, according to the
percentages found, it is expected that we have about 69 000 individuals with anti-
HCV, and it is expected that 105 000 are HBs Ag positive. It is possible that the
prevalence of HCV PCR positive individuals is much lower in the general asymp-
tomatic population. Even assuming a 50% prevalence of HCV RNA positive
among anti-HCV positive patients, it would result in about 34 500 individuals
with active infection and potentially needing treatment. Prevalence of elevated
aminotransferases among patients with either hepatitis B or C in the GP was not
different from those with negative markers (17.6% vs. 8.1%, p n.s.).
CONCLUSION: Hepatitis C showed high disparity in prevalence according to
the risk groups, with low prevalence on the general population and very high in
risk groups. Differently, the prevalence of hepatitis B showed a more homoge-
neous pattern of distribution. These results suggest that screening for hepatitis C
in the general population is not cost-effective, but risk groups such as drug-users
or people in prisons should be regularly screened.
Support: Cerega/SPG; Bolsa APEF, Roche Farmaceutica; Gilead Sciences
Disclosure of Interest: None declared
P0630 THE MITOGEN-ACTIVATED PROTEIN KINASE ERK5 IS
INVOLVED IN HEPATOCELLULAR CARCINOMA CELL
PROLIFERATION IN VITRO AND IN VIVO
G. Di Maira1, E. Rovida2,3, N. Navari1, S. Cannito4, P. Dello Sbarba 3,
M. Parola4, F. Marra1,*
1
Dip. Medicina Sperimentale e Clinica, 2University of Florence, Florence, Italy,
3
Dip. Patologia Oncologia Sperimentale, University of Florence, Florence, 4Dip.
Medicina Oncologia Sper. Universita` di Torino, University of Turin, Turin, Italy
Contact E-mail Address: giovanni.dimaira@unifi.it
INTRODUCTION: Despite great progress in the diagnosis and management of
hepatocellular carcinoma (HCC), the molecular mechanisms underlying the
tumor development and progression remain poorly understood, overall limiting
the patients outcome. ERK5 is a member of the MAPK family and has been
implicated in fundamental biologic processes relevant for tumor development.
AIMS & METHODS: The aim of this study is to evaluate the relevance of this
pathway ERK5 in HCC biology.
Huh-7 and HepG2 were cultured by standard methods. ERK5 was silenced by
siRNA transfection or with shRNA and lentiviral vectors. The specific ERK5
inhibitor XMD8-92 was also used. In vivo development of HCC was evaluated
using the Huh-7 xenograft model in athymic nude mice.
RESULTS: In vitro experiments demonstrated that ERK5 silencing or specific
inhibition, using an inhibitor called XMD8-92, causes growth arrest of HCC
cells, affecting in particular the G1/S transition. This phenotype was associated
with an increase in p27Kip protein expression a critical negative regulator of cell
cycle progression typically expressed in G0/G1 arrested cells. Additionaly knock
down of ERK5 activity induces a marked inhibition of c-Rel expression, a
member of NFk family required for the normal proliferative regeneration of
hepatocytes. In a mouse model of HCC xenograft, administration of XMD8-92
significantly decreased tumor volume This reduction is associated with a reduced
proliferation, as observed by Brdu incorporation assay. Moreover XMD8-92-
treated xenografts the expression of c-Jun, a proto-oncogene essential for cell
proliferation, was reduced compared to control samples. Finally as already
observed in vitro, XMD8-92 treatment induced a strong decrease of c-Rel tran-
scription factor expression.
CONCLUSION: This study disclose a strong regulation of cell proliferation in
HCC, affecting the biological activity of different oncogenic targets. Affecting
this pathway could be considered a novel and effective approach for the treat-
ment of HCC.
Disclosure of Interest: None declared
P0631 HEAT SHOCK FACTOR 1 (HSF1) INVOLVEMENT IN TUMOUR
RECURRENCE AFTER RADIOFREQUENCY ABLATION IN AN
ANIMAL MODEL OF SECONDARY LIVER CANCER
F. Zanieri1, V. Carloni1, S. Omenetti1, C. Amabile2, N. Tosoratti2, S. Cassarino2,
S.S. S. Velandy3, M. Kester3, M. Pinzani4, K. Rombouts4,*
1
Department of Experimental and Clinical Medicine and Center of Excellence for
the study at molecular and clinical level of chronic, degenerative and neoplastic
diseases to develop novel therapies DENOthe, University of Florence, Florence, INTRODUCTION: The human ncRNA gene RGM249 regulates the extent of
2
R&D Unit, Hospital Service S.p. A, Aprilia, Italy, 3Department of Pharmacology,
Penn State University College of Medicine, Hershey, United States, 4Division of
Medicine, University College of London, Institute for Liver & Digestive Health,
Royal Free, London, United Kingdom
Contact E-mail Address: k.rombouts@ucl.ac.uk
INTRODUCTION: Heat shock factor 1 (HSF1), is the master regulator of genes
encoding molecular chaperones and is involved in cellular processes such as stress
response, cell differentiation and carcinogenesis. Recent studies identified a
HSF1-regulated transcriptional program specific to high malignancy and distinct
from the classical HSF1-induced heat shock response. We investigated the
expression of HSF1 during tumour formation and after Radiofrequency
Ablation (RFA) in vivo. In vitro experiments were employed to mimic radio-
frequency ablation and to analyse the effect of shRNA-HSF1-nanoliposomes as
a possible adjuvant thermo-sensitizing therapy in combination with radiofre-
quency ablation (RFA) in metastatic liver cancer.
AIMS & METHODS: Colon carcinoma CT26 cells, expressing HSF1, HSP70
and HSP90, were used to assess shRNA-HSF1-nanoliposomal uptake, toxicity/
efficiency by employing immunofluorescence, Q-PCR and protein analysis.
In vitro sub-lethal heat experiments were performed to mimic radiofrequency
ablation, and this by using different time points/temperatures. An orthotopic
murine model of coloncarcinoma cancer - liver metastasis was used to analyse
United European Gastroenterology Journal 2(5S)
HSF1 expression during tumour formation. Radiofrequency ablation (RFA) in
small animals was optimized to investigate the HSF1-induced-and related signal-
ling pathways in the treatment of liver metastasis.
RESULTS: shRNA-HSF1-nanoliposomes were taken up by 99% of cells with-
out inducing cytotoxicity. Sub-lethal heat treatment of 45 and 50 degrees Celsius
induced p-ERK, p-AKT and HSF1-related proteins at different timepoints inves-
tigated and this coincided with a nuclear to cytosolic shift of HSF1, HSP70/90,
AKT and ERK. Apoptosis was only significantly induced after 10 days post-heat
treatment. In vivo, tumours highly expressed HSF1, HSP70/90, AURBK and p-
ERK and p-AKT. Radiofrequency-ablated tumours showed an increase in HSF1
and HSP70/90 protein expression after 6 and 10 days post-RFA, suggesting the
involvement of HSF1 during the process of tumour recurrence.
CONCLUSION: This study demonstrates that HSF1 is highly expressed in CRC
liver metastasis and suggest its possible involvement in tumour recurrence after
employing radiofrequency ablation.
Disclosure of Interest: F. Zanieri: no conflict to declare, V. Carloni: no conflict to
declare, S. Omenetti: no conflict to declare, C. Amabile: no conflict to declare, N.
Tosoratti: no conflict to declare, S. Cassarino: no conflict to declare, S. S. S.
Velandy: no conflict to declare, M. Kester: no conflict to declare, M. Pinzani: no
conflict to declare, K. Rombouts: no conflict to declare
P0632 BASIC FIBROBLAST GROWTH FACTOR MEDIATES ACQUIRED
RESISTANCE TO SORAFENIB IN HEPATOMA CELLS
M. Osawa1,*, Y. Matsuda2, T. Wakai3, M. Kubota1
1
Division of Pediatric Surgery, Niigata University Graduate School of Medical and
Dental Sciences, 2Department of Medical Technology, Niigata University Graduate
School of Health Sciences, 3Division of Digestive and General Surgery, Niigata
University Graduate School of Medical and Dental Sciences, Niigata, Japan
Contact E-mail Address: mamix.3211@gmail.com
INTRODUCTION: Sorafenib is a multikinase inhibitor used to treat patients
with hepatocellular carcinoma (HCC). The main obstacle to efficient cancer
treatment with this agent is the acquired drug resistance that develops in many
patients. We aimed to determine whether sorafenib-treated hepatoma cells
release soluble factors that cause sorafenib resistance.
AIMS & METHODS: HepG2 cells were incubated with sorafenib for 24 hours.
The culture medium was rinsed, the cells were maintained for 24 more hours, and
cytokines released into the medium were analysed by enzyme-linked immunosor-
bent assay. The culture medium was transferred to the newly seeded HepG2 cells,
which were then maintained with a different concentration of sorafenib for 2 to
48 hours. Cell growth and apoptosis in sorafenib-treated cells were analysed by
MTT and annexin V assay. Cell signalling was analysed by western blotting.
RESULTS: The level of basic fibroblast growth factor (FGF-2) in the culture
medium of sorafenib-treated cells was increased to 1.8-fold that of the controls
(14.3 vs. 7.7 pg/mL, respectively; p 5 0.05), while other growth factors such as
transforming growth factor beta and insulin growth factor were unchanged.
When the cells were maintained in the culture medium of sorafenib-treated
cells, the cell numbers were increased by 1.35-fold (p 5 0.05), and the levels of
phosphorylated Akt, extracellular signal-regulated kinases 1/2, and nuclear
factor kappa B were increased by 2.5- to 4.0-fold. The annexin V assay
showed that the effect of sorafenib on cell apoptosis was inhibited in the cells
maintained in the medium of sorafenib-treated cells (apoptotic rates after sora-
fenib treatment in control cells vs. cells maintained in the medium of sorafenib-
treated cells: 76.5% vs. 17.7%, respectively; p 5 0.05), which was rescued by
pretreatment with the FGF receptor inhibitor PD173074.
CONCLUSION: FGF-2 might be an essential mediator of acquired resistance to
sorafenib. Combination treatment with sorafenib and FGF-2 inhibitor may be
effectively used to treat patients with HCC in the future.
Disclosure of Interest: None declared
P0633 HEPATOMA CELLS CAN BE REVERTED TO ORIGINAL
NORMAL CELLS BY SINGLE SMALL RNA
N. Miura1,*, S. Tsuno1, J. Hasegawa1
1
Pharmacotherapeutics, TOTTORI UNIV., Yonago, Japan
Contact E-mail Address: mnmiura@med.tottori-u.ac.jp
differentiation of undifferentiated cancer cells. Because shRNA for RGM249
induced the upregulation of hsa-miR-520d that converted 293FT cells to
hiPSCs, we attempted to perform the functional analysis to examine the anti-
cancer effects of it on an undifferentiated hepatoma cell.
AIMS & METHODS: To identify the crucial factors underlying this process, we
investigated the effects of lentivirally inducing miR-520d expression in HLF cells
(520d-HLF) in vitro. To clarify the underlying mechanism, we performed gene
expression analysis, cell cycle analysis, cell sorting, metabolomic analysis, migra-
tion assay and DNA methylation assay in transfectants. Subsequently, we eval-
uated tumor formation in a xenograft model using 520d-HLF.
RESULTS: 520d-HLF cells or the cells sorted by both alkaline phosphatase and
GFP were Oct4 and Nanog positive within 24 h, showed p53 upregulation and
hTERT downregulation, and mostly lost their migration abilities. Cell cycle
analysis revealed homogeneous growth and metabolomic analysis showed that
the TCA cycle was not elevated. Methylation level in transfectants decreased to
the similar level to that in hiPSC. After lentiviral infection, the cells were intra-
peritoneally injected into mice, resulting in benign teratomas (6%), the absence of
tumors (87%) or differentiation into benign liver tissues (7%) at the injection site
after 1 month.
CONCLUSION: We are the first to demonstrate the loss of malignant properties
in cancer cells in vivo through the expression of a single microRNA (miRNA).
This miRNA successfully converted 293FT and hepatoma cells to hiPSC-like
United European Gastroenterology Journal 2(5S)
cells partly or mainly via both stemness- and demethylation-mediated process.
The regulation of malignancy by miR-520d appears to be through the conversion
of cancer cells to normal stem cells, maintaining p53 upregulation.
Disclosure of Interest: None declared
P0634 MATRINE INDUCED MITOCHONDRIAL-DEPENDENT
APOPTOSIS AND AUTOPHAGY IN HEPATOMA CELLS
S. Yao1,* on behalf of Li Wang, Chun Gao
1
Department of Gastroenterology, China-Japan Friendship Hospital, Beijing,
China
Contact E-mail Address: shukyao@126.com
INTRODUCTION: Matrine is an active component monomer that is extracted
from Sophora flavescens. Our previous study found that matrine could induce
cell apoptosis, and dramatically increase the generation of autophagosomes in
hepatocellular carcinoma cell lines. Autophagy, a self-defense mechanism, has
been found to be associated with drug resistance in hepatocellular carcinoma
(HCC) therapy. However, the effect and exact mechanisms of matrine-induced
autophagy and apoptosis in therapy of HCC are still not very clear.
AIMS & METHODS: Our study was aimed to investigate the role and related
mechanisms of matrine-induced apoptosis and autophagy in hepatoma cells
HepG2 and Bel7402.
Cell apoptosis was detected by flow cytometry analysis (Annexin VFITC/PI
double-staining assay), JC-1 probe, the activity and activating cleavages of cas-
pase-3, -8, and -9. MTT assay and colony forming assay were used to assess the
effect of matrine on viability and proliferation of HCC cells. Autophagic flux in
HCC cells was analyzed using the expression of LC3BI/II and p62/SQSTM1,
GFP-LC3 transfection and LysoTracker staining, and transmission electron
microscopy. Moreover, regarding to the associated mechanisms, Genechip tech-
nique was used to find matrine-induced autophagic related gene.
RESULTS: 1. Matrine at different concentrations could inhibit the viability and
proliferation of HepG2 and Bel7402 cells, and induce apoptosis in a concentra-
tion-dependent manner (p50.05).
2. Matrine could induce the decrease of mitochondrial membrane potential
(MMP) and up-regulation of cytochrome-c expression. After treated with
matrine, the expression of pro-caspase decreased and the cleaved caspase-8,-9,-
3 increased.
3. The turnover of LC3BI/IIratio, the increasing number of GFP-LC3 positive
cells (P50.05) and the formation of phagophores, autophagosomes, autolyso-
somes observed by transmission electron microscopy, implied that autophagy
was induced in matrine-treated HCC cells.
4. Genechip results showed that the level of lamp-1 elevated at 7.4 times. The
result was further proved by the detection of Realtime PCR and western blot.
Immunofluorescence results showed that Lamp-1 colocalized with lysosomes in
HepG2 cells, and localized at the autolysosomes after autophagy was induced.
CONCLUSION: 1. Matrine has the inhibitory effect of HCC celllines HepG2
and Bel7402,and could induce apoptotic cell death via mitochondrial mediated
caspase dependent way.
2. Matrine could induce autophagy in HepG2 and Bel7402 cells, and lamp-1 is
related to the formation of autolysosomes, and possibly involved in matrine-
induced autophagy.
Disclosure of Interest: None declared
P0635 EXPRESSION OF FERRITIN LIGHT CHAIN IN HEPATIC OVAL
CELLS IS A USEFUL BIOMARKER OF HEPATOCELLULAR
CARCINOMA DEVELOPMENT
Y. Matsuda1,*, M. Osawa2, T. Wakai3, M. Kubota2
1
Department of Medical Technology, Niigata University Graduate School of
Health Sciences, 2Divisions of Pediatric Surgery, 3Digestive and General Surgery,
Niigata University Graduate School of Medical and Dental Sciences, Niigata,
Japan
Contact E-mail Address: yasunobu@med.niigata-u.ac.jp
INTRODUCTION: Hepatic oval cells are unique bipotential progenitor cells
that differentiate into both bile duct cells and hepatocytes. Although it has
been widely recognised that oval cell-derived hepatocytes are possible progenitors
of hepatocellular carcinoma (HCC), the functional properties of these cells are
unclear.
AIMS & METHODS: To investigate the protein expression profile in oval cell-
derived hepatocytes, we compared proteomes from lysates from normal hepato-
cytes and oval cell-derived hepatocytes using two-dimensional (2D) gel sodium
dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and matrix-
assisted laser desorption ionization time-of-flight tandem mass spectrometry
(MALDI-TOF/TOF MS). Hepatocytes were isolated from normal rat livers by
the collagenase perfusion method, while oval cell-derived hepatocytes were
obtained from cultured rat oval WB-F344 cells or rat littermates treated with
2-acetamidofluorene plus partial hepatectomy. To verify the results of 2D SDS-
PAGE, the protein expression levels of ferritin light chain (FLC) in human liver
tissue samples (33 patients without HCC and 28 with HCC) were examined by
western blotting and immunohistochemical analysis.
RESULTS: Two-dimensional SDS-PAGE showed 11 major protein spots that
changed in abundance between normal hepatocytes and oval cell-derived hepa-
tocytes. Three of these differently expressed protein spots were analysed by
MALDI-TOF/TOF MS. The level of FLC expression was significantly higher
in oval cell-derived hepatocytes (7- to 10-fold, p 5 0.05). Western blotting of
human liver tissue samples showed that the levels of FLC expression were 4- to 8-
fold higher in patients with than without HCC. Immunohistochemical analysis
showed that hepatocellular FLC was strongly expressed in 21 of 28 patients with
A307
HCC, while strong expression of FLC was detected in 12 of 33 patients without
HCC (p 5 0.05).
CONCLUSION: Several proteins, including FLC, are distinctly overexpressed in
oval cell-derived hepatocytes. FLC expression is increased in human liver tissues
adjacent to HCC, indicating that FLC might be a useful biomarker for identifi-
cation of the development of HCC.
Disclosure of Interest: None declared
P0636 RNA BINDING PROTEIN NOVA1 PROMOTES TUMOR
GROWTH IN VIVO AND ITS POTENTIAL MECHANISM AS AN
ONCOGENE MAY DUE TO ITS INTERACTION WITH GABAAR2
Y. Zhang1,*, T. Liu1, X. Shen1
1
Gastroenterology, Zhongshan Hospital affiliated to Fudan University, Shanghai,
China
Contact E-mail Address: zyian2020@gmail.com
INTRODUCTION: Our previous study discovered the expression of Nova1 in
hepatocellular carcinoma and proved that high expression of Nova1 is associated
with poor prognosis of HCC. Recent research proved that Nova1 regulates the
alternative splicing of GABAA receptor 2(GABAAR2) pre-mRNA in central
nervous system. Moreover, the theory that the GABAergic system is involved in
HCC progression has also been illustrated before. However, the expression of
GABAAR2 and its relations with Nova1 in hepatocellular carcinoma remain
elusive.
AIMS & METHODS: The aim of this study is to explore the potential mechan-
ism of Nova1 as an oncogene for HCC. To make clear the existence of interac-
tions between Nova1 and GABAAR2 in HCC and their relations with
tumorigenesis. Immunohistochemical staining were used to identify the protein
expression level of GABAAR2 in HCC and its paired non-tumor tissue. Its
relations with clinicopathologic features were calculated. The HCC tumor xeno-
grafts animal models were established. The tumor size was estimated and then
removed for western blot analysis. For double immunofluorescence staining, the
slides were incubated with DyLight 448 Affinipure Rabbit Anti-Goat IgG and
DyLight 594 Affinipure Goat Anti-Rabbit IgG and analyzed via the microscope.
The cell-lysated proteins were precleared with 2 g anti-Nova1 or anti-GABA
AR2 antibodies and then incubated with protein G-agarose and antibodies. The
precipitates were analyzed by western blotting.
RESULTS: The expression level of GABAAR2 positive cell in the cancerous
tissue was lower than para-cancerous tissues. Univariate analysis and multivari-
ate Cox analysis showed that intratumoral Nova1 was significantly associated
with OS and TTR. Patients with higher intratumoral GABAAR2 had longer OS
rate and TTR time. In vivo test, our results showed that, the volume of the
xenotrans in the over-expression group surpassed that in the control group,
and the volume of the xenotrans in the knockdown group far smaller than its
control group. Immunohistochemical staining and Western blot showed down-
regulation of Nova1 accompanied with increased expression of GABAAR2 and
GABA. Up-regulation of Nova1 resulted decreased expression of GABAAR2
and GABA. Furthermore, the localizations of GABA and GABAAR2 were
visualized under microscopy. The SMMC-7721 cells expressing the GABA and
GABAAR2 protein exhibited fluorenscence concentrated in the cytoplasm, and
also in the nucleus. Co-localization of Nova1 and GABAAR2 proteins in the
cytoplasm was evidenced by overlapping fluorescence signals in Huh7 cell. Co-IP
results showed that Nova1 was easily detected through anti-Nova1 antibody in
the GABAAR2-immunoprecipitates. Reciprocal co-IP experiments using anti-
Nova1 antibody indicated the existence of GABAAR2, as confirmed by
immunoblotting.
CONCLUSION: Nova1 not only interacts with GABAAR2 in CNS but also in
the peripheral HCC tumor tissue. It is hypothesized that ectopic expression of
Nova1 may down regulate the expression of GABAAR2, and decrease the
influx of cl- and tumor cells membrane potential diffences, thus leading to the
proliferation of HCC.
Disclosure of Interest: None declared
P0637 EPIGENETIC SILENCING OF THE TUMOR SUPPRESSOR
MICRORNA-122 DURING HEPATOCARCINOGENESIS FROM
NONALCOHOLIC STEATOHEPATITIS
Y. Saito1,*, Y. Takaki1, K. Toshimitsu1, T. Muramatsu1, M. Kimura1,
H. Suzuki2, K. Sugiyama2, T. Kanai2, H. Saito1
1
Division of Pharmacotherapeutics, Keio University Faculty of Pharmacy,
2
Division of Gastroenterology, Keio University School of Medicine, Tokyo, Japan
INTRODUCTION: Nonalcoholic steatohepatitis (NASH) has emerged as a
common cause of chronic liver disease and virus-independent hepatocellular
carcinoma (HCC) in patients with obesity, diabetes and metabolic syndrome.
However, little is known about the pathogenesis of HCC derived from NASH.
AIMS & METHODS: To reveal the molecular mechanism underlying hepato-
carcinogenesis from NASH, microRNA (miRNA) expression profiles were ana-
lyzed. HCCs and non-tumor liver tissues from STAM mice, an animal model
developing HCC from NASH, and tissue specimens obtained from primary HCC
patients were used in this study. MiRNA expression profiles were analyzed by
microarray and quantitative RT-PCR. To investigate the regulatory mechanism
of miRNAs, DNA methylation assay and chromatin immunoprecipitation
(ChIP) assay were performed in liver cancer cells treated with the DNA methyla-
tion inhibitor 5-aza-2-deoxycytidine (5-Aza-CdR).
RESULTS: Histopathological images of the liver in STAM mice at the ages of 6,
8, 12, 18 weeks showed findings compatible with fatty liver, NASH, liver cirrho-
sis (LC), and HCC, respectively. MiR-122 expression in non-tumor LC at the age
of 18 weeks was significantly lower than that in LC at the age of 12 weeks. MiR-
122 expression was further decreased in HCCs compared with non-tumor LC at
A308
the age of 18 weeks. MiR-122 expression was also decreased in clinical HCC
samples. Treatment of liver cancer cells with 5-Aza-CdR reactivated miR-122
expression with decreased cell proliferation and down-regulation of its target,
CyclinG1. The results of ChIP assay indicated that 5-Aza-CdR activated miR-
122 expression by enhancing binding of peroxisome proliferator activated recep-
tor-gamma (PPAR-) to the miR-122 promoter region.
CONCLUSION: These findings indicate that epigenetic silencing of the tumor
suppressor miR-122 plays a critical role during hepatocarcinogenesis from
NASH. DNA methylation inhibitors such as 5-Aza-CdR may have clinical pro-
mise for the prevention and treatment of HCC derived from NASH.
Disclosure of Interest: None declared
P0639 PLASMA CYCLASE-ASSOCIATED PROTEIN 2 IS A NOVEL
BIOMARKER IN EARLY STAGE AND ALPHA-FETOPROTEIN
NEGATIVE HEPATOCELLULAR CARCINOMA PATIENTS
M. Chen1, Y. Yang1,*
1
Department of Gastroenterology and Hepatology, Peoples Hospital of Zhengzhou
University, Zhengzhou, China
INTRODUCTION: Hepatocellular carcinoma (HCC) is the third leading cause
of cancer related deaths worldwide, early detection of HCC is critical to monitor
disease progression, selection of therapeutic options and post-surgery surveil-
lance. Alpha-fetoprotein (AFP) is traditionally an indispensible marker for the
diagnosis of HCC, since 33.3% of small HCC patients are AFP negative, it is
crucial to discover new sensitive marker to compensate the negative AFP in HCC
diagnosis and surveillance. Cyclase-associated protein 2 (CAP2) has recently
been proposed to be a candidate biomarker for detection of early HCC.
AIMS & METHODS: We aim to evaluate the sensitivity and specificity of CAP2
as a biomarker for HCC patients with special attention to those at early stage and
AFP negative. The CAP2 and AFP plasma levels were analyzed by enzyme-
linked-immunosorbent assay in 86 HCC, 59 cirrhotic patients, and 30 normal
individuals.
RESULTS: The results showed that both CAP2 and AFP plasma levels in HCC
patients were significantly elevated when compared to cirrhosis. CAP2 level
correlates well with HCC patients histological grade, clinical stage and tumor
size; but not with patients age, gender, hepatitis B virus infection status and
plasma AFP level. CAP2 had better sensitivity (82.6%) as compared to AFP
(59.3%) alone for general HCC patients, and in early stage of HCC patients
(78.6% vs 40.4%). In addition, CAP2 is able to complementary to AFP to
predict 82.9% of HCC in AFP negative patients.
CONCLUSION: We concluded that CAP2 is a promising biomarker for the
prediction of HCC in both AFP negative and early stages of HCC patients.
Disclosure of Interest: None declared
P0640 USEFULNESS OF CONTRAST-ENHANCED SONOGRAPHY
(CEUS) IN THE SURVIVAL OF PATIENTS WITH
HEPATOCELLULAR CARCINOMA (HCCC) SUBMITTED TO NON-
SURGICAL TREATMENTS
F. Giangregorio1,*, R. Solimando1, G. Prati1, G. Marinone1, M.D. Stasi1,
G. Comparato1, G. Aragona1, F. Fornari1
1
Gastroenterology Unit, Guglielmo da Saliceto Hospital, Piacenza, Italy, Piacenza,
Italy
Contact E-mail Address: f.giangregorio@alice.it
INTRODUCTION: CEUS is an ultrasound technique with a good diagnostic
agreement with spiral CT in the evaluation of efficacy of non-surgical treatments
of HCC. The early evaluation of these treatments with CEUS may allow to
obtain a more complete necrosis of the tumoural nodules.
AIMS & METHODS: We evaluated if CEUS is able to affect the outcome of
these patients. 181 cirrhotic with HCC (M/F:112/69; mean age 71 yrs; Child A/B:
151/30), treated from 1/1999 to 12/2012 with non-surgical treatments for unre-
sectable lesions: 116 with RFTA; 44 with combined treatment of RFTA and
TACE and 21 with PEI; solitary nodule:132 pts; 2-3 hcc:32; multinodular
HCC:17 cases. All patients underwent to spiral CT one month after the proce-
dure; the first 66 patients (treated before January 2002), didnt perform CEUS,
(group-A); 115 patients were submitted to CEUS (after January 2002) 24 hours
after the treatments (group-B). We correlated the following variables with the
survival (S) and the disease-free-survival (DFS): number and diameter of HCCs;
AFP values; type of treatment; aetiology and class of Child; the early evaluation
of the treatment with CEUS. Statistics was performed with chi-square and
Kaplan-Meyer curves (SPSS release-18)
RESULTS: Mean follow-up of 181 pts: 52 months (group-A: 41,4; group-B:
60,2). During the follow-up 52/66(78,8%) pts in group-A and 49/115(42,6%)
pts in group-B died. Recurrence was found: group-A:45/56(80.3%) pts, group-
B:73/115 (63.47%) pts. The patterns of recurrence were: new lesions away from
the treated nodules: group-A: 23 cases; group-B: 47 cases; local tumour regrowth:
group-A: 22 pts; group-B:26 pts. At multivariate analysis the number and dia-
meter of the nodules, sex, and type of the treatment werent statistically corre-
lated with S and DFS. Value of AFP and Child class were correlated with S
(S:p 0.001), the early evaluation of the efficacy of the treatment with CEUS and
the association CEUS-AFP were statistically correlated (CEUS: DFS:
p 0.042);(CEUS and AFP: DFS: p 0.036)
CONCLUSION: The early evaluation of the efficacy of the non-surgical treat-
ments of HCC with CEUS lets to obtain a more complete necrosis of the tumour
and to reduce the recurrence for local regrowth of the HCC achieving a higher
percentage of disease-free survival
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0641 CUMULATIVE OPERATOR VOLUME IN RELATION TO TUMOR
RECURRENCE AFTER RADIOFREQUENCY ABLATION FOR
HEPATOCELLULAR CARCINOMA
J.-T. Lin1,*, T.-Y. Lee2, C.-Y. Wu2, H.J. Ho1, M.-S. Wu3
1
School of Medicine, Fu Jen Catholic University, New Taipei City, 2Division of
Gastroenterology, Taichung Veterans General Hospital, Taichung, 3School of
Medicine, National Taiwan University, Taipei, Taiwan, Province of China
Contact E-mail Address: dr.taiwan@yahoo.com.tw
INTRODUCTION: Radiofrequency ablation (RFA) is the main minimal-inva-
sive curative therapy for hepatocellular carcinoma (HCC). However, the recur-
rence rate remains unsatisfactory.
AIMS & METHODS: We aim to investigate the role of cumulative operator
volume on HCC recurrence after RFA. We conducted a retrospective cohort
study based on Taiwans National Health Institute Research Database
(NHIRD). We identified 52,096 patients with newly diagnosed HCC between
2004 and 2011. Among them, 5,890 received radiofrequency ablation (RFA) as
their first therapy for HCC. Patients were categorized into five quintiles accord-
ing the physicians experience (RFA volume). Patients in the lowest and highest
RFA volume quintiles were 1:1 matched by propensity score. Cumulative inci-
dences of HCC recurrence was analyzed.
RESULTS: Patients in the highest RFA volume quintile had significantly lower
5-year HCC recurrence cumulative incidence (65.8%; 95% CI: 59.5-72.1%) com-
pared to the risk for lowest RFA volume quintile (71.4%; 95% CI: 66.2-76.5%)
(P50.05). On multivariate analyses, the highest RFA volume was an indepen-
dent protective factor for HCC recurrence (HR 0.80; 95% CI: 0.67-0.97).
Multivarate stratified analyses confirmed the association between higher RFA
volume and lower HCC recurrence risk in nearly all subgroups.
CONCLUSION: More RFA experience was associated with reduced risk of
HCC recurrence.
Disclosure of Interest: None declared
P0642 INCIDENTAL HEPATOCELLULAR CARCINOMA: RISK
FACTORS AND LONG-TERM OUTCOME AFTER LIVER
TRANSPLANTATION
R. Senkerikova1, S. Frankova1, J. Sperl1, M. Oliverius2, E. Kieslichova3,
H. Filipova4, D. Kautznerova4, E. Honsova5, P. Trunecka6, J. Spicak1,*
1
Department of Hepatogastroenterology, 2Department of Transplant Surgery,
3
Department of Anesthesiology and Resuscitation, 4Department of Radiodiagnostic
and Interventional Radiology, 5Department of Clinical and Transplant Pathology,
6
Transplantacentre, Institute for Clinical and Experimental Medicine, Prague,
Czech Republic
Contact E-mail Address: renata.senkerikova@ikem.cz
INTRODUCTION: Orthotopic liver transplantation (OLT) currently represents
the treatment of choice for early hepatocellular carcinoma (HCC). Preoperatively
known HCC (pkHCC) is diagnosed via imaging methods prior to OLT or HCC,
denoted as incidental HCC (iHCC), is found postoperatively in the liver explant.
AIMS & METHODS: The aim of our study was a comprehensive analysis of
post-transplant survival of patients with iHCC and identification of risk factors
of iHCC occurrence in cirrhotic liver.
We retrospectively reviewed 33 adult cirrhotic patients with incidentally found
HCC comparing them with 606 tumor-free adult cirrhotic patients with end-stage
liver disease (group Ci) who underwent OLT in our center between January 1995
and August 2012. Within the same period, a total of 84 patients were trans-
planted for pkHCC. We compared post-transplant survival of iHCC, Ci group
and pkHCC patients. In the group of cirrhotic patients (Ci iHCC) we searched
for risk factors of iHCC occurrence.
RESULTS: There was no difference in sex, MELD score and time spent on the
waiting list in either group.
In the multivariate analysis we identified the age457 years (OR 3.37, 95% con-
fidence interval (CI) 1.75-8.14, P5.001), HCV or alcoholic liver disease (ALD)
(OR 3.89, 95% CI 1.42-10.7, P5.001) and alpha-fetoprotein (AFP) level46.4
mg/l (OR 6.65, 95% CI 2.82-15.7, p .002) to be independent predictors of iHCC
occurrence. Either 1-, 3- and 5-year overall survival (OS) or 1-, 3- and 5-year
recurrence-free survival (RFS) differed in iHCC patients compared with Ci group
(iHCC: OS 79%, 72% and 68%, respectively; RFS 79%, 72% and 63%, respec-
tively, vs. Ci group: OS RFS 93%, 94% and 87%, respectively; P5.001).
CONCLUSION: We conclude that the survival of iHCC patients is worse than in
tumor-free cirrhotic patients, but comparable with survival of pkHCC patients.
Independent risk factors for iHCC occurrence in cirrhotic liver are age, HCV or
ALD etiology of liver cirrhosis and AFP level.
Disclosure of Interest: None declared
P0643 SINGLE-STEP BALLOON-OCCLUDED PERCUTANEOUS
RADIO-FREQUENCY THERMAL ABLATION (RFA) PLUS
TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE)
FOR TREATMENT OF COMPLEX UNRESECTABLE
HEPATOCELLULAR CARCINOMA
M. Campanale1,*, C. Valentina2, F. Barbaro2, T.A. Di Rienzo2, M.L. Torre2,
A. Guerra2, S. Pecere2, G. Gigante2, R. Emanuele2, G. Caracciolo2,
F.R. Ponziani2, M. Siciliano2, B.E. Annicchiarico2, M.A. Zocco2, L. Riccardi2,
M. Pompili2, G.L. Rapaccini2, A. Grieco2, A.M. De Gaetano2, G.B. Gasbarrini3,
R. Iezzi2, L. Bonomo2, A. Gasbarrini2 on behalf of Hepatocatt Study Group
1
Internal Medicine and Gastroenterology, CATHOLIC UNIVERSITY OF
ROME, 2CATHOLIC UNIVERSITY, ROME, 3Fondazione Ricerca in Medicina
United European Gastroenterology Journal 2(5S)
"Falcone e Borsellino", BOLOGNA, Italy
Contact E-mail Address: chiaracampanale@hotmail.com
INTRODUCTION: To evaluate the feasibility, safety and efficacy of single-step
balloon-occluded-RFA followed by TACE in patients with complex unresect-
able HCC, previously not suitable to RFA alone due to their localization.
AIMS & METHODS: 63 consecutive patients with at least one HCC lesion
(mean diameter 4.351.8cm), adjacent to the diaphragm (25 lesions), proximal
to the hepatic veins (17), portal vein (19), glissons capsule (34), cholecistis (6)
and/or located on the intra-abdominal free surface (5), considered as complex
for their unfavourable location, and not suitable for RFA alone, were enrolled in
our single-center multidisciplinary pilot study. The treatment was composed of
RFA (single 2-cm or 3-cm monopolar needle insertion) during occlusion of the
feeding artery followed by superselective TACE (conventional-TACE or with
DC-BEAD). Adverse events and intra/periprocedural complications were clini-
cally assessed. Tumor response was evaluated on 1-month, 6 months and 1 year
follow-up multiphasic CT based on mRECIST criteria.
RESULTS: Technical success was achievied in all patients. 7 patients (11.2%)
experienced intra and periprocedural complications, such as fistuale (2), bleeding
(3), cholecistitis (1) and ascites (1), that resolved spontaneously. A mean total
treated diameter (necrotic diameter plus circonferential peripheral lipiodol
uptake for conventional TACE; mean necrotic diameter for TACE with DC-
Bead) of 4.962.37 was obtained. Based on mRECIST criteria, on 1- and 3-
months follow up CT, a tumor response was obtained in all patients, with a
complete response achieved in 31 out of 63 patients (49.2%), a partial response
in 38.1% (24 patients: residual tumor 5 30% in 14 patients, 430%4550% in 6
patients, 450% in 4 patients), and no response in 3 patients, without any pro-
gressive disease. 5 patients were lost to follow up. 18 out of 27 patients (66.6%)
that underwent a CT-scan on 6-months follow up maintained a complete
response.
CONCLUSION: Balloon-occluded-RFA plus TACE seems to be a safe and
effective therapy for the treatment of complex HCC, allowing to obtain a
high complete local response rate, without complications, also in patients not
suitable to RFA alone.
Disclosure of Interest: None declared
P0644 COMPARISON OF CLINICAL PRESENTATIONS AND
OUTCOME OF HEPATOCELLULAR CARCINOMA BETWEEN
HEPATITIS C AND NONALCOHOLIC FATTY LIVER CIRRHOSIS: A
SINGLE CENTRE EXPERIENCE
N.N. Than1,*, N. Tehami1, J. Hodson2, C. Coldham3, S. Shetty 3, P. Newsome3
1
Liver unit, 2University Hospital Birmingham NHS Trust, Birmingham, UK,
3
Centre for Liver Research and NIHR BRU, University of Birmingham,
Birmingham, United Kingdom
Contact E-mail Address: sophiathan@ymail.com
INTRODUCTION: Hepatocellular carcinoma (HCC) is the most common pri-
mary liver tumor, and represents the third leading cause of cancer death world-
wide [1, 2]. Chronic hepatitis C cirrhosis is one of the leading risk factors for
HCC but increasing cases are seen in nonalcoholic fatty liver disease (NAFLD).
AIMS & METHODS: The aim of the study was to compare demographics,
treatments and survival among hepatitis C virus (HCV/HCC) and NAFLD
(NAFLD/HCC) cohort of patients. Data were collected from medical electronic
case notes, imaging reports and reports from HCC multidisciplinary meetings.
RESULTS: Among 289 patients, 210 patients (73%) had underlying HCV/HCC
and 79 patients (27%) had NAFLD/HCC. The median age at diagnosis was
significantly higher in NAFLD/HCC patient cohorts (p50.001). The majority
(more than 80%) were male. Body mass index (BMI) was significantly higher in
NAFLD/HCC than HCV/HCC (p50.001). The majority of the patients in
NAFLD. HCC were Caucasian (96%), whilst the HCV/HCC cohort was signif-
icantly more ethnically diverse (p50.001). Diabetes mellitus was more common
in NAFLD/HCC patients (p50.001). The median alpha fetoprotein level in
HCV/HCC patients were 33.0 compared to 14.1 in NAFLD/HCC although it
did not reach the statistical significance (p 0.100). The size of HCC and the
numbers of HCC were similar between the two groups. Majority of patients in
HCV/HCC and NAFLD/HCC were Barcelona stage A (51% vs 48%) and stage
B (28% vs 39%). Treatment modalities such as radiofrequency ablation (RFA),
trans arterial chemoembolization (TACE) or sorafenib used in both groups of
patients were similar. Overall survival between the two groups did not differ
significantly (p 0.122), however we have found that HCV/HCC patients were
more likely to be transplanted (p 0.003).
Among 298 patients, 61 patients (29%) from HCV/HCC cohort and 11 patients
(14%) from NAFLD/HCC were transplanted. The only significance factors were
BMI (p 0.013) and presence of underlying diabetes mellitus (p 0.002) which
were more common in NAFLD/HCC patients. 15% were treated with RFA and
18% received TACE therapy prior to liver transplantation (LT) in HCV/HCC
compared to 18% and 9% in NAFLD/HCC respectively. Tacrolimus and
Mycophenolate Mofetil were two most common immunosuppression regimes
used post LT. Post transplant survival appeared to be slightly worsen in HCV/
HCC patients compared to NAFLD/HCC, although it did not reach statistical
significance (p 0.113). Post LT freedom from recurrence of HCC among the
two cohort was similar (p 0.848).
CONCLUSION: Despite the NAFLD/HCC being older and with higher meta-
bolic risk factors, a significant proportion could undergo active therapy.
Furthermore, patients with NAFLD/HCC selected for transplantation seemed
to have better long term outcomes, possibly due to stricter selection for trans-
plantation as well as variations in tumor biology between the two groups.
REFERENCES
1. Mittal S and El-Serag HB. Epidemiology of hepatocellular carcinoma: con-
sider the population. J Clin Gastroenterol 2013; 47(Suppl.): S2-S6.
A309
2. Lu T, et al. Prevention of hepatocellular carcinoma in chronic viral hepatitis B
and C infection. World J Gastroenterol 2013; 19: 8887-8894.
Disclosure of Interest: None declared
P0645 HIGH ALPHA-FETOPROTEIN LEVELS AND PRESENCE OF
CLINICALLY SIGNIFICANT PORTAL HYPERTENSION CAN
PREDICT THE OCCURRENCE OF HEPATOCELULLAR
CARCINOMA IN CIRRHOTIC PATIENTS
S. Bota1,*, F. Hucke1, M. Pinter1, M. Mandorfer1, T. Reiberger1, A. Ferlitsch1,
M. Trauner1, W. Sieghart1, M. Peck-Radosavljevic1
1
Division of Gastroenterology and Hepatology, Department of Internal Medicine
III, Medical University of Vienna, Vienna, Austria
Contact E-mail Address: bota_simona1982@yahoo.com
INTRODUCTION: The international guidelines strongly recommend the screen-
ing of hepatocellular carcinoma (HCC) in cirrhotic patients by ultrasound every
6 months  tumor markers (such as alfa feto protein AFP), but because of the
large number of patients and often limited resources some biomarkers for prior-
itizing patients for screening would be very helpful.
AIMS & METHODS: Our aim was to assess the HCC occurrence according to
AFP values, presence of clinically significant portal hypertension (HVPG  10
mmHg), Child-Pugh score, MELD score, liver stiffness values assessed by
Transient Elastography (TE), and liver disease etiology (viral vs. non-viral).
We retrospectively collected data of cirrhotic patients evaluated in our center
between January 2007-July 2013. In the same session HVPG measurements,
TE, lab values (used to calculate Child-Pugh and MELD score), and tumors
markers (AFP) were determined. The presence of HCC at baseline was excluded
by imaging techniques and patients were followed-up.
RESULTS: We identified 274 individual cirrhotic patients evaluated with all
tests. We had to excluded 11 patients whose follow-up was not available. Thus
in the final analysis 263 patients were included.
The median follow-up time was 21 months (3-83 months).
In our cohort of cirrhotic patients the HCC incidence was 5.7% and the median
time until the HCC diagnosis was 15 months (3 -72 months).
In univariate analysis the AFP values (r 0.174, p 0.006) and presence of
clinically significant portal hypertension (r 0.154, p 0.012) were statistically
correlated with HCC occurrence, while MELD score (r 0.092, p 0.13), viral
vs. non-viral etiology (r 0.050,p 0.41), TE (r 0.042, p 0.56) and Child-
Pugh score (r 0.042, p 0.49) were not correlated.
The HCC incidence was 13.7% in patients with AFP values  10 ng/ml, 7.9% in
cirrhotic with clinically significant portal hypertension and 16.6% in patients
with both risk factors.
All the patients which developed HCC had clinically significant portal hyperten-
sion (HVPG  10 mmHg), while in the group without HCC it was present in
70.1% of patients (p 0.02).
The proportion of cirrhotic patients with AFP 10 ng/ml at baseline was sig-
nificantly higher in the cohort of patients that developed HCC as compared with
the ones who did not: 46.6% vs. 20.4%, p 0.02.
Combining both HVPG and AFP values, we observed that the percentage with
both risk factors present (HVPG10 mmHg and AFP10 ng/ml) was three times
higher in cirrhotic patients developing HCC compared with those without HCC
during follow-up: 46.6% vs. 15.2%, p 0.005.
No patient with HVPG 5 10mmHg developed HCC during follow-up.
CONCLUSION: The absence of clinically significant portal hypertension seems
to be a protective factor against HCC development. The combination of HVPG
and APF values can identify the cirrhotic patients with high risk of HCC occur-
rence and probably a closer surveillance of patients with clinically significant
portal hypertension and AFP values  10 ng/ml should be performed.
Disclosure of Interest: None declared
P0646 OVERALL SURVIVAL IN RESPONSE TO SORAFENIB VERSUS
RADIOTHERAPY IN UNRESECTABLE HEPATOCELLULAR
CARCINOMA WITH MAJOR PORTAL VEIN TUMOR
THROMBOSIS: PROPENSITY SCORE ANALYSIS
T. Nakazawa1,*, H. Hidaka1, Y. Okuwaki2, A. Shibuya2, S. Kokubu3,
W. Koizumi2
1
Department of Gastroenterology, 2Kitasato University East Hospital,
Sagamihara, 3Shinyurigaoka general hospital, Kawasaki, Japan
Contact E-mail Address: tnakazaw@kitasato-u.ac.jp
INTRODUCTION: This study investigated the survival benefits of sorafenib vs.
radiotherapy (RT) in patients with unresectable hepatocellular carcinoma (HCC)
and portal vein tumor thrombosis (PVTT) in the main trunk or the first branch.
AIMS & METHODS: Ninety-seven patients were retrospectively reviewed.
Forty patients were enrolled by the Kanagawa Liver Study Group and received
w n
sorafenib, and 57 consecutive patients received RT in our hospital. Overall sur-
a
ithdr
vival was compared between the two groups with PVTT by propensity score (PS)
analysis. Factors associated with survival were evaluated by multivariate
analysis.
W
RESULTS: The median treatment period with sorafenib was 45 days, while the
median total radiation dose was 50 Gy. The Child-Pugh class and the level of
invasion into hepatic large vessels were significantly more advanced in the RT
group than in the sorafenib group. Median survival did not differ significantly
between the sorafenib group (4.3 months) and the RT group (5.9 months;
P 0.115). After PS matching (n 28 per group), better survival was noted in
the RT group than in the sorafenib group (median survival, 10.9 vs. 4.8 months;
P 0.025). A Cox model showed that des-g-carboxy prothrombin 51000 mAU/
mL at enrollment and RT were significant independent predictors of survival in
A310
ra w n
the PS model (P 0.024, HR, 0.508; 95% CI, 0.282 to 0.915; and P 0.007, HR,
0.434; 95% CI, 0.235 to 0.779; respectively).
t h d
CONCLUSION: RT is a better first-line therapy than sorafenib in patients who
i
have advanced unresectable HCC with PVTT.
W
Disclosure of Interest: None declared
P0647 PROGNOSTIC SIGNIFICANCE OF AFP AND PIVKA-II
RESPONSES TO INITIAL TRANSARTERIAL
CHEMOEMBOLIZATION IN PATIENTS WITH UNRESECTABLE
HEPATOCELLULAR CARCINOMA
T. Ichikawa1,*, N. Machida1, H. Sasaki1, Y. Tawa1
1
Department of Gastroenterology, Itabashi Chuo Medical Center, Itabashi-ku,
Tokyo, Japan
Contact E-mail Address: ichikawtakeshi@gmail.com
INTRODUCTION: It remains unclear whether response of alpha-fetoprotein
(AFP) and protein induced by vitamin K absence or antagonist-II (PIVKA-II)
to initial transarterial chemoembolization (TACE) are associated with improved
survival in patients with unresectable hepatocellular carcinoma (HCC).
AIMS & METHODS: The aims of this study were to evaluate the prognostic
significance of response of AFP and PIVKA-II to initial TACE and to identify
risk factors associated with outcomes in patients with unresectable HCC. We
retrospectively analyzed 114 patients with unresectable HCC not amenable to
surgery and radiofrequency ablation who had been treated with TACE between
September 2005 and October 2013. All laboratory values including AFP and
PIVKA-II were measured 1 week before TACE and 1 month after TACE. The
AFP or PIVKA-II response was assessed for patients who had a level before
TACE of 100 ng/ml or  100mAU/ml; a positive response was defined as a
reduction by 4 50% compared with the level before TACE. We compared
three groups of pre-TACE AFP  100 ng/ml with response vs. pre-TACE
AFP  100 ng/ml and no response vs. pre-TACE AFP 5 100 ng/ml using
univariate analysis. Three PIVKA-II groups were also compared. Prognostic
factors were evaluated using univariate (log-rank test) and multivariate analyses
(Cox proportional hazard model).
RESULTS: The median overall survival (OS) was 20.9 months. Pre-TACE AFP
level 100 ng/ml and tumor diameter 3 cm were associated with poor OS (AFP
100 ng/ml vs. AFP 5 100 ng/ml; 9.3 vs. 31.3 months; P 5 0.0001, tumor
diameter  3 cm vs. diameter 5 3cm: 12.5 vs. 31.3 months; p 0.0013) and
remained significant negative predictors for OS on multivariate analysis (AFP
4100 ng/ml; hazard ratio (HR) 3.5; p 0.0003, tumor diameter  3 cm; HR 3.1;
p 0.0015). In the difference of AFP response to TACE, the OS of pre-TACE
AFP  100 ng/ml with response compared with that of pre-TACE AFP  100
ng/ml and no response showed no significant difference (p 0.992). Although
there were not significant differences in OS between patients with pre-TACE
PIVKA-II 5 100 mAU/ml and those with pre-TACE PIVKA-II  100 mAU/
ml (p 0.1642), the OS of responders of PIVKA-II to initial TACE was signifi-
cantly longer than that of non-responders in those with pre-TACE PIVKA-II 
100 mAU/ml (p 0.0032).
CONCLUSION: The response of AFP to initial TACE does not prolong survival
in patients with unresectable HCC. The response of PIVKA-II to initial TACE is
associated with improved survival. Elevated AFP (100 ng/ml) and tumor dia-
meter  3 cm at diagnosis are associated with a dismal treatment response and
prognosis after TACE.
Disclosure of Interest: None declared
P0648 NEW ASSESSMENT OF THERAPEUTIC RESPONSE TO
SORAFENIB FOR ADVANCED HEPATOCELLULAR CARCINOMA:
AUTOMATIC MEASUREMENTS OF TUMOR VOLUME AND
DENSITY ON COMPUTED TOMOGRAPHY
Y. Kawaguchi1,2,*, T. Otsuka1, S. Nakashita1, T. Kumagai2, T. Akiyama2,
H. Mizobe3, J. Yamamichi3, S. Kawazoe2, T. Mizuta1, I. Ozaki1, Y. Eguchi1,
S. Kimura1
1
Department of Internal Medicine, Saga Medical School, 2Department of
Hepatobiliary and Pancreatology, Saga-ken Medical Centre Koseikan, Saga,
3
Global Healthcare IT Project, Canon Inc., Tokyo, Japan
Contact E-mail Address: kawaguy222@gmail.com
INTRODUCTION: Although sorafenib has been shown to have significant sur-
vival advantages in patients with hepatocellular carcinoma (HCC), Response
Evaluation Criteria in Solid Tumors (RECIST) 1.1 may underestimate the effi-
cacy because of modest tumor shrinkage. Additionally, discrepancy among eva-
luators may occur in the manual assessments.
AIMS & METHODS: The present study aimed to establish an objective evalua-
tion method for anti-tumor response of sorafenib with regard to survival, using
software that can automatically measure the diameter, volume and density of
target tumors on computed tomography (CT). Among 81 patients with advanced
HCC who were treated with sorafenib, 23 with ChildPugh class A, Barcelona
Clinic Liver Cancer stage C and performance status 0 or 1 were enrolled.
Automatic measurements on CT were performed using MEDIAN Lesion
Management Solutions. Conventional RECIST1.1 was compared with new
methods: automated RECIST (a-RECIST), enhanced RECIST (e-RECIST)
and Saga criterion. a-RECIST was RECIST1.1 using automatic measurements.
e-RECIST used volume evaluation classified as follows: partial response (PR) as
50% reduction in tumor volume; progressive disease (PD) as 50% increase in
tumor volume; and stable disease (SD) as 550% reduction or 550% increase in
tumor volume. Saga criterion was the same as e-RECIST except that SD with
15% reduction in tumor density in the arterial phase was classified as PR.
Overall survival (OS) time was estimated using the KaplanMeier method and
United European Gastroenterology Journal 2(5S)
expressed as median (95% confidence interval). The survival curves according to
best response were compared using the log-rank test.
RESULTS: Conventional RECIST1.1 could not stratify OS. Meanwhile, OS was
significantly stratified according to anti-tumor response in a-RECIST. Disease
control rate (DCR) 60.9%, DC vs. PD, 17.2 (6.328.1) vs. 9.3 (5.013.6)
months (p 0.048); objective response rate (ORR) 8.7%, OR vs. non-OR,
N/A vs. 10.4 (7.113.6) months (p 0.048). e-RECIST was superior to a-
RECIST: DCR 56.5%, DC vs. PD, 20.4 (13.926.8) vs. 9.0 (4.513.4)
months (p 0.011); ORR 8.7%, OR vs. non-OR, N/A vs. 10.4 (7.113.6)
months (p 0.048). In addition, Saga criterion was superior to e-RECIST:
DCR 56.5%, DC vs. PD, 20.4 (13.926.8) vs. 9.0 (4.513.4) months
(p 0.011); ORR 30.4%, OR vs. non-OR, 20.4 (14.226.6) vs. 9.0 (5.412.5)
months (p 0.007).
CONCLUSION: Our findings suggest that Saga criterion, a new imaging assess-
ment using automatic measurements of tumor volume and density on CT, has
potential as a surrogate marker for anti-tumor response to sorafenib with regard
to survival.
Disclosure of Interest: None declared
P0649 POPULATION SCREENING FOR LIVER DISEASE USING
HEPATIC TRANSIENT ELASTOGRAPHY
B.M. Goncalves1,*, L. Malheiro1, D. Fernandes1, J.-B. Soares1, C. Rolanda1,
R. Goncalves1, P. Bastos1
1
Gastroenterology, Hospital de Braga, Braga, Portugal
Contact E-mail Address: brunommgoncalves@gmail.com
INTRODUCTION: Transient Elastography (TE), a noninvasive technique for
liver fibrosis evaluation, has been used in patients with various types of chronic
liver diseases. It is a simple, fast, painless, reproducible and well-accepted tech-
nique with instantaneous results that could be a valuable screening tool.
However, there is a shortage of studies on its usefulness as a screening procedure
in apparently healthy people.
AIMS & METHODS: The purpose of the study was to evaluate the impact of TE
in the population screening of liver disease. It was conducted a prospective study
where TE was performed in 365 individuals without known liver disease that
attended general gastroenterology clinic in a referral hospital. A positive screen-
ing was defined for values of liver stiffness (LS) 8 kPa. For these individuals
additional clinical, laboratory and ultrasonographic investigation was proposed
for determination of liver disease.
RESULTS: Of the 365 individuals evaluated, 89 were excluded for invalid
(n 47) or failed (n 42) TE. In the multivariate analysis, body mass index
430Kg/m2 and waist circumference 4102cm in men or 488cm in women
were associated with failure of LS measurement (p 0.031 and 0.001, respec-
tively). Of the 276 valid exams, 21 (7.6%) obtained a LS value 8 kPa, including
nine patients with LS  13 kPa. The average value of LS in the remaining
participants with negative screening was 4.9  1.2 kPa. In the group with positive
screening it was observed that 28.6% patients had normal liver tests. In 17 (81%)
patients a cause of liver disease was determined, while all participants with LS 
13 kPa had a diagnostis. Alcoholic liver disease was the most prevalent etiology
(47%) followed by non-alcoholic fatty liver disease (41%).
CONCLUSION: TE revealed to be a useful method to screen liver disease in the
general population, diagnosing a significant number of asymptomatic patients.
In the presence of an abnormal LS, the patient should be referenced for further
evaluation.
Disclosure of Interest: None declared
P0650 MORBIDITY RISK IN AN ITALIAN COHORT OF HCV AND HBV
PATIENTS
C. Stasi*1,2,*, C. Silvestri*1, S. Bravi1, F. Voller1, F. Cipriani3
1
Epidemiology Unit, Health Agency of Tuscany, Florence, Italy, 2Department of
Experimental and Clinical Medicine, University of Florence, 3Health Agency of
Tuscany, Florence, Italy, Florence, Italy
INTRODUCTION: In Italy the HBV incidence progressively decreased from
1991 to 2005, because in 1991 infants and adolescents vaccination became
mandatory. Effective screening since the early 90s has reduced the risk of HCV
transmission through blood transfusion. Recently, World Health Organization
(WHO) for the first time produced guidelines for the screening, care and treat-
ment of persons with HCV infection. These guidelines are primarily targeted at
policy-makers in ministries of health working in low- and middle-income coun-
tries that formulate country-specific guidelines for treatment. Treatment for
HCV and HBV can reverse hepatic fibrosis and/or delay the development of
long-term complications such as decompensated cirrhosis. A recent study
shows that treatment of patients with compensated cirrhosis is cost-effective.
AIMS & METHODS: Therefore, the aims of this study were to evaluate the
HBV and HCV epidemiology in Florence (Tuscany, region in central Italy) in
2012 and to investigate the hospital admissions of these patients at least once, as
a risk of morbidity for cirrhosis, from 2000 to 2012. Methods: We analyzed the
database of one Hospital in Florence (Careggi University Hospital) and preva-
lence of hospital admissions from 2000 to 2012 of HBV (based on the presence of
antigene surface - HBsAg) and HCV patients (based on the presence of HCV
RNA; limit of detection: 15 IU/mL) for chronic liver disease and cirrhosis,
Fibrosis and cirrhosis of the liver, bleeding from esophageal varices, using
the International Classification of Diseases, 9th Revision, Clinical Modification
(ICD-9-CM) and 10th revision (ICD-10).
RESULTS: Out of 24,368 individuals, a total of 2,697 hepatitis cases were
reported, including 1,237 HBV and 1,460 HCV RNA positive patients. HBV
occurred more often in males (63%) than in females (37%). HCV occurred
slightly more often in males (59%) than in females (41%). In HCV group
United European Gastroenterology Journal 2(5S)
1,270 (87%) had at least one hospital admission, while in HBV group were
reported 492 hospital admissions (40%). When we divided the HBV patients
into 5 age groups, hospital admission was detected in 1% of people aged 15-30
years; in 10% of people aged 31-45; in 50% of people aged 46-60; in 39% of
people aged over 61 years; HCV hospital admission was detected in 1% in people
aged 15-30; 6% in people aged 31-45; 48% in people aged 46-60; 45% in people
aged over 61 years.
CONCLUSION: Our results show that there is a high prevalence of HCV and
HBV hospital admissions in the central of Italy, especially in people aged over 46
years, with the higher prevalence for HCV than HBV patients. Therefore, its
impact on the National Health Service could be important in the future. This
study also suggests that early screening creates the conditions for early treatment
in order to avoid the possibility of worsening of viral hepatitis on to develop
cirrhosis of the liver.
REFERENCES
http://apps.who.int/iris/bitstream/10665/111747/1/
9789241548755_eng.pdf?ua 1&ua 1
Obach D, Deuffic-Burban S, Esmat G, et al. Effectiveness and cost-effectiveness
of immediate vs. delayed treatment of HCV-infected patients in a country with
limited resources: the case of Egypt. Clin Infect Dis 2014; 58: 1064-1067.
Disclosure of Interest: None declared
P0651 A COST-CONSEQUENCE ANALYSIS OF SCREENING AND
TREATMENT FOR CHRONIC HEPATITIS B (CHB) VIRUS
INFECTION IN RESIDENT IMMIGRANTS OF AN ITALIAN NORTH-
EAST REGION
E. Rosa-Rizzotto1,*, A. Buja2, D. Martines1, A. Vinelli2, G. Bardelle2,
S. Lopatriello2, L. Peraro1, D. Caroli1, L. Scribano1, F. De Lazzari1, S. Lobello1,
V. Baldo2
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital,
2
Department of Molecular Medicine, Laboratory of Public Health and Population
Studies, Padua University, Padua, Italy
INTRODUCTION: Chronic hepatitis B virus (HBV) infection is a serious health
problem affecting 350 million to 400 million people worldwide. Although HBV
infection occurs everywhere in the world, nationality is strongly associated with
the prevalence of HBV infection. The epidemiology of hepatitis B in Europe is
changing, with migration causing significant increases in prevalence rates.
Immigration to Italy is a relatively new phenomenon that became relevant
only at the end of the 1990s. As of January 2013, there were 4,387,721 foreign
nationals resident in Italy.[ISTAT (2013). Statistiche report, 26 Luglio 2013.
Rome, Italian National Institute of Statistics]. This amounted to 7,4% of the
countrys population, mainly concentrated in the northern part of the country.
Veneto region is one of the main immigration destination areas. With about
500.000 foreign people staying in its territory, Veneto is the third Italian region
for the number of immigrants and the fourth one if you consider the immigration
rate on the overall population (10.2%). These influxes involve a considerable
proportion of citizens from countries where hepatitis B is highly (4 8%) ende-
mic, such as eastern Europe (Moldovans, Romanians and Ukrainians), from
Africa (especially Ghana and Morocco), Balkan states (especially Albania,
Montenegro and Serbia) and China, compared with less than 1 % of overall
Italian population. Systematic screening and early treatment of migrants for
chronic hepatitis B virus infection may have a large impact on liver-related
health outcomes and is likely to be cost-effective. In four cost-effectiveness ana-
lyses, the estimated average cost per life-year gained of screening ranged from E
8966 to E 46260 per QALY gained. A cost-consequence analysis (CCA) provides
an estimation of the costs as well as the expected health outcomes in terms of liver
disease progression and mortality. Cost-consequence analyses play an essential
part in the comprehensive economic assessment of a health care intervention.
AIMS & METHODS: We used the Markow model to examine the cost-conse-
quence of screening and treatment vs a no screening strategy in a cohort of
348,991 adult migrants resident in the Veneto Region. The rate of adherence
to the HBV screening program was judged to be 40%. The prevalence of HBV
infection and the chance of having active CHB was based on our recent screening
campaign in Padua involving 465 migrants (Tab.) Likelihood of HBV-related
events were obtained from literature.
RESULTS:
Rate of adherence
AGE GROUP HBsAg ACTIVE to screening
POPULATION 4 20 y N (%) CHB N (%) program n (%)
465322 348991 21048 (6) 6314 (30) 2525 (40)
The screening-treatment strategy prevented 273 cases of cirrhosis, 18 decompen-
sated cirrhosis, 28 HCC, and 54 CHB related deaths, over a period of 5 years.
The incremental cost of the screening strategy totaled 51.597.980 E in five years
(0,1% of the Veneto annual health budget).
CONCLUSION: This study provides information useful mainly to policy
makers, who need to establish whether the cost generated by a screening strategy
is affordable when set against the better health outcomes for resident immigrants.
Disclosure of Interest: None declared
A311
P0652 HEPATITIS VIRUSES IN HEALTHY IMMIGRANTS: TO SCREEN
OR NOT TO SCREEN?
E. Rosa-Rizzotto1,*, L. Peraro1, D. Caroli1, L. Scribano1, S. Gallo1, C. Magro1,
F. De Lazzari1, D. Martines1, S. Lobello1
1
Dpt of Specialized Medicine, Gastroenterology Unit, St Anthony Hospital, Padua,
Italy
INTRODUCTION: Over the past four decades international migrations have
increased up to an unprecedented rate. New migrants come from countries at
low hepatitis B prevalence [hepatitis B surface antigen (HBsAg) seroprevalence
52 per cent], intermediate (HBsAg seroprevalence between 2 per cent7 per cent)
or high hepatitis B prevalence (HBsAg seroprevalence 8 per cent). Over this
period both chronic HBV infection and HCC prevalence are increased in North
America and Western Europe, also because migrants have higher incidence of
chronic HBV infection and an increased mortality for cirrhosis and HCC com-
pared to host populations. Hepatitis viruses screening is a form of secondary
prevention to find early diseases amenable to antiviral treatments in order to
prevent liver diseases. Moreover the screening helps to vaccinate the people
cohabiting with HBsAg ve subjects. Worldwide HCV prevalence is generally
low and only in few countries it is over 3.5 per cent. Immigrants in Italy come
mainly from Eastern Europe, Asia and Africa. In all these areas HCV prevalence
is lower than HBV.
AIMS & METHODS: Regular healthy immigrants were sent to our clinic by
community leaders from March 2013 to October 2013, questioned about their
socio-demographic characteristics, tested for HBcAb and, when positive, for
HBsAg. HBsAgve subjects were studied for HBVDNA levels and enrolled
for clinic controls of liver disease. This population was also tested for HCV-
Ab. HCV-Abve subjects were tested also for HCV-RNA and HCV genotype.
RESULTS: 450 (264- M 58,7% - and 185 - F 41,3%) immigrants were screened.
39% were from Eastern Europe, 23% from Asia, 36% from Africa, and 2% from
other areas. This distribution is comparable with immigrants residing in Padua.
144 (32%) were anti-HBcAg ve, 31 (7%) HBsAg ve, 4 (1%) HBeAg ve.
HBVDNA levels were over 2000 IU/ml in 11/31 (35.5%). The prevalence of
HBsAg ve in the Eastern European group was 11.4%, 7.9% in the Asiatic
group and 1,2% in the African group. Eight immigrants resulted positive for
HCV (1.8%), but only 6 were HCV-Rna positive, all were Moldavian (8.4%).
CONCLUSION: The seroprevalence of chronic HBV infection in migrants is
similar to that of their countries of origin: high among migrants from East
Asia and Eastern Europe, where 32% were found to be anti-HBcAgve.
Hepatitis B virus screening on healthy migrants in our area is effective to identify
HBsAgve subjects and it seems useful to define the amount of patients with
HBV related liver disease. Targeted screening and vaccination of international
migrants can become an important aspect of HBV disease control efforts in
immigrant-receiving countries, thus changing the natural history of HBV chronic
infection. The prevalence of HCV in Padua immigrants seems to be very low
unlike HBV. HCV screening for immigrants does not appear useful to detect
Hepatitis C virus affected subjects. The HCV screening strategy could be effective
only in special populations of immigrants with higher HCV prevalence (i.e. East
Europe).
Disclosure of Interest: None declared
P0653 METABOLIC PHENOTYPING OF BILE ACIDS - STANDARDIZED
QUANTITATIVE BILE ACIDS ANALYSIS IN HUMAN PLASMA/
SERUM AND MOUSE PLASMA ON DIFFERENT LIQUID
CHROMATOGRAPHY TANDEM MASS SPECTROMETRY
PLATFORMS
H.P. Pham Tuan1,*, D. Kirchberg1, I. Zitturi1, F. Polato1, D. Seppi1, T. Koal1
1
Product/Method Development, BIOCRATES Life Sciences AG, Innsbruck,
Austria
Contact E-mail Address: Hai. Pham-Tuan@biocrates.com
INTRODUCTION: Bile acids are considered not only as endogenous markers
for liver cell functions, but also as signaling molecules regulating triglycerides,
cholesterol and glucose metabolism as well as inflammatory processes and apop-
tosis. Accurate determination of individual bile acids and their conjugates is very
important in assessing liver damage as well as hepatic and biliary tract diseases,
colon cancer, atherosclerosis and type 2 diabetes. Therefore, bile acid analysis
could provide a powerful tool for applications in precision medicine, toxicology,
and clinical biomarker research. We have developed and validated a standardized
(U)HPLC-ESI-MSMS assay for the analysis of ca. 20 bile acids from only 10 mL
human plasma/serum or mouse plasma samples. The panel consists of cholic
acid, deoxycholic acid, chenodeoxycholic acid, ursodeoxycholic acid, hyodeoxy-
cholic acid, muricholic acids and their glycine as well as taurine conjugates.
AIMS & METHODS: 10 mL sample and 10 mL IS mixture are pipetted onto the
paper filter spot suspended in a 96-well filter plate. After a short drying under
nitrogen stream, bile acids are extracted with 100 mL methanol. The methanolic
extract is filtered through the plate into the 96- deep well receiving plate, under
light centrifugation. 60 mL water is added to the extract before injecting into the
(U)HPLC-ESI-MSMS for analysis. The analysis runtime for UHPLC and HPLC
is 5 and 11 min, respectively. Bile acids detection is performed using MRM in
negative ESI mode. 7-points calibration curves are used for quantitation. The
assay has been rigorously validated according to the EMA guideline.
RESULTS: Due to the special arrangement of the paper filter spot, proteins
which have been precipitated are largely captured by the filter, while allowing
the target metabolites to be extracted and filtered through. Only 3 steps are
needed to complete the sample preparation. Seven calibrators levels and three
quality control levels are used to guarantee the accuracy and precision of the
measurements. This new assay in kit format has been validated for different LC-
MS/MS platforms from AB Sciex, Waters, and Thermo Scientific. In general an
A312
LLOQ of 0.01 to 0.02 mM have been achieved for all target bile acids. Among the
tested LC-MS/MS platforms, increasing sensitivity for bile acids analysis can be
graded as follows: Xevo TQ MS 5 TSQ Vantage 5 400QTRAP5 QTRAP5500.
CONCLUSION: With the help of the very simple and robust bile acids kit, the
analysis of several human plasma/serum samples and mouse plasma samples
reveals that the bile acid profile of mice is quite different from that of human.
While taurine conjugates of bile acids are prevalent and glycin conjugates are
amost absent in mouse plasma, the situation is reversed in human plasma/serum.
Moreover, the male/female differences found in mouse plasma is much more
profound than that found in human samples.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 9:0017:00
PAEDIATRIC: LIVER, BILIARY AND PANCREAS POSTER EXHIBITION HALL
XL_____________________
P0654 MACROAST - THE DIAGNOSTIC USEFULNESS AND CLINICAL
OBSERVATIONS IN CHILDREN
A. Wierzbicka-Rucinska1,*, W. Janczyk2, B. Oralewska3, M. Teisseyre3,
P. Socha3
1
Biochemistry, Radioimmunology and Experimental Medicine, 21Gastroenterology,
Hepatology and Eating Disorders, 3Gastroenterology, Hepatology and Eating
Disorders, Childrens Health Memorial Institute, Warsaw, Poland
Contact E-mail Address: aldona.wierzbicka@wp.pl
INTRODUCTION: Elevated aspartate aminotransferase (AST) may not be asso-
ciated with liver or muscle injury and can be caused by the presence of macroAST
which results from unusual combination of molecules of AST with serum macro-
globulins. MakroAST may be present in both healthy subjects and in the course
of other diseases, including autoimmune diseases. Only few reports in limited
number of patients described Macro AST and proposed diagnostic criteria.
AIMS & METHODS: The aim of this study was to evaluate the prevalence of
macroenzymes in children with increased activity of aspartate aminotransferase
and to compare two diagnostic methods- polyethylene glycol precipitation (PEG)
and electrophoresis.
Methods: 247 children with mean age of 6.2 years (from 0.03 to 16.19 years) with
isolated hypertransaminasemia were included in the study. The presence of
macroenzymes was first based on polyethylene glycol precipitation (PEG),
according to Levitt and Ellis [1]. Electrophoresis was used to confirm the pre-
sence of a macroAST.
RESULTS: In a group of 247 children with hypertransaminasemia (all with
increased AST, 48 children presented with increased AST and ALT) we received
the following results according to the different cut off values for precipitable
activity (% PPA) of the PEG test:
1/ according to Davidson and Watson [2] with a cut-off point of 54% PPA macro
AST was observed in 67 children (27.1% of the patients).
2/ according to Caropreso M, et al [3] with a cut-off point of 73.3% PPA macro
AST was observed in 5 children (2.0% of the population studied).
Samples with AST activities 450 U/l were analyzed with both PEG precipitation
and electrophoresis. AST isoenzyme electrophoresis showed macroAST in 35
children which is 14% of the population studied.
CONCLUSION: MacroAST has to be considered in differential diagnosis of
increased AST activity.
The cut off values for polyethylene glycol precipitable activity test need to be
further evaluated and requires further confirmation with electrophoresis.
The cut off value of 54% PPA can be used as a screening test for macroAST.
REFERENCES
1) Caropreso M, Fortunato G, Lenta S, et al. Prevalence and long-term course of
macro-aspartate aminotransferase in children. J Pediatr 2009; 154: 744-748.
2) Sakakibara S, Katsuhiko S, Kobayashi S i wsp. A convenient and sensitive
method for the determination of serum aspartate aminotransferase isoenzymes
after electrophoresis. Clin Chim Acta1983; 133: 119-123.
3) Fortunato G, Iorio R, Esposito P, et al. Macroenzyme investigation and
monitoring in children with persistent increase of aspartate aminotransferase
of unexplained origin. J Pediatr 1998; 133: 286-89.
4) J Remaley AT and Wilding P. Macroenzymes: biochemical charakterization
characterisation, clinical significance and laboratory detection. Clin Chem 1989;
35: 2261-2270.
Disclosure of Interest: None declared
P0655 ENVIROMENTAL RISK FACTORS OF PAEDIATRIC ONSET
AUTOIMMUNE LIVER DISEASE
A. Tenca1,*, M. Farkkila1, H. Jalanko2, K. Vapalahti3, O. Vapalahti4, K.-
L. Kolho5
1
Department of Medicine, Clinic of Gastroenterology, Helsinki University Central
Hospital, 2Department of Pediatric Nephrology and Transplantation, Childrens
Hospital, University of Helsinki, 3University of Helsinki, 4Department of Virology
and Immunology, Helsinki University Central Hospital, 5Childrens Hospital,
University of Helsinki, Helsinki, Finland
Contact E-mail Address: ante14@hotmail.it
INTRODUCTION: Primary sclerosing cholangitis (PSC), autoimmune hepatitis
(AIH) and PSC/AIH overlap syndrome are three autoimmune liver diseases
(AILD) of unknown origin.
AIMS & METHODS: Aim of this population-based observational case-control
questionnaire study was to investigate the environmental risk factors associated
with a paediatric onset AILD. All the patients (n 85) with a paediatric onset (5
16 years) AILD diagnosed between 1985-2011 at Helsinki University Central
Hospital (HUCS) were mailed a questionnaire, evaluating contact with
United European Gastroenterology Journal 2(5S)
environmental risk factors before the AILD diagnosis in 22 items, e.g., number
of siblings, place of living (i.e., country/town, downtown/suburb), type of hous-
ing (i.e., block of flats, town house, terraced house, duplex), having pets or
domestic animals (e.g., cat, dog, horse), smoking and other items. Two control
groups -matched for sex, age and place of residence- were used: 1) as AILD are
more frequent in patients affected by inflammatory bowel disease (IBD)1 a pae-
diatric group of patients with IBD without AILD (n 91; selected from IBD
Register of HUCS) was included and 2) a group of healthy subjects (n 716;
selected from Population Register Center). Univariate analysis (ORs; 95%CI)
was performed using the two control groups separately. A logistic regression
model for the multivariate analysis including (i) variables statistically significant
in univariate analysis and (ii) confounders and interactive factors, was calculated;
two models were constructed for controls: model 1 IBD and healthy controls,
model 2 healthy controls.
RESULTS: Baseline characteristics (Percentage of respondents. F female.
Median age: range years) AILD cases: 51/85 (60%; F 26; 22:8-36), IBD con-
trols: 59/91 (65%; F 34; 21:9-37), healthy controls: 292/716 (41%; F 162;
21:8-38). No difference between respondents and non-respondents. Median age
and range at AILD onset 10 years: 2-15. Univariate analysis Protective and risk
factors are shown in Table 1; others factors were not associated with AILD.
Multivariate analysis Children traveling abroad except those living in a block
of flats seemed to be protected for developing AILD (Model 1 OR: 0.07;
95%CI: 0.02-0.2. Model 2 OR: 0.06; 95%CI: 0.02-0.2). Living with a cat or a
dog was a risk factor (Model 1 OR: 2.7; 95%CI: 1.3-5.7. Model 2 OR: 2.1;
95%CI: 1.0-4.2). In models studying the effect of pet species individually,
those living in a block of flats with a cat had the highest risk (e.g., Model 2
OR: 6.4; 95%CI: 1.8-22.7).Table 1
IBD controls Healthy controls
OR 95%CI OR 95%CI
Traveling abroad 0.3 0.1-0.7 0.2 0.1-0.4
Having a pets (cat or dog) 3.4 1.5-7.8 2.5 1.2-5.0
CONCLUSION: In this postal questionnaire based survey of environmental risk
factor of AILD, children traveling abroad and living in a town house, terraced
house or duplex were less susceptible to develop AILD, suggesting a protective
role of a higher socioeconomic status. Intriguingly, living in a close contact with a
pet was a risk factor, suggesting an involvement of an unidentified agent (i.e.,
toxin or microbe) as a trigger of paediatric AILD.
REFERENCES
1 Deneau M, et al. Hepatology 2013; 58: 1392-400.
Disclosure of Interest: None declared
P0656 NOVEL JAG1 MUTATIONS IN PATIENTS WITH SUSPECTED
EXTRAHEPATIC BILIARY ATRESIA AND ALAGILLE SYNDROME
T. Dedic1,*, M. Jirsa2, R. Kotalova1, J. Snajdauf3, R. Keil4, M. Rygl3
1
Department of Pediatrics, Charles University 2nd Medical School and Motol
University Hospital, 2Laboratory of Experimental Hepatology, Institute for
Clinical and Experimental Medicine, 3Department of Pediatric Surgery,
4
Department of Internal Medicine Gastroenterology and Endoscopy, Charles
University 2nd Medical School and Motol University Hospital, Prague, Czech
Republic
Contact E-mail Address: dedict@seznam.cz
INTRODUCTION: Alagille syndrome (AGS, OMIM #118450) is an autosomal
dominant multisystem disorder affecting the liver, heart, face, eyes and skeleton.
In early infancy AGS may mimic biliary atresia (BA) and extrahepatic bile ducts
might not be visualised by endoscopic retrograde cholangiopancreatography
(ERCP) or postoperative cholangiography.
AIMS & METHODS: Our aim was to confirm the diagnosis in patients with
suspected AGS (n 4) and to identify carriers of JAG1 mutations among patients
with BA (n 72), all aged 2 months on average.
310 children with neonatal cholestasis were hospitalized at the Department of
Peaditrics, Faculty Hospital Motol, Prague, between January 1998 and January
2012. ERCP was indicated in 127 patients with suspected BA based on clinical
and laboratory examinations. Subsequent surgical revision was performed in 96
patients with pathological findings on the bile ducts. Mutational analysis of the
JAG1 gene was done in a subset of 72 living patients with isolated BA and in 4
patients with suspected AGS and normal extrahepatic biliary tree.
RESULTS: Sequence analysis of JAG1 revealed seven novel mutations including
one missense [c.401G4T (p. Leu135Phe)], one nonsense [c.1998T4A (p.
Cys633*)] and five frameshift mutations [c.327_330delCAAG (p.
Lys110Profs*50), c.1313_1314delGT (p. Cys438Serfs*10), c.879_880delTG (p.
Cys293*), c.2913-2914delAC (p. Pro971Argfs*10), c.2050delG (p.
Asp684Thrfs*59)], and one known nonsense mutation [c.960T4A (p.
Tyr320*)]. All 5 patients with proven JAG1 deficiency presenting initially as
BA developed clinical signs typical for AGS before 3 years of age. By contrast,
no JAG1 mutation were present in the remaining 67 patients with isolated BA.
CONCLUSION: Biliary atresia is not associated with JAG1 mutations in Central
Europeans. In addition to liver histology, early molecular diagnosis of AGS
could be useful in diagnosis of the gray zone AGS patients presenting as
extrahepatic biliary atresia in early infancy.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0657 STEATOSIS OF PANCREAS IN THE STRUCTURE OF
METABOLIC SYNDROME IN OVERWEIGHT AND OBESE
CHILDREN
M. Gurova1,*, A. GusevA2, V. Novikova3
1
Department of Pediatrics, Belgorod State National Research University,
Belgorod, 2Department of Pediatrics, Kursk Regional Children Hospital, Kursk,
3 A. Krishnan1,*, R. Ramakrishnan1 on behalf of None
Department of Pediatrics, Federal Centre of the Heart, Blood and Endocrinology,
named after V. A. Almazof, Saint-Petersburg, Russian Federation
INTRODUCTION: Involvement of pancreas in pathological process in case of
obesity is caused by its important role in regulation of metabolic processes, of
energetic balance and body weight.
AIMS & METHODS: This study is aimed at assessing frequency of detectability
of ectopic fat deposition in the pancreas in obese and overweight children and at
comparing this detection frequency of other components of metabolic syndrome
(MS).
Methods: The cross-sectional study was conducted among 120 children aged 11-
15 years, separated into 2 groups: 60 overweight children (1st group) and 60
obese children (2nd group). Diagnosis of the non-alcoholic fatty liver disease
(NAFLD) and non-alcoholic fatty pancreas disease (NAFPD) was based on
sonographic data. Peculiarities of carbohydrates and lipid metabolism and pan-
creatic exocrine function were investigated.
RESULTS: Complete MS was diagnosed only in 15% of children with obesity.
Some components of MS according IDF recommendations (2005) were found in
88.3% of obese children and 66.7% of overweight ones (p 0.002). The most
common components were the following hyperinsulinemia (90% vs 66.7%,
p 0.0027), insulin resistancy according results of HOMA-index (51.7% vs
65%, p 0.12), increasing triglycerides level (36.7% vs 6.7%, p 0.00l), decreas-
ing level of LPHD (78.3% vs 40%, p 0.001). Sonographic data compatible with
NAFLD were two times higher in children with obesity 56.7% vs. 30%
(o 0.005), whereas NAFPD data were found with equal frequency in over-
weight and obese children - 85% and 86.7% accordingly (p 0.88). These results
were associated with decreasing level of the elastase-1 in 23.3% children with
obesity.
CONCLUSION: Sonographic results compatible with NAFPD were found more
than in 2/3 cases in overweight and obese children and they had appeared earlier
than sonographic results of NAFLD which were found only in 1/3 cases of
overweight children and cases of obese patients. These results were associated
at first with carbohydrate metabolism disturbances (insulin resistancy), whereas
atherogenic dyslipidemia in our study was not prominent. In 23% obese children
with sonographic changes considered as pancreatic steatosis signs of mild exo-
crine insufficiency were found.
Disclosure of Interest: None declared
P0658 A REPORT OF 267 CASES OF CHILDHOOD PANCREATITIS:
INCREASING PREVALENCE, ETIOLOGIC CATEGORIZATION,
DYNAMICS, SEVERITY ASSESSMENT AND OUTCOME
U. Poddar1,*, S.K. Yachha1, A. Srivastava1, S.S. Baijal2, S. Kumar2, R. Lal3,
V.A. Saraswat4
1
Pediatric Gastroenterology, 2Radiology, 3Pediatric Surgery, 4Gastroenterology,
Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
Contact E-mail Address: ujjalpoddar@hotmail.com
INTRODUCTION: Paediatric pancreatitis although reported has not emanated
from developing world as a large single center study. More so, natural history of
acute pancreatitis as a continuum of recurrent acute and chronic pancreatitis is
not well established.
AIMS & METHODS: To look at prevalence, aetiologic categorization,
dynamics, severity assessment and outcome in children with pancreatitis.
METHODS: From January 2002 to December 2013 consecutive children (18
years of age) diagnosed to have pancreatitis were included for analysis.
Pancreatitis was classified as acute (AP), acute recurrent (ARP) and chronic
pancreatitis (CP) as per standard definitions. Severity of acute pancreatitis was
assessed by 2012: revised Atlanta classification. Follow-up data was assessed till
March 2014.
RESULTS: Pancreatitis was diagnosed in 267 children (mean age of 11.29  3.49
years). AP in 50% (n 133), ARP in 22% (60) and CP 28% (74). The number of
cases increased progressively from 18 in the 1st quarter of the study to 37 in 2nd
quarter, 64 in 3rd quarter and 148 in the last quarter. Aetiology of AP was trauma
in 22% (n 29), biliary 10.5% (14), viral infection 7% (9), drugs 5% (7), others
causes in 4.5% (6) and idiopathic 51% (68). Grading of pancreatitis was severe in
13% (17, 6 died), moderately severe (local complications) 55% (73) and mild
32% (43). Over a median follow-up of 12 (range, 3 to 96) months, 23.5% (27 /
115) developed either acute recurrent (n 9) or chronic pancreatitis (18).
Progression from acute to ARP/CP was observed mostly in idiopathic group
(22/27). In ARP group, 10 were due to biliary causes (choledochal cysts 8, gall-
stones 2), pancreas divisum 3, duodenal diverticulum 1 and the remaining 46
(76.6%) were idiopathic. Over a median follow-up of 12 (range 3 to 120) months
31% (11/35) of idiopathic ARP cases developed CP. Almost half of CP (39 /74)
were chronic calcific, 6 were familial, 4 had associated pancreas divisum and the
remaining 64 (86%) were idiopathic. Among CP (n 63), over a median follow-
up of 13 (range, 3-120) months, 3 cases developed diabetes mellitus, one steator-
rhoea, none had cancer and there was no mortality.
CONCLUSION: There is almost eight fold increase in the prevalence of pan-
creatitis over last 12 years. Among AP (mainly idiopathic subgroup) 23% pro-
gressed to ARP and chronic pancreatitis. The majority of ARP was idiopathic
(77%) and a third of them progressed to CP. Thus a subset of pancreatitis seems
to be a continuum of acute to ARP and CP.
Disclosure of Interest: None declared
A313
TUESDAY, OCTOBER 21, 2014 9:0017:00
PANCREAS II POSTER EXHIBITION HALL XL_____________________
P0659 EUS GUIDED NECROSECTOMY TEMPORARY
CYSTOGASTROSTOMY WITH COVERED STENT FOR
PANCREATIC NECROSIS
1
Fortis Malar Hospitals, Chennai, India
Contact E-mail Address: dr.arunkumarpillai@gmail.com
INTRODUCTION: Pancreatic pseudocyst with infected necrotic tissue is asso-
ciated with a high rate of complications and death. Standard treatment is open
necrosectomy but is associated with significant morbidity, mortality, and pro-
longed hospital stay. Endoscopic cyst drainage with necrosectomy is an alterna-
tive and less invasive technique.
AIMS & METHODS: Aim: to evaluate pseudocyst drainage with cystogastrost-
omy and endoscopic necrosectomy for infected pancreatic necrosis with fully
covered self-expanding metallic stents (CSEMS).
12 patients underwent endoultrasound guided endoscopic necrosectomy and tem-
porary cystogastrostomy for infected pancreatic necrosis by using CSEMSs.
Patient details, disease severity scores, scores for severity assessed at CT, treat-
ment procedures, length of hospital stay, and outcome for patients undergoing
endoscopic therapy were recorded. Patients proceed to intervention if infection is
strongly suspected on clinical and radiological grounds or is confirmed bacter-
iologically. After the necrosis cavity had been accessed, with the assistance of
endoscopic ultrasound, a large orifice was created and necrotic debris was
removed using special short fully covered 15mm diameter SEMS with large
flares was deployed across the tract under radiological control. Completeness
of the necrosectomy procedure was ascertained by visualization of a clear pseu-
docyst cavity on endoscopy.
RESULTS: A total of 12 patients (10 men, 2 women; median age 39, range 19 -
76) were treated successfully. Median APACHE 2 score on presentation was 11
(range 318). Two patients presented with organ failure and needed intensive
care. Necrosis was successfully treated endoscopically in all patients, requiring a
median of 2 endoscopic interventions (range 14). The tissue samples obtained at
the first necrosectomy confirmed infection in 12 patients. Complication included
superinfection in patient who made an uneventful recovery. After median of 5
weeks the metal SEMS was extracted by endoscopy. The patients have remained
asymptomatic and median follow-up was 4 (211) months.
CONCLUSION: Endoscopic necrosectomy and temporary cystogastrostomy
with self-expanding metallic stent approach is feasible, safe, and effective in
patient with infected pancreatic necrosis. The benefits of this endoscopic
approach using fully covered self-expandable metallic stent in terms of less mor-
bidity is conceivable and our report demonstrates that such an approach is
feasible.
Disclosure of Interest: None declared
P0660 EUS-GUIDED PANCREATIC PSEUDOCYST DRAINAGE: AN
ASSESSMENT OF EFFICACY, SAFETY, LONG-TERM FOLLOW-UP,
AND TECHNICAL FEASIBILITY OF SINGLE-STEP APPROACH
A. Krishnan1,*, R. Ramakrishnan1 on behalf of None
1
Fortis Malar Hospitals, Chennai, India
Contact E-mail Address: dr.arunkumarpillai@gmail.com
INTRODUCTION: Pancreatic pseudocyst is common complication of acute and
chronic pancreatitis. While surgery is associated with significant complications
and mortality, percutaneous drainage is associated with prolonged hospitaliza-
tion and often times the need for other adjunctive treatment.
AIMS & METHODS: Assess the safety and efEcacy of single-step EUS-guided
pseudocyst drainage, evaluate the technical Feasibility.
69 patients who had undergone Single-step EUS guided drainage of pancreatic
pseudocyst were included. Controlled radial expansion wire guided balloon dila-
tion of the puncture tract was performed followed by insertion 10 Fr double
pigtail stents were inserted into the pseudocyst from either the stomach or the
duodenum in adults and 7F stents in children.
RESULTS: The mean age of 39 years. Median size was 12.5 cm in diameter. 56
patients had infected and rest had non-infected pseudocyst. Stent placement was
successful in all. The technical success rate was 100%, and the treatment success
rate was 98.5%. 54 patients had cystogastrostomy and rest of the patients had
cystoduodenostomy with cyst drainage. There was one case with perforation and
required an emergency operation. 98.5% patients had complete resolution of a
pseudocyst. The double pigtail stent was removed in all cases after median dura-
tion of 10 weeks. Regarding long-term outcomes, recurrence of a pseudocyst was
not observed over a median follow-up of 58 weeks.
CONCLUSION: Single-step EUS-guided transmural drainage is safe and asso-
ciated with high success rate. It can be the first choice for therapy of pancreatic
pseudocyst with good technical feasibility, efficacy, and safety with long-term
results are acceptable.
Disclosure of Interest: None declared
A314 United European Gastroenterology Journal 2(5S)
of patients affected by an initial episode of AP admitted to a single tertiary
P0661 EUS-GUIDED INTERVENTION IN WALLED-OFF PANCREATIC
referral center.
NECROSIS (WOPN): SINGLE CENTER EXPERIENCE WITH LONG
AIMS & METHODS: 196patients admitted to our center for an initial episode of
TERM FOLLOW-UP
AP were consecutively enrolled and prospectively followed for 52.5 (26.8) month-
M.C. Sulz1, C. Meyenberger1,* s[mean (SD)]. Clinical characteristics,exogenously and endogenously associated-
1
Department of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. factors,and evolution to RAP and CP were analyzed.
Gallen, Switzerland RESULTS: 40patients developed RAP and 13 of these developed CP. The annual
Contact E-mail Address: michael.sulz@kssg.ch relapse rate was 5.4 (CI 95% 4.0-7.4) per 100 person-years. In univariate analysis,
RAP was associated with idiopathic etiology (p50.001), pancreas divisum (PD)
INTRODUCTION: Necrotising pancreatitis is associated with high morbidity (p 0.001), higher cigarettes and alcohol intake (p50.001; p 0.023). CP was
and mortality [1-3]. Walled-off pancreatic necrosis (WOPN) is defined as a associated with severe AP first-episode (p 0.048), PD (p 0.03), and cigarettes
mature, encapsulated necrotic collection with well defined wall. Early interven- smoking (p 0.038). By multivariate analysis,PD was an independent risk factor
tion (5 4 weeks) should be avoided whenever possible [4, 5]. Compared to the for RAP development (OR 11.5, 95% CI 1.6-83.3). Severe AP first episode
traditional surgical necrosectomy, the endoscopic treatment shows significant increased the risk of progressing to CP by nine-fold (OR 9.3, 95% CI 1.8-
reduction of major complications, of pancreatic fistula, and of pro-inflammatory 47.2). Mutation frequencies of CFTR and SPINK-1 N34S were substantially
response (IL-6). We present the largest prospective single-center experience higher compared to the general population but not statistically significant.
regarding endoscopic treatment of WOPN in Switzerland with long term CONCLUSION: Understanding the factors that may predispose to RAP and CP
follow-up and add data to the increasing experience with this technique. holds important clinical implications for the prevention of disease progression.
AIMS & METHODS: To evaluate the short- and long term outcome of patients Special attention should be given to patients who experienced a severe first attack
with walled-off pancreatic necrosis (WOPN) after endoscopic treatment. This of AP, given the increased risk of developing CP.
retrospective, observational study at a single center with tertiary care endoscopy Disclosure of Interest: None declared
in Switzerland included all patients with necrotising pancreatitis from 2002 until
2013 complicated by WOPN who underwent endoscopic treatment (two experi-
enced interventionalists). Clinical short term success (530 days) was defined as P0663 A PROSPECTIVE MULTICENTER EVALUATION OF THE
resolution of patients symptoms requiring no further interventions. Clinical fail- RADIOLOGICAL PERFORMANCE OF THE REVISED ATLANTA
ure was defined as failure to either resolve the collection, or requiring other CLASSIFICATION
interventions, and/or complications requiring other therapeutic modalities (e.g. H. Sternby1,*, R.C. Verdonk2, A. Dimova3, P. Ignatavicius 4, L. Ilzarbe5,
surgery), and/or death. Approval was obtained by the local Ethical committee. P. Koiva6, A. Nieminen7, T.L. Bollen8 on behalf of Pancreas 2000 Atlanta Group
RESULTS: 35 Caucasian patients with WOPN (median age 64.1 y, range 40-85 1
Dep of Surgery, ICS, Malmo, Sweden, 2Dep of Gastroenterology, AZ,
y; ASA II and III 51.3% and 35.9%; 73.1% males) underwent endoscopic treat- Nieuwegein, Netherlands, 3Dep of Surgery, UHP, Sofia, Bulgaria, 4Dep of
ment. The biliary disease was the primary cause of necrotising pancreatitis Surgery, HLUHS, Kaunas, Lithuania, 5Dep of Gastroenterology, HdM,
(57.1%). The median duration of pigtails was 52 days (range 8-552 days), the Barcelona, Spain, 6Dep of Gastroenterology, ETCH, Tallinn, Estonia, 7Dep of
median duration of transpapillary stents was 82.5 days (range 5-563 days). The Surgery, HUS, Helsinki, Finland, 8Dep of Radiology, AZ, Nieuwegein,
short- and long term results results are shown in Table 1. Netherlands
Contact E-mail Address: hannasternby@gmail.com
Short- and longterm outcome %
INTRODUCTION: The Revised Atlanta Classification defines morphological
Complete clinical success 62.3 features and descriptions of acute pancreatitis (AP) and its complications to
enable standardized reports and communication. New computer tomography
Radiological success 75.3 (CT) criteria are introduced to describe local complications in AP. However,
complete/ partial 20.8/54.5 these CT criteria have not yet been validated in an international setting.
Short term mortality (530d) 11.5 AIMS & METHODS: The aim of this study was to analyze the interobserver
Complication rate 26.7/15.4/11.5 agreement of the revised Atlanta criteria for CT findings in AP. Patients with a
Overall/related to endotherapy/to drainage first episode of AP who obtained a CT were consecutively enrolled at six
European centers. The CTs of each center were prospectively scored separately
Rate of additive radiological drainage 15.4 by a local radiologist at each center and an expert central radiologist (repre-
Rate of additive surgery 23.1 senting the reference standard) using the criteria stated in the Revised Atlanta
Hospital stay, days, median (range) 41 (3-114) Classification. No specific training was provided for the local radiologists before
Time of follow-up, months (median, range) 30.5 (1-180) scoring. Interobserver agreement was determined using Kappa statistics. Clinical
data was collected retrospectively.
Longterm clinical well-being 76.9 % RESULTS: 285 patients (56 % males) with a median age of 58 years with 388
Long term mortality (related to disease) 12.0 % CTs in total were enrolled. Aetiology of AP was gallstones in 36.6 %, alcohol in
After endoscopic treatment/after surgery 4.0/8.0% 35.9 %, and idiopathic in 27.5 % of the patients. AP was mild in 37,5 % of the
Secondary clinical failure (%) 21.7 % patients, in 51.5 % moderately severe, and severe in 10.9 %. Overall interobser-
ver agreement was moderate to substantial. However, the agreement differed
Re-treatments (%) 14.3 % substantially between the participating centers. The center independent kappa
Elective surgery 23.8 % values for the different categories are shown in the table below.

Category scored Kappa value - Agreement

CONCLUSION: Our short term and long term follow-up data confirm that
endoscopic interventions in WOPN are effective and safe. Future randomized Type of pancreatitis 0,370 - Fair
prospective multicenter trials are needed to increase the generalizability.
REFERENCES Parenchymal necrosis 0,539 - Moderate
1 Banks PA, et al. Am J Gastroenterol 2006; 101: 2379. Extrapancreatic necrosis (EXPN) 0,326 - Fair
2 Martinez J, et al. Pancreatology 2006; 6: 206. Presence of Collections 0,756 Substantial
3 Chauhan S, et al. Am J Gastroenterol 2010; 105: 443. Location of Collections 0,633 - Moderate
4 Freeman ML, et al. Pancreas 2012; 41: 1176-1194.
5 Baron TH, et al. Clin Gastroenterol Hepatol 2012; 10: 1202-1207. Characteristics of Collections 0,408 - Fair
Disclosure of Interest: None declared Presence and Characteristics of Wall 0,675 - Substantial
Presence of gas/fluid level 0,764 - Substantial
Collection most appropriate term 0,356 - Fair
P0662 SINGLE-CENTER PROSPECTIVE, COHORT STUDY OF THE
NATURAL HISTORY OF ACUTE PANCREATITIS
G.M. Cavestro1,*, G. Leandro2, M. di leo1, R.A. zuppardo1, O.B. Morrow3,
C. Notaristefano1, G. Rossi1, S.G. G. Testoni1, G. Mazzoleni1, M. Alessandri1, In four categories agreement was merely fair. Detailed analysis showed that the
E. Goni1, S.K. Singh4, A. Giliberti2, M. Bianco2, L. Fanti1, E. Viale1, low kappa values can be explained by discrepancies in the identification of extra-
P.G. Arcidiacono1, A. Mariani1, M.C. Petrone1, P.A. Testoni1 pancreatic necrosis (EXPN). In most centers, the local radiologists identified
1
Division of Gastroenterology and Gastrointestinal Endoscopy, Gastroenterology EXPN less frequently than the expert central radiologist (126 vs 230 cases).
and Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific CONCLUSION: For most findings, interobserver agreement is moderate to
Institute San Raffaele, Milan, 2Gastroenterology Unit 1, Gastroenterological good when CTs are scored according to the Revised Atlanta Classification
Hospital S. De Bellis IRCCS, Castellana Grotte, 3Gastroenterology and even without prior training or instructions. However, the identification of
Gastrointestinal Endoscopy, Vita-Salute San Raffaele University, Scientific EXPN remains problematic with poor interrater agreement. Previous studies
Institute San Raffaele, Milan, Italy, 4Section of Gastroenterology, Boston suggest that EXPN might be considered a separate entity in acute pancreatitis.
University School of Medicine and Boston Medical Center, Boston, United States Given the results of this study, the definition and recognition of EXPN deserves
Contact E-mail Address: cavestro.giuliamartina@hsr.it further study.
Disclosure of Interest: None declared
INTRODUCTION: The natural history of acute pancreatitis(AP) is based on
retrospective studies that elucidate the possible course of disease. The aim of this
prospective, observational study was to evaluate the long-term occurrence of
recurrent acute pancreatitis (RAP) and chronic pancreatitis (CP), in a cohort
United European Gastroenterology Journal 2(5S)
P0664 ORAL UDENAFIL AND ACECLOFENAC FOR THE PREVENTION
OF POST-ERCP PANCREATITIS IN HIGH-RISK PATIENTS: A
RANDOMIZED, PLACEBO-CONTROLLED, MULTICENTER STUDY
H.-C. Oh1,*, T.Y. Lee2, J.S. Choi3, T.Y. Park1, J.H. Do1, Y.K. Cheon2,
T.J. Song4
1 1
GASTROENTEROLOGY, CHUNG-ANG UNIVERSITY COLLEGE OF
MEDICINE, 2GASTROENTEROLOGY, Konkuk University, Seoul,
3
GASTROENTEROLOGY, Inje Univ Busan Paik Hosptial, Busan,
4
GASTROENTEROLOGY, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: ohcgi@cau.ac.kr
INTRODUCTION: Acute pancreatitis is a common complication of ERCP.
Combination therapy with oral udenafil and aceclofenac may reduce the occur-
rence of post-ERCP pancreatitis by targeting different pathophysiological
mechanisms underlying acute pancreatitis. This study aimed to determine
whether combining udenafil and aceclofenac reduces the rates of occurrence of
post-ERCP pancreatitis.
AIMS & METHODS: A prospective, randomized, double-blind, placebo-con-
trolled, multicenter study was conducted in four academic medical centers.
Between January 2012 and June 2013, a total of 216 patients who underwent
ERCP were analyzed for the occurrence of post-ERCP pancreatitis. Patients
were determined to be at high risk for pancreatitis on the basis of validated
patient and procedure-related risk factors.
RESULTS: Demographic features, indications for ERCP, and therapeutic pro-
cedures were similar in each group. There was no significant difference in the rate
(15.8% [17/107] vs. 16.5% [18/109], p .901) and severity of post-ERCP pan-
creatitis between the udenafil/aceclofenac and placebo groups. One patient in
each group developed severe pancreatitis. On multivariate analyses, suspected
sphincter of Oddi dysfunction and endoscopic papillary balloon dilatation with-
out sphincterotomy were associated with post-ERCP pancreatitis.
CONCLUSION: Combination therapy with udenafil and aceclofenac was not
effective for the prevention of post-ERCP pancreatitis.
Disclosure of Interest: None declared
P0665 NASOGASTRIC TUBE FEEDING VERSUS NASOJEJUNAL TUBE
FEEDING IN SEVERE ACUTE PANCREATITIS
J.M. Rubio1,*
1
Section of Gastroenterology, Philippine General Hospital, Manila, Philippines
Contact E-mail Address: jowi5271@yahoo.com
INTRODUCTION: Severe acute pancreatitis is a major cause of morbidity and
mortality. Reviews have advocated enteral nutrition over parenteral nutrition in
its management. Nasogastric tube is easier to insert than nasojejunal tube. The
objective of this study is to determine the efficacy of nasogastric tube feeding in
terms of exacerbation of pain, mortality, pancreatic infection and complications
such as diarrhea in comparison to nasojejunal feeding.
AIMS & METHODS: RCTs among patients with severe acute pancreatitis
comparing NGT feeding to NJT feeding were selected for inclusion. Search for
randomized controlled trials was carried out using search engines such as
PubMed, Ovid, Google scholar. Search terms were severe acute pancreatitis, early risk stratification and APACHE-IL score for fluid collection prediction.
enteral nutrition and other synonyms listed in MeSH. The data were analyzed Disclosure of Interest: None declared
using Review Manager RevMan5.
RESULTS: 86 studies were found. Only 3 studies were included. NGT feeding
did not result in an increase in exacerbation of pain as compared to NJT feeding
(CI 0.31-3.22, p value 0.99). There was no significant difference between NGT
and NJT feeding in terms of mortality (CI 0.38-2.06, p value 0.77). NGT feeding
showed a trend towards benefit in reducing pancreatic infection (CI 0.17-1.76, p
value 0.31). NGT feeding showed a trend toward causing diarrhea (CI 0.56- 4.05,
p value 0.42).
CONCLUSION: NGT feeding is comparable to NJT feeding in exacerbation of
pain, incidence of infection, complications such as diarrhea and mortality. NGT
feeding can be used as an alternative to NJT feeding in institutions where an
endoscopy guided NJT insertion cannot be done
REFERENCES
1. Kumar A, Singh N, Prakash S, et al. Early enteral nutrition in severe acute
pancreatitis: A prospective randomized controlled trial comparing nasojejunal
and nasogastric routes. Clin Gastroenterol 2006; 40: 431-434.
2. Eatock FC, Chong P, Menezes N, et al. A randomized study of early naso-
gastric tube versus nasojejunal feeding in severe acute pancreatitis. Am J
Gastroenterol 2005; 100: 432-439.
3. Singh N, Sharma B, Sharma M, et al. Evaluation of early enteral feeding
through nasogastric and nasojejunal tube in severe acute pancreatitis. Pancreas
2012; 41: 153-159.
4. Petrov M, Correia M and Windsor J. Nasogastric tube feeding in predicted
severe acute pancreatitis. A systematic review of the literature to determine safety
and tolerance.
5. McClave S, Chang W, Dhaliwal R, et al. Nutrition support in acute pancrea-
titis: A systematic review of the literature. J Parenter Enteral Nut
6. Feldman M, Friedman L and Brandt L. Sleisenger and Fordtrans gastrointest-
inal and liver disease. 9th ed., 2010.
Disclosure of Interest: None declared
A315
P0666 CLINICAL PREDICTABILITY OF FLUID COLLECTIONS IN
ACUTE PANCREATITIS USING INTERLEUKIN-6 LEVEL AND
NOVEL APACHE-IL SCORE
S. Appasani1,*, J. Basha1, M. manrai1, P. Siddappa1, T. Yadav2, V. Gupta2,
P. Sarotra3, S.K. Sinha1, R. Kochhar1
Gastroenterology, 2Surgery, 3Clinical Pharmacology, PGIMER, Chandigarh,
India
Contact E-mail Address: drasreekanth@gmail.com
INTRODUCTION: Cytokine storm occurring in early phase of acute pancrea-
titis (AP) plays an important role in development of local & systemic complica-
tions. Fluid collections contribute significantly to the morbidity of this illness,
hence its predictability in early phase could help in clinical triage.
AIMS & METHODS: AIMS
To prospectively evaluate the role of cytokine estimation at admission to predict
the formation of fluid collections and correlate it with standard scoring systems.
MATERIALS AND METHODS
110 consecutive patients (69% males, age 1770yrs) with AP were evaluated after
an informed consent from Jan2012-March2013. Patients were stratified into
mild, moderate & severe pancreatitis as-per revised Atlanta criteria and were
treated with nutritional & organ support. Serum cytokine (Interleukin (IL) 6,
10, Tumor Necrosis Factor (TNF) Alpha) and fibronectin levels were analyzed
quantitatively at admission (ELISA). APACHE, BISAP & SIRS scores were also
calculated. Cytokine levels were compared with standard parameters while ana-
lyzing severity, development of fluid collections and outcome of AP using SPSS
v17.0.
RESULTS: The median levels of IL-6 were higher in patients with severe pan-
creatitis (761.78pg/ml, n 42) than in those with mild pancreatitis (277.80pg/ml,
n 40) and moderate pancreatitis (397.50pg/ml, n 28, p 0.038). At a cut off
of 488pg/ml, IL-6 had a sensitivity of 85% & specificity of 75% in predicting
severe pancreatitis (AUC 0.702, p 0.016). The median IL-6 levels were higher
in patients with necrosis (635.0pg/ml) than in those without (372.5pg/ml,
p 0.008) as well in patients with organ failure than those without (540.35pg/
ml vs. 406.42pg/ml, p 0.046). Serum IL-10, TNF Alpha and fibronectin levels
did not correlate with these events. Pearson & Spearman bivariate analysis
revealed good correlation of IL-6 with CTSI (0.432, p 0.001), APACHE
score (0.354, p 0.032), BISAP score (0.316, p 0.019) and SIRS score (0.487,
p 0.007).
Patients who developed fluid collections had higher IL-6 levels than those who
did not (524.28pg/ml vs 358.21pg/ml, p 0.031). IL-6 levels also correlated with
the type of collection (acute necrotic collection vs. acute peripancreatic fluid
collection, p 0.017). Standard APACHE score predicted only severity and
necrosis but did not correlate with fluid collections. Hence we postulated a
new APACHE-IL score by adding 2 points to standard APACHE score if IL-
6 levels were elevated (4488pg/ml). At a cut off of 6, APACHE-IL score had a
sensitivity of 85% and specificity of 80% in predicting development of fluid
collections (AUC 0.746, p 0.027).
CONCLUSION: IL-6 level at admission is an effective predictor of severity of
acute pancreatitis (as per revised Atlanta) as well as of development of organ
failure, necrosis and fluid collections. We recommend IL-6 to be measured for
P0667 SLC26A6 VARIANTS ARE NOT ASSOCIATED WITH CHRONIC
PANCREATITIS
A. Balazs1,*, E. Hegyi1,2, B.C. Nemeth3, I. Hritz1, F. Izbeki4, J. Gervain5,
A. Szepes6, G. Gyimesi7, Z. Dubravcsik7, A. Csiszko8, D. Kelemen9,
Z. Szentkereszty8, B. Bod10, J. Sumegi11, J. Novak12, A. Parniczky13,
N. Lasztity13, G. Veres14, C. Andorka14, R. Szmola15, J. Czelecz16, A. Vincze17,
J. Bajor17, G. Farkas18, L. Czako1, T. Takacs1, Z. Rakonczay19, J. Maleth19,
A. Pap15, P. Hegyi1 on behalf of Hungarian Pancreatic Study Group
1
First Department of Medicine, University of Szeged, Szeged, Hungary, 22nd
Department of Pediatrics, University Childrens Hospital, Comenius University
Medical School, Bratislava, Slovakia, 3Department of Molecular and Cell Biology,
Boston University, Boston, United States, 4Fejer Megyei, Szent Gyorgy Hospital,
5
Fejer Megyei, Szent Gyorgy Hospital, Szekesfehervar, 6Bacs-Kiskun County,
7
Bacs-Kiskun County, Municipality Hospital, Kecskemet, 8Department of Surgery,
University of Debrecen, Debrecen, 9Department of Surgery, University of Pecs,
Pecs, 10Dr Bugyi Istvan, Hospital, Szentes, 11B-A-Z County, Hospital, Miskolc,
12
Pandy Kalman, County Hospital, Gyula, 13Heim Pal Childrens Hospital,
14
Paediatric Department, Semmelweis University, 15National Institute of
Oncology, 16Bethasda Childrens Hospital, Budapest, 17Department of Internal
Medicine, University of Pecs, Pecs, 18Department of Surgery, University of Szeged,
19
First Department of Medicine, University of Szeged, Szeged, Hungary
Contact E-mail Address: anitabalazs@outlook.com
INTRODUCTION: Cystic Fibrosis Transmembrane Conductance Regulator
(CFTR) mutations are established risk factors for chronic pancreatitis (CP).
CFTR variants increase disease risk by causing impairment of pancreatic
ductal bicarbonate secretion. However, the role of genetic variations in the bicar-
bonate secreting SLC26A6 anion transporter has remained largely unexplored so
far.
AIMS & METHODS: Our aim was to investigate the role of the SLC26A6 gene
in CP. 96 subjects with CP (cases) and 99 subjects with no pancreatic disease
(controls) were recruited from the Hungarian National Pancreas Registry. In a
discovery cohort of 30 idiopathic CP cases the entire SLC26A6 coding sequence,
including 21 exons and the exon-intron boundaries were amplified and
sequenced. Further genotyping of p. V206M and p. P397P mutations in CP
and controls was carried out by RFLP.
A316
RESULTS: Sequencing analysis of the discovery cohort revealed four common
mutations: intronic mutations c.2371_23103del, c.183-4C4A and
c.113432C4A; and exonic missense mutation p. V206M. These four mutations
were found in linkage disequilibrium indicating a conserved haplotype. We found
this haplotype in 18 heterozygous and 2 homozygous cases, and in 24 hetero-
zygous and 2 homozygous controls (allele frequency 11.4% and 14.1% respec-
tively). A synonymous mutation p. P397P was also detected in a single case.
CONCLUSION: We found a novel, common haplotype in the SLC26A6 gene,
which did not show association with CP. Supported by TAMOP and OTKA
Disclosure of Interest: None declared
P0668 PANCREATIC EXOCRINE INSUFFICIENCY IN PATIENTS WITH
HIV AND CHRONIC DIARRHOEA
A. Jeevagan1,*, M. AUSTIN1, S. Soni2
1
Gastroenterology, 2Sexual Health and HIV, Lawson Unit, Royal Sussex County
Hospital, BRIGHTON, United Kingdom
Contact E-mail Address: arun.jeevagan@nhs.net
INTRODUCTION: Chronic Diarrhoea (CD) in HIV-infected patients is an
important cause of morbidity and has significant impact on their quality of
life. Pancreatic exocrine insufficiency has been shown to be associated with
HIV and has been suggested as an important non-infective cause of diarrhoea
and fat malabsorption in these individuals.
AIMS & METHODS: HIV-positive patients undergoing investigation for CD
between January 2011 and August 2013 were identified. Demographics and clin-
ical data including measurement of faecal elastase were taken from the patients
medical records.
RESULTS: 60 patients were referred by the HIV team to Gastroenterology clinic
for investigation of CD. There were 55 (92%) male and mean age was 44 years.
All were receiving antiretroviral therapy. No patients had a diagnosis of chronic
pancreatitis. 31/60 patients had raised faecal calprotectin, one had stool culture
positive for giardiasis, one had lymphocytic gastritis and so 34 patientswere
excluded from the study. Out of these, 27 patients who had faecal elastase mea-
surements and 9/27 (30%) had pancreaticin sufficiency.
CONCLUSION: In patients with HIV on antiretrovirals, in whom inflammation
and infection had been excluded, approximately 30% of patients were confirmed
to have pancreatic exocrine insufficiency. This prevalence is greater than that
seen in HIV-negative individuals with chronic diarrhoea. HIV treatment with
didanosine or stavudine-containing antiretroviral regimens used to be the main
culprit but these drugs are seldom used in the management of HIV nowadays and
other causes must be considered. Faecal elastase sampling should form part of
the routine work-up for HIV-positive patients with chronic diarrhoea. Treatment
with pancreatic enzyme supplementation is effective treatment of chronic diar-
rhoea in these patients.
Disclosure of Interest: None declared
P0669 THE ROLE OF SPINK1 PROXIMAL PROMOTER VARIANTS IN
CHRONIC PANCREATITIS
E. Hegyi1,2, A. Geisz3, T. Takacs2, G. Farkas, Jr4, Z. Szepes2, J. Novak5,
F. Izbeki6, J. Gervain6, I. Hritz2, A. Szepes7, D. Kelemen8, Z. Dubravcsik7,
B. Bod9, R. Szmola10, J. Sumegi11, Z. Szentkereszti12, Z. Rakonczay, Jr2,
A. Balazs2,*, P. Hegyi2, M. Sahin-Toth3, L. Czako2 on behalf of Hungarian
Pancreatic Study Group
1
2nd Department of Pediatrics, Comenius University Medical School, University
Childrens Hospital, Bratislava, Slovakia, 2First Department of Medicine,
University of Szeged, Szeged, Hungary, 3Department of Molecular and Cell
Biology, Boston University Medical Center, Boston, United States, 4 Department
of Surgery, University of Szeged, Szeged, 5Bekes Megyei Pandy Kalman Hospital, UNIVERSITY SCHOOL OF MEDICINE, ROME, Italy, 2Dept of
Gyula, 6Fejer Megyei Szent Gyorgy Hospital, Szekesfehervar, 7Bacs-Kiskun Cardiovascular Medicine, Amsterdam Medical Center, Amsterdam, Netherlands,
Megyei Hospital, Kecskemet, 8Department of Surgery, University of Pecs, Pecs,
9
Dr. Bugyi Istvan Hospital, Szentes, 10National Institute of Oncology, Budapest,
11
Borsod-Abauj-Zemplen Megyei Hospital, Miskolc, 12 Department of Surgery,
University of Debrecen Medical School and Health Science Center, Debrecen,
Hungary
Contact E-mail Address: hegyi.peter@med.u-szeged.hu
INTRODUCTION: Serine protease inhibitor Kazal type 1 (SPINK1) provides
an important line of defense against premature trypsinogen activation within the
pancreas. The most common SPINK1 mutation p. N34S seems to increase the
risk of chronic pancreatitis (CP), but the precise pathophysiological mechanism
of this mutation remains a subject of debate.
AIMS & METHODS: To determine the frequency of the p. N34S SPINK1
mutation in Hungarian patients with alcoholic chronic pancreatitis (ACP) and
idiopathic chronic pancreatitis (ICP) and to identify a possible pathogenic pro-
moter variant linked with the p. N34S mutation. 70 subjects with CP (cases) (34
ACP and 36 ICP) and 70 subjects with no pancreatic disease (controls) were
enrolled from the Hungarian National Pancreas Registry. Direct sequencing of
the SPINK1 proximal promoter region (1 kb) was performed. The p. N34S
SPINK1 mutation was analysed by RFLP.
RESULTS: The p. N34S mutation was present in 3/70 patients, all with the
diagnosis of ICP, while it was absent in healthy controls (P 0.24). Two pro-
moter variants (c.-253T4C and c.-807C4T) were found as common polymorph-
isms indicating no clinical significance. Additionally, three rare promoter
variants (c.-14G4A, c.-108G4T, and c.-215G4A) were identified in cases.
The c.-215G4A variant was linked with the pathogenic c.1942T4C mutation.
The clinical significance of the c.-14G4A and c.-108G4T variants is unclear so
far.
CONCLUSION: We identified two novel variants in the proximal promoter
region of SPINK1 which will be further investigated to determine their possible
United European Gastroenterology Journal 2(5S)
association with CP. No associations were found between the p. N34S mutation
and promoter region variants of the SPINK1 gene.
Supported by TAMOP, OTKA and MTA and Collegium Talentum scholarship
(to E. H.).
Disclosure of Interest: None declared
P0670 QUANTIFICATION OF EXOCRINE DUCTAL PANCREATIC
FUNCTION USING A SHORT ENDOSCOPIC SECRETIN TEST AND
AUTOMATIC DUODENAL BICARBONATE MEASUREMENT
F. Erchinger1,2,*, O.A. Gudbrandsen2, T. Engjom2,3, E. Tjora4, D. Hoem5,
T. Hausken2,3, O.H. Gilja2,6, G. Dimcevski2,3
1
Medical Department, Voss Hospital, Voss, 2Department of Clinical Medicine,
University of Bergen, 3Department of Medicine, 4Department of Pediatrics,
5
Surgical Department, 6National Centre for Ultrasound in Gastroenterology,
Haukeland University Hospital, Bergen, Norway
Contact E-mail Address: friedemann.erchinger@helse-bergen.no
INTRODUCTION: A short endoscopic secretin test has recently been evaluated
in different patient groups and provides useful information about exocrine ductal
pancreatic function(1-3). Bicarbonate in duodenal juice is an important parameter
in direct pancreas function testing. Gold standard is measurement of bicarbonate
by back titration right after endoscopy, but this is time consuming, and requires
specialised equipment and highly skilled laboratory staff. A simplified method is
warranted.
AIMS & METHODS: The aim was to determine if back titration can be replaced
by an automated spectrophotometric method.
Patients examined with short endoscopic secretin test suspected to have decreased
pancreatic function of various reasons. Bicarbonate in duodenal juice was ana-
lysed both by back titration and automatic spectrophotometry. In our short
endoscopic secretin test duodenal juice is suctioned in three aliquots of 5 minutes.
Both fresh and thawed samples were analysed.
RESULTS: 122 samples from 49 patients (25 men/24 women) were analysed.
Correlation coefficient of all measurements was r 0.98. Correlation coefficient
of fresh versus frozen samples conducted with automatic spectrophotometry
(n 27): r 0.96.
CONCLUSION: The measurement of bicarbonate in both fresh and thawed
samples, by automatic spectrophotometric analysis correlates excellent with mea-
surements made by back titration. This is a major simplification of direct pan-
creas function testing, and makes it possible to perform such tests standardised in
all hospitals, in a time- and centre-independent way.
REFERENCES
(1) Erchinger F, Engjom T, Tjora E, et al. Quantification of pancreatic function
using a clinically feasible short endoscopic secretin test. Pancreas 2013.
(2) Tjora E, Wathle G, Erchinger F, et al. Exocrine pancreatic function in hepa-
tocyte nuclear factor 1beta-maturity-onset diabetes of the young (HNF1B-
MODY) is only moderately reduced: compensatory hypersecretion from a hypo-
plastic pancreas. Diabet Med 2013.
(3) Tjora E, Wathle G, Engjom T, et al. Severe pancreatic dysfunction but
compensated nutritional status in monogenic pancreatic disease caused by car-
boxyl-ester lipase mutations. Pancreas 2013.
Disclosure of Interest: None declared
P0671 EFFICACY OF ANTIOXIDANT THERAPY IN IMPROVING
PAINFUL CHRONIC PANCREATITIS: A SYSTEMATIC REVIEW
G. Ianiro1,1,*, L. Valerio2, M. Siciliano1, F. Scaldaferri1, I. Boskoski3,
G. Costamagna3, A. Gasbarrini1
1
Dept of Internal Medicine, Division of Gastroenterology, CATHOLIC
3
Digestive Endoscopy Unit, CATHOLIC UNIVERSITY SCHOOL OF
MEDICINE, ROME, Italy
Contact E-mail Address: gianluca.ianiro@hotmail.it
INTRODUCTION: To date, there is no standardized treatment for pain caused
by chronic pancreatitis. Medical, endoscopic or surgical therapy are the currently
available approaches. Antioxidants have been proposed on the rationale that
they may slow down the damage of the gland produced by oxidative stress.
Although several trials have been carried out over the years, no one of them
showed convincing results.
AIMS & METHODS: Our aim was to systematically review the literature related
to the efficacy of antioxidants in improving painful chronic pancreatitis. This
systematic review was conducted in accordance with the PRISMA guidelines. All
the original reports in which human subjects, both children and adults, with
chronic pancreatitis were treated with antioxidants were considered for inclusion.
Inclusion criteria also required the pain as endpoint, and the report of efficacy
outcomes. No language restriction was set up. Animal model studies, studies
presented only as abstracts, case reports and case series with less than 10 patients
were excluded. The following databases were used to perform the literature
search: PubMed, SCOPUS, Web of Science, the Cochrane Library. The last
search was run on 27 February 2013. The following MeSH terms and keywords
were used alone or in combination: antiox*; vitamin supplement; antioxidant
supplement; vitamin A supplement; vitamin B6 supplement; vitamin B12 supple-
ment; folic acid supplement; vitamin C supplement; vitamin D supplement; vita-
min E supplement; selenium supplement; beta-carotene supplement; lycopene
supplement; isoflavone supplement; chronic pancreatitis. A quality appraisal of
the selected studies was performed.
RESULTS: The literature search retrieved 3590 studies; of these, 9 met our
inclusion criteria. Six were blinded randomized clinical trials, 2 open trials, and
1 a prospective cohort study. Their comparability was severely limited because of
United European Gastroenterology Journal 2(5S)
differences in the endpoints chosen, which include pain-free days, pain scores,
quality of life scores, and supportive care needed; possibly severe selection bias
and low statistical power due to small sample size were found in some studies.
The few points of partial convergence include a potential reduction in the need of
supportive therapies and inefficacy of antioxidants in alcoholic pancreatitis.
CONCLUSION: Available evidence is inconclusive: confirmation or refusal of
the efficacy of antioxidant therapies against pain in chronic pancreatitis needs to
be investigated by further randomized controlled trials, with adequate design and
standardized outcome variables, so as to allow for comparison.
Disclosure of Interest: G. Ianiro: nothing to declare, L. Valerio: nothing to
declare, M. Siciliano: nothing to declare, F. Scaldaferri: nothing to declare, I.
Boskoski: nothing to declare, G. Costamagna: nothing to declare, A. Gasbarrini:
nothing to declare
P0672 AUTOIMMUNE PANCREATITIS IN CHILDREN- SINGLE
CENTRE EXPERIENCE
G. Oracz1,*, B. Cukrowska2, K. Wejnarska1, E. Kolodziejczyk1, J. Kierkus1,
J. Ryzko1
1
Dep. of Gastroenterology, Hepatology and Feeding Disorders, 2Dep. of Pathology,
The Childrens Memorial Health Institute, Warsaw, Poland
Contact E-mail Address: grzegorz_oracz@poczta.onet.pl
INTRODUCTION: The etiology of chronic pancreatitis in children is varied and
includes gene mutations, anatomic anomalies, and others. The reported paedia-
tric experience with chronic pancreatitis (CP) is small and little is known about
the role of autoimmune pancreatitis (AIP).
AIMS & METHODS: The aim of the study was to assess the frequency of
autoimmune markers in children with CP.
136 children with CP hospitalized at the Department of Gastroenterology, The
Childrens Memorial Health Institute, between 2005 and 2014 were examined for
the presence of AIP; the level of IgG4 was determined, and the tests for anti-
tissue antibodies were conducted. AIP was diagnosed according to the IAP
guidelines, i.e. on the basis of immunological criteria (presence of antibodies:
IgG4 and autoantibodies), radiological criteria (swelling of the pancreatic
head, and changes in the pancreatic duct), and response to corticosteroid ther-
apy. Clinical data were recorded and analyzed.
RESULTS: Anti-tissue antibodies were detected in 85/136 children (62.5%), and
29/75 patients (38.6%) showed an increased IgG4 level. Based on the IAP cri-
teria, a suspicion of AIP was raised in 8 patients. This diagnosis was definitely
confirmed in 4 cases, based on clinical improvement observed after corticosteroid
therapy. Due to the inactive phase of the disease, the immunosuppressive therapy
was not implemented in the remaining suspected patients. In 41/85 (48.2%)
patients with autoimmune markers we found gene mutations predisposing to
CP. In 18/85 children (21.2%) anatomic anomalies were fund. There was no
difference in the severity of the disease and clinical course between children
with autoimmune stigmata and patients without autoimmune markers.
CONCLUSION: In children with CP, similarly to adults, there is a high fre-
quency of biochemical markers of autoimmunity. AIP can be the cause of CP in
children.
Disclosure of Interest: None declared
P0673 MATERIAL OBTAINED BY ENDOSCOPIC ULTRASOUND-
GUIDED FINE NEEDLE BIOPSY IS NOT ADEQUATE FOR THE
HISTOLOGICAL DIAGNOSIS OF EARLY CHRONIC PANCREATITIS
J. Iglesias-Garc a1,*, J. Larino-Noia1, I. Abdulkader2, B. Lindkvist3,
J.E. Dominguez-Munoz1
1
Gastroenterology, 2Pathology, University Hospital of Santiago de Compostela.
Foundation for Research in Digestive Diseases, Santiago de Compostela, Spain,
3
Institute of Medicine, Sahlgrenska Academy, University of Gothenburg,
Gothenburg, Sweden
INTRODUCTION: Diagnosis of early chronic pancreatitis (CP) is a clinical
challenge and it is hampered by the lack of methods for histological confirma-
tion. Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB), with the use
of ProcoreTM histology needles provides adequate samples for the histological
evaluation of solid pancreatic lesions, but the efficacy and safety of this technique
for early CP is unknown.
AIMS & METHODS: We aimed at evaluating the efficacy and safety of EUS-
FNB with ProcoreTM needles for the histological diagnosis of early CP.
Methods: A prospective, pilot study with consecutive inclusion of patients
between January and September 2013 was designed. Inclusion criteria: Patients
4 18 years old submitted to our Endoscopy Unit to undergo EUS examination
because of the clinical suspicion of chronic pancreatitis. Only patients with 3-4
EUS criteria of CP were finally included. EUS-guided FNB was performed by
two experienced endosonographers in these patients under deep sedation after
signing the informed consent. A linear slim Pentax echoendoscope (EG 3270 UK)
attached to a Hitachi Ascendus ultrasound device was used for EUS. FNB of the
body of the pancreas was performed with ProcoreTM needles of different sizes.
Samples obtained were immersed into a Cytolit solution for cytohistological
evaluation. All samples were evaluated by a single expert pathologist. The quality
of the samples obtained and the histological findings (inflammatory cells infiltra-
tion and fibrosis) were evaluated. Complications were recorded.
RESULTS: The study was stopped after the inclusion of 10 patients (mean age
50.3 years, range 33-70 years, 6 male) due to unsatisfactory results. Pancreatic
EUS-FNB was feasible in all cases. A 19G ProcoreTM needle was used in 5 cases,
a 22G needle in 2 and a 25G needle in 3 cases. Sample quality was considered
adequate for histological evaluation in only 3 cases (30%), (2 performed with a
19G needle and one with a 25G needle). Two out of these three biopsies revealed
a normal pancreatic tissue and the diagnosis of CP could not be confirmed. The
A317
remaining biopsy revealed pancreatic tissue with some areas of fibrosis. Samples
from the other seven patients (70%) were not adequate for cytohistological
diagnosis due to the absence of tissue and a poor cellularity. There was one
complication (10%), a mild acute pancreatitis requiring hospitalization for 48
hours.
CONCLUSION: EUS-FNB is feasible in the context of patients with EUS find-
ings of early CP. Samples obtained by the commercially available needles are
however not adequate for histological evaluation. In addition, the risk of com-
plications exists. EUS-FNB for the diagnosis of early CP should be avoided
unless new more appropriate needles are developed and can be evaluated for
efficacy and safety in well-designed clinical trials.
Disclosure of Interest: J. Iglesias-Garc a Lecture fee (s) from: Cook-Medical,
Consultancy for: Cook-Medical, J. Larino-Noia: None declared, I.
Abdulkader: None declared, B. Lindkvist: None declared, J. E. Dominguez-
Munoz: None declared
P0674 A CROSS SECTIONAL STUDY TO ASSESS THE PREVALENCE
OF PANCREATIC EXOCRINE INSUFFICIENCY AMONG DIABETES
MELLITUS PATIENTS IN TURKEY
K. Demir1,*, C. Karaca1, E. Ahishali2, M. Mastanzade3, N. Gul4, F. Turker4,
S. Celik4, F. Akyuz1, F. Besisik1, K. Karsidag4
1
Gastroenterology Department, Istanbul University Medical School,
2
Gastroenterology Department, Dr. Lutfi Kirdar Kartal Training and Research
Hospital, 3Internal Medicine Department, 4Endocrinology Department, Istanbul
University Medical School, Istanbul, Turkey
Contact E-mail Address: mehmet.berktas@kappa-crt.com.tr
INTRODUCTION: Pancreatic exocrine function insufficiency (PEI) is common
in diabetes mellitus patients. Apparently, some patients with decreased exocrine
function are type 3c diabetes mellitus (DM) and misdiagnosed as type 2 or type 1
DM. There are only few data about PEI in DM patients in Turkey. This study
aims to investigate exocrine insufficiency among DM patients in Turkey.
AIMS & METHODS: The objective of the study is to assess the prevalence of
pancreatic exocrine insufficiency among type 1 and type 2 diabetes mellitus
patients in Turkey. The abstract aims to present preliminary results of the study.
This is a cross sectional, non-interventional study which was conducted in
Turkey between October 2013 and February 2014. Adult patients (older than
18 years) previously diagnosed type 1 or 2 DM, admitted to endocrinology
department with or without symptomatic gastrointestinal problems, followed
for more than five years were included to the study.
PEI was evaluated by measuring faecal elastase-1 concentration, level 5100 g/g
stool was evaluated as severe PEI, whereas 100, 5200 g/g stool as mild-to-
moderate PEI and  200 g/g stool as normal (1). Upper detection limit of
method used for faecal elastase-1 concentration was 500 g/g stool.
RESULTS: Based on data of 211 DM patients [58.8% female, median (min-max)
age 58.2 (18.5-85.7) years], 146 (69.2%) were previously diagnosed type 2 DM
whereas others were type 1 DM. Median (min-max) DM duration of type 1 and 2
patients was 15.6 (5.0-43.6) and 13.5 (5.5-37.5) years, respectively.
Median (min-max) faecal elastase-1 concentration of type 1 and 2 DM patients
was 465.5 (104.0-500.0) and 474.0(52.0-500.0) g/g stool, respectively.
In entire study population, severe PEI prevalence was 1.9% (0.0% for type 1
DM, 2.7% for type 2 DM) whereas mild-to-moderate PEI prevalence was 12.3%
(17.2% for type 1 DM, 10.3% for type 2 DM). Overall; 14.2% of patients (17.2
% of type 1 DM, 13.0% of type 2 DM patients) have reduced PEI.
CONCLUSION: Preliminary results of the study revealed that PEI prevalence
among type 1 and type 2 patients was higher in Turkey and many DM patients
might be misclassified. In conclusion, evaluation of pancreatic exocrine function
in DM patients should be essential part of daily practice.
REFERENCES
1. Luth S, Teyssen S, Forssmann K, et al. Fecal elastase-1 determination: gold
standard of indirect pancreatic function tests? Scand J Gastroenterol 2001; 36:
1092-1099.
Disclosure of Interest: K. Demir Financial support for research from: Research
grant from Abbott Turkey, C. Karaca: None declared, E. Ahishali: None
declared, M. Mastanzade: None declared, N. Gul: None declared, F. Turker:
None declared, S. Celik: None declared, F. Akyuz: None declared, F. Besisik:
None declared, K. Karsidag: None declared
P0675 STUDY OF THE LIPID PROFILE AND THE OXIDATIVE STRESS
OF DIABETIC PATIENTS WITH CHRONIC PANCREATITIS
M. Sliwinska-Mosson1,*, S. Milnerowicz2, W. Sajewicz1, H. Milnerowicz1
1
Department of Biomedical and Environmental Analyses, 2Department of
Gastrointestinal and General Surgery, University of Medicine Wroclaw, Wroclaw,
Poland
Contact E-mail Address: mariola.sliwinska-mosson@umed.wroc.pl
INTRODUCTION: Smoking patients with chronic pancreatitis (CP) are at high
risk for antioxidant deficiencies (1). Moreover, this disease may lead to the
development of diabetes mellitus type II (DM2), which additionally enhances
the oxidative stress (2). The main characteristics of DM2 are insulin resistance
in muscle and liver cells accompanied by loss of -cell function. However, adi-
pose tissue and pancreatic cell activity, may be involved in disease development
(3). Most recently a trend for positive correlation between HDL cholesterol and
amylase in DM2 patients was shown.
AIMS & METHODS: In the present study we evaluated the lipid profile and
total peroxyl radical trapping potential (TRAP), glutathione (GSH), thiobarbi-
turic acid reactive substances (TBARS) in non-smoking and smoking patients
with CP suffering from diabetes. The relationship between different parameters
was examined. The blood was collected from 50 healthy persons and 63 patients
A318
with diagnosed chronic pancreatitis (CP). Diabetes mellitus was diagnosed in 24
patients. The concentration of cotinine and lipid profile in plasma was estimated
by the ELISA and diagnostic tests, respectively. Lipid peroxidation levels were
assessed by TBARS, and TRAP was measured by using luminescence.
Glutathione level was determined in blood hemolysates with the colometric
method.
RESULTS: The concentration of HDL were statistically lower in smoking
patients with CP with or without diabetes as compared to the control group,
while the concentration of TG and LDL were statistically highest in smoking
diabetics compared to all groups (p50.001). It was also observed that the con-
centration of TBARS was statistically significant increased in non-smoking and
smoking patients with CP (3.5  1.3 [mmol /l], 4.75  1.0 [mmol /l]), and patients
with CP and DM (5.3 2.6 [mmol/l]) as compared with control group (3.41.9
[mmol/l]). In smoking patients with DM, a statistical highest level of TRAP
compared to all study groups was found (p50.0001). Statistical analysis of the
results showed that the decline in the concentration of GSH is associated with
cigarette smoking and diabetes. The lowest concentration of GSH was observed
in smoking patients with CP and diabetes, the highest in non-smoking control
group (p50.0001).
CONCLUSION: The lipid profile is altered in smoking patients with CP, parti-
cularly in those who also have DM. In these patients, a glutathione deficiency
and an elevated plasma concentration of lipid peroxidation products were asso-
ciated with significantly higher LDL. In the diabetic patients group, a positive
correlation between TRAP and TBRAS was found, which points to the induction
of the antioxidant potential on intensification of lipid peroxidation.
REFERENCES
1.Sliwinska-Mosson M, et al. Pancreatology 2012; 12: 295-304.
2.de M Bandeira S, et al. Int J Mol Sci 2013; 5: 3265-3284.
3. Eleftheriou P, et al. Hell J Nucl Med 2014; 17(Suppl. 1): 35-39.
Disclosure of Interest: None declared
P0676 CLINICAL FEATURES OF PANCREATIC INVOLVEMENTS OF
VON HIPPEL-LINDAU DISEASE IN KOREA
T. Park1,*, S. Lee1
1
Department of Gastroenterology, Asan medical center, University of Ulsan
College of Medicine, Seoul, Korea, Republic Of
Contact E-mail Address: ptymd@hotmail.com
INTRODUCTION: Von Hippel-Lindau disease (VHL) is autosomal dominant
disorder characterized by development of multiple tumors in central nervous
system and visceral organs. There have been reported a few studies about clinical
courses of pancreatic involvements of VHL.
AIMS & METHODS: In this study, we report clinical features of pancreatic
involvements of VHL in Korea. We conducted retrospective cohort study of
55 patients who were diagnosed with VHL-associated pancreatic lesions from
1995 to 2013 in Asan Medical Center. Demographic, genetic, radiologic features
and clinical features of VHL-associated pancreatic lesions were analyzed by
medical record review.
RESULTS: 55 patients had VHL-associated pancreatic lesions (87.3%). Median
onset of age was 33 years (12-67 years) and male and female ratio was 31:24.
Median observation period was 1731 days (3-5077). Genetic test was performed
in 35/55 patients (63.6%) and VHL gene mutations were confirmed in 28/35
patients (80%). VHL gene mutation was located on exon 1 in 13 patients
(46.4%), exon 2; 4 (14.3%), exon 3; 9 (32.1%) and others 2 (7.2%). Mean
involved number of organs was 2.51  0.72. Most common subtype of VHL
was type I as 44/55 patients (80%). Pancreatic involvements were included single
simple cyst (n 5, 9.1%), multiple simple cysts (n 14, 25.5%), serous cystade-
noma (n 29, 52.7%) and neuroendocrine tumor (n 17, 30.9%). Initial pre-
sented VHL-associated tumors as only pancreatic lesions were observed in only 2
of 55 patients (3.6%) and pancreatic symptoms were only 4 patients (7.3%). Of
55 patients, 11 patients received surgical treatment and 2 patients received EUS-
guided ethanol ablation therapy as local treatment for neuroendocrine tumor and
42 patients were observed regularly without intervention (20%, 3.6%, 76.4%
respectively). One patient received distal pancreatectomy as radiologic diagnosis
of neuroendocrine tumor, however, final pathologic diagnosis was serous cysta-
denoma, which was thought to be solid microcystic serous adenoma (SMSA).
One patient was died of pulmonary hemorrhage due to pulmonary metastasis of
VHL-associated renal cell carcinoma.
CONCLUSION: Most common presentation of pancreatic involvement in VHL
was serous cystadenoma. Pancreatic tumors as primary presenting lesion in VHL
are relatively rare and most of pancreatic lesions were asymptomatic. Nationwide
epidemiologic study is needed to verify natural course and prognosis of pancrea-
tic involvement in VHL.
REFERENCES
1. Lonser RR, Glenn GM, Walther M, et al. von Hippel-Lindau disease. Lancet
2003; 361: 2059-2067.
2. Lee KH, Lee JS, Kim BJ, et al. Pancreatic involvement in Korean patients with
von Hippel-Lindau disease. J Gastroenterol 2009; 44: 447-452.
3. Hammel PR, Vilgrain V, Terris B, et al. Pancreatic involvement in von Hippel-
Lindau disease. The Groupe Francophone dEtude de la Maladie de von Hippel-
Lindau. Gastroenterol 2000; 119: 1087-95.
4. Igarashi H, Ito T, Nishimori I, et al. Pancreatic involvement in Japanese
patients with von Hippel-Lindau disease: results of a nationwide survey. J
Gastroenterol 2014; 49: 511-516.
5. Neumann HP, Dinkel E, Brambs H, et al. Pancreatic lesions in the von Hippel-
Lindau syndrome. Gastroenterology 1991; 101: 465-471.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0677 CONTRAST ENHANCED ULTRASOUND OF THE PANCREAS
SHOW IMPAIRED PERFUSION IN PANCREAS INSUFFICIENT
CYSTIC FIBROSIS PATIENTS
T. Engjom1,2,*, K. Nylund1,2, F. Erchinger2,3, B. Lrum4,5, G. Dimcevski1,2,
R. Jirik6, O.H. Gilja2,7
1
Department of gastroenterology, Haukeland University Hospital, 2Department of
Clinical Medicine, University of Bergen, Bergen, 3Department of medicine, Voss
Hospital, Voss, 4Department of Thoracic Medicine, Haukeland University
Hospital, 5Department of Clinical Science, University of Bergen, Bergen, Norway,
6
International Clinical Research Center - Center of Biomedical Engineering, St.
Annes University Hospital, Brno, Czech Republic, 7National Centre for
Ultrasound in Gastroenterology, Haukeland University Hospital, Bergen, Norway
Contact E-mail Address: trond.engjom@helse-bergen.no
INTRODUCTION: Pancreatic insufficiency is a prevalent feature of cystic fibro-
sis (CF). The affected CF pancreas is dominated by fatty infiltration, atrophy
and necrosis. Little is known about pancreatic perfusion in CF.
AIMS & METHODS: We aimed to evaluate pancreatic perfusion assessed by
contrast-enhanced ultrasound (CEUS) in CF patients with known exocrine pan-
creatic function.
CEUS was performed in CF patients (n 39) and healthy controls (n 32).
Exocrine pancreatic function was assessed by secretin-stimulated endoscopic
short test and/ or faecal elastase. The CF patients were defined as pancreas
sufficient through fecal elastase 4200mg/g or duodenal bicarbonate 480mmol/
L. Perfusion data was analyzed on stored DICOM-files using DCE-US software
(http://www.isibrno.cz/perfusion/) and a dedicated perfusion model. Mean tran-
sit-time (MTT), blood flow (BF) and blood-volume (BV) was calculated.
Exclusions due to image quality and image analysis in the CF group were
made without knowledge of pancreatic function.
RESULTS: 26 CF patients and 20 controls were included. 13 CF patients and 12
controls were excluded due to poor image quality. Subjects were divided as
follows: CF, pancreatic insufficient (CFI, n 13), CF pancreatic sufficient
(CFS, n 13) and healthy controls (HC, n 20). Results are displayed in the
table (meanSD) (s seconds, ml millilitre)
CFI (n 13) CFS (n 13) HC (n 20) P
MTT (s) 8.03.2 4.01.9 2.91.4 P50.001
BF (ml/min/100ml) 18.410.5 76.8.054 117.470 P50.001
BV (ml/100mL): 2.31.3 4.12.5 4.82.5 P50.05
CONCLUSION: The pancreatic insufficient CF patients had significantly longer
MTT (p50.001), lower BF (p50.001) and lower BV (p50.05) compared to
healthy controls and pancreatic sufficient CF patients. CEUS can non-invasively
differentiate between healthy pancreatic tissue and exocrine insufficient pancrea-
tic tissue due to cystic fibrosis.
Disclosure of Interest: None declared
P0678 PARADUODENAL PANCREATITIS MANAGED BY PANCREAS-
SPARING DUODENAL RESECTIONS. WHY, WHEN AND HOW
V. I. Egorov1,*, A. Vankovich2, R. Petrov3, N. Starostina4
1
Surgical Oncology, 5th City Hospital, Sechenov First State Medical University,
2
Surgical Oncology, Vishnevsky Institute of surgery, 3Surgical Oncology,
Ostroumov 14th City Hospital, Sechenov First State Medical University,
4
Radiology, 5th City Hospital, Moscow, Russian Federation
Contact E-mail Address: v.egorov61@gmail.com
INTRODUCTION: The term paraduodenal pancreatitis (PP) was proposed as
an umbrella for cystic dystrophy in heterotopic pancreas (duodenal dystrophy),
paraduodenal cyst and groove pancreatitis, by reasoning that these conditions
mimic pancreatic head tumors and share certain histological evidences. It is still
unclear what organ paraduodenal pancreatitis originates of.
AIMS & METHODS: To assess the results of different types of treatment for
paradudenal pancreatitis.
1. Prospective analysis of 65 cases of PP (2004-2013), comparing preoperative
and histopathological findings in 42 surgical specimens; 2. Assessment of clinical
presentation and the results of DD treatment.
RESULTS: Preoperative diagnosis was correct in all the cases except one, when
cystic tumor of the pancreatic head was suspected (1.9%). Patients were pre-
sented with abdominal pain (100%), weight loss (76%), vomiting (30%) and
jaundice (18%). CT, MRI and endoUS were the most useful diagnostic modal-
ities. Ten patients were treated conservatively, 26 underwent pancreaticoduode-
nectomies (PD), pancreatico- and cystoenterostomies(8), Nakao procedures(4),
duodenum-preserving pancreatic head (DPPH) resections(5), and 12 pancreas-
preserving duodenal resections (PPDR). No mortality. Full pain control was
achieved after PPRDs in 83%, PDs in 85%, and after PPPH resections and
draining procedures in 18% of cases. Diabetes mellitus developed thrice after PD.
CONCLUSION: 1. The diagnosis of PP can be confidently determined by
modern methods prior to surgery; 2. PD is the main surgical option for PP
treatment at present; 3. Early diagnosis makes pancreas-preserving duodenal
resection the treatment of choice for PP; 4. The effectiveness of PPDR provides
compelling proof that paraduodenal pancreatitis is an entity of duodenal
origin.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0679 CHANGED PLASMA ADIPONECTIN CONCENTRATION AND
ITS CORRELATION WITH CLINICOPATHOLOGICAL
PARAMETERS IN PANCREATIC ADENOCARCINOMA PATIENTS
A. Saray1,*, R. Mesihovic1, Z. Vukobrat-Bijedic1, N. Vanis1, S. Gornjakovic1,
A. Husic-Selimovic1, A. Mehmedovic1, V. Papovic1, S. Glavas1, A. Valjevac2
1
Dept. of gastroenterology and hepatology, CLINICAL CENTER UNIVERSITY
OF SARAJEVO, 2Laboratory for molecular medicine, Medical Faculty, University
of Sarajevo, Sarajevo, Bosnia and Herzegovina
Contact E-mail Address: sarayaida19@gmail.com
INTRODUCTION: Recently it has been shown that low prediagnostic plasma
adiponectin levels are associated with an elevated risk of pancreatic cancer (PC).
However, no studies exist in which association between adiponectin levels and
pancreatic tumor stage were tested.
AIMS & METHODS: The aim of the study was to analyze plasma concentra-
tions of adiponectin in PC patients and to compare these concentrations to
clinicopathological parameters. Baseline levels of adiponectin were determined
in 40 consecutive patients with newly diagnosed pancreatic adenocarcinoma and
40 healthy control subjects. The association between adiponectin and tumor
stage (TNM classification) and tumor grade were evaluated using nonparametric
Spearmans correlation test. Control subjects were matched to case patients by
smoking status, age and BMI.
RESULTS: Overall median adiponectin concentrations were lower in PC
patients versus control subjects (7.1 vs 9.3 mg/mL, p50.001). In PC patients
with TNM stage III-IV (n 21) median adiponectin concentrations were signifi-
cantly lower than in PC patients with TNM stage I-II (n 19) (5.7 vs 7.3 mg/mL,
p50.001). Mean adiponectin concentrations were lower in high grade intrae-
pithelial neoplasia tumors (n 18) compared to low grade tumors (n 13) (5.1
vs 6.5 mg/mL, p50.05). Adiponectin concentrations were inversely correlated
with tumor size and tumor TNM stage (r -0.834, p50.01) and tumor grading
(r -0.615, p50.01) of pancreatic adenocarcinoma patients.
CONCLUSION: This study identified, for the first time, an inverse correlation
between adiponectin levels and tumor size and TNM stage suggesting a potential
role for adiponectin in progression of pancreatic adenocarcinoma.
Disclosure of Interest: None declared
P0680 PREOPERATIVE ENDOSCOPIC BILIARY DRAINAGE
PROCEDURES INFLUENCE SURVIVAL FOLLOWING RESECTION
FOR AMPULLARY CARCINOMAS
K. Urbonas1, A. Gulbinas2,*, J. Pundzius1, G. Barauskas1
1
Surgery, 2Institute for Digestive Research, Lithuanian University of Health
Sciencies, Kaunas, Lithuania
Contact E-mail Address: kestasu@gmail.com
INTRODUCTION: Carcinoma of Papilla of Vater has the best survival rate of
all periampullary carcinomas. Patients typically manifest symptoms early in the
course of the disease with abdominal pain, jaundice, and weight loss. This may
account for early diagnostic and relatively high resection rate. Aim of our study
was to identify the independent factors influencing a long term survival for
patients who underwent pancreatodudenectomy for ampullary adenocarcinoma.
AIMS & METHODS: of our study was to identify the independent factors
influencing a long term survival for patients who underwent radical surgical
treatment for ampullary adenocarcinoma.
Methods. Data of 64 patients with ampullary adenocarcinoma who underwent
major surgery was prospectively collected and analyzed. Demographic, clinical
and histopathological examination data were assumed to have the impact on
survival. The Kaplan-Meier method and log-rank tests were used for univariate
analysis. Cox proportional hazard model was applied to indentify prognostic
factors that were independently associated with survival.
RESULTS: The mean of survival time was 109 months, whereas five years
cumulative survival was 62 percent. Univariate analysis revealed preoperative
endoscopic biliary drainage (stenting) (p50.001), microvessels infiltration
(p50.001), patients age over 70 years (p50.005), lymphonodes infiltration
(p50.021) and T stage (p50.048) as a factors influencing survival.
Preoperative endoscopic biliary drainage (HR 5.25; CI (1.94-14.21)), microvessels
infiltration (HR 3.85; CI (1.09-13.51)) and patients age 470yrs (HR 2.35; CI
(1.03-5.39) were independent factors influencing survival in multivariate analysis.
CONCLUSION: Preoperative endoscopic biliary drainage seems to have the
most significant influence on survival, therefore necessity of procedure should
be carefully assessed before the operation.
Disclosure of Interest: None declared
P0681 HIGH-INTENSITY FOCUSED ULTRASOUND (HIFU) THERAPY
FOR LOCALLY ADVANCED PANCREATIC CANCER
A. Sofuni1,*, F. Moriyasu1, T. Sano1, M. Fujita1, T. Tsuchiya1, K. Ishii1,
N. Ikeuchi1, J. Umeda1, R. Tanaka1, R. Tonozuka1, S. Mukai1, K. Kamata1,
S. Tsuji1, F. Itokawa1, T. Itoi1
1
Gastroenterology and hepatology, TOKYO MEDICAL UNIVERSITY, Tokyo,
Japan
Contact E-mail Address: a-sofuni@amy.hi-ho.ne.jp
INTRODUCTION: Even with recent advances in the diagnostic imaging tech-
nology, most cases of pancreatic cancer (PC) are diagnosed at an unresectable
stage. The results of chemotherapy and chemo-radiotherapy for the condition
were not satisfactory. However, locally advanced PC can expect the possibility of
additional therapy including the surgical treatment and the prolongation of the
prognosis by the strategy of combination therapy. HIFU therapy being pro-
moted as a new method to ablate the tumor is expected for locally advanced PC.
A319
AIMS & METHODS: We have evaluated the therapeutic effect of HIFU therapy
for locally advanced pancreatic body cancer (PBC). We treated PBC patients
using HIFU therapy as optional local therapy as well as systemic chemo /
chemo-radiotherapy, with whom an agreement was obtained in adequate IC,
from the end of 2008 in our hospital. This study took approval of member of
ethic society of our hospital. HIFU device used is FEP-BY02 (Yuande Bio-
Medical Engineering, Beijing, China). The subjects were 20 locally advanced
PBC patients.
RESULTS: The mean tumor size after HIFU therapy changed to 36.5 (15-57)
mm from 39.5 (20-57) mm at pre-therapy. There were no significant changes in
tumor size. The mean treatment data was the following; mean number of treat-
ment sessions, 2.7 (2-5); mean total treatment time, 2.3 (1.8-4.7) hours, and mean
total number of ablation: 2852 (760-6420) shots. The effects of HIFU therapy
was the following; the rate of complete tumor ablation was 75%, the rate of
symptom relief effect was 82%, the effectiveness of primary lesion was CR:0, PR:
3, SD:14, PD:3, and primary disease control rate (DCR) more than SD was
83.3%. There was no adverse event. The following therapy after HIFU therapy
was; operation 2, chemotherapy 15, and BSC 3 cases, respectively. Mean survival
time (MST) after diagnosis was 41.5 months, and MST after HIFU therapy was
19.1 months. Mean duration time from diagnosis till HIFU therapy was 16.3
months. MST after diagnosis in HIFU with chemotherapy or chemo-radiother-
apy and chemotherapy alone (10 patients in our hospital) was 41.5 vs 23.1
months, respectively (p50.05, p 0.04, Log-rank). Combination therapy with
HIFU was better result than common chemotherapy alone.
CONCLUSION: This study suggested that HIFU therapy has the potential of
new method of combination therapy for locally advanced pancreatic body
cancer.
Disclosure of Interest: None declared
P0682 EVALUATION OF UPFRONT SURGERY AS CURATIVE-INTENT
THERAPY CONCEPT IN LOCALLY ADVANCED PANCREATIC
CANCER
C. Ansorge1,*, G. Saliba1, M. Karimi2, N. Kartalis3, L. Lundell1, M. Del Chiaro1,
J. Blomberg1, R. Segersvard1
1
Department of Surgical Gastroenterology, Karolinska University Hospital,
2
Department of Oncology, Karolinska University Hospital, Division of Surgery,
Department of Clinical Science, Intervention and Technology (CLINTEC),
Karolinska Institutet, 3Department of Radiology, Karolinska University Hospital,
Division of Medical Imaging and Technology, Department of Clinical Science,
Intervention and Technology (CLINTEC), Karolinska Institutet, Stockholm,
Sweden
INTRODUCTION: Representing the 4th most common cancer mortality, pan-
creatic cancer remains an unsolved health problem. The majority of patients are
diagnosed at an advanced disease stage with limited therapy options. Currently,
in addition to the limitations, the treatment of non-metastatic locally advanced
pancreatic cancer (LAPC) is characterized by substantial methodological hetero-
geneity among pancreatic centers due to variation of applied definitions, regimes
and surgical procedures. Based on radiological criteria of mesenteric vessel invol-
vement, the radiological assessment of technical resectability in our institution
distinguishes between primarily resectable LAPC (B-tumors, superior mesenteric/
portal vein involvement 450% of the circumference, 52cm length) and primar-
ily unresectable LAPC assessed as potentially resectable after neoadjuvant che-
moradiotherapy (NACRT, C-tumors, SMV/PV 450%, 42cm and/or superior
mesenteric artery involvement 550%, 52cm).
AIMS & METHODS: The aim of the present study was to evaluate the perfor-
mance of primary resection and neoadjuvant treatment followed by attempted
resection as curative-intent concepts in LAPC. A single-center prospective cohort
study was conducted including patients with B- and C-tumors in the pancreatic
head between 2008 and 2013. Histological confirmation preceded NACRT
(Gemcitabine and Capecitabine). Toxicity, therapy response and postoperative
complications were recorded according to established classifications. Overall
(OS) and progression-free survival (PFS) was analyzed; OS was calculated
from date of decision until death, PFS either from date of surgery or date of
confirmed stable disease/partial remission (SD/PR) after NACRT until date of
tumor progression. Patients with specimen histology other than ductal adenocar-
cinoma were retrospectively excluded.
RESULTS: Ninety-nine patients with histologically confirmed pancreatic cancer
were included. Of 30 patients with B-tumors, 22 underwent curative-intent resec-
tion (CIR). Of 69 patients with C-tumors, 64 underwent NACRT, 22 had SD/
PR, and 15 underwent CIR. The resection rate in B-tumors was significantly
higher (73%) than in C-tumors (22%); however, both groups had comparable
median OS rates (B-tumors 10.5, C-tumors 11 months). In B-tumors, median OS
in intra-operatively confirmed unresectability was 8, in CIRs 11.5, and if fol-
lowed by adjuvant treatment 14 months (median PFS in CIRs 9.6 months). In C-
tumors, median OS in patients with discontinued NACRT was 4, with post-
NARCT tumor progression 11, and with confirmed SD/PR 19 months
(median PFS after CIR 21 months).
CONCLUSION: In patients with technically resectable LAPC, primary resection
was not proven to be a sustainable therapy concept, and the preoperative radi-
ological resectability assessment does not seem to have prognostic significance.
Provided that a timely histological confirmation can be guaranteed, the indica-
tion for NACRT, and followed by attempted resection in SD/PR cases, should be
extended to patients with technically resectable LAPC.
Disclosure of Interest: None declared
A320
P0683 STENT ON DEMAND IS SAFER THAN PROPHYLACTIC
DOUBLE BYPASS SURGERY WHEN A PLANNED RESECTION
FOR PANCREATIC CANCER CANNOT BE PERFORMED
J. Wennerblom1,*, C. Williamsson2, B. Tingstedt2, C. Jonsson1
1
Dept. of Surgery, Gothenburg University, Gothenburg, 2Dept. of Surgery, Lund
University, Lund, Sweden
INTRODUCTION: For decades routine use of prophylactic hepaticojejunost-
omy and gastroenterostomy has been advocated when a curative intention must
be abandoned due to peroperative findings of locally advanced or metastatic
disease in pancreatic cancer (1). The development of Self Expanding Metal
Stents (SEMS) has challenged this routine.
AIMS & METHODS: The aim of the present study was to retrospectively com-
pare the results for patients operated 2004-2013 from two Swedish referral cen-
tres with local guidelines for different surgical strategies when signs of
irresectability were discovered during surgery.
At Lund University Hospital, Lund the abdomen was closed immediately in
patients without gastric outlet syndrome (GOS) and if the patient later developed
jaundice and/or GOS a SEMS was inserted (n 74). At Sahlgrenska University
Hospital, Gothenburg prophylactic double bypass surgery (DBS) was performed
when the patient was found to have a non-curable disease (n 77).
RESULTS: There was no difference between the cohorts regarding age, sex and
ASA-class. The need for immediate reoperations did not differ between the two
groups. However, delayed gastric emptying (DGE) as well as other complications
according to the Clavien-Dindo system (2) was significantly more frequent after
DBS than when using the stent strategy. These findings probably explain the
longer post operative hospital stay in the DBS group (11 vs. 9 days
(p 0.001). The long term survival after surgery was not better in the DBS-
group than for the SEMS patients (318 vs. 380 days, p 0.075).
Double Bypass SEMS P-value
Survival 318 (23-808) 380 (15-1151) 0.075
Length of Stay 11 (6-66) 9 (4-42) 0.001
Removal nasogastric tube 2 (1-17) 1 (1-22) 0.046
Fluid intake 4 (1-18) 2 (1-23) 0.005
Food intake 6 (3-19) 4 (1-31) 0.0001
DGE (A,B or C)* 27 (35%) 14 (19%) 0.03
Reoperations * 5 (6.5%) 7 (9.4%) 0.55
Complications* 42 (55%) 25 (34%) 0.013
Overall Clavien-Dindo Score 0.001
CONCLUSION: The more conservative approach to primarily close the abdo-
men and to treat the patient with SEMS on demand seems safer and results in a
shorter initial hospital stay and does not seem to impair the long time survival for
the patients compare to the DBS-routine.
REFERENCES
1. Lillemoe KD, Cameron JL, Hardacre JM, et al. Ann Surg 1999; 230: 322-328.
2. Dindo D, Demartines N and Clavien PA. Classification of surgical complica-
tions: a new proposal with evaluation in a cohort of 6336 patients and results of a
survey. Ann Surg 2004; 240: 205-213.
Disclosure of Interest: None declared
P0685 POTENTIAL BIOMARKERS EVALUATED FROM TISSUE
SAMPLES OBTAINED BY ENDOSCOPIC ULTRASOUND-GUIDED
FINE NEEDLE BIOSPY (EUS-FNB) MAY PREDICT PROGRESSION
AND RESPONSE TO GEMCITABINE THERAPY IN UNRESECTABLE
PANCREATIC CANCER
J. Iglesias-Garc a1,*, M. Luaces-Regueira2, L. Nieto-Garc a2, M. Castineira-
Alvarino2, I. Abdulkader3, J. Larino-Noia1, J.E. Dominguez-Munoz1
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, 2Foundation for Research in Digestive Diseases,
3
Pathology, University Hospital of Santiago de Compostela, Santiago de
Compostela, Spain
INTRODUCTION: Due to the poor prognosis of advanced unresectable pan-
creatic cancer (PC), predicting response to palliative chemotherapy is essential to
avoid adverse events of otherwise unnecessary treatments. The majority of stu-
dies on expression of tumor proteins have been performed on surgical specimens
of resectable PC. We hypothesize that the expression of some tumor proteins may
predict prognosis and response to gemcitabine in patients with unresectable PC.
AIMS & METHODS: Aim of the present study was to analyze the role of several
tumor proteins evaluated in EUS-FNB samples as biomarkers of progression and
response to treatment in patients with unresectable PC.
Patients diagnosed with unresectable PC by EUS-FNB, who received palliative
treatment with gemcitabine were retrospectively included. Availability of EUS-
FNB tissue samples embedded in paraffin block was required for final inclusion.
Candidate proteins (collagen-I, annexinA1, FAK, FAS, HSP70, SSH and MMP)
were evaluated by specific immunohistochemistry. Statistical analysis was per-
formed by Mann-Whitney U and McNemar test.
RESULTS: From 277 EUS-FNB samples of patients with unresectable PC, an
adequate sample for ancillary studies in patients who received palliative treat-
ment with gemcitabine was available in 37 patients (65.111.7 years, 62.2%
men). Mean survival time was 220 days (range 16 to 519 days). Tumor size
was 41.212.8mm. Frequencies of protein expression in tumor areas were
United European Gastroenterology Journal 2(5S)
AnnexinA1: 96.9%; SSH: 93.6%; FAK: 59.4%; collagen-I: 32.3%; FAS:
28.6%; MMP: 12.9; HSP70: 14.3%. Expression of collagen-I was associated
with a shorter survival (150.898.2 vs 285.4147.2 days, p 0.029). FAK
expression was associated with a smaller tumor size (36.19.5 vs 48.214.2,
p 0.02). Finally, lack of SHH was associated with normal serum Ca19.9 levels.
CONCLUSION: Some tumor proteins expressed in unresectable PC can be
evaluated by immunohistochemistry in EUS-FNB samples to predict survival
and response to palliative chemotherapy. Expression of collagen-I is associated
with a shorter survival in patients receiving palliative therapy with gemcitabine.
Further prospective studies including a larger number of patients are required to
confirm these data.
Disclosure of Interest: None declared
P0686 CLINICAL IMPACT OF KL-6 MEASUREMENT OF PANCREATIC
JUICE FOR DIAGNOSING PANCREATIC MASSES
K. Matsumoto1,*, K. Harada1, Y. Takeda1, T. Onoyama1, S. Kawata1, M. Ueki2,
Y. Murawaki1
1
Gastroenterology, 2Promoting next-generation highly advanced medicine, Tottori
University Hospital, Yonago, Japan
Contact E-mail Address: ayano0620@hotmail.co.jp
INTRODUCTION: Pancreatic juice cytology (PJC) is considered optimal for the
differential diagnosis of pancreatic masses and is thought to be the most exact
diagnostic modality for intraductal papillary mucinous carcinoma (IPMC).
However, the accuracy of PJC has been unsatisfactory, ranging from 46.7% to
93.0%. Therefore, to improve the accuracy of diagnosis for pancreatic malig-
nancy, alternative modalities are needed. MUC1, a membrane-associated mucin
widely expressed in gastrointestinal tissues, has a variety of types based on dif-
ferent glycoforms in its extracellular domain. Many investigations have shown
that aberrant expression of MUC1 in gastrointestinal cancer tissue has clinico-
pathological and biological importance in cancer. KL-6 mucin, one kind of
MUC1, has also been investigated; it appears to have a significant relationship
with malignant tumor behavior, especially cancer cell invasion and metastasis in
various gastrointestinal cancers.
AIMS & METHODS: The aim of this study was to evaluate the clinical impact
of the KL-6 concentration of pancreatic juice for diagnosing pancreatic masses.
This study comprised 70 consecutive patients with pancreatic masses (34 pan-
creatic ductal adenocarcinomas [PDACs], 5 intraductal papillary mucinous car-
cinomas [IPMCs], 12 pancreatic inflammatory lesions and benign stricture of the
main pancreatic ducts [MPDs] and 19 intraductal papillary mucinous adenomas
[IPMAs]). All patients underwent PJC and measurement of the KL-6 concentra-
tion of pancreatic juice, which was obtained from the pancreatic duct. After
pancreatic juice was centrifuged at 1000 rpm for 5 minutes, cytological examina-
tion of the cell pellet was performed. The supernatant (10 L) was used to
measure the KL-6 concentration. Human KL-6 levels were assayed in duplicate
using a PICOLUMI KL-6 kit (EIDIA, Tokyo, Japan) an electrochemilumines-
cence immunoassay (ECLIA) specific for human KL-6.
RESULTS: The average KL-6 concentration of pancreatic juice was significantly
higher for PDACs (167.7  396.1 U/mL) than for pancreatic inflammatory
lesions and benign MPD strictures (17.5  15.7 U/mL P 0.034).
Furthermore, KL-6 was significantly higher in IPMCs (86.9  21.1 U/mL)
than in IPMNs (14.4  2.0 U/mL P 0.026). The cut-off level of KL-6 concen-
tration was 16 U/mL for differentiating PDACs and IPMCs from pancreatic
inflammatory lesions and IPMNs. The sensitivity, specificity, positive predictive
value, negative predictive valu, and accuracy of KL-6 concentration alone were
79.5%, 64.5%, 73.8%, 71.4% and 72.9%, respectively, whereas those of PJC
alone were 82.1%, 96.8%, 97.0%, 81.1% and 88.6%, respectively. Adding the
KL-6 concentration to PJC diagnosis increased the sensitivity and accuracy of
PJC by 15.3% (P 0.025) and 8.5% (P 0.048), respectively.
CONCLUSION: The KL-6 concentration of pancreatic juice may be useful for
diagnosing PDAC, as well as PJC.
Disclosure of Interest: None declared
P0687 NEW DIAGNOSTIC STRATEGIES FOR THE EARLY DIAGNOSIS
OF PANCREATIC CANCER
K. Hanada1,*, A. Okazaki1, M. Shinzato1, Y. Izumi1, Y. Teraoka1,
K. Kanemitsu1, J. Ikemoto1, N. Hirano1
1
Gastroenterology, Onomichi General Hospital, Onomichi, Japan
Contact E-mail Address: kh-ajpbd@nifty.com
INTRODUCTION: Detection of pancreatic cancer (PC) at an early stage with
curative surgery is the approach with the potential to significantly improve long-
term patient outcome. However, the rate of tumor detection of computed tomo-
graphy (CT) in the case with small pancreatic cancer was not satisfied. For the
diagnoses of PC less than 10mm, the rate of tumor detection was higher for
endoscopic ultrasonography (EUS) than for CT or other modalities, and the
histologic diagnosis with EUS guided fine needle aspiration (EUS-FNA) was
helpful in confirming the diagnosis. For the diagnosis of PC in situ, EUS and
magnetic resonance pancreatocholangiography (MRCP) played important roles
in detecting of the local irregular stenosis of the pancreatic duct. Endoscopic
retrograde pancreatography (ERP) and sequential cytodiagnosis of pancreatic
juice using endoscopic nasopancreatic drainage (ENPD) multiple times were
useful in the diagnosis of PC in situ.
AIMS & METHODS: In 2007, Onomichi Medical Association tried to start a
social program for diagnosis of the small pancreatic cancer. Specialized doctors
for pancreatic cancer (SDPC) in medical centers enlightened practicing doctors
about risk factors of PC, abnormal findings of US, or elevated serum pancreatic
enzymes. Simultaneously, if practicing doctors experienced the patient with these
previous problems, they actively consulted SDPC.
United European Gastroenterology Journal 2(5S)
RESULTS: From January 2007 to June 2013, a total of 4969 cases were con-
sulted with SDPC in Onomichi General Hospital. Methods of image diagnosis of
CT, MRI, and EUS were performed in 4157, 2303, and 1692 cases. Among these
cases, ERP was performed in 550 cases. ENPD and the repeated cytology using
pancreatic juice were performed in 59. EUS-FNA was performed in 257. As a
result, 338 cases were proved as adenocarcinoma histocytologically. There were
13 cases with stage 0, and 28 cases with stage Ia and Ib histopathologically.
CONCLUSION: To detect of early stage of PC, the relationship between SDPC
in medical centers and practicing doctors is very important. ENPD and repeated
cytology using pancreatic juice also may play important roles in diagnosis of the
early stage of PC.
Disclosure of Interest: None declared
P0688 A COMPARATIVE STUDY BETWEEN A 22-GAUGE ASPIRATION
NEEDLE AND A 25-GAUGE BIOPSY NEEDLE FOR EUS-GUIDED
SAMPLING OF PANCREATIC MASS LESIONS
Y.S. Moon1,*, J.H. Kim2, M.J. Yang2, J.C. Hwang2
1
Gastroenterology, Haeundae Paik Hospital, Busan, 2Gastroenterology, Ajou
Unversity School of Medicine, Suwon, Korea, Republic Of
INTRODUCTION: EUS biopsy needles have recently been developed in order to
obtain both histologic and cytologic specimens.
AIMS & METHODS: We conducted this study to compare 22-gauge (G) aspira-
tion needles (FNA) and 25G biopsy needles (FNB) for EUS-guided sampling of
solid pancreatic masses. Thirty-four patients with solid pancreatic masses under-
went EUS-guided sampling with a 25G FNB from June 2012 to April 2013, and
thirty-four patients with solid pancreatic masses, who underwent EUS-guided
sampling with a 22G FNA from June 2011 to May 2012, served as the historical
control group. EUS-guided sampling was performed using the standard techni-
que without an on-site cytopathologist.
RESULTS: The diagnostic rates of cytology were 97.1% (33/34) with 22G FNA
needles and 85.3% (29/34) with 25G FNB needles (P 0.197). The diagnostic
rates of histology were 23.5% (8/34) with 22G FNA needles and 41.2% (14/34)
with 25G FNB needles (P 0.194). There was no significant difference in the
mean number of needle passes (5.09 vs 5.76, P 0.089) or needle malfunctions
(2.9% vs 11.8%, P 0.356) between 22G FNA and 25G FNB needles, respec-
tively. No complications were identified in either group.
CONCLUSION: The 25G FNB needle was not superior to the 22G FNA needle
in the diagnostic yield of histology for EUS-guided sampling of pancreatic mass
lesions, as the diagnostic yield, technical performance, and safety profiles were
comparable between both of them.
Disclosure of Interest: None declared
TUESDAY, OCTOBER 21, 2014 9:0017:00
ENDOSCOPY AND IMAGING II POSTER EXHIBITION HALL
XL_____________________
P0689 EFFECTIVENESS OF ENDOSCOPIC MANAGEMENT FOR
ANASTOMOTIC LEAKAGE AFTER GASTRECTOMY IN GASTRIC
CANCER
J.Y. Lee1,*, Y.-W. Kim1, I.J. Choi1, C.G. Kim1, S.-J. Cho1, K.W. Ryu1,
H.M. Yoon1, B.W. Eom1, S.J. Kim1
1
Center for Gastric Cancer, National Cancer Center, Goyang, Korea, Republic Of
Contact E-mail Address: jylee@ncc.re.kr
INTRODUCTION: Anastomotic leakage after gastrectomy is an important
determinant of early and late morbidity and mortality. Various methods for
postoperative leakage are used including conservative, endoscopic or surgical
treatment.
AIMS & METHODS: We aimed to evaluate the effectiveness and safety of
endoscopic intervention for the management of leakage after gastrectomy. We
retrospectively reviewed 57 patients with anastomotic leakage after gastrectomy
for gastric cancer that was treated with endoscopic interventions between
December 2007 and March 2014. Clinical aspects of leakages and endoscopic
managements, closure rates and treatment related complications were evaluated.
RESULTS: Anastomotic leakages were found at esophagojejunostomy (n 26),
duodenal stump (n 14), gastroduodenostomy/gastrojejunostomy (n 10),
wedge resection (n 3), esophagogastrostomy (n 2) or jejunal stump (n 2).
Median size of leak was 8mm (range, 2 - 40mm). The leakages were treated by
endoclips (n 13), endoclips with detachable snare (n 31) or stent (n 13).
Simultaneously, abscess around the leak was drained by external drains
(n 32). After endoscopic treatment, complete closure was achieved in 42
patients (73.7%) and partial closure in 13 patients (22.8%). In all patients with
partial closure, final closure of leak was achieved by continuing conservative
treatment. Among remaining two patients, one with failed endoscopic treatment
went on to receive surgery and the other died due to septic shock during endo-
scopic treatment. Treatment related complication (esophageal fistula) occurred in
one patient who was treated with stent. The complete closure rate of the leaks at
duodenal or jejunal stump was significantly lower than that of leaks at other sites
(P 0.027), whereas the size of leak and the method of endoscopic management
were not associated with the complete closure rate.
CONCLUSION: Endoscopic management using clips or stent represents an
effective and safe method for anastomotic leakage after gastrectomy in gastric
cancer and it can be an easily available minimally-invasive option which may
reduce leakage related mortality and morbidity.
Disclosure of Interest: None declared
A321
P0691 RISK FACTORS OF DELAYED ULCER HEALING AFTER
GASTRIC ENDOSCOPIC SUBMUCOSAL DISSECTION
J.H. Lim1,*, S.G. Kim1, J. Choi1, J.P. Im1, J.S. Kim1, H.C. Jung1
1
Departement of Internal Medicine and Liver Research Institute, Seoul National
University College of Medicine, Seoul, Korea, Republic Of
INTRODUCTION: Post-endoscopic submucosal dissection (ESD) iatrogenic
ulcer is known to have specific histologic features and heal faster than peptic
ulcer. However, some iatrogenic ulcers show delayed healing.
AIMS & METHODS: The aim of this study is to clarify risk factors of delayed
ulcer healing after gastric ESD. For this, we reviewed medical records of patients
who had ESD for gastric high-grade adenoma or early gastric cancer between
January 2005 and February 2012. Delayed ulcer healing was defined as sustain-
n
ing unhealed iatrogenic ulcer at 3 months after the ESD. To find potential risk
w
factors we reviewed following parameters: age, sex, comorbidity that might influ-
ithdra
ence mucosal healing, history of peptic ulcer, laboratory abnormalities, antipla-
telet or NSAID usage, size of the specimen, location and histologic type of lesion,
Helicobacter pylori status, and hot biopsy.
W
RESULTS: Among 2040 subjects, 11 were excluded because of anticoagulation,
3 because of embolization for post-ESD bleeding, and 346 were excluded because
of loss of 3 month follow-up endoscopy. Out of the total 1680 patients enrolled,
95 had delayed ulcer healing. In multivariate analysis, diabetes (OR 1.743; 95%
CI: 1.017-2.989, p 0.043), coagulation abnormality (OR 3.195; 95% CI: 1.535-
6.650, p 0.002), specimen size greater than 4cm (OR 2.999; 95% CI 1.603-5.611,
p 0.001), and hot biopsy (OR 7.149; 95% CI 1.738-29.411, p 0.006) were
revealed to be independent risk factors of delayed ulcer healing. Meanwhile,
persistent Helicobacter pylori infection was not shown to be related to the delayed
ulcer healing.
CONCLUSION: Patients those who undergo ESD for large gastric lesions and
massive hemostasis, especially with diabetes or coagulation abnormalities, tend
to have delayed healing of iatrogenic ulcer. For such patients initial dosage
increment of PPI or addition of other anti-ulcer agents after ESD should be
considered.
Disclosure of Interest: None declared
P0692 CHARACTERISTIC ENDOSCOPIC FINDINGS OF
HELICOBACTER PYLORI-NEGATIVE EARLY GASTRIC
UNDIFFERENTIATED ADENOCARCINOMA
J. Fujisaki1,*, Y. Horiuchi1, H. Osumi1, T. Hirasawa1, T. Yoshio1,
Y. Yamamoto1
1
Department of Gastroenterology, Cancer Institute Hospital, Japanese Foundation
for Cancer Research, Tokyo, Japan
Contact E-mail Address: junko.fujisaki@jfcr.or.jp
INTRODUCTION: Helicobacter Pylori (HP) negative gastric cancer is rare.
Recently, we experienced HP negative early gastric cancer.
AIMS & METHODS: The purpose of this study is to evaluate the clinical char-
acteristics of HP-negative Early Gastric Undifferentiated adenocarcinoma. We
examined 35 cases (19 males and 16 females) with 36 lesions of Helicobacter
Pylori (H.pylori)-negative Early gastric undifferentiated adenocarcinoma. All
cases were treated by Endoscopic Submucosal Dissection. All cases had no his-
tory of H.pylori eradication, no inflammatory changes on the resected specimen,
and no sign of atrophy on endoscopy, with negative results for pepsinogen and
urea creath tests.
RESULTS: Of the 36 lesions, 35 were diagnosed as signet-ring cell carcinoma,
with only 1 case of poorly differentiated adenocarcinoma. The mean lesion size
was 7.4mm. The macroscopic type was 0-IIc in 30 (83%) lesions and 0-IIb in 6
lesions. 33 (92%) lesions showed pale lesion in color. The depth classification was
intramucosal in 36 lesions. Of the 36 intramucosal lesions, 3 (8%) were limited to
the proliferative of the mucosa, 22 (61) invaded from the proliferative zone to the
upper side, and only 1 (2%) case invaded the lower mucosa. With respect to the
background mucosa, 25 (69%) lesion originated from the fundic gland area, 5
(14%) originated from the intermediated zone, and 6 (17%) originated from the
pyloric glands. The inciddent of HP-N-UEG was 2.3% of all ESD cases.
CONCLUSION: HP negative early gatric cancer was rare. However, we experi-
enced HP negative early gastric undifferentiated adenocarcinoma. These cases
may have considerable relevance in the near future.
Disclosure of Interest: None declared
P0693 CHROMOENDOSCOPY WITH INDIGO CARMINE DYE ADDED
TO ACETIC ACID FOR DELINEATING EARLY GASTRIC CANCERS
IS USEFUL AND EASIER THAN MAGNIFYING ENDOSCOPY WITH
NARROW BAND IMAGING
K. Nagao1,*, H. Noda1,1, N. Ogasawara1, T. Shimura2, M. Ebi2, S. Izawa1,
Y. Kondo1, Y. Ito1, Y. Tamura1, M. Sasaki1, K. Kasugai1
1
Gastroenterology, Aichi Medical University School of Medicine, Nagakute,
2
Gastroenterology and Metabolism, Nagoya City University Graduate School of
Medical Sciences, Nagoya, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) was developed to
improve the rate of en bloc resection for early gastric cancer (EGC). Although a
clear diagnosis of EGC demarcation is important for proper treatment, demarca-
tions are often obscure. To achieve a successful ESD outcome, it is very impor-
tant to accurately determine the lateral extent of the tumor. The determination of
EGC demarcation has traditionally been performed with conventional endo-
scopy and chromoendoscopy (CE) using indigo carmine dye. However, it is
sometimes difficult to identify the margins of the tumors, especially those of
superficial or flat-type tumors. Various techniques using magnifying endoscopy
A322
(ME) have been developed to enhance images of EGC demarcations. Magnifying
endoscopy with narrow band imaging (ME-NBI) has reportedly been useful in
overcoming this problem but the use of MENBI is limited by the technical
difficulties in manipulating the scopes. Therefore, easier methods are required
that make it possible to accurately determine the lateral extent of these tumors.
Chromoendoscopy with indigo carmine dye added to acetic acid (CE-IA) has
recently been reported to improve the diagnostic yield in terms of recognizing the
tumor borders in patients with EGC. Our purpose was to compare the diagnostic
performance of CE-IA with that of ME-NBI and conventional ME (CME). We
investigated three methods to determine which is more effective in enhancing the
recognition of EGC demarcations.
AIMS & METHODS: The study group included 266 lesions of consecutive 259
patients with differentiated EGC who underwent ESD at Aichi Medical
University Hospital between January 2006 and March 2014. The recognition
of demarcations were evaluated using CME (n 193), ME-NBI (n 43) and
CE-IA (n 30). All observations were made on optimal foci and at the highest
magnification ratios possible. For CE-IA, 2030 mL of 1.5% acetic acid was
sprinkled onto the lesion and 10-20 mL of 0.2% indigo carmine dye was similarly
sprinkled 30-60 seconds later using a washing pipe. The recognition of demarca-
tions between the lesion and the normal mucosa were classified as distinct or
indistinct by observation of CME, ME-NBI and CE-IA.
RESULTS: The demarcations of the lesions were distinct in 64.8% (125/193)
with CME, in 81.4% (35/43) with ME-NBI and in 90.0% (27/30) with CE-IA.
ME-NBI and CE-IA clarified the demarcation in a significantly higher percen-
tage compared with CME (P50.05). However, the determination rate of EGC
demarcation did not differ between ME-NBI and CE-IA. The mean duration of
determination procedure for demarcation with CE-IA was significantly shorter
than that with ME-NBI (6.973.75 min vs. 8.57 4.33 min, P50.05).
CONCLUSION: CE-IA and ME-NBI are useful in determining the lateral extent
of EGCs. The mean duration of determination procedure for EGC demarcation
was significantly reduced using CE-IA compared with ME-NBI. The demarca-
tions of EGDs were recognized most easily using CE-IA.
Disclosure of Interest: None declared
P0694 CLINICOPATHOLOGICAL FACTORS INFLUENCE ACCURATE
ASSESSMENT OF ENDOSCOPIC ULTRASONOGRAPHY FOR
EARLY GASTRIC CANCER
K. Yanamoto1,*, N. Ogasawara1, T. Shimura2, A. Shimozato1, Y. Kondo1,
H. Noda1, Y. Ito1, M. Sasaki1, K. Kasugai1
1
Aichi Medical University School of Medicine, Nagakute, 2Department of
Gastroenterology and Metabolism, Nagoya City University Graduate School of
Medical Sciences, Nagoya, Japan
INTRODUCTION: The advent of endoscopic ultrasonography (EUS) has sig-
nificantly improved the preoperative diagnosis and staging of gastric cancers.
EUS is the most reliable nonsurgical method available for assessing primary
tumor with a high diagnostic rate of accuracy in staging gastric cancer. This
assessment is an important factor in choosing a proper treatment such as endo-
scopic resection or surgery. Especially in early gastric cancers (EGC), the size,
gross appearance, histologic diagnosis, degree of differentiation, and depth of
invasion are very important factors to be considered for therapeutic decision
making. Endoscopic submucosal dissection (ESD) currently is widely accepted
as a standard treatment strategy for EGC without any risk of lymph node
metastasis because the ESD procedure facilitates en bloc resection even in
patients with large or ulcerous lesions. Therefore, it has become more important
in treatment planning to determine the depth of invasion accurately before treat-
ment. The aim of this study was to evaluate the clinicopathological factors affect-
ing the diagnostic accuracy of EUS and to compare the diagnostic accuracy
evaluated by endoscopic findings with that by EUS in EGCs.
AIMS & METHODS: During the period from April 2009 to January 2014, 136
patients (94 men and 42 women; age range, 44-88 years; mean age, 72.1 years)
with an endoscopic diagnosis of EGCs underwent EUS to define pretreatment
staging. Diagnoses of invasion depth by EUS or endoscopic findings were
divided into intramucosal (M) and submucosal invasion (SM). All patients
underwent curative treatment by either ESD or standard surgical intervention,
and all lesions were evaluated by histopathological examination. Both EUS-
determined diagnosis and conventional endoscopy-determined diagnosis were
compared with the final histopathological evaluation of resected specimens,
and the impact of various clinicopathological parameters on diagnostic accuracy
was analyzed.
RESULTS: The accuracy of invasion depth were 83.0 % for EUS and 74.5 % for
conventional endoscopy, respectively. There was significant difference related
with the accuracy of invasion depth between EUS and endoscopic findings
(p50.01). The diagnostic accuracy of EUS for predicting tumor invasion depth
was significantly affected by the tumor location and the tumor size. Lesions
located in the posterior wall of the stomach larger than 3 cm were significantly
associated with lower diagnostic accuracy in predicting the tumor invasion. These
lesions had higher probability of overstaging estimated by EUS. However, no
significant differences were found in histopathological differentiation, tumor
gross appearance and ulceration. Unexpectedly, the observation time for EUS
was the same as that for conventional endoscopy (6.83.1 minutes vs. 6.14.2
minutes).
CONCLUSION: EGCs larger than 3 cm located in the posterior wall of the
stomach should be cautiously considered in the decision on treatment modality
by pretreatment EUS staging. Moreover, observation time for EUS was so short
that a sedation was not considered to be required during EUS investigation.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0695 ADDITORY RISK FACTORS FOR PYLORIC STENOSIS AFTER
ENDOSCOPIC SUBMUCOSAL DISSECTION, AND VARIOUS
MANAGEMENTS
K.S. Lee1,*, M.J. Yang1, S.J. Ahn1, S.J. Shin1
1
Department of Gastroenterology, Ajou University School of Medicine, Suwon,
Korea, Republic Of
Contact E-mail Address: kiseong@hotmail.com
INTRODUCTION: Endoscopic mucosal dissection (ESD) is useful method for
local resection of early gastric neoplasia. 1,2 But, ESD can cause early and late
complications commonly known as bleeding, perforation, and stricture forma-
tion. 3 In previous study, Coda S, et al., circumferential extent of a mucosal
defect 4 3/4 and longitudinal extent 45 cm were each significantly related to
the occurrence of post-ESD stenosis in both cardiac and pyloric resections. And
endoscopic balloon dilatation can be an effective treatment of them. 4
AIMS & METHODS: The aim of this study is to clarify the previous risk factors
and determine the additory risk factor. And we report another management
methods for pyloric stenosis after ESD. Retrospectively a total of 1621 early
gastric neoplasia resected by ESD at a single institution between 2005 and
2012. Pyloric stenosis is defined when a 1 cm diameter endoscope could not
passed through the pyloric ring.
RESULTS: Among 126 cases which resected from the pylorus, stenosis occurred
in six cases. Significant differences were found between longitudinal diameter
of resected specimen (5cm) and the others (55cm) (odd ratio 15.362,
p 0.037), circumferential mucosal defect over the half (270 ) and the others
(5270 ) (odd ratio 23.840, p 0.015). Also the number of repeated ESD was
significant different between the single lesion and the others (2 times) (odd
ratio 26.169, p 0.040). Six patients of pyloric stenosis received endoscopic
balloon dilatation for treatment of post-endoscopic resection stricture and 4
patients has improved symptoms. But two patients received an additional pro-
cedure for treatment of pyloric stenosis. One of them underwent subtotal gas-
trectomy and other was treated with metallic pyloric stent.
CONCLUSION: The risk factors of pyloric stenosis were the longitudinal dia-
meter of resected specimen (45cm) and circumferential mucosal defect over 75%
of pyloric ring in this study. In addition, repeated ESD limited pylorus also
caused pyloric stenosis. We thought the diameter of specimen and circumferential
defect are important factors as previous study. 4 And this study revealed another
risk factor: repeated procedure is additional risk factor of pyloric stenosis after
ESD. In treatment of post-endoscopic resection stricture, balloon dilatation is
effective treatment. But, according Coda S, et al., procedure is needed more than
nine times on average. 4 Frequent the procedures decrease quality of life.
Therefore more confident short-term treatment is needed. Pyloric stent is
useful management of pyloric stricture. But it is too expensive and has complica-
tions like stent-migration. This is must be resolved first.
REFERENCES
1. Rembacken BJ, Gotoda T, Fujii T, et al. Endoscopic mucosal resection.
Endoscopy 2001; 33: 709-718.
2. Soetikno RM, Gotoda T, Nakanishi Y, et al. Endoscopic mucosal resection.
Gastrointest Endosc 2003; 57: 567-579.
3. Oda I, Suzuki H, Nonaka S, et al. Complications of gastric endoscopic sub-
mucosal dissection. Dig Endosc 2013; 25(Suppl. 1): 71-78.
4. Coda S, Oda I, Gotoda T, et al. Risk factors for cardiac and pyloric stenosis
after endoscopic submucosal dissection, and efficacy of endoscopic balloon dila-
tion treatment. Endoscopy 2009; 41: 421-426.
Disclosure of Interest: None declared
P0696 ULTRA THIN ENDOSCOPE WITH NARROW BAND IMAGING
(NBI) IN DIAGNOSTIC OF GLUTEN DEPENDENT AND
INDEPENDENT SMALL INTESTINAL ATROPHY IN INFANT AND
UP TO 36 MONTHS AGE CHILDREN
K. Marakhouski1,*
1
Endoscopy, RSPC "Mother and child", Minsk, Belarus
INTRODUCTION: Using high-resolution endoscopy is sharply limited at this
age. It remains unclear whether there are differences in the high-resolution endo-
scopic assessment of the small intestinal mucosal pit pattern at congenital intest-
inal atrophy (non gluten) and atrophy at a gluten sensitivity enteropathy.
AIMS & METHODS: Inclusion criteria were: child wasnt older 36 month and
has low weight gain (WHO criteria) and non bloody diarrhea. Investigation
performed with permission and control of the local ethic committee. We analyzed
endoscopy results of 32 cases (13 girls).
Endoscopy: the EXERA III with an endoscope GIF - N180 4.9 mm in diameter
was used Evaluation of duodenal mucosa was done with narrow band imaging
(NBI, more brightly than in EXERA II light source) and for additional sign of
atrophy water flow with addtion of semethicon was done too. Two biopsy speci-
mens were taken minimally. The description of a biopsy was carried out by a
standard technique with special orientation biopsies specimens, by two indepen-
dent pathology experts. Four criteria were used for endoscopic and histological
(HYS) intestinal atrophy assessment: definitely yes, probably yes, probably no,
definitely no. The main group was divided on two subgroups: A - age up to 6
months (group of strictly non gluten enteropathy) and B - 6 - 36 months (prob-
ably gluten dependent enteropaty).
RESULTS: Age in group A (N 17) was: mean 2.9 (CI 95% 2-4), median -
3.0 (CI 95% 1-4). Frequency of the HYS definitely yes atrophy was in 5,
probably yes- 1. Atrophy rate was 35% (Exact 95% C. I. (Fishers) 14.2-
61.7). Frequency of the endoscopic definitely yes atrophy was in 6, probably
yes- 2. Endoscopy sensitivity 0.67(CI 95% 0.35 - 0,88, specificity 1,00 (CI
95% 0.68 - 1,0), odds ratio (Fleiss)- 33(CI 95% 1,6 - 151,23). If endoscopy
negative, expected HYS negative will definitely to no atrophy.
United European Gastroenterology Journal 2(5S)
Age in group B (N 15) was: mean 23,5 (CI 95% 18,5-28,4), median - 21,0
(CI 95% 17-33). Frequency of the HYS definitely yes atrophy was in 4, prob-
ably yes- 0. Atrophy rate was- 26,7% (Exact 95% C. I. (Fishers) 7,8-55,1), and
not different significant from group A. Frequency of the endoscopic definitely
yes - atrophy was in 4, probably yes - 1case. Sensitivity 0.8 (CI95% 0.38 - 0,96;
specificity 1,00 (CI95% 0.72 - 1,00), odds ratio (Fleiss) 63 (2,22 - 313,23), and
LR (Test Negative) 0.2.
CONCLUSION: In infant and up to 36 months age children with low weight
gain and non bloody diarrhea small intestinal atrophy rates are from 14.2% to -
61.7%. We found no difference in the two groups (gluten associated or not) used
to assess ultra thin with NBI endoscopy sensitivity, specificity, and it has value as
a good standard for visual endoscopic evaluation of duodenal villi changes as a
method for exclusive intestinal atrophy.
Disclosure of Interest: K. Marakhouski Other: "Olympus" CIS expert
P0697 PROSPECTIVE ASSESSMENT OF THE LEVEL OF TEMPORAL
AROUSAL AND SAFETY OF NURSE-ADMINISTERED PROPOFOL
SEDATION FOR ESOPHAGOGASTRODUODENOSCOPY
K. Kusumoto1,*, A. Hamada1, Y. Mizumoto2
1
Tango central hospital, Kyotango, 2National Hospital Organization Kyoto
Medical Center, Kyoto, Japan
Contact E-mail Address: kusumoto1024@gmail.com
INTRODUCTION: Propofol sedation is widely used, mainly in Europe and the
US, not only as an induction agent for general anesthesia but also in the field of
gastroenterological endoscopy. Especially in the US, the certified registered nurse
anesthetists perform general and local anesthesia for many endoscopic proce-
dures under anesthesia management, independently from doctors. However,
quite a few states prohibit individuals other than anesthetists from performing
propofol sedation from the safety aspect. Propofol sedation, which is easy to
give and wean off, by nurse-administered propofol sedation (NAPS) is quite
meaningful, and could thereby reduce labor costs and charges for recovery rooms
and curb medical expenses.
AIMS & METHODS: We prospectively examined the safety of propofol seda-
tion at the time of esophagogastrodudenoscopy (EGD). Between July 2013 and
January 2014, EGD was performed under NAPS in outpatients, and time to
arousal and safety were prospectively assessed. Propofol was administered manu-
ally in a prespecified regimen, and, before the test and at 10 and 60 min after the
test, the mean blood pressure, Sp02, grasping power of both hands, visual acuity
of both eyes, Mini Mental State Examination (MMSE) score, and reflex nerve
test were assessed and compared.
We hypothesized that MMSE score recovers to the pretest value 60 min after
the completion of EGD under propofol sedation. To prove this hypothesis, we
tested non-inferiority of MMSE at 60 min after the test against that before the
test. We calculated that 87 eligible patients were needed to obtain a significant
difference, and estimated the number of patients to be included at 104, expecting
20% of the patients to be ineligible. Quantitive variables were evaluated by t-test,
and the significance level of 50.05 was considered statistically significant.
RESULTS: 95 patients (mean age: 55.5  14.9 years; male/female ratio: 37/58
cases; mean examination time: 315.6  115.8 s; mean induction dose of propofol:
0.097  0.019 mL/kg; and mean total dose: 0.129  0.027 mL/kg) were included
for analysis. All patients could be successfully sedated and opened their eyes
immediately after the test. Before the test vs. 10 min after the test, the mean
blood pressure (mmHg) was 95.19  13.20 vs. 90.13  12.34 (p 5 0.01); grasping
power of right hand (kg) was 27.7  8.08 vs. 26.2  8.49 (p 5 0.01); grasping
power of left hand (kg) was 26.4  8.08 vs. 25.3  8.22 (p 5 0.01); and MMSE
(points) was 27.3  2.2 vs. 26.8  2.4 (p 5 0.05); all of which showed significant
differences. Before the test vs. 60 min after the test, the mean blood pressure
(mmHg) was 95.19  13.20 vs. 91.80  11.88 (p 5 0.01), showing a significant
decline. No occasional symptoms were observed in all patients.
CONCLUSION: EGD under NAPS was performed safely and all factors other
than mean blood pressure returned to the pretest condition 60 min after the test.
Blood pressure was also in an acceptable range as per discharge criteria, and the
patients were considered to be allowed to be safely discharged from hospital after
60 min.
REFERENCES
Dumonceau JM, Riphaus A, Aparicio JR, et al. European society of gastroin-
testinal endoscopy, european society of gastroenterology and endoscopy nurses
and associates, and the european society of anaesthesiology guideline: non-
anesthesuiologist administration of propofol for GI endoscopy. Endoscopy
2010; 42: 960-974.
Disclosure of Interest: None declared
Table to abstract P0698
A323
P0698 DEVELOPMENT OF PROPOFOL SEDATION FOR
THERAPEUTIC ENDOSCOPY UNDER DEEP SEDATION WITH
SPONTANEOUS RESPIRATION
K. Matsumoto1,*, K. Matsumoto1, A. Nagahara1, Y. Nakagawa1, H. Ueyama1,
Y. Shimada1, D. Asaoka1, M. Hojo1, S. Watanabe1
1
gastroenterology, juntendo univ., bunkyo-ku, Japan
INTRODUCTION: In recent years, propofol sedation has attracted attention for
use during therapeutic endoscopy under deep sedation with spontaneous respira-
tion. However, a standard protocol for propofol sedation has not yet been
established.
AIMS & METHODS: Our aim was to establish a simple and safe protocol for
propofol sedation during therapeutic endoscopy. This study retrospectively
investigated 89 patients (67 male, 22 female; mean age 71.2 years) who underwent
endoscopic submucosal dissection (ESD) or endoscopic mucosal resection
(EMR) of the esophagus and stomach under anaesthesia with 1.0% propofol.
Patients were assigned to 1 of 5 groups (phases 1 5) each corresponding to a
different dosing protocol. After beginning phase 1, when it was deemed that the
dose of propofol was insufficient or excessive, the dose was adjusted and the next
phase was begun in a different group of patients. In all phases, the initial dose of
1.0% propofol was administered after bolus injection of pethidine hydrochloride
(0.5 mg/kg), and 1.0 mL of propofol was added every minute until anaesthesia to
level 6 on the Ramsey Sedation Scale was achieved. Subsequently, continuous
drip infusion was performed to maintain the depth of sedation. Induction and
maintenance doses in each phase are shown in the table below. When the patient
showed movement, a bolus injection of 1.0 mL propofol was repeated every
minute until suitable sedation was obtained, and continuous drip infusion was
increased to a dose of 5 mL/h. Oxygen saturation and blood pressure were
monitored during all procedures. A BIS monitor was used at phase 5.
Continuous drip infusion was stopped temporarily under the following condi-
tions: SpO2 590%, BP 580 mm Hg, or BIS score 560 (5 seconds or more).
Following recovery, the rate of continuous drip infusion was decreased to 5 mL/
h. We calculated the dose of propofol at the time of induction and during the
maintenance phase, the number of additional bolus injections, and the average
total dose of propofol. The incidence of cardiorespiratory suppression was eval-
uated for each phase. The incidence of BIS below 60 was also evaluated in phase
5.
RESULTS: During induction, no cardiorespiratory suppression occurred in any
of the phases. During the maintenance phase, circulatory suppression occurred
more frequently in phases 1-4 than in phase 5. In contrast, no respiratory sup-
pression occurred in any of the phases.
Table: Propofol dosing and the incidence of adverse events during each phase of
study
CONCLUSION: This newly developed propofol anesthesia protocol (phase 5)
could be safe for therapeutic endoscopy under deep sedation with spontaneous
respiration.
Disclosure of Interest: None declared
P0699 MAGNIFICATION ENDOSCOPY WITH ACETIC ACID-
ENHANCEMENT AND NARROW-BAND IMAGING FOR
PREDICTING HISTOLOGIC CHARACTERISTICS OF GASTRIC
MUCOSAL NEOPLASMS
K. Shibagaki1,*, Y. Amano2, N. Ishimura3, H. Taniguchi4, H. Fujita1,
K. Kobayashi5, Y. Kinoshita3
1
Gastroenterology, Tottori Municipal Hospital, Tottori, 2Gastroenterology, Kaken
Hospital, International University of Health and Welfare, Ichikawa,
3
Gastroenterology, Faculty of Medicine, Shimane University, Izumo, 4Tottori
Municipal Hospital, Tottori, Japan, 5Pathology, Tottori Municipal Hospital,
Tottori, Japan
INTRODUCTION: Magnification endoscopy with narrow-band imaging
(NBIME) that visualizes the capillary patterns of gastric surface structure is
useful for predicting the histologic characteristics of superficial gastric neo-
plasms. NBIME with acetic acid-enhancement (A-NBIME) clearly visualize the
microstructure pattern of gastric mucosal surface.
AIMS & METHODS: We performed a prospective study to compare the diag-
nostic reliability of white light endoscopy (WLE), NBIME, and A-NBIME for
the histologic characteristics of gastric mucosal neoplasms. Consecutive 220 gas-
tric neoplasms (49 adenomas, 144 differentiated adenocarcinomas, and 27 undif-
ferentiated adenocarcinomas) were photographed with WLE, NBIME and A-
NBIME.
Macroscopic patterns by WLE, capillary patterns by NBIME and microstructure
patterns by A-NBIME were respectively classified into type M1/M2/M3, type
C1/C2/C3/C4 and type S1/S2/S3, by referring to the previously reported

Phase1 (n27) Phase 2 (n11) Phase 3 (n7) Phase 4 (n14) Phase 5 n30)

Dose of initial bolus injection (mg/kg) 0.5 0.33 0.5 0.5 0.5
Dose of continuous drip infusion (mg/kg/h) 5 3.3 3.3 2.5 2.5
Average number of additional bolus injections at introductory phase 1.07 (06) 4.0 (113) 1.6 (05) 3.8 (07) 3.6 (017)
Average number of increasing maintenance dose 0.7 (05) 1.5 (02) 1.3 (05) 2.6 (15) 1.9 (07)
Average total dose (mL) 48.5(17109) 60.1 (24135) 49.6 (16133) 44.4 (1295) 52.1 (7.5170)
SpO2 5 90% 0 0 0 0 0
Blood pressure 5 80 mm Hg 11 (40.7%) 3 (27.3%) 3 (42.9%) 4 (28.6%) 3 (4.8%)
BIS score 5 60 (45 seconds) NA NA NA NA 1 (1.6%)
A324
classifications as described below. Macroscopic pattern; Type M1: the protruded
and whitish lesions with roundish edge and smooth or often nodular surface.
Type M2: the irregular-shaped and depressed, flat, or elevated lesion in red or
similar color to the surrounding mucosa. Type M3: the depressed and whitish
lesions often with variously sized nodules on the lesion. Capillary pattern; Type
C1: capillaries with homogenous diameters and distributions. Type C2: capil-
laries with heterogeneous diameters and irregular distributions. Type C3: capil-
laries grow in disorder with unclear mucosal microstructure. Type C4: capillaries
are invisible or obviously decreased. Microstructure pattern; Type S1: glandular
crypts present, homogeneously sized, shaped and arranged foveolae or grooves.
Type S2: glandular crypts present, heterogeneous. Type S3: glandular crypts are
absent or severely decreased.
Endoscopic images were independently reviewed by three expert endoscopists.
Type M1/M2/M3 in WLE, type C1/C2/C3 in NBIME, and type S1/S2/S3 in A-
NBIME were used as the indicator of adenoma/differentiated adenocarcinoma/
undifferentiated adenocarcinoma, respectively. Type C4 in NBIME was excluded
from the analysis of histologic diagnostic accuracy. The histologic diagnostic
accuracy and interobserver diagnostic agreement was compared among
modalities.
RESULTS: The kappa values of interobserver agreement for WLE, NBIME, and
A-NBIME diagnosis were 0.33(0.31-0.36), 0.58(0.55-0.61), and 0.61(0.54-0.67),
showing an insufficient diagnostic agreement for WLE and a statistically good
diagnostic agreement for both NBIME and A-NBIME. Adenomas/differentiated
adenocarcinomas/undifferentiated adenocarcinomas were statistically related to
type M1/M2/M3 in WLE, type C1/C2/C3 in NBIME and type S1/S2/S3 in A-
NBIME, respectively (P50.01). Type C4 of capillary pattern by NBIME did not
show a statistical correlation to the specific histologic characteristics. The diag-
nostic accuracy of WLE, NBIME, and A-NBIME were 79.0%, 74.1%, and
90.5%, showing statistical superiority of A-NBIME (P50.01). No additional
effect of NBIME to WLE.
CONCLUSION: A-NBIME is superior to WLE and NBIME in the predictive
histological diagnosis of gastric mucosal neoplasms with good clinical feasibility.
Disclosure of Interest: None declared
P0700 HIGHEST POWER MAGNIFICATION IS SUPERIOR TO LOW
POWER MAGNIFICATION FOR DELINEATION OF EARLY
GASTRIC CANCERS USING NARROW BAND IMAGING
K. Uchita1,*, K. Yao2, N. Uedo3, T. Iwasaki1, K. Kjima1, A. Kawada1,
M. Okazaki1, S. Iwamura1
1
Gastroenterology, Kochi Redcross Hospital, Kochi, 2Endoscopy, Fukuoka
University Chikushi Hospital, Fukuoka, 3Gastrointestinal Oncology, Osaka
Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan
Contact E-mail Address: ucchy31@yahoo.co.jp
INTRODUCTION: Curative endoscopic submucosal dissection (ESD) of early
gastric cancers requires accurate determination of the horizontal extent of inva-
sion. A number of studies have since reported superior diagnostic ability for
magnifying endoscopy with narrow-band imaging (ME-NBI) over conventional
endoscopy (CE) in delineating the lateral extent of early gastric neoplasias.
However, there are few studies that have reported the actual magnifying ratio
used when performing ME. The added benefits of ME-NBI over CE in terms of
the difference in magnification level have yet to be elucidated.
AIMS & METHODS: The aim of this study was to investigate the improvement in
diagnostic accuracy for tumor delineation obtained with different magnification
levels of ME-NBI following CE. This study comprised a series of 161 consecutive
early gastric cancers resected en bloc using ESD in 158 patients between July 2008
and June 2012. Each patient underwent sequential CE, LM-NBI and HM-NBI
examinations during the same procedure as preoperative diagnostic examinations
1 to 2 weeks prior to ESD. On the day of the ESD procedure, or the preceding day,
using HM-NBI we again identified the lesion margin, and made markings 3-5 mm
outside the DL. After ESD with reference to the pathohistological findings, we
identified the markings, and reconstructed the lateral extent of the cancer on the
each endoscopic image (CE, LM-NBI, HM-NBI). The histologically determined
cancer margins were used as the gold standard. The primary endpoint was the
added benefit, as measured using the successful delineation rate, for the delineation
of gastric cancer margins using CELM-NBI vs CE, and for CELM-NBIHM-
NBI vs CELM-NBI. We derived the successful delineation rate with 95% con-
fidence intervals (CI) for early gastric cancers using each examination method, CE,
CELM-NBI, and CELM-NBIHM-NBI and used McNemars test with
Bonferronis multiple comparison correction to calculate p values.
RESULTS: The clinical characteristics were as follows: average age 71 years; 116
males and 45 females; mean lesion diameter 19.2 mm (14.4 mm, range 5-120
mm); and macroscopic type using the Paris classification type 0-I 4 lesions
(2.5%), type 0-IIa 64 lesions (39.8%), type 0-IIb 38 lesions (23.6%), and type
0-IIc 55 lesions (34.2%). The location of the lesion was the upper part of the
stomach in 46 cases (28.6%), middle part in 41 (25.5%), and lower part in 74
(46.0%). The successful delineation rates (95% CI) using CE, CELM-NBI and
CELM-NBIHM-NBI were 72.7 (68.5-79.9%), 88.9 (83.9-93.7%), and 98.1
(95.8-100%). The diagnostic accuracy improved significantly for CELM-NBI
compared with CE (P50.001) and for CELM-NBIHM-NBI compared with
CELM-NBI (P50.001).
CONCLUSION: ME-NBI is an extremely useful modality for the delineation of
the margins of early gastric cancers. HM-NBI is superior to LM-NBI in improv-
ing the successful delineation rate, following CE.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0701 GASTRIC ATROPHY WAS A RISK FACTOR FOR THE
PRESENCE OF MISSED SYNCHRONOUS LESION AFTER
ENDOSCOPIC SUBMUCOSAL DISSECTION
K.H. Kim1,*, S. I. Seo1, B.Y. Choi1
1
Department of Internal Medicine, Division of Gastroenterology & Hepatology,
Kangdong Sacred Heart Hospital of Hallym University Medical Center, Seoul,
Korea, Republic Of
Contact E-mail Address: minsoksumin@naver.com
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been widely
accepted as a minimally invasive therapy for gastric adenoma or early gastric
cancer (EGC). However, the risk of secondary gastric neoplasms developing
during the surveillance period after ESD has become a important medical pro-
blem. In particular, there is a high possibility that ESD can miss synchronous
gastric neoplasms compared with surgery.
AIMS & METHODS: In the present study, we aimed to investigate predictive
factors associated with the presence of missed synchronous gastric neoplasms
after ESD for gastric adenoma or EGC. We performed ESD in 370 patients
with EGC or gastric adenoma from January 2008 through December 2012 at
our institution. The patients with endoscopic surveillance interval less than 1
year, patients without curative resection, and patients with additional surgery
were excluded from the study. Missed synchronous gastric neoplams were
defined as any gastric neoplasms detected within one year after ESD, but initially
unidentified. We compared clinical, endoscopic, and pathological factors
between patients with missed synchronous gastric neoplasms and patients with-
out missed synchronous gastric neoplasms.
RESULTS: Missed synchronous gastric neoplasms were found in 4.3% (16/370)
of the patients. Among the 16 missed synchronous gastric neoplasms, three
(18.8%) cases were carcinomas. In the univariate analysis, open-type gastric
atrophy, gastric atrophy and intestinal metaplasia more than moderate degree
were significantly associated with the presence of missed synchronous gastric
neoplasms. In multivariate logistic regression analysis, only gastric atrophy
more than moderate degree was the independent risk factor for the presence of
missed synchronous gastric neoplasms (Exp (B) 8.608, 95%CI: 1.03645.549).
CONCLUSION: Gastric atrophy could be an independent risk factor for the
presence of missed synchronous lesion after ESD. Careful endoscopic surveil-
lance should be performed after ESD for patients with severe gastric atrophy.
Disclosure of Interest: None declared
P0702 EFFECT OF ELECTRICAL CURRENT MODE ON CLINICAL
COURSE AFTER GASTRIC ENDOSCOPIC SUBMUCOSAL
DISSECTION
K.H. Song1,*, S.M. Kim1, J.H. Park1, K.C. Huh1
1
Konyang University, Deajon, Korea, Republic Of
Contact E-mail Address: postit2@daum.net
INTRODUCTION: Several modes of electrical current are available for endo-
scopic submucosal dissection (ESD) of gastric epithelial tumor. There has been
no data regarding whether the electrical current mode effects on clinical course
after gastric ESD, including incidence of post ESD coagulation syndrome, ulcer
healing rate.
AIMS & METHODS: AIM Clinical courses were surveyed according to the
setting of two different dissecting mode: endocut or swift, to provide relating
data on optimal adoption of mode for gastric ESD.
METHODS Among 286 consecutive sessions of gastric ESD, 200 lesions were
surveyed after excluding cases: usage of endoknives other than IT2 knife, tumor
with nearby scar, synchronous tumor, subepithelial tumor. Only one of endocut
or swift mode was adopted for submucosal dissection in eaach session of ESD.
All the procedure were performed using an electrosurgical unit, VIO 300D
(ERBE, Germany). The ESD pathology, location of tumor, procedure and resec-
tion time, incidence of post ESD syndrome were assessed with demographic data.
Patients with pyrexia (body temperature 438.3_C) and upper abdominal pain or
tenderness after ESD, with or without symptoms of peritoneal irritation were
defined as having post ESD coagulation syndrome. Follow up endoscopy was
performed at 3 months after the endoscopic therapy and rated as ulhealed if the
ulcer was in A1 to H2 rated by Sakita-Miwa stage.
RESULTS: In total of 200 sessions, we applied endocut mode for 116 cases
(58%) and swift mode at for 84 cases (42%). The demographic data between
the two groups were not significantly different. Total of 16 post ESD coagulation
syndromes were notified. Multivariate analysis revealed adoption of swift mode
(OR 6.90, 95%CI: 1.83-25.92) and malignant pathology (OR 5.93, 95%CI: 1.46-
24.02) was related post ESD coagulation syndrome. Ulcer healing rate judged at
3 months after ESD tended to be delayed for endocut mode, even though it was
not statistically significant.
CONCLUSION: Mode of electrical current may be related to the incidence of
post ESD coagulation syndrome or ulcer healing after gastric ESD. Randomized
and controlled studies are warranted.
REFERENCES
Lee H, et al. Clinical features and predictive factors of coagulation syndrome
after endoscopic submucosal dissection for early gastric neoplasm. Gastric
Cancer 2012; 15: 83-90.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S) A325
Table 1. Demographic, endoscopic procedures, propofol dose and adverse events
P0703 TRANASAL VERSUS PERORAL PERCUTANEOUS
in both groups
ENDOSCOPIC GASTROSTOMY: A PROSPECTIVE CASE
Table to abstract P0704
CONTROL STUDY
L.-F. Lin1,* Propofol AE (%)
1
Gastroenterology, Pingtung Christian Hospital, Pingtung, Taiwan, Province of ASA I/II/III Colonoscopy dose EGD / Desaturation/
China Age Weight (%) EGD n n (%) Colonoscopy Bradycardia
Contact E-mail Address: lin.lian.feng@gmail.com
75 years 81  4 68.56  12,4 17.3/70.3/12.4 439 307 72.99 37.4/ 2.6/0.3
80.5934
INTRODUCTION: Percutaneous endoscopic gastrostomy (PEG) is a challenge
575 years 51.3 13 68.55  12,4 62.8/34.9/2.3 439 307 120.54 4.8**/ 0.8/0.3*
in patients with difficult oral intubation. Some cases of successful transnasal 129.12 55.9**
insertion of PEG were reported. But no any case control study was conducted
to compare transnal and oral insertion of PEG.
AIMS & METHODS: This work is to investigate the difference between trans-
nasal and peroral insertion of percutaneous endoscopic gastrostomy in clinical Data are presented as mean  SD (range: 95% CI of the mean). Abbreviations:
outcome. A prospective, case-control study was conducted to compare transnasal ASA (American Society of Anaesthesiology); EGD
(T-PEG) and peroral (O-PEG) placement of a 20 Fr PEG tube in dysphagic (Esophagogastroduodenoscopy). AE: adverse events. *P 5 .005; **P 5 .001
patients without conscious sedation. Additional spraying lidocain solution and CONCLUSION: Propofol is safe when administered by non-anesthesiologists.
epinephrine solution to the nasal cavity and using ultrathin 5 mm endoscope Patients 75 years globally require almost 40% less propofol than patients 575
(Olympus GIF-N-260) were applied to the T-PEG. The other premedication years. These results support the use of a lower dose of propofol in the elderly.
and procedure are same as conventional pull-method PEG. Neither the nasal REFERENCES
cavity nor the oral cavity were decolonized in all patients. The success rate, Disclosure of Interest: None declared
operation time, occurrence of choking during PEG, nasal bleeding, stomal site
infection, post-PEG complication were recorded and analyzed.
RESULTS: Thirty-nine insertions of T-PEG and thirty-eight insertions of O- P0705 CHANGES IN GASTRIC INTESTINAL METAPLASIA
PEG were attempted in 77 chronic dysphagic patients form home or nursing EXTENSION IN ANNUALLY FOLLOWED-UP PATIENTS: 1-YEAR
home. Mean age is (T-PEG vs O-PEG) 76.310.3 vs 79.56.9 years, male RESULTS OF A STUDY PERFORMED BY MEANS OF NARROW
gender 67% vs 48%, operation time 14.6  4.0 vs 113 minutes (p: 0.028), BAND IMAGING WITH MAGNIFICATION ENDOSCOPY
choking occurred in 3 vs 5 patients. One failed insertion and two nasal bleeding L. Gemignani1, P. Dulbecco1, E. Giambruno1, G. Bodini1,*, M. Furnari1,
occurred in T-PEG. There are nine stomal site infection (8 pseudomonas aeru- M. Giacchino1, F.E. Gianiorio1, L. Mastracci2, F. Grillo2, F. Sarocchi2,
ginosa infection including one systemic infection) in T-PEG and 14 stomal site V. Savarino1, E. Savarino3
infects (8 pseudomonas aeruginosa) in O-PEG (p 50.001). One systemic infec- 1
Department of Internal Medicine, 2Department of Pathologic Anatomy,
tion of urinary tract, one buried bumper, and one soiling of stoma were observed University of Genoa, Italy, Genoa, 3Department of Surgical, Oncological and
respectively in T-PEG and O-PEG. No PEG related mortality occurred within 3 Gastroenterological Sciences, University of Padua, Padua, Italy
months after all PEG procedures. Contact E-mail Address: alphaone81@gmail.com
CONCLUSION: Transnasal insertion is feasible in placing a 20 Fr PEG but it
causes rare nasal bleeding rate and needs longer operation time. Stomal site INTRODUCTION: Gastric Intestinal Metaplasia (GIM) is a precancerous con-
infection is less but more dominant pseudomonas infection occurred in T- dition potentially leading to gastric cancer. However, this occurs in a limited
PEG. In conclusion, T-PEG is an alternative for patients who had difficulty in number of cases and, therefore, the need of endoscopic surveillance and
oral intubation. It needs more studies to concern the prophylaxis of pseudomo- follow-up is controversial. Moreover, there is no universal consensus regarding
nas infection. which patients should be better investigated and followed-up in the long-term
Disclosure of Interest: None declared period. Most of the experts among pathologists and gastroenterologists recom-
mend to perform an upper endoscopy with multiple biopsies every three-year
only in patients with extensive GIM, but no studies have validated the effective-
P0704 PROPOFOL REQUIREMENTS FOR GASTROINTESTINAL ness of this protocol, so far.
ENDOSCOPY IN PATIENTS OLDER THAN 75 YEARS OLD AIMS & METHODS: Our aim was to investigate whether changes in extension
L. Achecar1,*, X. Garc a Aguilera1, A. Gonzalez1, M. Del R o1, G. Arranz1, and/or progression of GIM occur during a strict yearly endoscopic follow-up
M.Van Domselaar1 program. Between November 2011 and December 2013, we prospectively eval-
1
Endoscopy unit, Hospital Universitario de Torrejon de Ardoz, Madrid, Spain uated consecutive patients with an histologically defined diagnosis of GIM by
Contact E-mail Address: xagarcia@torrejonsalud.com means of Narrow Band Imaging with Magnification Endoscopy (NBI-ME) and
multiples gastric biopsies (2 antrum 1 angulus 2 corpus). Helicabacter pylori
INTRODUCTION: Numerous studies support the efficacy and safety of propo- infection was excluded. Patients with a GIM extension higher than 20% were
fol in digestive endoscopy in which propofol is administered by non-anesthesiol- offered to repeat the endoscopic examinations every year and, to date, 20 out of
ogist during endoscopic procedures. There is literature on the safety of sedation 121 accepted and were included in the follow-up program. Endoscopic examina-
with propofol in elderly patients. However, there are no clear guidelines regard- tions have been performed by experienced endoscopists (each of them with more
ing the dose of propofol to be used in this group of patients in which comorbidity than 1000 NBI-MEs performed). Biopsies were taken at sites suggestive for GIM
can make them more fragile, making the standard dose/kg of weight excessive to based on NBI-ME appearance (i.e. presence of light blue crests on the surface of
achieve a safe sedation. gastric mucosa) or randomly if no evident mucosal alterations were seen. Biopsies
AIMS & METHODS: The aims of this study were to establish the dose of were assessed by two expert and blinded pathologists, who evaluated the percen-
propofol in patient 75 years compared with patients 575 years and to evaluate tage of extension of GIM at both times.
the safety of propofol when is administered by non-anesthesiologist. Between RESULTS: The median time between the two observations was 13 months
June 2012 and March 2014, we prospectively recorded all endoscopic procedures (range 11-18). As shown in the Table, patients were divided in three categories,
and safety data. Only diagnostic procedures were included for this study. We according to the changes in GIM extension, which was considered stable if there
excluded: patients 518 years, not sedated by endoscopist, therapeutic and were tiny variations (0-5%) between the two observations, or raised/lowered
incomplete procedures, and also patients with two endoscopies performed on otherwise. At 1-year, in all patients, the second evaluation confirmed the presence
the same day. To reduce variability and determine whether the differences of GIM. In patients with worsened extension, the mean percentage of GIM
between the doses of propofol in both groups were related to age, all patients increase was 20%, whereas the mean percentage of GIM lowering was 26%in
75 years were matched on a 1:1 basis with the 575 years group in terms of patients with a reduced GIM extension.
weight, body mass index (BMI) and endoscopic procedure. All esophagogastro-
duodenoscopies (EGDs) and colonoscopies received an initial dose of propofol GIM STABLE GIM
0.5-1 mg/kg. Colonoscopies also received a fixed dose of 50 mcg of fentanyl. MEDIAN AGE EXTENSION GIM EXTENSION
Subsequently, boluses of 10-20 mg propofol were administered to maintain an N AGE RANGE LOWERED EXTENSION RAISED
adequate level of sedation. Vital signs were recorded before, during and after the
procedure. A statistical analysis was performed with the SPSS v20.0 program. Females 13 67 56-71 3 (23%) 3 (23%) 7 (54%)
RESULTS: There were 439 diagnostic EGDs and 307 diagnostic colonoscopies
performed in patients 75 years. When compared with patients 575 years, there Males 7 64 53-85 4 (57%) 1 (14%) 2 (29%)
were significant differences between groups in mean propofol dose, and mild OVERALL 20 64 53-85 7 (35%) 4 (20%) 9 (45%)
adverse events. No serious adverse events occurred. Patients 75 years required
significantly less propofol than patients 575 years, 72.99 37.4mg vs. 120.54
4.8mg for EGDs (P 5 0.001) and 80.5934mg vs 129.12 55.9mg (P 5 0.001) CONCLUSION: Our results demonstrate that already at 1-year the extension of
for colonoscopies (39.4% less in EGDs and 37.5% in colonoscopies). Table 1 GIM and, therefore, the risk of developing a gastric cancer GIM-related, worsens
shows the demographic, endoscopic procedures, propofol dose and adverse in about 45% of the patients. Thus, these data seem to support a more close
events in both groups. follow-up in patients with a GIM extension higher than 20% at histologic
assessment.
Disclosure of Interest: None declared
A326
P0706 DOES MAGNIFYING ENDOSCOPY WITH NARROW BAND
IMAGING IMPROVE DIAGNOSTIC ACCURACY FOR DEPTH OF
INVASION IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA?
M. Imajoh1,*, T. Yano1, T. Kadota1, T. Kato1, S. Osera1, H. Morimoto1,
T. Odagaki1, Y. Oono1, H. Ikematsu1, K. Kaneko1
1
Department of Gastroenterology, Endoscopy Division, National Cancer Center
Hospital East, Kashiwa city, Japan
Contact E-mail Address: maomiimajo@gmail.com
INTRODUCTION: While accurate estimation for the depth of invasion in eso-
phageal squamous cell carcinoma (ESCC) is essential to indicate relevant treat-
ment methods, it is difficult to evaluate conventional endoscopy alone.
Microvascular patterns identified using magnifying narrow band imaging (M-
NBI) have been reported to be useful for the diagnosis in the depth of invasion
for superficial ESCC. Recently, a classification regarding the microvascular pat-
terns of superficial ESCC using M-NBI was advocated from the Japan
Esophageal Society, however, it is not clear whether the depth of invasion can
be estimated more accurately according to this classification compared with
estimation using conventional white light endoscopy (WL) alone.
AIMS & METHODS: The aim of this study was to evaluate whether the diag-
nostic accuracy of in M-NBI is higher than that in WL alone. In this study, we
enrolled patients with superficial ESCC who had undergone pretreatment eva-
luation using both WL and M-NBI, and who received endoscopic resection or
surgery in our institution from June 2012 to December 2013. The patients who
had been previously treated with chemotherapy or chemoradiotherapy were
excluded. The microvessels of tumor surface observed by M-NBI were classified
into 3 groups; type B1 consisted of loop-like vessels with atypia, including dilata-
tion and meandering; type B2 were non-loop vessels; and type B3 were large
vessels 3 or more times larger than type B2. Type B1, B2, and B3 vasculatures
were correlated with lesions invading to EP/LPM, MM/SM1, and SM2 or
deeper, respectively. Investigators who were blinded to the pathological diagnosis
estimated retrospectively the depth of invasion in the endoscopic pictures by WL
alone, and then using the pictures by M-NBI. We sorted the lesions into 3 groups
(EP/LPM, MM/SM1, and SM2/SM3) and the diagnoses for individual modal-
ities were compared to the pathological results. Finally, sensitivity, specificity,
and positive predictive value (PPV) were analyzed.
RESULTS: A total of 198 lesions were examined. Sensitivity, specificity, and
PPV of WL-alone were 92%, 85%, 90% for EP/LPM; 63%, 89%, 51% for
MM/SM1; and 74%, 97%, 90% for SM2/SM3, respectively. Sensitivity, specifi-
city, and PPV of M-NBI were 85%, 71%, 81% for EP/LPM; 50%, 75%, 28% for
MM/SM1; and 39%, 100%, 100% for SM2/SM3, respectively. The concordance
rate for diagnoses between both modalities was 87% in EP/LPM, 59% in MM/
SM1, and 45% in SM2/SM3. In cases of a concordance between WLE and NBI-
ME, the PPV was 90% for EP/LPM, 61% for MM/SM1, and 100% for SM2/
SM3.
CONCLUSION: While the concordance rates between WL and M-NBI was
unfavorable in MM/SM1, and SM2/SM3, PPV was high in the diagnosis was
concordant cases between both modalities. However, the difficulty of evaluating
the invasion depth for MM/SM1 lesions remains unsolved.
REFERENCES
1 Oyama T and Monma K. A new classification of magnified endoscopy for
superficial esophageal squamous cell carcinoma. Esophagus 2011; 8: 247-251.
2 Muto M, Horimatsu T, Ezoe Y, et al. Improving visualization techniques by
narrow band imaging and magnification endoscopy. J Gastroenterol Hepatol
2009; 24: 13331346.
Disclosure of Interest: None declared
P0707 RJ 4 JUMBO VS. RJ 4 LARGE CAPACITY FORCEPS IN TISSUE
SAMPLING IN PATIENTS WITH BARRETTS ESOPHAGUS: FINAL
RESULTS OF A PROSPECTIVE, RANDOMIZED STUDY
M. Kollar1,*, J. Maluskova1, E. Honsova1, J. Krajciova2, J. Spicak2, J. Martinek2
1
Clinical and transplant pathology department, 2Hepatogastroenterology depart-
ment, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
Contact E-mail Address: marek.kollar1@seznam.cz
INTRODUCTION: Good quality of biopsy specimen is required for reliable
diagnosis of early neoplasia in patients with Barretts esophagus (BE). Studies
comparing large capacity vs. jumbo forceps have shown inconsistent results.
The aim of this study was to assess the quality of biopsy specimen obtained by
2 different-sized biopsy forceps (Radial Jaw 4 large capacity (outer diameter 2.4
mm) vs Radial Jaw 4 jumbo (outer diameter 2.8 mm) in patients with BE. We
hypothesized that RJ4 jumbo forceps if used with a standard diagnostic endo- B. Murakami1, M. Azuma2, S. Tanabe2, M. Kida2, W. Koizumi2
scope (channel 2.8 mm) provides a better quality of biopsy specimen as compared
to the large capacity forceps.
AIMS & METHODS: A single center, randomized (forceps order), prospective
and single blind (pathologist) study. Twenty-one patients with BE (5 women, 16
men) were enrolled. All patients underwent an upper GI endoscopy with trimodal
imaging. Targeted or random biopsies with both types of forceps used in random
order were obtained from each patient during a single endoscopy with a diag-
nostic endoscope. Main outcome measurement was specimen adequacy (defined
as a well oriented biopsy specimen 2 mm in diameter or greater with mucosa
present).
RESULTS: A total of 288 biopsy specimen were analyzed (large capacity: 159,
jumbo forceps: 129). A significantly higher proportion of biopsy samples
obtained with jumbo forceps was adequate as compared to large capacity forceps
(54.3 % vs. 18.9 %, p50.0001).
Biopsies with jumbo forceps had a larger diameter (median 2.4 mm vs. 2 mm;
p50.001). Muscularis mucosae was detected in 67.4 % of specimen with jumbo
forceps vs. 31.4 % with large capacity forceps (p50.0001). Excellent or good
United European Gastroenterology Journal 2(5S)
specimen orientation was present in 79.8 % of samples with jumbo forceps and in
59.1 % with large capacity forceps (not significant). Intestinal metaplasia was
present in 69.8 % with jumbo forceps vs. 78.6 % of samples with large capacity
(not significant). The diagnostic yield of both types of forceps was comparable.
CONCLUSION: Radial Jaw 4 Jumbo biopsy forceps, if used with diagnostic
endoscope, provides more adequate biopsy specimen as compared to Radial Jaw
4 large capacity biopsy forceps. The diagnostic yield seems to be comparable.
Disclosure of Interest: None declared
P0708 OPTIMIZED IMPEDANCES OF INJECTION SOLUTIONS LEAD
TO IMPROVED CUTTING RESULTS IN ENDOSCOPIC RESECTION
N. Al-Dayaa1, M. Losle1,2, K.-E. Grund1,2,*
1
Surgical Endoscopy and Experimental Endoscopy, University Hospital, Tubingen,
2
supported by: Federal Ministry of Economics and Technology based on a resolu-
tion of the Bundestag, Berlin, Germany
Contact E-mail Address: chir.endo@uni-tuebingen.de
INTRODUCTION: The endoscopic resection of large ( 4 20 mm) lesions in the
gastrointestinal tract is a high challenge for interventional endoscopy and radio-
frequency surgery. There is no easy, fast and safe way to remove large lesions en-
bloc. An important reason is the interaction between submucosal injection, tissue
and high-frequency parameters in respect to electrical impedances. This interac-
tion is only partly understood and poorly investigated. Preliminary studies led to
the conclusion that problems in the cutting process like cutting delay, perforation
and thermal artifacts are due to unsuitable impedances.
AIMS & METHODS: Our aim was to improve the cuttings results (avoiding of
cutting delay and high thermal load of the intestinal wall) by optimizing the
impedances of the tissue. Therefore we analyzed various submucosal injection
solutions in respect to impedances (surface and tissue) and rf-cutting.
With standardized gold probes (1 mm/15 mm) and a special RF-impedance-
meter (f 100 kHz, 10 V - 1 MV) the specific impedances of various solutions
and the impedances on the surface and in the tissue after submucosal injection of
3 ml were measured in a standardized bio-model (porcine stomach). Additionally
the elevations during 30 min were observed. The following solutions were injected
into the submucosa: 0.9% saline, 4% gelatin, 6% hydroxyethyl starch, 10%
glycerol/5% fructose in 0.9% saline, 10% glucose and aqua destillata.
Additionally 5% albumin, 20% albumin, human blood and blood plasma and
a new experimental substance.
RESULTS: Aqua destillata and 10% glucose showed a highly significant higher
(p  0.0001) specific impedance compared to the standard 0.9% saline (factor
360). After injection also the impedances on the surface and in the tissue were
significantly higher (p  0.01, resp. p  0.0001). The elevation showed no sig-
nificant difference between the tested solutions. Cutting experiments in a stan-
dardized setting showed the expected improvements: no cutting delay, less
thermal load of the intestinal wall, smooth cut without carbonization but with
adequate zone of hemostasis.
CONCLUSION: Clinically used injection solutions show a highly significant
difference of specific impedances. After injection they lead to different impe-
dances on the surface and in the tissue. Better cutting results (avoidance of
delayed cut, high thermal load and thermal artifacts) obviously depend on an
optimized impedance of the tissue. Therefore injection solutions with optimal (i.e.
higher) impedances should be further investigated and preferred to conventional
agents.
REFERENCES
Park YM, Cho E, Kang HY, et al. The effectiveness and safety of endoscopic
submucosal dissection compared with endoscopic mucosal resection for early
gastric cancer: a systematic review and metaanalysis. Surg Endosc 2011; 25:
2666-2677.
Kim YJ, Kim ES, Cho KB, et al. Comparison of clinical outcomes among
different endoscopic resection methods for treating colorectal neoplasia. Dig
Dis Sci 2013; 58: 1727-1736.
Farin G and Grund KE. Principles of electrosurgery, laser, and argon plasma
coagulation with particular regard to colonoscopy. In: Waye JD, Rex DK and
Williams CB (eds) Colonoscopy prociple and practice. Singapore: Wiley-
Blackwell Verlag, 2009, pp. 328345.
Disclosure of Interest: None declared
P0709 PERCUTANEOUS TRANSESOPHAGEAL GASTROTUBING
WITHOUT RADIATION EXPOSURE WITH ENDOSCOPIC
ASSISTANCE
M. Murakami1,2,*, K. Nishino1, S. Murakami1, Y. Takaoka1, K. Mori1,
1
Internal medicine, MURAKAMI MEMORIAL HOSPITAL, saijo,
2
Gastroenterology, Kitasato University East Hospital, Sagamihara, Japan
Contact E-mail Address: masato@mrakami-kinen.or.jp
INTRODUCTION: Percutaneous transesophageal gastrotubing (PTEG) was
developed as an alternative route to access the gastrointestinal tract for patients
where Percutaneous Endoscopic Gastrostomy was contraindicated with condi-
tions such as prior gastrectomy, gastric anterior wall malignancies, or massive
ascites. PTEG was originally developed to be performed under fluoroscopy with-
out endoscopy. However, endoscopy may enhance the safety of the procedure.
AIMS & METHODS: The aim of this study is to evaluate the clinical usefulness
of PTEG supported by endoscopy. A rupture-free balloon (RFB) catheter is
inserted into the lower esophagus. Percutaneous balloon puncture with a specia-
lized needle is then performed from the left side of patients neck under ultra-
sonographic control. A guide wire is inserted through the needle into the RFB,
followed by a dilator and sheath. A placement tube is then inserted through the
sheath, and the sheath is removed. We started to perform PTEG under
United European Gastroenterology Journal 2(5S)
endoscopy without fluoroscopy in a total of 99 patients (63 men and 36 women,
mean age 74.0 years) in whom PEG was not feasible. PTEG was performed for
nutrition in 53 patients and for decompression in 46.
RESULTS: Satisfactory results were achieved in all 100 patients. Median follow-
up was 60.5 days in patients who received decompression because of the obstruc-
tion due to malignancies and 231.0 days in those who received nutrition. Two of
the 99 patients in the endoscopic assistance required fluoroscopy because of the
tube insertion into the jejunum. There were no major complications, but one
patient had tracheal penetration, which was managed conservatively. Other com-
plications were minor oozing bleeding in six patients that did not require blood
transfusion, subcutaneous emphysema in two patients, which were managed
conservatively. Nine accidental (four self) tube removals occurred more than 2
weeks after the procedure, without any problem in reinsertion. The overall com-
plication rate associated with endoscopically assisted PTEG was 14.1%. No
patient required surgical treatment or died after PTEG.
CONCLUSION: PTEG supported by endoscopy is as feasible, safe, and useful
as PTEG supported by fluoroscopy, the original procedure. The use of endo-
scopy enhances the safety of the procedure and allows better confirmation of
each step involved.
Disclosure of Interest: None declared
P0710 ASSESSMENT OF THE SIMPLIFIED NARROW BAND IMAGING
PATTERN CLASSIFICATION IN BARRETTS OESOPHAGUS
M. Kato1,*, K. Goda2, Y. Shimizu3, A. Dobashi2, M. Takahashi3, M. Kato3
1
Endoscopy, The Jikei University Katsushika Medical Center, 2Endoscopy, The
Jikei University School of Medicine, Tokyo, 3Gastroenterology and Hepatology,
Hokkaido University Hospital, Sapporo, Japan
Contact E-mail Address: masakato89@gmail.com
INTRODUCTION: Various narrow band imaging (NBI) pattern classifications
in Barretts oesophagus (BO) have been proposed, but are not readily applied to
routine clinical practice due to their multiplicity or complexity.
AIMS & METHODS: We evaluate inter- and intra-observer agreement as well as
accuracy of a new simplified NBI pattern classification using NBI magnifying
endoscopic images.
A simplified binary classification is based upon NBI mucosal and vascular pat-
terns: 1) regular pattern (non-neoplastic BO) 2) irregular (Barretts neoplasia,
BN). Four endoscopists consisting of 2 experts and 2 non-experts assessed 248
NBI magnifying endoscopic images (neoplasia 72, non-neoplasia 176) based on a
simplified binary NBI pattern classification. The endoscopists assessed two times
a randomly-arranged NBI magnifying endoscopic image sequence. The interval
between the 1st and the 2nd assessment was 6 weeks. Primary endpoint was inter-
observer agreement among endoscopists. Secondary endpoints were intra-obser-
ver agreements in each endoscopist and diagnostic accuracies of sensitivity, spe-
cificity, positive predictive value (PPV) and negative predictive value (NPV) in
predicting BN as well as scores of diagnostic confidence level and image quality.
RESULTS: A median score for image quality was 5 (excellent) in both the 1st and
2nd assessment. Inter-observer agreement (multi-kappa value) among endoscoc-
pists for BN prediction was calculated as 0.79 (substantial) and 0.86 (almost
perfect) for the 1st and 2nd assessment. Intra-observer agreement (kappa-value)
which were 0.95, 0.94 (experts) and 0.83, 0.83 (non-experts), respectively, were all
almost perfect. Mean sensitivity and specificity of NBI patterns for predicting
BN were 92.7% (experts, 90.3%; non-experts, 95.1%) and 95.9% (experts,
99.4%; non-experts, 92.3%) in the 1st assessment as well as 95.5% (experts,
95.8%; non-experts, 95.1%) and 95.7% (experts, 99.1%; non-experts, 92.3%)
in the 2nd assessment, respectively, with high confidence level in both assess-
ments. NPV was 98.9% (experts, 96.2%; non-experts, 97.9%) and 99.3%
(experts, 98.3%; non-experts, 97.9%) in the 1st and 2nd assessment, respectively.
CONCLUSION: A simplified binary NBI pattern classification for BO showed
substantial to almost perfect inter- and intra-observer agreement and signifi-
cantly high diagnostic accuracies in both experts and non-experts. A simplified
binary NBI pattern classification seems applicable to routine clinical practice.
Disclosure of Interest: None declared
P0711 PREDICTIVE FACTORS FOR LYMPH NODE METASTASIS
AFTER NONCURATIVE ENDOSCOPIC RESECTION FOR EARLY
GASTRIC CANCER
M. Inoue1,*, T. Omori1, R. Nakamura1, T. Takahashi1, N. Wada1,
H. Kawakubo1, H. Takeuchi1, Y. Saikawa1, Y. Kitagawa1
1
Department of Surgery, School of Medicine, Keio University, Shinjyuku-ku,
Tokyo, Japan
INTRODUCTION: Endoscopic resection (ER) is widely accepted as an appro-
priate treatment modality for early gastric cancer. The indication criteria for ER
is established, and additional treatment, including gastrectomy with lymph node
dissection, is recommended when pathological examination of resected specimens
do not meet the criteria. In some non-curative ER cases, pathological examina-
tion after additional surgery reveals lymph node metastasis which have not been
detected before ER. There is a possibility that the discovery of risk factors of LN-
metastasis in non-curative ER case can expand the indications of endoscopic
treatment for early gastric cancer.
AIMS & METHODS: The aim of this study is to examine the predictive factors
of LN- metastasis which could not be detected before ER in non-curative ER
cases. The indication criteria for ER in Japan is as follows; the lesion clinically
diagnosed as intramucosal differentiated cancer which is 52 cm in size with no
ulceration findings. Expanded indications for some differentiated cancers (intra-
mucosal cancers either 53 cm in size with ulceration findings or with no ulcera-
tion findings regardless of tumor size) and some undifferentiated cancers
(intramucosal cancers 52 cm in size with no ulceration findings) have been
A327
accepted by high volume ER centers like our institution. If the pathological
examination of resected specimens show that they do not meet the criteria includ-
ing expanded indications, we diagnose them as non-curative. From Apr 2000 to
Jul 2013, 75 patients underwent ER as the expanded indication lesion, and were
diagnosed as non-curative by pathological examination in our hospital. They
underwent additional gastrectomy and their pathological findings in ER and
surgical specimens were retrospectively analyzed. And the cases with pathological
LN- metastasis, which have not been detected before ER, were picked up and
their characteristics were analyzed.
RESULTS: LN- metastasis was found in 9 cases (12%). 7 cases were primary
gastric cancers, and 2 cases were residual gastric cancers. In the 7 primary cases, 5
cases had no residual cancer in surgical specimen, while LN- metastases existed.
Focus on these complete endoscopic resection cases, 1 case was pathologically
undifferentiated type and 5 cases were mixed type. The depth of invasion was
SM1 in 1 case, and SM2 in 4 cases. Lymphatic-vascular capillary involvement
was found in all cases. In these cases, LN- metastases were found only in local D1
lymph node lesion. Lymph node relapse was found in 2 SM2 cases in the com-
plete endoscopic resection cases at an early date, one case was in 5 months and
another in 6 months after surgical resection. Both of them had not only lympha-
tic capillary involvement but also vascular one.
CONCLUSION: Our data indicate that SM1/SM2 gastric cancer with patholo-
gically mixed type, regardless of predominant type, have high risk of LN- metas-
tasis even if complete endoscopic resection of local lesion has been performed.
Lymphatic-vascular capillary involvement also may be a predictive factor of LN-
metastasis and risk factor of recurrence. In these cases, we should perform gas-
trectomy with appropriate LN- dissection keeping the risk of recurrence in mind
and consider adjuvant chemotherapy according to the risks.
Disclosure of Interest: None declared
P0712 HIGH DEFINITION (HD) ENDOSCOPY WITH I-SCAN FOR THE
DETECTION OF MARKERS OF COELIAC DISEASE: A FEASIBILITY
STUDY
P.D. Mooney1, M. Kurien1,*, S. Wong1, D.S. Sanders1
1
Regional GI and Liver Unit, Royal Hallamshire Hospital, Sheffield, United
Kingdom
Contact E-mail Address: peter.mooney@sth.nhs.uk
INTRODUCTION: Coeliac disease (CD) remains underdiagnosed. Previous stu-
dies have shown that up to 13% of patients with CD have undergone a previous
gastroscopy where the opportunity to take duodenal biopsies and make a diag-
nosis had been missed. Clinicians may rely on the presence of endoscopic markers
of CD to guide biopsy however these have been shown to lack the required
sensitivity. A routine duodenal biopsy approach may solve this problem but
this is time consuming and expensive. Methods to improve the macroscopic
detection of CD at endoscopy to guide biopsy would seem advantageous. A
single trial on I-Scan, a commercially available digital enhancement technique,
has shown promising results in identifying markers of villous atrophy (VA)1.
However this was an uncontrolled, unblinded trial in high prevalence population
(35% CD). We aimed to assess the utility of I-Scan in a lower prevalence popula-
tion in a randomised controlled trial.
AIMS & METHODS: Patients on a single coeliac enriched endoscopy list were
randomised into 2 groups. Group 1 standard HD white light endoscopy (WLE)
and group 2 WLE plus I-Scan. The presence of endoscopic markers of CD,
scalloping, mosaic pattern, nodularity, loss of duodenal folds or increased vas-
cularity was noted throughout the duodenum. All patients received 4 biopsies
from the second part of the duodenum and at least 1 biopsy from the bulb.
Coeliac serology was taken at the time of endoscopy. Macroscopic markers of
CD are compared VA on histology as the gold standard. 3, 10-point likert scales
for pain, discomfort and distress were used to assess tolerability.
RESULTS: 253 patients (149 female, mean age 53.3 SD 18.2) have been recruited
to date (127 into group 1 and 126 in group 2). In total 27 (prevalence 10.7%) new
diagnoses of CD have been made (14 in group 1 and 13 in group 2). I-Scan
appears to enhance the appearance of markers for CD and in 2 patients in
group 2 CD markers that were not noted to be seen on WLE became apparent.
Preliminary results show that endoscopic markers of CD across both groups
currently have a sensitivity of 78.6% (58.5 91.0), specificity 87.6% (82.4
91.5), positive and negative predictive values of 44.0% (30.3 58.7) and 97.1
(93.4 98.8). Median tolerability scores were good in both groups but better in
the I-Scan group than WLE alone (4/30 versus 8/30 p0.005)
CONCLUSION: The addition of I-Scan to standard endoscopy to aid the diag-
nosis of CD is well tolerated and is feasible. I-Scan appears to enhance the
markings of coeliac disease, however a larger study is required to truly evaluate
the effectiveness of I-Scan as an adjunct to standard endoscopy to increase CD
diagnosis.
REFERENCES
1. Cammarota G, Ianiro G, Sparano L, et al. Image enhanced endoscopy with I-
Scan technology for the evaluation of duodenal villous patterns. Dig Dis Sci
2012; 58: 1287-1292.
Disclosure of Interest: None declared
P0713 EFFECT OF AGING ON COMPLICATIONS OF ENDOSCOPIC
SUBMUCOSAL DISSECTION (ESD) FOR EARLY GASTRIC
CANCER (EGC)
M. Kato1,*, T. Michida1, A. Soga1, A. Kusakabe1, M. Kato1, C. Hibino1,
Y. Shiode1, K. Murai1, Y. Matumura1, T. Kawai1, T. Saito1, Y. Nakada1,
M. Hamano1, K. Yamamoto1, M. Naito1, T. Ito1
1
Japan Community Health care Organization Osaka hospital, Osaka, Japan
Contact E-mail Address: minoru-kato-514@okn.gr.jp
A328
INTRODUCTION: As ESD has been widely used as a minimally invasive treat-
ment for EGC, opportunity to perform it for elderly patients is increasing.
However, there are few reports about safety and efficacy of ESD for them. We
evaluated the effect of aging on complications of ESD for EGC.
AIMS & METHODS: We perform a prospective study of the expanded indica-
tion of ESD for EGC (Soetikno, et al. J Clin Oncol. 23(20):4490-8). ESD was
performed in 891 patients from April 2006 to March 2013 according to the
indication. Patients were divided into elderly group (75 years or older; 344
cases) and non-elderly group (the rest; 547 cases). We compared the incidence
of complications such as post-ESD bleeding, perforation, pneumonia, and delir-
ium between the groups.
RESULTS: No emergent surgery was experienced in all cases. One patient in
non-elderly group died of pneumonia. The incidence of pneumonia and delirium
were significantly higher in elderly group than in non-elderly group (7.0% in
elderly group vs 1.7% in non-elderly group; P50.01, 10.2% in elderly group
vs 1.0% in non-elderly group; P50.01, respectively). There was no significant
difference between two groups in the incidence of post-ESD bleeding and per-
foration (3.8% in elderly group vs 4.9% in non-elderly group; p 0.42, 7.0% in
elderly group vs 5.7% in non-elderly group; p 0.57, respectively). Among the
elderly group, the incidence of delirium was significantly higher in patients who
have dementia than in those who havent (79.2% in dementia patients vs 5% in
non-dementia patients; p50.01), and pneumonia was observed relatively more
often in patients who have a history of chronic obstructive pulmonary disease
(COPD) than in those who havent (10.9% in COPD patients vs 6.1% in non-
COPD patients; p 0.17).
CONCLUSION: ESD for EGC were safely performed even in elderly patients
without critical complications. However, pneumonia and delirium would be more
encountered after ESD in elderly patients, so we have to take care additionally
about them.
REFERENCES
Soetikno, et al. J Clin Oncol 23: 4490-4498.
Disclosure of Interest: None declared
P0714 ENDOSCOPIC INJECTION OF AUTOLOGOUS BLOOD VERSUS
DILUTED EPINEPHRINE FOR CONTROL OF ACTIVELY BLEEDING
GASTRODUODENAL ULCERS: A RANDOMIZED CONTROLLED
STUDY
M.H. Emara1,*, E. Darwiesh1, A.S. Bihery1, T. I. Zaher1
1
Tropical Medicine, ZAGAZIG UNIVERSITY, Zagazig, Egypt
Contact E-mail Address: emara_20007@yahoo.com
INTRODUCTION: A variety of endoscopic methods are available to achieve
hemostasis from an actively bleeding ulcer and reduce the risk of rebleeding e.g.
endoscopic injection of diluted epinephrine, applications of endoscopic clips and
argon plasma coagulation. Preliminary report showed that autologous blood
through tamponade effect, cellular components and its viscosity is effective
and easy applicable technique that can control bleeding from the actively bleed-
ing gastroduodenal ulcers.
AIMS & METHODS: The aim of this study was to test if endoscopic injection of
autologous blood is superior to endoscopic injection of diluted epinephrine in
controlling bleeding from gastroduodenal ulcers. One hundred patients with
actively bleeding gastroduodenal ulcers were randomly assigned to autologous
blood injection (Group A, n 50) or diluted epinephrine (group B, n 50) along
the edges of the ulcers. Groups were compared for rates of initial hemostasis,
rebleeding and complications.
RESULTS:
Group A Group B
(Autologous blood) (Diluted epinephrine)
N 50 (No & %) N 50 (No & %) P Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
CONCLUSION: Autologous blood is effective, comparable to diluted epinephr-
ine in achieving initial hemostasis from actively bleeding gastroduodenal ulcers,
associated with 8% rebleeding rate and had no complications.
Disclosure of Interest: M. Emara: none, E. Darwiesh: none, A. Bihery: none, T.
Zaher: none
P0715 ENDOSCOPIC RESECTION AS A DIAGNOSTIC THERAPY FOR
BORDERLINE LESION OF GASTRIC CANCER; A MULTICENTRE
PROSPECTIVE OBSERVATIONAL STUDY
M. Kato1,2,*, A. Maekawa2, S. Egawa3, M. Komori4, T. Yamada2,5,
K. Yamamoto6, H. Ogiyama7, M. Nakahara8, N. Kawai9, T. Yabuta10,
A. Mukai11, Y. Hayashi2, T. Nishida6, M. Tsujii2, T. Takehara2
1
Department of Gastroenterology, National Hospital Organization, Tokyo Medical
Centre, Meguro-ku, Tokyo, 2Department of Gastroenterology and Hepatology,
Osaka University Graduate School of Medicine, Suita, 3Department of
Gastroenterology, Kansai Rosai Hospital, Amagasaki, 4Department of
Gastroenterology, Osaka Rosai Hospital, Sakai, 5Department of Gastroenterology,
National Hospital Organization Osaka National Hospital, Osaka, 6Department of
Gastroenterology, Toyonaka Municipal Hospital, Toyonaka, 7Department of
Gastroenterology, Itami City Hospital, Itami, 8Department of Gastroenterology,
Ikeda Municipal Hospital, Ikeda, 9Department of Gastroenterology, Osaka Police
Hospital, Osaka, 10Department of Gastroenterology, Sakai Municipal Hospital,
Sakai, 11Department of Gastroenterology, Sumitomo Hospital, Osaka, Japan
INTRODUCTION: It is often difficult to discriminate between gastric adenocar-
icinoma and dysplasia/adenoma using endoscopic forceps biopsy. Endoscopic
resection (ER) is, therefore, applied for borderline malignant lesions for the
purpose of total biopsy in clinical practice. We have reported that about 40% of
patients with borderline lesion were diagnosed as adenocaricinoma after ER from
a multicenter retrospective analysis (M. Kato, et al. J Gastroenterol. 2010).
However, true incidence rate of adenocarcinoma is still unknown due to its
retrospective study design.
AIMS & METHODS: The aim of this study is to confirm the feasibility of ER
for gastric borderline malignant lesions.
This is a multi-centre prospective observational study from 10 hospitals (UMIN
Clinical Trials Registry: UMIN000007476). Patients were included if they were
diagnosed as Category 3.1 or 4.1 based on Vienna classification using endoscopic
forceps biopsy specimen. After inclusion, patients underwent ER in each hospital
and data was prospectively collected concerning macroscopic findings (size and
morphological type based on Paris classification), findings of magnified endo-
scopy with narrow band imaging (NBI-ME), outcomes of ER, and pathological
findings. Primary endpoint was cancer-bearing rate in patients diagnosed as
adenocarcinoma after ER. Secondary endpoints were the association between
final diagnosis and findings of macroscopic appearance and NBI-ME, and the
short-term outcomes of ER.
RESULTS: A total of 105 patients were included from April 2012 to February
2014. Among them, 48 patients were diagnosed as adenocarcinoma after ER and
cancer-bearing rate was 46%. Larger ( 20mm) and smaller (5 20mm) lesions
were not significantly different in cancer-bearing rates (43% vs 57%, p 0.2589).
Similarly, depressed and elevated lesions were not significantly different (50% vs
55%, p 0.7469). NBI-ME could predict accurately the pathological diagnosis
after ER in 52% of the patients. En bloc margin negative resection was achieved
in 103 patients (98.1%). Perforation and post-procedural bleeding occurred in 3
patients (2.9%) and 2 patients (1.9%), respectively. All these adverse events were
managed conservatively and no patients required emergent operation or blood
transfusion.
CONCLUSION: The present study showed that diagnostic ER for gastric bor-
derline malignant lesion is clinically safe and useful because of acceptable com-
plication and high cancer-bearing rate.

Ulcer size 0.523

P0716 THIENOPYRIDINE DERIVATIVE CAN BE A RISK FACTOR FOR
Small (52 cm) 32(64.0) 35(70.0) POSTOPERATIVE BLEEDING WHEN PERFORMING GASTRIC
Large (42 cm) 18(36.0) 15(30.0) ENDOSCOPIC SUBMUCOSAL DISSECTION WITHOUT
Ulcer site 0.424 DISCONTINUATION OF ASPIRIN: STRAP STUDY (SAFE
TREATMENT ON ANTIPLATELETS)
Bulbar 20(40.0) 20(40.0)
Antral 15(30.0) 20(40.0) N. Yoshida1,*, S. Ono2, M. Fujishiro2,3, H. Doyama1, T. Kamoshida4, S. Hirai4,
T. Kishihara5, Y. Yamamoto5, H. Sakae6, A. Imagawa6, M. Hirano7, K. Koike2
Corporal 15(30.0) 10(20.0) 1
Gastroenterology, Ishikawa prefectural central hospital, Ishikawa,
2
Ulcer type 1.0 Gastroenterology, 3 Endoscopy and Endoscopic Surgery, Graduate School of
Forest Ia (spurting) 30(60.0) 30(60.0) Medicine, The University of Tokyo, Tokyo, 4Internal Medicine, Hitachi General
Forest Ib (oozing) 20(40.0) 20(40.0) Hospital, Ibaraki, 5Gastroenterology Center, The Cancer Institute Hospital of
JFCR, Tokyo, 6Gastroenterology, Mitoyo General Hospital, Kagawa,
Volume/cc 0.022* 7
Gastroenterology, Niigata Prefectural Central Hospital, Niigata, Japan
(blood/epinephrine) Contact E-mail Address: naohilow@yahoo.co.jp
MeanSD 7.41.8 8.94.1
Range (5-10) (5-21) INTRODUCTION: Endoscopic procedures for patients taking aspirin were
recently reported[1,2]. However, there was not enough evidence to support
these procedures. We evaluated the safety of endoscopic procedures in Asian
patients with a high risk of bleeding without perioperative discontinuation of
All patients initially achieved hemostasis (100%). Rebleeding occurred in 4 cases aspirin.
of group A (8%) and 5 cases of group B (10%) but this difference was not AIMS & METHODS: A multicenter prospective cohort study was conducted at
statstically significant. Two cases in group B developed cardiovascular complica- six high-volume endoscopy centres in Japan (UMIN000009176). Patients regu-
tions (arrhythmia and ischemic heart attack) while none of group A developed larly taking antiplatelet agents and with a high risk of thromboembolism upon
complications. Ulcer characteristics showed no difference regarding ulcer size, discontinuation of administration were enrolled in this study. All patients under-
site and Forrest classification (the table). There was a significant difference in the went endoscopic procedures with a high risk of bleeding while continuing aspirin
amount needed for injection, little amounts of blood were needed to achieve including endoscopic submucosal dissection (ESD), endoscopic mucosal resec-
hemostasis in group A than the amounts of epinephrine needed in group B tion (EMR), and endoscopic polypectomy of the upper and lower
(p 0.022)
United European Gastroenterology Journal 2(5S)
gastrointestinal tracts. The primary endpoint was the rate of major bleeding
complications after endoscopic procedures.
RESULTS: This study was terminated in accordance with predetermined criteria
because seven of 28 consecutive patients experienced major bleeding complica-
tions (25.0%; 95% confidence interval, 10.7%44.9%). All major bleeding com-
plications occurred after ESD (stomach n 6; colon, n 1). Univariate analysis
revealed that postoperative administration of a thienopyridine derivative was the
only significant factor associated with postoperative bleeding (p 0.04).
Subanalysis of gastric ESD of 23 lesions in 19 patients also confirmed that
administration of a thienopyridine derivative was the only significant factor
through multivariate analysis (p 0.01). All complications of postoperative
bleeding (postoperative day 11.2  3.5; range, 717) occurred after resuming
administration of thienopyridine derivatives postoperatively (postoperative day
2.3  2.4; range, 17). No patients experienced thromboembolic events during
the course of the study.
CONCLUSION: Endoscopic procedures with a high risk of bleeding require
careful consideration of the indications for Asian patients taking thienopyridine
derivatives. This especially applies to patients undergoing gastric ESD without
discontinuation of or with a switch to aspirin.
REFERENCES
1. Cho SJ, Choi IJ, Kim CG, et al. Aspirin use and bleeding risk after endoscopic
submucosal dissection in patients with gastric neoplasms. Endoscopy 2012; 44:
114-121.
2. Lim JH, Kim SG, Kim JW, et al. Do antiplatelets increase the risk of bleeding
after endoscopic submucosal dissection of gastric neoplasms? Gastrointest Endosc
2012; 75: 719-727.
Disclosure of Interest: N. Yoshida: None declared, S. Ono: None declared, M.
Fujishiro Lecture fee(s) from: Eisai Co., H. Doyama: None declared, T.
Kamoshida: None declared, S. Hirai: None declared, T. Kishihara: None
declared, Y. Yamamoto: None declared, H. Sakae: None declared, A.
Imagawa: None declared, M. Hirano: None declared, K. Koike: None declared
P0717 A SECOND-LOOK ENDOSCOPY AFTER GASTRIC
ENDOSCOPIC SUBMUCOSAL DISSECTION MAY NOT BE
USEFUL FOR PREVENTING POSTOPERATIVE BLEEDING
N. Yoshitake1,*, F. Takahashi1, T. Akima1, H. Kino1, M. Nakano1,
C. Tsuchida1, K. Tsuchida1, K. Tominaga1, T. Sasai1, H. Masuyama1,
H. Hiraishi1
1
Gastroenterology, Dokkyo Medical University, Mibu, Shimotsuga, Japan
INTRODUCTION: Gastric endoscopic submucosal dissection (ESD) has gradu-
ally come to be recommended as the optimal treatment for early gastric cancer;
however, one of the primary issues is postoperative bleeding. Although second-
look endoscopy is conventionally performed to reduce the risk of postoperative
bleeding, its benefit has not yet been clearly elucidated. The objective of this
study was to elucidate the benefit of second-look endoscopy.
AIMS & METHODS: From among 488 lesions in patients who underwent
gastric ESD between May 2004 and April 2013 at our hospital, a total of 29
lesions in patients who had a residual lesion, perforation, or concurrent aspira-
tion pneumonitis, or in patients in whom the treatment modality had been
switched to open surgery or there was no evidence of cancer in the resected
specimen were excluded, and the remaining 459 lesions were included in the
analysis. The patients were divided into those who had bleeding within 24
hours after ESD (immediate bleeding) and those in whom bleeding occurred
24 hours or more after the procedure (delayed bleeding); the underlying disease,
age, lesion site, diameter of the resected specimen, and lesion diameter were
analyzed to identify the risk factors for postoperative bleeding after ESD.
RESULTS: Post-ESD immediate or delayed bleeding occurred in 23 of the 459
cases (5.0%). Second-look endoscopy was performed in 210 of 447 cases (47.0%)
excluding 12 cases with immediate bleeding; in the remaining 237 of the 447 cases
(53.0%), it was not performed. Post-ESD delayed bleeding occurred in 6 of the
210 cases (2.9%) and 5 of the 237 cases (2.1%), with no statistically significant
difference between the two groups. Overall, the following factors were identified
as the risk factors for postoperative bleeding: young age (P 0.005), lesions in
the L segment (P 0.042), and large size of the resected specimen (P 0.005).
The risk factors identified in the immediate bleeding group were lesions in the L
segment (P 0.032), large size of the resected specimen (P 5 0.001), and large
tumor size (P 0.011), and those in the delayed bleeding group were young age
(P 0.013) and concomitant renal disease (P 0.011).
CONCLUSION: The results of this study suggest that second-look endoscopy
after gastric ESD may not be useful for preventing postoperative bleeding.
Disclosure of Interest: None declared
P0718 EARLY CLINICAL EXPERIENCE OF THE EFFECTIVENESS OF
HEMOSPRAY IN ACHIEVING HAEMOSTASIS IN PATIENTS WITH
ACUTE NON-VARICEAL BLEEDING
N. Sagar1,*, T. Iqbal1
1
Gastroenterology, Queen Elizabeth Hospital Birmingham, Birmingham, United
Kingdom
Contact E-mail Address: dr.nidhisagar@gmail.com
INTRODUCTION: Despite advances in management, mortality from acute
upper gastrointestinal bleeding remains high at 10%1. Current endoscopic mod-
alities have found to be effective in achieving haemostasis in 85-95% of cases,
however 5-10% of patients still experience rebleeding despite combination ther-
apy2. Bleeding may occur from sites, which are challenging to access or lesions
that are large and actively bleeding causing poor views for effective endoscopic
therapy. Hemospray is a novel powder designed to be a simple endoscopic tech-
nique in applying to large surface areas even in difficult positions.
A329
AIMS & METHODS: This was a retrospective review of patients at the Queen
Elizabeth Hospital Birmingham where Hemospray was used for an acute non-
variceal upper gastrointestinal bleed. Eight patients (4 male and 4 female) were
identified between May 2012 and February 2013.
RESULTS: The median age was 63 years (range 37 84 years). Two patients had
a Forrest classification of 1a, 2 were 1b, 1 was 2a and 3 were 2b. Causes of
bleeding were duodenal ulcer (4), gastric ulcer (2), oesophageal cancer (1) and
Diuelafoy lesion in stomach (1). Hemospray was used as the sole endoscopic
modality in 1 patient and in combination with other modalities in 7 patients.
Other modalities used were adrenaline (3), clips (1), adrenaline and clips (1),
adrenaline and heater probe (1), adrenaline, clips and heater probe (1).
Immediate haemostasis was achieved in all 8 patients. 3 patients re-bled within
7 days. All 3 patients had a duodenal ulcer (Forrest classification 1a, 1b and 2b).
Two patients required further definitive therapy: radiological coiling of gastro-
duodenal branches (1) and endoscopic therapy with adrenaline and clips (1).
CONCLUSION: From the small number of patients in this study, we can con-
clude that Hemospray is an effective method in achieving immediate haemostasis
when combined with other endoscopic modalities. However, there is a high
rebleeding rate within 7 days in patients with duodenal ulcers, irrespective of
their Forrest classification, who mostly required further definitive management.
Larger studies are required to assess the efficacy of Hemospray in this particular
group of patients to determine whether they are truly at higher risk.
REFERENCES
1. http://www.nice.org.uk/nicemedia/live/13762/59549/59549.pdf
2. Sung JJY, Luo D, Wu JCY, et al. Early clinical experience of the safety and
effectiveness of Hemospray in achieving hemostasis in patients with acute peptic
ulcer bleeding. Endoscopy 2011; 43: 291-295.
Disclosure of Interest: None declared
P0719 USEFULNESS OF CHROMOENDOSCOPY WITH INDIGO
CARMINE AND ACETIC ACID FOR IDENTIFYING THE
DEMARCATION LINE PRIOR TO ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR EARLY GASTRIC CANCER
N. Numata1,*, S. Oka1, S. Tanaka1, Y. Yoshifuku2, T. Miwata2, Y. Sanomura1,
K. Arihiro3, F. Shimamoto4, K. Chayama2
1
Department of Endoscopy, 2Department of Gastroenterology and Metabolism,
3
Department of Pathology, Hiroshima University Hospital, 4Faculty of Human
Culture and Science, Prefectural University of Hiroshima, Hiroshima-shi, Japan
Contact E-mail Address: nnumata@hiroshima-u.ac.jp
INTRODUCTION: Identification of a precise demarcation line (DL) is indis-
pensable for performing pathological complete en bloc endoscopic submucosal
dissection (ESD) for early gastric cancer (EGC). Recently, chromoendoscopy
with combination use of indigo carmine and acetic acid was reported as a
novel technique for identifying the DL; however, this technique is not effective
in all EGC cases.
AIMS & METHODS: The aim of this study was to evaluate the usefulness of
chromoendoscopy with indigo carmine and acetic acid for marking dots around
lesions during ESD for EGC. We examined 98 consecutive patients with 109
intramucosal EGCs (mean diameter, 17.8  12.4 mm; location, U 21/M 34/L
54; main histologic type, 96 intestinal and 13 diffuse) resected by en bloc ESD
after chromoendoscopy with indigo carmine and acetic acid at Hiroshima
University Hospital between December 2012 and February 2014. We identified
the DL by chromoendoscopy with indigo carmine and acetic acid just before
ESD (mean chromoendoscopy observation time, 71.6 s), and then marking dots
were placed around the EGC. Four physicians participated in the evaluation of
improved EGC visibility. Conventional endoscopic images were presented to
each of the physicians in random order for comparison with chromoendoscopy
images. Physicians scored each of the chromoendoscopy images for visibility of
the DL, and the four physicians scores for each image were tallied. EGCs were
classified into two groups: useful for identifying the DL or useless. The tumor
diameter, histologic type (intestinal/diffuse), macroscopic type (elevated, 0-I &
IIa & IIb; depressed, 0-IIaIIc & IIc), tumor lesion (U or M/L), tumor depth
(intramucosal/submucosal), tumor color (reddish/normal or pale), atrophic gas-
tritis around tumor (present/absent), intestinal metaplasia around tumor (pre-
sent/absent), and rate of histologically positive horizontal margin were evaluated
in each group.
RESULTS: Forty-two of the 109 cases (38.5%) were useful for chromoendo-
scopy with indigo carmine and acetic acid, which were compared to the other 67
cases. Univariate analysis showed that histologic type (intestinal type), macro-
scopic type (elevated type), and atrophic gastritis around the tumor (present)
were associated with the usefulness of chromoendoscopy using indigo carmine
and acetic acid. Multivariate analysis with logistic regression showed that macro-
scopic type (elevated type) and atrophic gastritis around the tumor (present) were
independently associated with the usefulness of chromoendoscopy using indigo
carmine and acetic acid for identifying the DL of EGCs (P 5 0.05). The histo-
logically positive horizontal margin after ESD was 0% (0/42) in useful cases, and
7.5% (5/67) in useless cases.
CONCLUSION: To make precise markings around EGCs before ESD, chro-
moendoscopy with indigo carmine and acetic acid is useful for elevated-type
EGC or in cases of existing atrophic gastritis around EGCs.
Disclosure of Interest: None declared
A330
P0720 THE DIAGNOSIS OF INVASION DEPTH IN SUPERFICIAL
ESOPHAGEAL CANCER: A COMPARISON BETWEEN A
MAGNIFYING NARROW-BAND IMAGING (NBI) OBSERVATION
AND EUS
1,* 1 1 1 1
N. Matsuura , N. Hanaoka , R. Ishihara , S. Yamamoto , T. Akasaka ,
Y. Takeuchi1, K. Higashino1, N. Uedo1, H. Iishi1
1
Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular
Diseases, Osaka-city, Japan
Contact E-mail Address: matuura-no@mc.pref.osaka.jp
INTRODUCTION: The diagnosis of cancer invasion depth is crucial for select-
ing the optimal treatment strategy for esophageal cancer. Endoscopic ultrasono-
graphy (EUS) is regarded as the standard modality for diagnosing invasion
esophageal cancer depth in the West. In Japan, magnifying endoscopy has
been used for diagnosis by observing the architecture of the esophageal micro-
vasculature. This modality represents a rapid and simple diagnostic procedure
without the need for any additional equipment. However, the accuracy of mag-
nifying endoscopy has not been compared with that of EUS for the diagnosis of
cancer invasion depth.
AIMS & METHODS: Patients with esophageal squamous cell carcinoma suspi-
cious for muscularis mucosa or submucosal invasion in non-magnifying white
light imaging were included. All patients received magnifying narrow-band ima-
ging (NBI) observation followed by EUS. Magnifying NBI observation was
performed by endoscope with magnification (GIF-Q240Z, or H260Z;
Olympus, Tokyo, Japan). EUS was performed using a high-resolution probe
by jelly-filled method. Before examination, several syringes (5 mL) containing
sufficient amounts of jelly (K-Y lubricating jelly, Johnson and Johnson, k. k.)
were prepared. After endoscope insertion (GIF-2TQ260M; Olympus) into the
target area within the esophagus, a 30-MHz miniature probe was then inserted
through the left channel of the endoscope and 30 to 40 mL of echo jelly was
instilled through the right channel until the esophageal lumen was filled. Cancer
invasion depth was diagnosed as T1a or T1b using both modalities. The diag-
nostic accuracy of magnifying NBI observation was compared with that of EUS
while the histologic diagnosis of resected specimen served as reference standard.
RESULTS: From January 2011 to February 2014, 166 patients with esophageal
squamous cell carcinoma were examined using the two modalities. Of the 166
patients, 91 treated with chemoradiotherapy or photodynamic therapy were
excluded from analysis because histologic specimens were not obtained.
Seventy-five patients treated either by esophagectomy (n 15) or endoscopic
resection (n 60) were included in the final analysis. Histologic diagnosis was
T1a in 43 lesions, T1b in 31 lesions, and T2 in one lesion. The overall accuracy of
diagnosing invasion depth was 66.7% (50/75 lesions) by magnifying NBI and
70.7% (53/75 lesions) by EUS (P 0.602). The accuracy of diagnosing invasion
depth in lesions with protrusions was 58.8% (20/34 lesions) and 76.5% (26/34
lesions) by magnifying NBI and EUS, respectively (P 0.194). The accuracy of
diagnosing invasion depth in lesions without protrusions was 73.2% (30/41
lesions) and 65.9% (27/41 lesions) by magnifying NBI and EUS, respectively
(P 0.632).
CONCLUSION: EUS and magnifying NBI exhibited high diagnostic accuracy
in lesions with and without protrusion. Furthermore, there was no significant
difference in the overall accuracy of these two modalities. Considering its sim-
plicity of use, magnifying NBI has the potential to be the standard modality for
diagnosing invasion depth of esophageal squamous cell carcinoma.
Disclosure of Interest: None declared
P0721 ENDOSCOPIC DIAGNOSIS OF HIATUS HERNIAS
VARIABILITY BETWEEN ENDOSCOPISTS
O.S. Omer1,*, J.S. Nayagam1, J. Hayat1
1
Kingston Hospital, London, United Kingdom
Contact E-mail Address: oso04@ic.ac.uk
INTRODUCTION: There is a wider discrepancy in the diagnosis of hiatus her-
nias (HH) at upper gastro-intestinal endoscopy (OGD) compared to other tech-
niques, such as manometry and barium swallow, or during surgery.1 Endoscopic
diagnosis may be affected by the method used (eg during intubation or extuba-
tion2), and variable definition of the gastro-oesophageal junction (eg proximal
margin of the gastric folds, squamo-columnar junction or distal margin of the
palisade zone).
AIMS & METHODS: Our aim was to assess variability in diagnosis of hiatus
hernias by different endoscopists.
A retrospective review of the endoscopy database at Kingston Hospital, was
performed. Consecutive OGD were analysed over a 3 month period (2/4/13 -
28/6/13). Complete data was obtained for 451 endoscopies, from 21 different
endoscopists. Mean age for patients was 60.1 years (range 20-98), female to
make ration of 1:1.04. Unpaired t-test and one-way ANOVA with Tukeys
Test were used for normal data, and Chi-squared for proportional differences.
RESULTS: Of the 451 OGD, HH were diagnosed in 168 (36.6%), most HH
under 5cm (81.55%). Main indications were for dyspepsia (14.2%), reflux symp-
toms (17.7%), abdominal pain (22%), anaemia (14%). There was a wide varia-
bility in the diagnosis of HH depending on speciality and grade (range 0-100%).
Age, indications and gender were similiar between groups of endoscopists.
Surgical Consultants were more likely to diagnose HH than Gastroenterology
Consultants (p50.002) or Registrars (p50.04), and Nurse Endoscopists more
likely than Gastroenterology Consultants (p50.0001) or Registrars (p50.0004).
United European Gastroenterology Journal 2(5S)
Number of Number of
Speciality & Grade endoscopies HH diagnosed % HH
Gastroenterology Consultants 142 27 19%
Gastroenterology Registrars 34 6 17.7%
Surgical Consultant 55 23 41.8%
Surgical Registrars 19 11 57.9%
Nurse Endoscopists 189 99 52.4%
GP Endoscopists 12 2 16.7%
CONCLUSION: Endoscopic diagnosis of HH is highly variable and may be
affected by level of training and speciality of the endoscopist. This may lead to
under or overdiagnosis. A standardised approach to landmark measurement may
lead to a more consistent diagnosis of HH.
REFERENCES
1. Khajanchee YS, Cassera MA, Swanstrom LL, et al. Diagnosis of Type-1 hiatal
hernia: a comparison of high-resolution manometry and endoscopy. Dis
Esophagus 2013; 26: 1-6.
2. Burch NE, Saraj O, Lichfield B, et al. Study assessing landmark height altera-
tion during endoscopic evaluation. Gut 2011; 60: A126.
Disclosure of Interest: None declared
P0722 THE EFFECT AND USEFULNESS OF CHROMOENDOSCOPY
WITH INDIGO CARMINE DYE ADDED TO ACETIC ACID IN
DIAGNOSIS OF EARLY GASTRIC CANCER DIFFERS DEPENDING
ON ITS MUCIN HISTOCHEMISTRY
O. Yoneyama1,*, K. Furukawa1, H. Hashidate2, M. Ogawa1, S. Ikarashi1,
A. Osaki1, M. Sato1, T. Aiba1, N. Waguri1, K. Igarashi1
1
Gastroenterology and Hepatology, Niigata City General Hospital, NIigata,
2
Diagnostic Pathology, Niigata City General Hospital, NIigata City, Japan
INTRODUCTION: Endoscopic submucosal dissection (ESD) became a very
popular technique of therapeutic endoscopy for superficial gastrointestinal neo-
plasms, and it made possible to perform a reliable en bloc resection with higher
success rate and lower recurrence rate compared with conventional endoscopic
mucosal resection. For a complete en bloc resection of cancer lesions, it is indis-
pensable to accurately delineate the margin, in other words, the lateral extent of
the cancer. Chromoendoscopy with indigo carmine dye added to acetic acid is
thought to be useful in the diagnosis of early gastric cancer. Usually this method
helps to clarify the lateral extent of gastric cancer. But in some cases, this method
can not help satisfactorily to delineate the margin between cancer and non-cancer
parts. We assumed that the difference of dyeing pattern arises from quantity and
character of mucus secreted from each lesion.
AIMS & METHODS: Subjects were 33 early gastric cancer lesions resected by
using ESD technique in our institution, and were divided in two groups. We
defined the lesions which were delineated clearly by acetic acid-indigo carmine
method as group A (n 17), and lesions which were not delineated clearly
enough as group B (n 16). We evaluated the mucin histochemistry of the speci-
mens about stain levels of d-PAS and immunohistochemistry of MUC2,
MUC5AC and CD10, and compared between the two groups.
RESULTS: Both group showed lower level of d-PAS stain in its cancer tissue
- than its non-cancer parts, suggesting that mucin productivity is decreased in the
cancer tissue compared with non-cancer parts. Classification grouping using
immunohistochemistry of MUC2, MUC5AC and CD10 showed that many
cases of group A have intestinal type mucin (68.8%), and group B tends to
have gastro-intestinal type mucin (64.7%).
CONCLUSION: Chromoendoscopy with indigo carmine dye added acetic to
acid is generally useful and effective in case of early gastric cancer which has
intestinal type mucin histochemistry. But on the other hand, cancer lesions
having gastro-intestinal type mucin often show unclear margin even if using
this technique.
Disclosure of Interest: None declared
P0723 FULL SPECTRUM ENDOSCOPY VS. TRADITIONAL FORWARD-
VIEWING COLONOSCOPY WITH AND WITHOUT RIGHT-COLON
RETROFLEXION: A RANDOMIZED, BICENTRIC BACK-TO-BACK
STUDY
I.S. Papanikolaou1,*, P. Apostolopoulos2, I. Beintaris1, A.D. Sioulas1,
D. Polymeros1, C. Malli1, E. Vlachou2, G. Vlachonikolou1, G. Alexandrakis1,
G. Dimitriadis1, K. Triantafyllou1
1
Department of Hepatogastroenterology, ATTIKON UNIVERSITY HOSPITAL,
2
Department of Gastroenterology, Army Veterans (NIMTS) Hospital, Athens,
Greece
Contact E-mail Address: ispapn@hotmail.com
INTRODUCTION: Colonoscopy can reduce colorectal cancer (CRC) incidence
and mortality through early detection and removal of adenomas, but estimates
suggest that up to 24% of adenomas are missed; various colonoscopic techniques
are evolving to improve its diagnostic yield and avoid interval CRC. Recently a
new colonoscopy platform (FUSETM system, EndoChoice Inc., Atlanta, GA,
USA) was introduced with promising initial results. FUSE-colonoscopy (F-C)
provides a 330 -field of view instead of the 170 of standard colonoscopy (S-C);
this allows polyps hidden behind folds or flexures to be seen easier.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: The aim of this study is to evaluate F-C additive con-
tribution to detection of polyps/adenomas, compared to S-C, with and without
the addition of right-colon retroflexion (R-C), in a series of patients undergoing
same-day, back-to-back randomized (1:1) tandem colonoscopies in 2 tertiary
endoscopy centres. ClinicalTrials.gov Identifier: NCT02117674
RESULTS: Of 150 totally planned, 84 pts have been enrolled until now; 40
(47.6%) of them were randomized to undergo F-C first. There were 7 incomplete
cases for both F-C and S-C (including 1 failed case for both F-S and S-C and 1
case where F-C was not performed due to technical failure). Thus, 83 (46 screen-
ing/surveillance, 32 symptomatic and 5(6%) with polyps) were included in the
per-protocol analyses. R-C was attempted in 57/83 cases; successful in 37.
Insertion time did not differ between F-C and S-C (5min, IQR:4-10.25 vs.
5min, IQR: 4-8, respectively, p 0.4), whereas, withdrawal was marginally
longer for F-C (8min, IQR:6-10 vs. 7min, IQR:6-9, respectively, p 0.05).
Overall, 133 polyps were found (53 right colon); of these 61 were adenomas,
32 in the right colon (histology available for 24/28 pts with polyps).
By per-lesion anlaysis, F-C detected significantly more missed polyps compared
to S-C overall (26 vs. 4, p 0.033) and right-sided ones (14 vs. 2, p 0.038) and
detected more adenomas (9 vs. 3, p 0.162) overall and right-sided ones (7 vs. 2,
p 0.184). R-C offered no additional gain in polyp or adenoma detection in the
right colon.
CONCLUSION: Our initial results show that F-C could be an advancement in
colonoscopy by detecting more polyps. However, if this improvement actually
represents detection of more adenomas requires further investigation.
REFERENCES
Gralnek IM, et al. A prospective cohort study evaluating a novel colonoscopy
platform featuring full-spectrum endoscopy. Endoscopy 2013; 45: 697-702.
Gralnek IM, et al. Standard forward-viewing colonoscopy versus full-spectrum
endoscopy: an international, multicentre, randomised, tandem colonoscopy trial.
Lancet Oncol 2014; 15: 353-360.
Disclosure of Interest: None declared
P0724 ORALLY ADMINISTRATION OF OTILONIM BROMIDE BEFORE
COLONOSCOPY IMPROVES ADENOMA DETECTION RATES
S. GULITER1, F. SAPMAZ1, I.H. KALKAN1,*, P. ATASOY2
1
Gastroenterology, 2Pathology, Krkkale University Faculty of Medicine, Ankara,
Turkey
Contact E-mail Address: drismailster@gmail.com
INTRODUCTION: We aimed in this randomized prospective controlled trial to
evaluate the effect of orally administration of Otilonium bromide over the quality
of the colonoscopy in the meanings of adenoma detection rate, caecal intubation
time, and the tolerability.
AIMS & METHODS: Two-hundred consecutive volunteer outpatients were ran-
domized to Otilonium Bromide group (100 patients) and the control group (100
patients). The patients in the Otilonium Bromide group received 30 mg
Otilonium Bromide 3 times a day for five days with the last dose given two
hours before colonoscopy. The bowel preparation quality was graded according
to the Boston bowel preparation scale. For each colon area, a distension scale
was awarded by using a previously validated 5-point scale. The pain experienced
during colonoscopy was determined by using a 1-10 visual analog pain scale.
RESULTS: Twenty-one patients in Otilonium bromide group and 22 patients in
control group were excluded from the study because of uncompleted colono-
scopy. Caecum intubation time was comparable between groups (p 0.4).
There was no statistically difference between groups in the terms of mean
bowel preparation quality scores (p 0.4), while mean distension score was
greater in Otilonium bromide group (p 0.007). Polyp detection rate (26
polyps in 22 patients vs. 14 polyps in 12 patients) (32.9% vs. 17.9%, p 0.03)
was significantly higher in OB group. Also, adenoma detection rate (22 adeno-
mas in 21 patients vs. 11 adenomas in 11 patients) (27.8% vs. 14.1%, p 0.03)
was significantly higher in OB group. The visual analog pain scale scores were
comparable between groups (p 0.07)
CONCLUSION: Otilonium bromide administration before colonoscopy
increases colonic distension, polyp detection and adenoma detection rates.
Further clinical investigations are required to determine the utility of relieving
colonic spasm with oral antispasmodics to improve adenoma detection rates.
Disclosure of Interest: None declared
P0725 NEW GENERATION FLEXIBLE SPECTRAL IMAGING COLOR
ENHANCEMENT IS USEFUL TO PREDICT HISTOLOGY OF
SMALL COLORECTAL POLYPS
J. Weigt1,*, A. Kandulski1, P. Malfertheiner1
1
Gastroenterology, Hepatology & Infectious Diseases, UNIVERSTITY
MAGDEBURG, Magdeburg, Germany
Contact E-mail Address: jochen.weigt@med.ovgu.de
INTRODUCTION: Prediction of colon polyp histology is decisive as small non
advanced adenoma may be discarded after resection and hyperplastic lesions may
be left in place. The NICE classification system for NBI endoscopy and magni-
fication has been shown to be effective in prediction of histology. There is only
little data for the flexible spectral imaging color enhancement (FICE). Newest
generation of endoscopes have over mega pixel CMOS sensors that allow FICE
aligned with electronic zoom without loss of image quality. With this new tech-
nology, histology prediction may easily be possible during standard colonoscopy
without using optical zoom endoscopes.
AIMS & METHODS: To assess the accuracy of endoscopic prediction of histol-
ogy of small colorectal polyps using white light (WLE) and FICE and CMOS
endoscope
Methods:
A331
We randomly assigned patients for colonoscopy using a CMOS colonoscope
(EC-600 WM, Fujifilm Europe Dusseldorf). All detected polyps were assigned
to Types 1-3 according to the NICE classification system criteria using WLE and
FICE (modes 1,8,9) with and without electronic zoom. Classification was
assessed during the examination. Before starting the study, the endoscopist
underwent endoscopic training using NBI. All detected polyps were removed
for histopathology. The concordance of endoscopic classification and histology
was calculated.
RESULTS: We investigated 27 polyps in 11 patients. Median polyp size was 4
mm (range 3-20 mm) Polyps location were in the rectum and sigmoid colon
(n 15) in the right colon (n 10) and in the left colon (n 2). According to
the endoscopic classification 18 polyps were hyperplastic (Type 1) and 9 polyps
were adenomas (Type 2). No colorectal cancer or high grade adenoma were
identified. Histology proofed that 100 % of polyps were classified correctly.
One polyp classified as adenoma revealed serrated adenoma in histology.
CONCLUSION: The NICE classification system criteria can successfully be
applied for colorectal polyps being investigated with FICE and electronic
zoom using a CMOS colonoscope.
Disclosure of Interest: J. Weigt Lecture fee(s) from: Fujifilm, A. Kandulski: None
declared, P. Malfertheiner: None declared
P0726 MEASUREMENT OF COLONIC POLYPS. IS VISUAL
ESTIMATION ACCURATE?
J. Woo1,*, H. Rozati1, K. Besherdas1
1
Gastroenterology, Barnet and Chase Farm Hospitals NHS trust, London, United
Kingdom
Contact E-mail Address: jwoo@nhs.net
INTRODUCTION: Colon polyp size is a critical biomarker for clinical manage-
ment of colonic polyps. Larger polyps have a greater malignant potential. During
colonoscopy, it is important to correctly measure the size of the polyps because of
the direct correlation of size with colon cancer.1 During polypectomy, size of the
colonic polyps encountered are often gauged by visual estimation or the open
forceps method.2 However, some data exists on the questionable reliability of a
visual estimate even amongst expert colonoscopists. We aim to compare the
estimation of polyp size using the visual estimation of colon polyp with or with-
out the open biopsy forceps technique against actual polyp size measurement by
our histopathology department for all polyps 41cm in size.
AIMS & METHODS: A single centre, retrospective analysis using the Unisoft
GI auditors software was used to identify patients who have had polypectomies
done for polyps 41cm in size from October 2005 till September 2013. The size of
the polyps documented in the endoscopy report was then compared to the lab
measured actual polyp size.
RESULTS: A total of 39 patients were identified with polyps 41cm in size who
has had polypectomy done. Results are as below:
Visual estimated Actual lab measured size (mm)
size (mm)
39 1014 1519 2024 2529 430
39
1014 XXXXXXX XXXX XXXX
1519 XXXX X X X
2024 XXX X X
2529 X X XXX X X
430 X X XX X
CONCLUSION: From this study we can conclude that visual estimation with or
without the open biopsy forceps technique is completely inaccurate with wide
variations between the reported size and the actual size of the polyps when
measured in our laboratory. Accurate measurement of colonic polyps is impor-
tant as inaccuracies can lead to potentially larger polyps not being tattooed and
subsequent difficulty in identification during surgery and surveillance. We advo-
cate that the gold standard practice of direct measurement of the polyp once
excised and outside the body be adopted and the actual size should be documen-
ted according to direct measurement.
REFERENCES
1) Gopalswamy N, Shenoy V, Choudhry U, et al. Is in vivo measurement of size
of polyps during colonoscopy accurate? Gastrointest Endosc 1997; 46: 497-502.
2) Rex D and Rabinovitz R. Variable interpretation of polyp size by using open
forceps by experienced colonoscopists. Gastrointest Endosc 2013: pii: S0016-
5107(13)02317-1.
Disclosure of Interest: None declared
P0727 THE VALUE OF ENDOSCOPIC INVESTIGATION IN PATIENTS
WITH BOWEL THICKENING ON COMPUTED TOMOGRAPHY
IMAGING. A 4 MONTH RETROSPECTIVE STUDY BASED IN A
DISTRICT GENERAL HOSPITAL IN THE UK
J. Digby-Bell1,2,*, S. Powles2, A. Gunasekera2
1
Gastroenterology, Frimley Park Hospital, Farnborough, 2Gastroenterology, St
Peters Hospital, Chertsey, United Kingdom
Contact E-mail Address: jdigbybell@doctors.org.uk
A332
INTRODUCTION: Bowel wall thickening is a common and often unexpected
finding on abdominal computed tomography (CT) scans, and yet its significance
and further investigation is unclear from the literature. This study aims to clarify
the incidence of bowel wall thickening, and its investigation and outcomes in a
District General setting.
AIMS & METHODS: In this retrospective observational study, all in-patients
who underwent abdominal CT imaging were included over a 4 month period
regardless of indication. Radiology reports were analysed, and patients with
gastrointestinal wall thickening were identified for further analysis.
RESULTS: 1227 patients underwent abdominal CT imaging over the 4 month
period, of which 116 (9.5%) were found to have bowel wall thickening. 53
patients subsequently had an endoscopic examination and in 49 cases the area
of interest was visualised. 33 patients had positive endoscopic findings at the site
of bowel thickening, of which 16 had mucosal inflammation, 8 had malignancy, 6
had diverticulosis and 3 had polyps.
In the remaining 63 patients who did not have endoscopic examination, 42 were
investigated by other means including surgery or other imagining modalities, or
further investigation was not appropriate. In 21 patients, it was unclear as to why
further investigation did not take place.
CONCLUSION: Endoscopic evaluation of gastrointestinal wall thickening
found on CT imaging led to a positive diagnosis in 62.3% (33/53) patients of
which 15% (8/53) were found to have malignancy. This highlights both the
importance of further investigating GI wall thickening and the value of endo-
scopic visualisation.
Disclosure of Interest: None declared
P0728 THE COMPARATIVE STUDY OF SPLIT-DOSE OF
POLYETHYLENE GLYCOL (PEG) BETWEEN LOW VOLUME PEG
PLUS ASCORBIC ACID FOCUSING ON THE BOWEL CLEANSING
EFFICACY, PATIENTS AFFINITY TO PREPARATION SOLUTION
AND MUCOSAL INJURY: A PROSPECTIVE RANDOMIZED TRIAL
J. Park1,*
1
Department of Internal Medicine, Haeundae Paik Hospital, Inje University School
of Medicine, Busan, Korea, Republic Of
Contact E-mail Address: mechant79@hanmail.net
INTRODUCTION: Adequate bowel cleansing is essential for a high-quality,
effective, and safe colonoscopy. The aims of this study were to compare the
efficacy and patients affinity to preparation solution and mucosal injury of
split dose of polyethylene glycol (PEG) solution with low volume PEG plus
ascorbic acid for outpatients who underwent scheduled colonoscopy.
AIMS & METHODS: This study was prospective randomized investigator-
blinded. Overall, 160 patients were enrolled for split-dose of PEG and 159 for
the low volume PEG plus ascorbic acid, respectively. The bowel cleansing effi-
cacy of preparation was rated according to the Ottawa bowel preparation scale
and patients affinity to preparation solution was assessed using a questionnaire.
All mucosal abnormalities observed during colonoscopy were noted and biop-
sied. These biopsy specimens were reviewed by pathologists.
RESULTS: Of the 319 patients, 308(96%) ingested more than 75% of the bowel
preparation. There was no significant difference between the two groups for the
mean total score using the Ottawa bowel preparation scale (p 0.376).
Significantly greater residual colonic fluid was observed in the low volume
PEG plus ascorbic acid group (0.81  0.54) than in the split-dose PEG group
(0.66  0.62) (p 0.023). There was significant difference in the Ottawa bowel
preparation score for the middle colon (split-dose PEG vs. low volume PEG plus
ascorbic acid: 1.19  0.94 vs. 1.42  0.73; p 0.014). In patients preference and
acceptance, low volume PEG plus ascorbic acid group showed better results
(p 0.001). The overall incidence of adverse events was not significantly different
between the two groups (69/160 [43.1%], 69/159 [43.4%], p 0.972); however,
the split-dose PEG group tended to had less headache and dizziness (p 0.056).
Endoscopically, mucosal lesions, possibly associated with two preparation regi-
men, were observed in total 11 patients (split-dose PEG: 5, low volume PEG plus
ascorbic acid: 6, respectively). Mucosal ulceration occurred in 1 patient taking
split-dose PEG compared with 2 patients receiving low volume PEG plus ascor-
bic acid.
CONCLUSION: Low volume PEG solution plus ascorbic acid, compared with
split-dose PEG, was associated with more residual fluid, but showed equivalent
colon cleansing efficacy and resulted in more patient preference, and acceptance.
There was no significant difference in mucosal injury.
REFERENCES
1) Lawrance IC, Willert RP and Murray K. Bowel cleansing for colonoscopy:
prospective randomized assessment of efficacy and of induced mucosal abnorm-
ality with three preparation agents. Endoscopy 2011; 43: 412-418.
2) Valiante F, Pontone S, Hassan C, et al. A randomized controlled trial evalu-
ating a new 2-L PEG solution plus ascorbic acid vs 4-L PEG for bowel cleansing
prior to colonoscopy. Dig Liver Dis 2012; 44: 224-227.
Disclosure of Interest: None declared
P0729 COLON STENTING: CAN WE PREDICT PERFORATION?
CONSIDERING FACTORS BEFORE PLACING A COLON STENT
J.R. Umana Mejia1,*, A. Alvarez Delgado1, A. Velasco Guardado1, C. Pinero
Perez1, A. Fernandez Pordomingo1, A. Mora Soler1, V. Prieto Vicente1
1
servicio de aparato digestivo, hospital clinico universitario de salamanca, sala-
manca, Spain
Contact E-mail Address: josueum1@hotmail.com
INTRODUCTION: In the last decade, Colon Stenting has become a well
accepted technique for use as bridge to surgery or as palliative treatment in
cases of malignant colon strictures. None the less, recent meta-analysis had
United European Gastroenterology Journal 2(5S)
suggested that there is a high rate of complication due to this procedure carrying
an increase in morbidity in these patients that in some cases must be treated with
emergency surgery due to Peritonitis in relation to colon perforation secondary
to the procedure. In that matter we focused our study on identifying factors,
before the procedure, that can predict colon perforation.
AIMS & METHODS: Data from 213 (n 213) patients admitted in our hospital
between January 2004 to November 2012 were analyzed. All of the items
reviewed were before the procedure. Demographic factors were age and sex.
Clinical factors include length of symptoms, presence of peritoneal irritation,
cardiac frequency, temperature and blood pressure. Laboratory tests were
CRP, LDH, WBC, pH and lactate. Radiologic features included the presence
of colon dilatation, measurement in centimeters of the cecum and the most
dilatated area, function of the ileo-cecal valve and the presence of metastasis in
CT scan. Factors analyzed from the procedure include timing (urgent or elective)
(548 hrs or 448 hrs), length of the procedure, level of expertise of the endos-
copist, location of the tumor, angulations of the tumor, length of the Stent and
the visualization of feces coming through the Stent after released.
RESULTS: We review data from 213 cases, after statistical analysis, rate of colon
perforation found was 12% (21 patients); factors with statistic significance
related to patients demonstrated that the presence of colonic dilatation in the
radiologic study was associated with a higher risk of perforation compared with
patients that did not have dilatation (18.1% vs 2.3%, p 0.009), being the risk of
perforation increased almost eight times [R 7.9 (IC 95%: 1.1-57.1)]. The mean
in centimeters of colon dilatation in patients that had perforation was signifi-
cantly longer (8.75 cm vs 6.79 cm, p 0.012). In the other hand, factors related to
the procedure with statistic significance, revealed that seeing feces coming
through the stent after released was associated with a lower risk of perforation
(10.3% vs 31,3%, p 0.004), there was an increased risk of three times, for colon
perforation, in patients that did not present the pass of feces through the stent
after liberation [R 3.04 (IC 95%: 1.5-6.1)].
CONCLUSION: Colon dilatation and the length of dilatation before procedure
is an important factor to take in consideration when deciding to place a colon
stent, in our study we saw an important increase in colon perforation when the
length of the cecum was more than 8 cms. In the other side, seeing feces passing
through the stent when it is released, reveals an adequate function of the stent,
and demonstrated a less number of perforations. In the future, predictive models
taking these factors into consideration might be developed with the objective to
select better the patients for this procedure reducing the rate of complications.
Disclosure of Interest: None declared
P0730 THE OFFER OF ADVANCED ENDOSCOPIC IMAGING
TECHNIQUES LEADS TO HIGHER ACCEPTANCE RATES FOR
COLONOSCOPY A PROSPECTIVE STUDY
J. Gallitz1,*, M. Vieth2, G.E. Tontini1,3, M.F. Neurath1, H. Neumann1
1
UNIVERSITY OF ERLANGEN-NUREMBERG, Erlangen, 2Klinikum
Bayreuth, Bayreuth, Germany, 3IRCCS Policlinico San Donato, San Donato
Milanese, Italy
INTRODUCTION: In Germany patients over the age of 55 years should
undergo colonoscopy for colorectal cancer screening. The acceptance rate of
patients undergoing screening colonoscopy is still low.
AIMS & METHODS: Aim was to evaluate whether the offer of advanced endo-
scopic imaging techniques including chromoendoscopy, magnification endo-
scopy, spectroscopy, confocal laser endomicroscopy, endocytoscopy, capsule
endoscopy, CT-colonography or device-assisted enteroscopy may lead to an
increased awareness and improved acceptance rates of patients to undergo
colonoscopy.
Prospectively, 372 patients were randomly included (168 female, 204 male). At
baseline, a standardized questionnaire was developed. Afterwards, knowledge of
advanced imaging techniques was inquired and if the patient was motivated by
the specific offer of these imaging techniques to undergo colonoscopy. In the
second phase, several media campaigns through press, internet, TV coverage, and
information events were organized reporting about advanced imaging techni-
ques, followed by repeat evaluation of the patients. This sequence (media cam-
paign and patients evaluation) was repeated every 3 months over a period of 12
months.
RESULTS: At baseline, 64% of the patients reported that knowledge about new
endoscopic methods is completely unknown. After the evaluation period this was
reported by only 34% of patients (P 50.05). Despite general information about
all advanced imaging techniques was given in the media campaigns, patients were
most interested in chromoendoscopy (baseline: 5% - after 12 months: 22%),
endomicroscopy (5% vs. 17%), CT colonography (16% vs. 37%) and capsule
endoscopy (12% vs. 47%). The overall grade of information increased signifi-
cantly from 14% at baseline to 35% after 12 months (P 50.05). The percentage
of patients who decided to undergo colonoscopy because of the offer of new
imaging methods increased significantly from 12% at baseline to 42% after 12
months (P 50.05).
CONCLUSION: Patients were highly interested in advanced endoscopic imaging
techniques and patients knowledge about new imaging methods increased sig-
nificantly over the study period. The offer of advanced imaging techniques lead
to higher acceptance rate for screening or surveillance colonoscopies.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0731 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR HUGE COLORECTAL NEOPLASMS:
COMPARISON BETWEEN SESSILE TUMORS AND LATERALLY
SPREADING TUMORS
J.H. Bae1,*, D.-H. Yang1, J.-S. Byeon1, J.S. Soh1, S. Lee1, H.-S. Lee1, H.J. Lee1,
S.H. Park1, K.-J. Kim1, B.D. Ye1, S.-J. Myung1, S.-K. Yang1, J.-H. Kim1
1
Department of Gastroenterology, University of Ulsan College of Medicine, Asan
Medical Center, Seoul, Korea, Republic Of
INTRODUCTION: Although endoscopic submucosal dissection (ESD) is
thought as an effective treatment for large laterally spreading tumors (LSTs)
of the colorectum, the therapeutic effectiveness of ESD for large sessile colorectal
tumors has not been evaluated.
AIMS & METHODS: We aimed to evaluate the outcomes of ESD for the huge
colorectal tumors (30 mm or larger in diameter) and compare therapeutic out-
comes between sessile tumors and LSTs. We retrospectively reviewed medical
records of the patients who underwent ESD for huge sessile tumors and LSTs
of the colorectum from July 2007 to November 2013. En-bloc resection rate,
complete resection rate, procedure time and procedure-related complications
were evaluated in the sessile tumor and LST groups. Multivariate analysis was
performed to identify independent factors for incomplete resection.
RESULTS: ESD was attempted for a total of 191 patients with huge colorectal
tumors (48 with sessile colorectal tumors and 143 with LSTs) by two endosco-
pists. The mean ( SD) time required for ESD was 82.5  4.4 minutes (range, 17-
392), and mean size and height of the lesions were 43.2  1.1 mm (range, 30-135)
and 9.6  0.5 mm (range, 1-33). The rate of en bloc resection and complete
resection were 85.9% and 75.9%. With regard to complications, 11.0% (21/
191) cases of intra-procedural bleeding and 15.7% (30/191) cases of perforation
were observed in total; none of the complications required surgical intervention.
In the sessile colorectal tumors, the endoscopic en bloc resection and complete
resection rate were 72.9% (35/48) and 62.5% (30/48) respectively. In the LSTs,
they were 90.2% (129/143) and 80.4% (115/143) respectively. Although endo-
scopic findings suggesting submucosal (sm) invasion such as Vi or Vn pit pattern
were not different between the two groups, higher sm invasion rate was noted in
the sessile tumors than the LSTs (39.6% vs 23.1%, p 0.026). Intra-procedural
bleeding was more frequent in sessile tumors than LSTs (22.9% vs 7.0%,
p 0.002). There was no significant difference in procedure time and perforation
between the two groups. The rate of operation, caused by non-curative resection,
was higher in sessile tumors (14.6% vs 5.6%, p 0.045). There was no mortality
associated with procedure or operation. On multivariate analysis, sessile mor-
phology (OR 2.125; 95% confidence interval (CI) 1.006-4.488; p 0.048) and
presence of fibrosis (OR 2.290; 95% CI 1.216-5.251; p 0.013) were independent
risk factors of incomplete resection in ESD of huge colorectal neoplasia.
CONCLUSION: The complete resection rate of ESD for sessile tumors was
relatively lower than that of ESD for LSTs. Presence of fibrosis was another
independent risk factor of incomplete resection in ESD of huge colorectal
neoplasia.
REFERENCES
1. Zhou PH, Yao LQ and Qin XY. Endoscopic submucosal dissection for color-
ectal epithelial neoplasm. Surg Endosc 2009; 23: 1546-1551.
2. Fujishiro M, Yahagi N, Kakushima N, et al. Outcome of endoscopic submu-
cosal dissection for colorectal epithelial neoplasms in 200 consecutive cases. Clin
Gastroenterol Hepatol 2007; 5: 678-683.
Disclosure of Interest: None declared
P0732 THE FEASIBILITY OF ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR EARLY COLORECTAL NEOPLASM WITH
HIGHLY TECHNICAL DIFFICULTY
K. Sasajima1,*, R. Chinzei1, M. Takahashi1, Y. Koushima1
1
Gastroenterology, SAITAMA RED CROSS HOSPITAL, Saitama, Japan
Contact E-mail Address: qqfa98m9@mist.ocn.ne.jp
INTRODUCTION: Colorectal endoscopic submucosal dissection (ESD), has not
been widely spread because of technical difficulty and high incidence of perfora-
tion. Before ESD, we need to recognize whether a lesion can be removed with or
without technical difficulty. The aim of study is to assess the feasibility of color-
ectal ESD for lesions accompanied by highly techinical difficulty.
AIMS & METHODS: We established the indication of colorectal ESD as fol-
lows: LST-NG, LST-G (mixed nodular type), local recurrent lesion after previous
endoscopic piecemeal mucosal resection (EPMR)=20mm, and Is/Isp=30mm. 330
colorectal consecutive lesions were enrolled in this study. Flush knife was used in
all cases. From the viewpoint of morphological type and tumor size, we defined
(1) LST-NG=40mm, (2) LST-G (mixed nodular type)=50mm, (3) Is/Isp=40mm,
and (4) local recurrent lesion after EPMR=20mm, as highly difficult lesion. A
lesion except for these four groups was defined as an ordinary lesion (5). We
investigated {tumor size(mm), en bloc resection rate(%), operative time(min),
perforation/delayed bleeding rate(%), moderate/severe fibrosis rate(%)}, respec-
tively. Each highly difficult group was respectively compared to the group (5) for
all factors. A P value 5 .05 was considered statistically significant.
RESULTS: The total average diameter of lesions was 33.8mm. For morpholo-
gical type, 153 lesions were LST-NG, 110 LST-G, 37 protruded, 15 depressed
and 15 recurrent lesions. By histological examination, 226 intramucosal cancers,
49 slightly invasive submucosal cancers, 19 massively submucosal invasive can-
cers, and 36 tubular adenomas. The average operative time was 85.8 minutes, and
the en bloc resection rate was 97.9% (323/330). With regard to complications,
postoperative bleeding was observed 0.9% (3/330). Microperforation which
occurred in only 1 case was conservatively repaired with endoscopic clipping.
The clinical outcome of each group is as follows: (1) LST-NG=40mm, n 31
{44.4mm, 93.5%, 149.8min, 0%/0%, 25.8%/6.5%} (2) LST-G(mix)=50mm,
A333
n 29 {62.9mm, 93.1%, 169.7min, 3.4%/6.9%, 25.8%/6.5%} (3) Is/
Isp=40mm, n 12 {51.3mm, 100%, 121.3min, 0%/0%, 25.0%/41.7%} (4)
local recurrent lesion after EPMR=20mm, n 15 {29.9mm, 100%, 118.3min,
0%/0%, 0%/100%} (5) ordinary lesion, n 243 {28.7mm, 99.2%, 63.3min,
0%/0.4%, 24.7%/2.1%}. The tumor size was significantly larger for the group
(1) (2) (3) than the group (5), respectively. Operative time was significantly longer
for these four groups than the group (5). En bloc resection rates didnt signifi-
cantly differ respectively between the two groups. Except for local recurrent
lesion, moderate severe fibrosis rates were respectively similar between the two
groups. Furthermore, all recurrent lesions had severe fibrosis and the severe
fibrosis rate was significantly higher for the group (3) than the group (5). The
perforation rates were respectively similar between the two groups. The delayed
bleeding rate was significantly higher only for the group (2) than the group (5).
CONCLUSION: It is confirmed that we should regard both LST-NG and Is/
Isp=40mm as lesions with highly technical difficulty. We acquired the high cur-
ability and safety even for highly difficult lesions irrespective of longer operative
time.
Disclosure of Interest: None declared
P0733 DISTINCT MOLECULAR FEATURES OF DIFFERENT
MACROSCOPIC SUBTYPES OF COLORECTAL NEOPLASMS
K. Konda1,*, K. Konishi1, T. Yamochi1, Y.M. Ito2, H. Nozawa1, M. Tojo1,
K. Shinmura1, M. Kogo1, A. Katagiri1, Y. Kubota1, Y. Yano1, Y. Kobayashi1,
T. Kihara1, T. Tagawa1, R. Makino1, M. Takimoto1, M. Imawari1, H. Yoshida1
1
1-5-8 hatanodai shinagawa-ku, 142-8666 - Tokyo, Japan, Tokyo, 2Kita 8, Nishi 5,
Kita-ku, Sapporo city, Hokkaido, Japan
Contact E-mail Address: kenichi_konda@yahoo.co.jp
INTRODUCTION: Colorectal adenoma develops into cancer with the accumu-
lation of genetic and epigenetic changes. We studied the underlying molecular
and clinicopathological features to better understand the heterogeneity of color-
ectal neoplasms (CRNs).
AIMS & METHODS: We evaluated both genetic (mutations of KRAS, BRAF,
TP53, and PIK3CA, and microsatellite instability [MSI]) and epigenetic (methy-
lation status of nine genes or sequences, including the CpG island methylator
phenotype [CIMP] markers) alterations in 158 CRNs including 56 polypoid
neoplasms (PNs), 25 granular type laterally spreading tumors (LST-Gs), 48
non-granular type LSTs (LST-NGs), 19 depressed neoplasms (DNs) and 10
small flat-elevated neoplasms (S-FNs) on the basis of macroscopic appearance.
RESULTS: S-FNs showed few molecular changes except SFRP1 methylation.
Significant differences in the frequency of KRAS mutations were observed
among subtypes (68% for LST-Gs, 36% for PNs, 16% for DNs and 6% for
LST-NGs) (P 5 0.001). By contrast, the frequency of TP53 mutation was higher
in DNs than PNs or LST-Gs (32% vs. 5% or 0%, respectively) (P 5 0.007). We
also observed significant differences in the frequency of CIMP between LST-Gs
and LST-NGs or PNs (32% vs. 6% or 5%, respectively) (P 5 0.005). Moreover,
the methylation level of LINE-1 was significantly lower in DNs or LST-Gs than
in PNs (58.3% or 60.5% vs. 63.2%, P 5 0.05). PIK3CA mutations were detected
only in LSTs. Finally, multivariate analyses showed that macroscopic morphol-
ogies were significantly associated with an increased risk of molecular changes
(PN or LST-G for KRAS mutation, odds ratio [OR] 9.11; LST-NG or DN for
TP53 mutation, OR 5.30; LST-G for PIK3CA mutation, OR 26.53; LST-G or
DN for LINE-1 hypomethylation, OR 3.41).
CONCLUSION: We demonstrated that CRNs could be classified into five
macroscopic subtypes according to clinicopathological and molecular differ-
ences, suggesting that different mechanisms are involved in the pathogenesis of
colorectal tumorigenesis.
Disclosure of Interest: None declared
P0734 ENDOCYTOSCOPY CAN PREDICT THE VENOUS AND
LYMPHATIC VESSEL PERMEATION OF EARLY COLORECTAL
ADENOCARCINOMA
K. Takeda1,*, S.-E. Kudo1, K. Wakamura1, K. Ichimasa1, M. Kutsukawa1,
M. Misawa1, Y. Mori1, T. Kudo1, T. Hayashi1, H. Miyachi1, E. Hidaka1,
F. Ishida1
1
Digestive Disease Center, Showa University Northern Yokohama Hospital,
Yokohama city, Japan
INTRODUCTION: Endocytoscopy (EC), which enables observation of in vivo
cells and nuclei at about 380-fold magnification, provides more detailed informa-
tion about the lesions.
AIMS & METHODS: The aim of our study is to evaluate the possibility of EC
with regard to prediction of venous and lymphatic vessel permeation.
The subjects were 117 colorectal differentiated adenocarcinomas (53 Tis, 41 T1
carcinomas, 12 T2 carcinomas, 11 T3 carcinomas) from 115 patients treated by
endoscopic or surgical resection after observation with EC at Showa University
Northern Yokohama Hospital from February 2009 to March 2014. In observing
EC images, we defined the average scale of four vessels as vessel diameter and
proportion between maximum portion and minimum portion of the vessel as
vessel caliber variation. We analyzed the correlationship between these para-
meters (vessel diameter and vessel caliber variation) and venous or lympha-
tic vessel permeation.
RESULTS: The mean vessel diameter of venous permeation positive tumors was
41.0mm, and that of negative tumors was 31.4mm. The mean vessel caliber varia-
tion of venous permeation positive tumors was 0.45, and that of negative tumors
was 0.38 (P 5 0.05). In lymphatic vessel permeation, the mean vessel diameter of
lymphatic vessel permeation positive tumors was 39.1mm, and that of negative
tumors was 34.4mm. The mean vessel caliber variation of venous permeation
positive tumors was 0.45, and that of negative tumor was 0.40 (P 5 0.05).
A334
There were differences in vessel diameter and vessel caliber variation between
venous permeation positive tumors and that of negative tumors especially in
T1carcinomas (p 5 0.05).
CONCLUSION: EC has the possibility to evaluate the venous and lymphatic
vessel permeation by observing the vessel formation, especially in T1 carcinoma.
Disclosure of Interest: None declared
P0736 NATURE OF WHITE OPAQUE SUBSTANCE WITHIN
COLORECTAL NEOPLASTIC EPITHELIUM AS VISUALIZED BY
MAGNIFYING ENDOSCOPY WITH NARROW-BAND IMAGING: A
NOVEL BIO-MARKER FOR COLORECTAL NEOPLASIA
K. Imamura1,2,*, K. Yao3, T. Hisabe1, K. Otsu1, H. Ishihara1, T. Nagahama1,
T. Kanemitsu1, T. Matsui1, M. Nambu2, A. Ota2, A. Iwashita2
1
Gastroenterology, 2Pathology, 3Endoscopy, Fukuoka University Chikushi
Hospital, Chikushino, Japan
Contact E-mail Address: kentaro2316@live.jp
INTRODUCTION: Background: We previously reported the presence of a white
opaque substance (WOS), opaque to the endoscope light, inside the epithelium
when we use magnifying endoscopy (ME) to examine gastric epithelial neoplasia
(adenomas and carcinomas) and chronic gastritis (intestinal metaplasia)1).
Through further pathohistological study we elucidated that this substance is
comprised of minute lipid droplets (LDs) accumulated within the mucosal epithe-
lium of gastric epithelial neoplasia or intestinal metaplasia.2) These minute LDs
strongly backscatter the projected light, and are visualized as a white substance.
When we examined colorectal neoplastic lesions (adenomas and carcinomas)
using ME, we observed WOS as in the stomach. However, it is unclear whether
WOS in colorectal epithelial tumors is in fact an accumulation of LDs as in the
stomach.
AIMS & METHODS: Aims: To elucidate whether WOS observed in colorectal
epithelial tumors (adenomas and carcinomas) is composed of LDs.
Methods: We analyzed a continuous series of both 40 WOS-positive and 40
WOS-negative colorectal epithelial tumors. We examined colorectal neoplastic
lesions (adenomas and carcinomas), prior to planned treatment, using ME with
narrow-band imaging (NBI), determining whether WOS was present in the sur-
face layers of the most anal part of the colorectal epithelial tumor. We took
targeted biopsies from this part of the tumor. Biopsy specimens were immediately
frozen, slices taken, and the slides were stained for lipids using oil-red O. Slides
were examined using light microscopy immediately after staining for the presence
of LDs within the neoplastic epithelium. We investigated the correlation between
the presence of WOS as visualized by ME with NBI and the presence of LDs in
the histological specimens.
RESULTS: The prevalence of LDs in WOS-positive vs WOS-negative lesions
was 47.5% (19/40) and 5% (2/40), respectively (P 5 0.001, Fishers exact test).
CONCLUSION: Conclusion: LDs do not accumulate in the normal colorectal
epithelium. However, this study elucidated for the first time that endoscopically
visualized WOS may be composed of LDs accumulated in colorectal epithelium.
This phenomenon has the potential to be a new biomarker for the pathology and
diagnosis of colorectal neoplasia.
REFERENCES
1. Yao K, Iwashita A, Tanabe H, et al. White opaque substance within super-
ficial elevated gastric neoplasia as visualized by magnification endoscopy with
narrow-band imaging: a new optical sign for differentiating between adenoma
and carcinoma. Gastrointest Endosc 2008; 68: 574-580.
2. Yao K, Iwashita A, Nambu M, et al. Nature of white opaque substance in
gastric epithelial neoplasia as visualized by magnifying endoscopy with narrow-
band imaging. Dig Endosc 2012; 24: 419-425.
Disclosure of Interest: None declared
P0737 QUANTITATIVE AUTOFLUORESCENCE IMAGING IS USEFUL
FOR ASSESSING THE SEVERITY OF ULCERATIVE COLITIS
K. Moriichi1,*, M. Fujiya1, M. Ijiri1, K. Tanaka1, A. Sakatani1, T. Doukoshi1,
K. Ando1, N. Ueno1, S. Kashima1, Y. Inaba1, T. Ito1, Y. Kohgo1
1
Division of Gastroenterology and Hematology/Oncology, Department of
Medicine, Asahikawa Medical University, Asahikawa, Japan
Contact E-mail Address: morimori@asahikawa-med.ac.jp
INTRODUCTION: Maintaining remission in patients with ulcerative colitis
(UC) is the most important achievement for the present treatments. Although
precise evaluation of the mucosal inflammation is necessary to keep the remission
status as long as possible, the procedures have been inadequate to detect this
inflammation. Autofluorescence imaging (AFI) is a novel technology that can
capture the fluorescence emitted from living tissues. While AFI has been demon-
strated to be useful for diagnosing colorectal neoplasms, it is unclear whether
AFI can assess the severity of ulcerative colitis (UC).
AIMS & METHODS: The aim of this prospective study was to evaluate the
efficacy of AFI and its quantification for detecting mucosal inflammation in
patients with UC. Forty-three patients diagnosed with UC who underwent
AFI at Asahikawa Medical University Hospital between 2007 and 2010 were
enrolled in this study. One hundred and thirty-five areas of the colon in the
enrolled patients were first photographed using conventional endoscopy, fol-
lowed by AFI. Eleven endoscopists separately evaluated the photographs cap-
tured with WLE and AFI, and quantified the intensities of fluorescence. Biopsy
specimens were evaluated according to Matts criteria, and active inflammation
was defined when Matts grade was 2 or higher. 1) When the WLE image corre-
sponded to a Mayo endoscopic subscore 0 or 1, the inflammation was categor-
ized as inactive. AFI images were visually categorized into two groups, green-
dominant (G) and magenta-dominant (M) (vAFI). 2) AFI images were quanti-
fied using an image-analytical software program. The ratio of the reverse gamma
United European Gastroenterology Journal 2(5S)
value of green (fluorescence) divided by that of red (reflex) was defined as the
fluorescence index (F index). These endoscopic assessments and the F index were
compared with the histological findings. A cutoff value for the F index of active
inflammation was determined using an ROC analysis. 3) The inter-observer
consistency of WLE, vAFI and the quantified AFI for eleven endoscopists was
calculated.
RESULTS: 1) The average diagnostic accuracy of WLE and vAFI for the his-
tological activity was 78.5% and 78.6%, respectively. No significant difference
was observed between these modalities. 2) The correlation coefficient between the
F index and the histological findings was closely associated with the inflamma-
tory grade (r -0.558, p50.0001). The ROC analysis showed that active inflam-
mation was defined when the F index was less than 0.906. The average diagnostic
accuracy of the F index (84.7%) was higher than that of WLE and AFI (p50.01,
p50.05). 3) The kappa value for inter-observer agreement of WLE, vAFI and
the F index by the overall observers, residents and experts were 0.58, 0.56 and
0.95, 0.53, 0.49 and 0.97 and 0.67, 0.64 and 0.93, respectively.
CONCLUSION: The quantified AFI is therefore considered to be a useful and
objective modality for assessing the activity of ulcerative colitis, particularly by
residents.
Disclosure of Interest: None declared
P0738 EFFICACY OF COLORECTAL ENDOSCOPIC SUBMUCOSAL
DISSECTION FOR THE TREATMENT OF RESIDUAL OR
LOCALLY RECURRENT TUMOR OCCURRING IN THERAPEUTIC
SCAR
K. Hirasawa1,*, R. KOBAYASHI1, H. KANEKO1, M. MAKAZU1, C. SATO1,
S. MAEDA2
1
Division of Endoscopy, Yokohama City University Medical Center, 2Department
of Gastroenterology, Yokohama City University Graduate School of Medicine,
Yokohama-City, Japan
Contact E-mail Address: kingo-h@urahp.yokohama-cu.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) has been wide-
spread as a treatment of superficial gastric neoplasm even for ulcerative scar
cases. This technique has been recently introduced as a treatment option for
colorectal tumor; however, the efficacy of ESD for residual or locally recurrent
colorectal tumor occurring in therapeutic scar has not been fully evaluated.
AIMS & METHODS: To clarify the clinical outcomes of colorectal ESD for
residual or locally recurrent tumor occurring in therapeutic scar.
Between April 2008 and March 2014, 285 consecutive superficial colorectal
tumors in 267 patients were treated using ESD. Of these, 17 lesions in 17 patients
were treated as residual or locally recurrent tumor with therapeutic scar. These
contained 12 that recurred after endoscopic mucosal resection (EMR) and 5 after
transanal endoscopic microsurgery (TEM) (scar group). The others were defined
as non-scar group and treatment outcomes and complications were evaluated
between two groups.
RESULTS: In all patients, the rates of en bloc resection, R0 resection and
curative resection were 98.9% (282/285), 90.2% (257/285) and 82.5% (235/285)
respectively, and mean tumor size was 33.3 mm, mean treatment time was 67.2
minutes, and perforation rate was 9.5%. All patients with perforation were man-
aged with conservative medical treatment after endoscopic closure with clipping
and did not need emergent surgery.
No significant differences were observed between the two groups with respect to
the rate of en bloc resection, R0 resection and curative resection; however, uni-
variate analysis showed that perforation rate and treatment time were signifi-
cantly higher and longer in the scar group compared with the non-scar group.
In addition, we evaluated age, sex, tumor location, tumor depth, tumor size,
tumor morphology and the presence of therapeutic scar by multivariate analysis,
and found that large tumor size and the presence of therapeutic scar were an
independent risk factor for both perforation and long treatment time.
CONCLUSION: This finding implies that colorectal ESD may be used as a
treatment choice for residual or locally recurrent tumor occurring in therapeutic
scar. However, we need to perform ESD in consideration of the risk for perfora-
tion, and it will require cooperation with surgery when treating those cases.
Disclosure of Interest: None declared
P0739 EDUCATION FOR WARD NURSES INFLUENCES ON THE
QUALITY OF INPATIENTS BOWEL PREPARATION FOR
COLONOSCOPY
K.B. Cho1,*, E.S. Kim1, K.S. Park1, E.S. Choi1, S.M. Lee1, C.H. Yang2
1
Internal Medicine, KEIMYUNG UNIVERSITY SCHOOL OF MEDICINE,
Daegu, 2Internal Medicine, Dongguk University School of Medicine, Gyeongju,
Korea, Republic Of
Contact E-mail Address: dandy813@hanmail.net
INTRODUCTION: Although adequate bowel preparation is prerequisite to
colonoscopy, preparation for inpatients is often suboptimal.
AIMS & METHODS: This study aimed to evaluate the impact of education for
ward nurses on the quality of inpatients bowel preparation. A prospective,
endoscopist-blinded, non-randomized, controlled study was performed.
Gastroenterology experts provided the education to nurses who belonged to
educated ward and this education was repeated every week for 1 month. 103
inpatients in educated ward and 102 inpatients in control ward of gastroenterol-
ogy department who were scheduled for colonoscopy were enrolled. The primary
outcome was the quality of the bowel preparation using the Ottawa Bowel
Preparation Scale (OBPS). The secondary outcomes were polyp detection rate
(PDR), patient compliance and subjective feelings.
RESULTS: Baseline data including patient characteristics, indication of proce-
dure, and preparation quality before the study were comparable between 2
United European Gastroenterology Journal 2(5S) A335

Table to abstract P0740

Ileoscopy abnormal Ileoscopy normal

Indication (n) P value (all / clinically relevant)
Number Biopsy abnormal Clinically relevant Number Biopsy abnormal Clinically relevant

Diarrhoea (67) 15 11 9 52 7 3 50.001 / 50.001

Abdo pain (39) 12 9 8 27 3 2 50.001 / 50.001
IBD assessment (29) 12 10 9 17 3 3 50.001 / 0.006
Other* (18) 2 2 1 16 3 1 0.194 / 0.284
Total6 (129) 34 25 21 95 14 1 50.001 / 50.001

wards. Mean scores of OBPS were 4.422.23 and 6.152.38 in educated and
control ward, respectively (p50.001). Rate of poor preparation (OBPS 56) in
educated ward was significantly lower than that of control (31.1% vs. 58.8%,
p50.001). PDR of educated ward was significantly higher than that of control
ward (74.8% vs. 52.0%, p 0.001). Compliance with preparation and diet
instructions in education group was superior to that in control (p50.001).
Control group was more likely to be anxious before colonoscopy (p50.001)
while education group showed a higher level of satisfaction with better sleep
quality (p50.001). In multivariate analysis, no ward nurse education (OR 2.36,
p 0.025), constipation (OR 6.52, p50.001) and no additional water ingestion
(OR 2.05, p 0.042) were factors associated with poor bowel preparation.
CONCLUSION: Ward nurse education is effective to improve the quality of
inpatient bowel preparation, PDR, and compliance. Additional effort is needed
to control constipation and to encourage additional water ingestion for better
inpatient bowel preparation.
Disclosure of Interest: None declared
P0740 WHEN SHOULD I TAKE TERMINAL ILEAL BIOPSIES?
EXPERIENCE FROM A SINGLE UNIT
L.J. Neilson1,2,*, R. Bevan1,2, C.J. Rees1,2
1
South Tyneside District Hospital, South Shields, 2Northern Region Endoscopy
Group, Newcastle, United Kingdom
Contact E-mail Address: neilson.laurajane@hotmail.co.uk
INTRODUCTION: Terminal ileum (TI) intubation at colonoscopy may be
useful in the investigation of patients with diarrhoea or possible inflammatory
bowel disease.1,2 The yield of TI biopsies has been shown to be variable and there
are no standards for current practice.2,3 Furthermore, in the UK, concerns
remain regarding the potential for prion transmission.
AIMS & METHODS: We aim to establish the yield of TI biopsies in a single
unit.
All TI biopsies recorded on the pathology system in a 3-year period were
reviewed. Colonoscopy reports for these cases were reviewed, as well as case
records to establish if biopsy results were clinically relevant (defined as leading
to a change in management). Statistical analysis was performed using SPSS. P
values were calculated using the Fishers exact test to show any difference in
biopsy yield between normal and abnormal looking mucosa for each indication.
The values were calculated for all abnormal biopsy results, and for clinically
relevant biopsy results.
RESULTS: 129 TI biopsies were taken between September 2010 and September
2013, 49 (38%) male and 80 (62%) female. Mean age 44 years (s.d. 17.2). There
were 29 (22.5%) cases of known inflammatory bowel disease (IBD). 5 (3.9%)
cases were completion colonoscopies after colorectal cancer surgery, where TI
biopsies are taken to prove a complete examination.
CONCLUSION: We demonstrate that when investigating patients with diar-
rhoea, abdominal pain, or IBD, if the terminal ileum is visually normal, biopsies
do not add to the clinical picture. There is a higher yield of relevant biopsy
abnormalities when the TI appears abnormal. We can recommend within our
practice that a visual assessment of a normal terminal biopsy is adequate, thereby
reducing unnecessary biopsies. This reduces the workload for pathology labora-
tories, reduces risk from biopsies, and improves patient care as normal results can
be communicated sooner to the patient.
Table to abstract P0741
Table Pharmacodynamics of different technical formulations (TF)/administration volumes of NER1006
REFERENCES
1. Geboes K, Ectors N, DHaens G, et al. Is ileoscopy with biopsy worthwhile in
patients presenting with symptoms of inflammatory bowel disease? Am J
Gastroenterol 1998; 93: 201-206.
2. Morini S, Lorenzetti R, Stella F, et al. Retrograde ileoscopy in chronic non-
bloody diarrhea: A porspective, case-control study. Am J Gastroenterol 2003; 98:
1512-1515.
3. Melton SD, Feagins LA, Saboorian MH, et al. Ileal biopsy: Clinical indica-
tions, endoscopic and histopathologic findings in 10.000 patients. Dig Liver Dis
2011; 43: 199-203.
Disclosure of Interest: None declared
P0741 PHARMACODYNAMIC AND CLINICAL EVALUATION OF LOW-
VOLUME POLYETHYLENE GLYCOL (PEG)-BASED BOWEL
CLEANSING SOLUTIONS (NER1006) USING SPLIT DOSING IN
HEALTHY AND SCREENING COLONOSCOPY SUBJECTS
M. Halphen1,*, B. Tayo1, S. Flanagan1, L. Clayton1, R. Kornberger2
1
Norgine Ltd, Uxbridge, United Kingdom, 2PAREXEL International, Berlin,
Germany
Contact E-mail Address: MHalphen@norgine.com
INTRODUCTION: The effectiveness of PEG3350electrolytes based solutions
for bowel cleansing prior to endoscopy is well established but require patients to
drink 3L of fluid. Reducing this volume without compromising efficacy/safety
is the next challenge.
AIMS & METHODS: This open-label, randomised, 2-part (Part A: healthy
subjects; Part B: screening colonoscopy subjects), phase II study investigated
the pharmacodynamics (stool weight), tolerability, and clinical efficacy of dose-
and taste-optimised low-volume PEG-based formulations (NER1006) after split
dosing compared with MOVIPREP. Subjects (4070y) were randomised to 1 of
4 treatment arms in Parts A and B (1:1:1:1): 3 formulation arms for NER1006; 1
for MOVIPREP. NER1006 consisted of different PEG3350 formulations,
mineral salts (including ascorbate), electrolytes and flavouring, reconstituted
with water plus additional intake of specified volumes of water (Table).
Treatment was administered on Day 1 (evening dose) and Day 2 (morning
dose). The primary endpoint in Parts A and B was 24h stool weight (desired
target 2750g). Cleansing success rate (Harefield Cleansing Scale) was a co-
primary endpoint in Part B. Secondary endpoints included time and volume of
study drug to reach clear effluent, safety and tolerability (vomiting rate).
RESULTS: 120 subjects were included in each part (n 30/arm). 24h stool
weight was significantly 42750g for NER1006 formulations OPT002 and
OPT003 in Part A, and OPT003 and OPT007 in Part B. Reversed order of
administration of the split dose (i.e., TF043 morning/TF048 evening) in
OPT002 was as efficacious, with a similar safety profile. Most subjects in the
NER1006 arms reached clear effluent. Mean volume of study drug required and
time to reach clear effluent are shown in the Table. In Part B, cleansing success
rate was: 100% for OPT003 and OPT007; 90% for OPT006 and OPT004. For
subjects who completed dosing, vomiting rates were 57.0% and 53.5% for all
treatments in Parts A and B, respectively, with no significant differences between
arms in either part.
CONCLUSION: In healthy and screening-colonoscopy subjects, the new low-
volume, split-dose bowel preparation NER1006 achieved high quality bowel
cleansing comparable with MOVIPREP. Stool output was consistently higher
with NER1006 treatments, and safety/tolerability profiles between treatments
were comparable.

Evening dose Morning dose

formulation formulation Mean stool Mean volume of
Arm (reconstitution (reconstitution weight, g Mean time to drug required to reach
(formulation) voladditional vol, mL) voladditional vol, mL) (p-value vs target) clear effluent, h clear effluent, mL

Part A:
1 (OPT001) TF048 (750875) TF043 (500875) 2951 (0.2176) 15.8 1139
2 (OPT002) TF043 (500875) TF048 (750875) 3219 (0.0042) 12.3 900
3 (OPT003) TF047 (5001000) TF043 (5001000) 3399 17.8 944
4 (OPT004) MOVIPREP (1000500) MOVIPREP (1000500) (50.0001)
2491 (0.8764) 17.7 1929
Part B:
1 (OPT003) TF047 (5001000) TF043 (5001000) 3050 (0.0268) 14.9 860
2 (OPT007) TF047 (500500) TF043 (500500) 3215 (0.0004) 16.9 956
3 (OPT006) TF047 (5001000) TF044 (5001000) 2675 (0.4907) 17.7 935
4 (OPT004) MOVIPREP (1000500) MOVIPREP (1000500) 2487 (0.9691) 16.3 1790
A336
Disclosure of Interest: M. Halphen Consultancy for: Norgine, B. Tayo Other:
Norgine, S. Flanagan Other: Norgine, L. Clayton Other: Norgine, R.
Kornberger Financial support for research from: Norgine
P0742 OLYMPUS NEAR FOCUS NARROW BAND IMAGING (NBI) VS
CONVENTIONAL NBI FOR IN VIVO ENDOSCOPIC HISTOLOGY OF
COLONIC POLYPS: A RANDOMIZED CONTROLLED TRIAL
M. Bustamante1,*, L. Puchades1, M. Ponce1, L. Arguello1, V. Pons1
1
Gastrointestinal Endoscopy Unit, Hospital Universitari i Polite`cnic La Fe,
Valencia, Spain
Contact E-mail Address: bustamante_mar@gva.es
INTRODUCTION: A lower diagnostic accuracy of pathologic in vivo diagnosis
with NBI has been described in nonacademic settings compared to expert centers.
Recently, Olympus has launched the 190 series, which has a pushbutton-con-
trolled optical magnification system (near focus).
AIMS & METHODS: Aims: to assess the reliability of the near focus system
compared to conventional NBI in the histologic prediction (adenoma vs hyper-
plastic) of small (6-9 mm) and diminutive (1-5 mm) colonic polyps. Secondary
objective was to assess the fulfillment of PIVI criteria.1
Patients and methods: Patients scheduled for colonoscopy were consecutively
included. Patients were assigned to 190 series (group 1) or 180 series (group 2)
endoscopes using a computer-generated random number sequence. A sample size
calculation was performed, and a minimum of 136 lesions per group was pro-
grammed. All examinations were performed by the same endoscopist (MBB) with
expertise in NBI analysis. NICE classification criteria2 were used for in vivo
histological diagnosis.
RESULTS: 98 patients were included (49 women, 50%), median age 63 yr. CRC
screening was the most frequent indication (51%). Group 1 was comprised of 51
patients (52%). Finally 333 lesions were included, 82.6% from 1 to 5 mm of
diameter, and 231 (69.4%) adenomas. Under NBI examination, the histology of
277 lesions (83.2%) was predicted with high confidence. The 51 patients from
group 1 harbored 171 lesions (142 predicted with high confidence) and the 48
patients from group 2 harbored 162 lesions (135 predicted with high confidence).
Sensitivity, specificity and diagnostic accuracy for lesions diagnosed with high
confidence in both groups are summarized in table 1. There were no differences
in diagnostic accuracy between both groups (92.2% vs 89.6%, p 0.5).
(%) Group 1 Group 2
(CI 95%)
High
High confidence confidence
High Diminutive High Diminutive
confidence lesions confidence lesions
Sensitivity 91.8 (85.9-97.7) 90.0 (82.8-97.2) 91.2 (84.8-97.6) 87.7 (78.9-96.5)
Specificity 93.2 (84.6-100) 94.1 (84.7-100) 86.4 (75.1-97.6) 86.4 (75.1-97.6)
Accuracy 92.2 (87.5-97.0) 91.2 (85.6-96.9) 89.6 (84.1-95.1) 87.2 (80.4-93.9)
Six (10.3%) of the 54 diminutive lesions located in rectum and sigmoid colon and
diagnosed as hyperplastic with NBI were finally categorized as adenomas. The
overall NPV for the diagnosis of adenoma was 89.7%. In 61 (95.3%) out of the
64 patients in whom a colonoscopy control was scheduled, there was an agree-
ment between NBI and the final pathological diagnosis (kappa 0.9), without
differences between groups.
CONCLUSION: The near focus technology does not increase the diagnostic
accuracy of conventional NBI at least for an expert examinator. NBI achieves
a good accuracy for in vivo pathological diagnosis, fulfilling PIVI criteria; there-
fore it may represent an alternative to pathological diagnosis in a near future.
REFERENCES
1 ASGE PIVI on real-time endoscopic assessment of the histology of diminutive
colorectal polyps. Gastrointest Endosc 2011; 73: 419-422.
2 Hewett DG, et al. Validation of a simple classification system for endoscopic
diagnosis of small colorectal polyps using narrow-band imaging.
Gastroenterology 2012; 143: 599-607.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
describe the white light findings in CD. CLE findings were classified using the 4
grade classification system of inflammation, describing crypt architecture, infil-
tration of the cells, microvasculature alteration and leakage of fluorescein. CLE
images were collected for each segment of the colon, and targeted biopsies were
taken for histologic analysis.
RESULTS: Of the 24 PSC patients, 20 had co-existent IBD (10UC, & 10CD).
Absence of rectal inflammation based on CLE findings was seen in 20/24
patients. 10/24 had moderate to severe inflammation present in the right colon
with irregular, decreased or necrotic crypts. Two patterns of fluorescein leakage
were observed. A) In 10 patients leakage of fluorescein were observed in spaces
amongst epithelial cells, or non-uniform abundant leakage in the lumen of the
crypts associated with moderate to severe inflammation; B) In 12 patients we
observed uniform leakage of the fluorescein into the lumen of crypts in the left
side of the colon, associated with normal crypt architecture and micro-vascula-
ture - the absence of active inflammation was confirmed by histology. The
remaining 2 patients did not showed leakage of fluorescein. Four patients did
not have a diagnosis of IBD but 3 of these patients had subtle inflammation on
CLE characterized by cellular infiltration within the lamina propria in the sig-
moid colon and rectum (by histology). One had a new diagnosis of UC after
examination by CLE and colonoscopy.
CONCLUSION: CLE effectively characterizes the inflammation of PSC IBD
patients, confirming that these patients are likely have a different phenotype with
inflammation in the right side of the colon and rectal sparing. The finding of
uniform leakage of fluorescein into the lumen of the crypts, in the absence of
active inflammation, may represent a defect in the intestinal barrier. Even
patients not known to have IBD associated with PSC may demonstrate subtle
infiltration of mononuclear cells into the lamina propria as demonstrated at
CLE.
Disclosure of Interest: None declared
P0744 ANALYSIS OF THE ENDOCYTOSCOPIC IMAGE OF
COLORECTAL LESION FROM THE ASPECT OF MICRO
VASCULAR PATTERN
M. Misawa1,*, S.-E. Kudo1, H. Nakamura1, S. Kataoka1, S. Hayashi1,
H. Oikawa1, N. Toyoshima1, Y. Mori1, T. Kudo1, N. Ogata1, T. Hayashi1,
K. Wakamura1, Y. Wada1, H. Miyachi1, F. Ishida1
1
Digestive disease center, Showa University Northern Yokohama Hospital,
Yokohama-shi, Japan
INTRODUCTION: Endocytoscopy (EC) is an ultra-magnification technique,
which can be performed to evaluate structural and cellular atypia with observa-
tion of lumens and nuclei in the surface layer of the mucosa. EC has made it
possible to diagnose living tumor cells in vivo and to obtain an ultra-magnifica-
tion pathological image simply by applying the scope to the target mucosa during
an endoscopic examination. On the other hand, analysis of the surface micro-
vessels of colorectal lesions using magnifying narrow-band imaging is useful for
identifying the appropriate treatment method for colorectal lesions. In addition,
the surface microvessels can be analyzed using EC.
AIMS & METHODS: The aim of this study was to investigate whether the
observation of surface microvessels using EC was useful in predicting the histo-
pathology of colorectal lesions.
The study included 273 patients who underwent complete colonoscopy and endo-
scopic or surgical treatment between April 2006 and December 2013. A total of
337 lesions (10 normal mucosae, 23 hyperplastic polyps, 210 adenomas, and 94
submucosally invasive cancers) were retrospectively evaluated. The colonic sur-
face micro-vascular patterns observed using EC were classified into the following
3 groups: EC-V1, the surface microvessels were obscure; EC-V2, the surface
microvessels were clearly observed, and their caliber and arrangement were uni-
form; and EC-V3, the surface microvessels were thick, and their caliber and
arrangement were non-homogeneous.
RESULTS: The sensitivity, specificity and accuracy of EC-V1 for diagnosis of
hyperplastic polyp were 97.0%, 99.0% and 98.8%, respectively. As regards the
sensitivity, specificity and accuracy of EC-V3 for diagnosis of invasive cancer
were 84.7%, 97.7% and 94.1%, respectively.
CONCLUSION: Vascular patterns of colorectal cancers observed by endocyto-
scopy were useful in predicting the histopathology of colorectal lesions.
Disclosure of Interest: None declared

P0745 EXCELLENT PROGNOSIS OF ENDOSCOPICALLY RESECTED

P0743 CONFOCAL LASER ENDOMICROSCOPY FINDINGS
PRIMARY SCLEROSING CHOLANGITIS (PSC) -IBD PATIENTS
M. Iacucci1,*, X. Gui2, R. Panaccione 1, S. Ghosh3, B. Eksteen4
1
Inflammatory Bowel disease clinic, 2pathology departement, 3Departement of
Medicine, 4Division of Gastroenterology&Hepatology, University of Calgary,
Calgary, Canada
Contact E-mail Address: miacucci@ucalgary.ca
IN RECTAL NEUROENDOCRINE TUMORS DESPITE THE FREQUENT
PRESENCE OF LYMPHOVASCULAR INVASION
M. Sekiguchi1,*, S. Sekine2, T. Sakamoto1, Y. Otake1, T. Nakajima1,
T. Matsuda1, H. Taniguchi1, R. Kushima2, Y. Saito1
1
Endoscopy Division, 2Pathology DIvision, National Cancer Center Hospital,
Tokyo, Japan
Contact E-mail Address: masekigu@ncc.go.jp

INTRODUCTION: Controversy exists as to whether the colitis seen in patients
with primary sclerosing cholangitis (PSC) represents a different entity than that
classically observed in patients with Crohns disease (CD) or ulcerative colitis
(UC). Specific differences have been described in the nature of the endoscopic
and histological findings. Confocal laser endomicroscopy (CLE) is a new tech-
nology which enables real time endoscopy and histological investigation. PSC
colitis has not been investigated by CLE.
AIMS & METHODS: To describe the CLE appearance in the colon in patients
with PSC, with or without associated IBD. Patients and Methods 24 patients (16
male: median age 43y, range 20-71y) with PSC underwent colonoscopy with CLE
(Pentax, Tokyo) between 02/12 and 12/13. The Mayo endoscopy sub-score was
used to grade endoscopic findings in UC, and the SES-CD score was used to
INTRODUCTION: Endoscopic resection (ER) is increasingly used to treat small
rectal neuroendocrine tumors (NETs). Currently, several guidelines recommend
ER as a treatment of rectal NETs less than 10 mm without muscularis invasion.
However, limited data are available on the long-term outcomes of rectal NETs
treated by ER. In addition, the significance of known risk factors for metastasis
of rectal NETs, including lymphovascular invasion, remains elusive.
AIMS & METHODS: The aim of this study was to clarify the prognosis of rectal
NET patients treated by ER and to characterize the known risk factors for
metastasis of these lesions. Ninety-eight patients underwent ER for rectal
NETs at our institution between 1997 and 2011. Among them, 3 patients who
underwent colectomy for colorectal cancers after ER of rectal NETs and 8
patients with a follow-up period shorter than 1 year were excluded. Thus, a
United European Gastroenterology Journal 2(5S)
total of 87 patients with 91 lesions were included in this study. The patients
records were retrospectively analyzed for clinical outcomes and pathological
findings including size, invasion depth, and lymphovascular invasion. Also, we
additionally evaluated tumor proliferation by Ki-67 immunohistochemistry and
lymphovascular invasion using elastic staining and double staining immunohis-
tochemistry (CD31/synatophysin and D2-40/synaptophysin).
RESULTS: ER procedures included endoscopic submucosal resection with a
ligation device (ESMR-L) (n 82), EMR (n 5), and ESD (n 4), with an R0
resection rate of 90.1% (ESMR-L 76/82, EMR 3/5, and ESD 3/4, respectively).
No major complications were observed. All cases were followed up without
surgery after ER; with the median follow-up period of 68 months (range, 12
167), no metastasis or recurrence was detected and the 5-year overall survival rate
was 95.9%. The median tumor size of these cases was 5 mm (range, 213) and no
lesion showed invasion beyond the submucosal layer. Based on the results of Ki-
67 immunohistochemistry, all 91 lesions were classified as NET G1 (WHO 2010
classification). The original diagnoses based on haematoxylin and eosin staining
identified no case with lymphatic invasion and only one case with positive venous
involvement. However, additional analysis using elastic staining and double
staining immunohistochemistry revealed lymphovascular invasions in 33 lesions
(36.3%) by elastic staining, 9 lesions (9.9%) by CD31/synaptophysin double
staining, and 23 lesions (25.3%) by D2-40/synaptophysin double staining.
Collectively, lymphovascular invasion was identified in a total of 42 lesions
(46.2%) with at least one of these staining procedures. Size of NETs with lym-
phovascular invasion (median, 5 mm; range, 313) was significantly but only
slightly larger than that of NETs without lymphovascular invasion (median, 4
mm; range, 210; p 0.02, MannWhitney U test). copies. 164 procedures (32.1%) did not meet the criteria for repeat procedures,
CONCLUSION: Long-term clinical outcomes of rectal NETs following ER were
favorable. While lymphovascular invasion was believed to be a strong risk factor
for metastasis, a detailed analysis revealed that it was frequently present even in
minute rectal NETs. The present results raise a question on the clinical signifi-
cance of lymphovasucalar invasion in small rectal NETs.
Disclosure of Interest: None declared
P0746 HIGH PRESSURE JET INJECTION OF VISCOUS SOLUTIONS
FOR ENDOSCOPIC SUBMUCOSAL DISSECTION (ESD): ABOUT
THE 45 FIRST HUMAN CASES IN 4 EXPERT CENTERS
M. Pioche1,2,*, V. Lepilliez3,4, P. Deprez5, M. Giovannini6, F. Caillol6,
H. Piessevaux7, J. Rivory4, O. Guillaud4, M. Ciocirlan8, D. Salmon9,
I. Lienhart4, C. Lafon2, J.-C. Saurin4, T. Ponchon4
1
Gastroenterology and endoscopy, Edouard Herriot Hospital, 2Inserm U1032,
3
Gastroenterology and endoscopy, Hopital Prive Jean Mermoz, 4Gastroenterology
and endoscopy, Hopital Edouard Herriot, Lyon, France, 5Gastroenterology and
endoscopy, Hopital Saint-Luc, Louvain, Belgium, 6Gastroenterology and endo-
scopy, Institut Paoli Calmette, Marseille, France, 7Gastroenterology and endo-
scopy, Hopital Saint Luc, Louvain, Belgium, 8Carol Davila institute, Bucharest,
Romania, 9Pharmacy, Hopital Edouard Herriot, Lyon, France
Contact E-mail Address: mathieupioche@free.fr
INTRODUCTION: Long lasting lifting is a key factor during ESD and can be
obtained by water-jet injection of saline solution or by injection of viscous
macromolecular solutions. In a previous animal study, we assessed the ability
of the Nestis Enki II system to combine jet injection and macromolecular viscous
solutions. In the present work, we used this combination in humans in the dif-
ferent sites of the digestive tract.
AIMS & METHODS: To assess the effectiveness and safety of Nestis system
using viscous solutions. We report retrospectively all the consecutive cases of
ESD procedures made with Nestis Enki II system with injection of viscous solu-
tions. Information was collected about: the lesion (site, histology), the procedure
(time, perforations, bleedings, monobloc or piece meal resection), the piece (size,
R0, Rx or R1 resection) and the outcomes for the patient (curative treatment,
surgery, recurrence, delayed complications).
RESULTS: 45 resections were complete macroscopically. Procedures were per-
formed by 6 operators: 5 experts and one beginner with only one previous
experience in human ESD (11). The lesions were: 22 lateral spreading tumors
of the rectum 11 gastric lesions, 10 esophageal lesions, 1 of the right colon and 1
of the second duodenum. The average maximal lesion diameter was 4.8 cm (SD
2.4, range 2-11 cm), the average surface was 19.8 cm2 (SD 17.7, range 2.2-72
cm2) and the average time of procedure was 79.9 min (SD /- 50.3, range 19-225
min). Three adverse events occurred with two diminutive perforations (and two
delayed bleedings treated conservatively. R0 resection rate was 91.1%.
Obstruction of the catheter occurred in 6 cases in bloody situations.
CONCLUSION: This is the first multicenter report on a new water jet system
allowing injection of viscous solutions. This system is safe and effective and
allows working in retroflexed position with different viscous solutions.
Disclosure of Interest: M. Pioche Financial support for research from: Nestis, V.
Lepilliez: None declared, P. Deprez: None declared, M. Giovannini: None
declared, F. Caillol: None declared, H. Piessevaux: None declared, J. Rivory:
None declared, O. Guillaud: None declared, M. Ciocirlan: None declared, D.
Salmon: None declared, I. Lienhart: None declared, C. Lafon: None declared, J.-
C. Saurin: None declared, T. Ponchon: None declared
A337
P0747 OPTIMISATION OF ENDOSCOPIC FOLLOW-UP WAITING
LISTS IN A NEW ZEALAND DISTRICT HEALTH BOARD
N. Bhala1,*, H. Myint1, J. Lewis1, C. Virtue1, A. Simpson1, R. Cameron1
1
Department of Gastroenterology, Capital & Coast District Health Board,
Wellington Hospital, New Zealand
Contact E-mail Address: neeraj.bhala@ccdhb.org.nz
INTRODUCTION: New Zealand (NZ) has the one of the highest bowel cancer
death rates in the Western world, so prompt access to lower GI endoscopy for
new referrals is of importance in diagnosis, treatment and prevention. However,
partly as a result of follow-up colonoscopy demands, waiting lists have increased
substantially, and so the NZ Ministry of Health has funded initatives to ensure
appropriate clinical investiagtions are being done for the right indication at the
right time.
AIMS & METHODS: We sought to evaluate an optimisation exercise of follow-
up lower GI endoscopy lists in a single District Health Board covering a popula-
tion of around 300.000 people in the lower North Island of North New Zealand.
Evidence-based criteria were agreed by the endoscopy user multi-disciplinary
group for recall criteria for repeat colonoscopy for a number of conditions,
including: colorectal cancer resections; colorectal adenoma follow-up; family
history of colorectal cancer; and inflammatory bowel disease surveillance.
These were then applied to those patients on the waiting list for repeat endo-
scopic appearances in 2014 by a single consultant gastroenterologist.
RESULTS: Of 511 patients on the waiting list, 497% were for repeat colonos-
and were cancelled. Within 2 months of this exercise, only four primary care
practitioners (2.5%) sent queries regarding cancellation, which were dealt with.
183 (35.8%) did meet the criteria, but were not being done at the appropriate
time interval, so were deferred (range 6 months - 3 years). 165 (32.3%) did meet
the indication for repeat procedure in the appropriate time interval, and were
approved and duly listed.
CONCLUSION: Initiatives to apply evidence-based criteria for repeat endo-
scopic procedures can improve quality, productivity and prevent unnecessary
procedures. In this real-life application in NZ, a third of repeat endoscopy work-
load were removed from waiting lists, and more than an additional third were
deferred to a clinically appropriate time, allowing new referrals to be seen sooner.
Centrally funded initiatives to apply evidence-based guidelines to help manage
waiting lists may be relevant to other populations.
Disclosure of Interest: None declared
P0748 PICOSALAX PROVIDES SUPERIOR BOWEL CLEANSING TO
TRADITIONAL POLYETHYLENE GLYCOL IN THE ELDERLY
POPULATION
R. Gingold-Belfer1,*, A. Geller1, A. Vilkin1, Y. kelner1, Y. Niv1, Z. Levi1
1
Gastroenterology Department, Rabin Medical Center, Petah Tikva, Israel
Contact E-mail Address: rachelgingoldbelfer@gmail.com
INTRODUCTION: Lately, life expectancy was prolonged. Therefore, endo-
scopic procedures are performed in an elderly population too. The level of
bowel cleansing during colonoscopy is one of the quality indicators that were
determined in order to improve the procedures efficacy. An elder age is one of
the factors for poor preparation.
AIMS & METHODS: Aims: We aimed to evaluate the level of bowel cleansing
of the elderly population, by assessing the bowel preparation with Picosalax as
compared to polyethylene glycol (PEG).
Methods: Included 6,844 patients aged 75y (mean 81.1y4.6) who underwent
colonoscopy at our endoscopy unit during 2003-2013. 3,659 (53.5%) patients
were men. 1,258 patients had preparation with Picosalax and 5,444 with PEG.
The quality of bowel cleansing was assessed according to the Aronchick scale.
Multivariable logistic regression analysis for good preparation were used and
included: the patients age, gender and bowel preparation type.
RESULTS: Total, good preparation was achieved in 1,024 (79.8%) patients who
used Picosalax as compared to 3,528 (63.4%) with PEG (p50.001). Fair pre-
paration was achieved in 183 (14.5%) patients by Picosalax as compared to 1,322
(24.3%) by PEG. Bad and poor preparations were reported in 44 (3.5%) and 7
(0.6%) patients who used Picosalax as compared to 544(10%) and 50 (0.9%),
respectively. By using multivariable logistic regression analysis, good prepara-
tion, was significantly associated with female gender [OR: 1.38 95% confidence
interval (CI) 1.24-1.52, p50.001] and Picosalax preparation [OR: 2.15 95% CI
1.85-2.5, p50.001, PEG- ref]. An increased age, was negatively associated with
good preparation [OR: 0.9595% CI 0.97-0.99, p 0.009].
CONCLUSION: Female gender is significantly associated with good preparation
in patients aged 75y. The usage of Picosalax was associated with a 2.15 odds
ratio for predicting good bowel preparation. Despite lack of conventional guide-
lines of bowel preparations regimens for the elderly population, the usage of
Picosalax is indicated as an effective preparation for this age group, too.
REFERENCES
1. Jang JY and Chan HJ. Bowel preparations as quality indicators for colono-
scopy. World J Gastroenterol 2014; 20: 2746-2750.
2. Romero VR and Mahadeva S. Factors influencing quality of bowel prepara-
tion for colonoscopy. World J Gastroenterol 2013; 5(2): 39-46.
Disclosure of Interest: None declared
A338
P0749 MULTIPURPOSE USE OF THE OVER-THE-SCOPE-CLIP
SYSTEM: SWISS EXPERIENCE IN A TERTIARY CENTER
M.C. Sulz1, R. Bertolini1, R. Frei1,*, G.-M. Semadeni1, C. Meyenberger1
1
Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen,
Switzerland
Contact E-mail Address: michael.sulz@kssg.ch
INTRODUCTION: The Over-the-scope-clip (OTSC) system (Ovesco Endoscopy
AG, Tubingen, Germany) is a fairly new endoscopic device suitable to close
gastrointestinal (GI) perforations, post-surgical fistulae or to resect submucosal
tumors. It can also be used as hemostatic tool in GI bleeding and for esophageal
stent fixation. To the best of our knowledge, in literature there are only case
reports or small case series regarding the efficacy and safety, so far human
clinical randomized controlled trials are not available. The available case series
and reports are inhomogeneous concerning indication, study design, site of appli-
cation and definition of success.
We present a prospective case series reflecting our all-day clinical experience with
OTSC in a tertiary endoscopy center in Switzerland. This case series illustrates
the primary successful closure in over 80% of GI lesions, mainly fistulae or
anastomotic leakages and adds data to the increasing experience with this tool.
AIMS & METHODS: Aim: To evaluate the outcome of the over-the-scope-clip
system (OTSC) regarding various indications in all-day clinical practice in
Switzerland.
Methods: This is a prospective, consecutive case series conducted at a hospital
with tertiary care endoscopy from September 2010 until January 2014.
Indications were fistulae, anastomotic leakages, perforations, deroofed submu-
cosal lesions for biopsy, refractory bleeding and stent fixation in the gastroin-
testinal (GI) tract. Primary technical success was defined as an adequate
deployment of the OTSC on the target lesion. Clinical success was defined as
resolution of the problem, for instance no need for surgery or further endoscopic
intervention. In case of recurrence retreatment of a lesion with a second inter-
vention was possible. Complications were classified into those related to seda-
tion, endoscopy or deployment of the clip.
RESULTS: A total of 28 OTSC system applications were carried out in 21
patients (median age 64 years [range 42-85], 33% females). Main indications
were fistulae (52%), most of them after percutaneous endoscopic gastrostomy
(PEG) tube removal and anastomotic leakage after GI surgery (29%). Further
indications were unroofed submucosal lesions after biopsy, upper gastrointestinal
bleeding or esophageal stent fixation. 48% of the OTSC were applied in the
upper and 52% in the lower GI tract. The range of lesion size was 2-20 mm
(mean 8 mm). Primary technical success and clinical success were achieved in
85% and 67%, respectively. In 53% of cases the suction method was used with-
out accessories like Twin grasper or Tissue anchor. No endoscopy-related or
OTSC-related complications were described.
CONCLUSION: OTSC is a useful tool for endoscopic closure of various GI
lesions like fistulae or leakages. Future randomized prospective multicenter trials
are needed.
Disclosure of Interest: None declared
P0750 INVESTIGATING THE INVESTIGATION - INCIDENTAL
COLONIC HOTSPOTS ON PET-CT SCANS
R. Sinha1,*, W.S. Ngu2, A. Ramadas1, A. Reddy2, R. Anandavelu1, D. Aitken2,
M. Jha2
1
Gastroenterology, 2Colorectal surgery, South Tees NHS Foundation Trust,
Middlesbrough, United Kingdom
Contact E-mail Address: rohits78@gmail.com
INTRODUCTION: Positron emission tomography (PET) measures metabolic
changes at a cellular level enabling detection of early stage disease. Incidental
2-deoxy-[18FF]fluoro-2-D-glucose (FDG) colonic uptake is detected in 1.3-3% of
patients with up to a third resulting in false positive results 1. Follow-up endo-
scopy is recommended to further distinguish these FDG avid lesions 2. Cancer
detection rates of 7.8-18.9% have been quoted in various studies 1,3
AIMS & METHODS: Our aim was to evaluate incidental colonic FDG avid
lesions on PET-CT by endoscopy.
An analysis of retrospectively collected database of all patients (n 1564) who
had PET-CT for extra-colonic malignancy between January 2011 to September
2013 was performed.
RESULTS: Fifty-nine (3.77%) patients had focal colonic FDG uptake and 44
(2.87%) patients went on to have colonoscopy.
Indications for PET CT for those undergoing endoscopy was lung carcinoma
(22), oesophageal carcinoma (5), gastric carcinoma (3), head and neck carcinoma
(7), lymphoma (6) and unknown primary (1).
Median age was 68 with a male preponderance (2.4:1).
Location on PET CT was categorized to sigmoid (22), rectal (9), anorectal (4),
caecal (3), hepatic flexure (2), transverse (1), splenic flexure (1), ascending (1) and
descending (1).
Findings on endoscopy ranged from polyps (21), normal (9), diverticulosis (8),
sigmoid cancer (4), caecal cancer (1) and colitis (1).
In total, out of the all patients who had endoscopy, 19 (43.2%) were found to
have low-grade tubullovillous adenomas, 5 (11.1%) had cancer, whilst 2 (4.4%)
had hyperplastic polyps on histology.
CONCLUSION: These findings are in keeping with other series and suggests to
carry on with current practice of following up these "hot-spots" with endoscopic
investigations.
REFERENCES
1. Israel O, Yefremov N, Bar-Shalom R, et al. PET/CT detection of unexpected
gastrointestinal foci of 18F-FDG uptake: incidence, localization patterns, and
clinical significance. J Nucl Med 2005; 46: 758762.
United European Gastroenterology Journal 2(5S)
2. Tatlidil R, Jadvar H, Bading JR, et al. Incidental colonic fluorodeoxyglucose
uptake: correlation with colonoscopic and histopathologic findings. Radiology
2002; 224: 783787.
3. Putora PM, Muller J, Borovicka J, et al. Relevance of incidental colorectal
FDG-PET/CT-enhanced lesions. Onkologie 2013; 36: 200-204.
Disclosure of Interest: None declared
P0751 VARIATIONS IN ADENOMA DETECTION RATES IN THE
ENGLISH FLEXIBLE SIGMOIDOSCOPY SCREENING
PROGRAMME
R. Bevan1,2,*, C. Nickerson3, R. Blanks4, J. Patnick3, R. Loke5, B. Saunders6,
J. Stebbing7, R. Tighe8, A. Veitch9, J. Painter1, C. Rees1,2
1
South of Tyne Bowel Cancer Screening Centre (BCSC), Gateshead, 2Northern
Region Endoscopy Group, Newcastle, 3NHS Cancer Screening Programmes,
Sheffield, 4Cancer Epidemiology Unit, Oxford, 5West Kent & Medway BCSC,
Tunbridge Wells, 6St Marks BCSC, London, 7Surrey BCSC, Guilford, 8Norwich
BCSC, Norwich, 9Wolverhampton BCSC, Wolverhampton, United Kingdom
Contact E-mail Address: roisinbevan@hotmail.com
INTRODUCTION: The English Bowel Cancer Screening Programme has been
expanded to include a one-off flexible sigmoidoscopy offered to all 55 year olds,
called BowelScope Screening. Screening commenced in May 2013, with 6 pilot
sites performing flexible sigmoidoscopies in the first 8 months of screening.
AIMS & METHODS: We aim to describe ADR in BowelScope Screening. The
NHS Bowel Cancer Screening System database was interrogated and ADRs
reviewed for each screening centre and screening endoscopist. ADR was reviewed
graphically, with a funnel plot, constructed using the log odds method.
RESULTS: 49 endoscopists have performed 4444 sigmoidoscopies at 6 screening
centres. Endoscopists had performed 2-330 procedures (median 66, mean 91). 29
endoscopists had performed 50 procedures; of these, 17 had performed 100
procedures.
Centre 2 has a higher ADR than the other centres. When considering all proce-
dures, this difference reaches statistical significance when compared to centres 3,
5, and 6 (p50.05), and approaches significance when compared to centre 1
(p 0.0687) and centre 4 (p 0.0548). When considering only the procedures
done by endoscopists who have performed 50 or 100 sigmoidoscopies, there
remains a significant difference (p50.05) between centre 2 compared to centres 5
and 6, but not to the other centres. A funnel plot of individual endoscopist ADRs
demonstrates one endoscopist below the 99.8% control limit.
Overall BowelScope ADR is 8.6%. ADR by centre is shown in Table 1.
Table 1 - ADR by centre and endoscopist volume
All Centres
Centre 1 Centre 2 Centre 3 Centre 4 Centre 5 Centre 6
Endoscopist
procedure ADR ADR ADR ADR ADR ADR ADR ADR
counts % % % % % % % range %
All 8.8 11.7 8.9 7.6 6.5 7.3 8.6 0.0-60.0
50 8.9 11.3 8.1 8.6 6.4 6.4 8.6 3.1-14.0
100 9.0 11.3 8.9 8.6 3.1 5.2 8.7 3.1-13.0
CONCLUSION: Adenoma detection rates within BowelScope screening show
variation between centres. There is also variation between endoscopists in terms
of individual ADRs, although all but 1 endoscopist are above the 99.8% lower
control level on funnel plot. These variations require further exploration at both
centre and individual level, and feedback and education methods will be used to
improve ADRs.
Disclosure of Interest: None declared
P0752 FLEXIBLE SIGMOIDOSCOPY SCREENING IN THE ENGLISH
BOWEL CANCER SCREENING PROGRAMME - EARLY RESULTS
FROM THE BOWELSCOPE PILOT SITES
R. Bevan1,2,*, C. Nickerson3, J. Patnick3, R. Loke4, B. Saunders5, J. Stebbing6,
R. Tighe7, A. Veitch8, J. Painter1, C. Rees1,2
1
South of Tyne Bowel Cancer Screening Centre, Gateshead, 2Northern Region
Endoscopy Group, Newcastle, 3NHS Cancer Screening Programmes, Sheffield,
4
West Kent & Medway Bowel Cancer Screening Centre, Tunbridge Wells, 5St
Marks Bowel Cancer Screening Centre, London, 6Surrey Bowel Cancer Screening
Centre, Guilford, 7Norwich Bowel Cancer Screening Centre, Norwich,
8
Wolverhampton Bowel Cancer Screening Centre, Wolverhampton, United
Kingdom
Contact E-mail Address: roisinbevan@hotmail.com
INTRODUCTION: UK population colorectal cancer (CRC) screening has been
successfully implemented with Bowel Cancer Screening Programme (BCSP)
faecal occult blood testing biannually from age 60-75.
A large UK study of once-only flexible sigmoidoscopy (FSIG) demonstrated a
reductions in CRC incidence of 33% & death rates of 43%1. This, with the
screening centre infrastructure developed for the FOB programme, allowed pro-
vision of a new arm of BCSP, offering FSIG to 55 year olds in England, known
as BowelScope screening.
BowelScope screening began May 2013, with 6 pilot sites performing FSIGs in
the first 7 months.
AIMS & METHODS: We aim to describe procedural data from the early
months of BowelScope screening. Data were obtained from The Bowel Cancer
Screening System (BCSS) database for all participants invited and participating
in BowelScope FSIGs May-Dec 2013. Procedural data were recorded, including
United European Gastroenterology Journal 2(5S) A339
insertion depth, adenoma detection rates (ADR), cancer detection, discomfort
P0754 PATIENTS EXPERIENCE OF COLONOSCOPY IN THE ENGLISH
levels, entonox usage & colonoscopy conversion rates.
BOWEL CANCER SCREENING PROGRAMME
RESULTS: 13927 people have been invited to or opted into BowelScope screen-
ing at 6 screening centres. Overall uptake is 43.5% (range 37.0-51.9%). 4 cancers A. Ghanouni1, A. Plumb2, C. Rees3,4, P. Hewitson5, H. Miller3, R. Bevan3,6,*,
have been detected. Polyps were detected in 16.4-23.8% of procedures (mean C.Von Wagner1
1
20.7%). Mean ADR was 8.4%. One centre has a significantly higher ADR Epidemiology and Public Health, 2Centre for Medical Imaging, UCL, London,
3
than the other 5 sites (p50.05). (see Table 1). South of Tyne Bowel Cancer Screening Centre, Gateshead, 4School of Medicine,
Table 1 BowelScope outcomes by anonymised centre Pharmacy and Health, Durham University, Stockton on Tees, 5Nuffield
Department of Population Health, University of Oxford, Oxford, 6Northern Region
Screening Attended B/S with ADR Colonoscopy Entonox Endoscopy Group, Newcastle, United Kingdom
Centre Invitees (%) adenoma(s) % Cancer required (%) used
INTRODUCTION: In the English Bowel Cancer Screening Programme, colono-
1 3125 1128 (51.9) 100 8.9% 1 39 (3.5) 121 scopy is the standard investigation to exclude cancer in participants who receive a
2 1866 524 (37.0) 64 12.1% 0 23 (4.4) 94 positive faecal occult blood test result. A questionnaire is sent to all patients 30
3 3779 1070 (40.9) 90 8.4% 0 50 (4.7) 60 days post-test. These data were used to assess patients experience of
4 986 311 (46.6) 25 8.0% 0 12 (3.9) 15 colonoscopy.
AIMS & METHODS: Anonymised data were extracted from the Bowel Cancer
5 1970 625 (47.4) 38 6.1% 2 21 (3.4) 28
Screening System. These included all patients who had colonoscopy between 01/
6 2181 479 (37.2) 30 6.2% 1 18 (3.8) 25
01/11 and 31/12/12. Questionnaire items on the pre-test experience (whether
TOTAL 13927 4135 347 8.4% 4 163 (3.9) 343 patients understood the risks/benefits), the hospital experience (the test itself,
issues of dignity/privacy) and post-test complications (bleeding/pain) were ana-
lysed. Pearson chi-square tests were used to compare experiences by gender, high
Most (52.7%) procedures were completed in 6-10 minutes. 78.6% of procedures vs. low levels of socioeconomic deprivation (using Index of Multiple Deprivation
were reported as causing no or minimal pain only, with only 34 procedures scores), and whether patients reported receiving sedation or not.
(0.8%) reporting severe pain. RESULTS: After excluding patients outside the target date range and those who
CONCLUSION: Uptake has varied between centres, but is lower than for the did not have colonoscopy, 76,717 patients were eligible for analysis, of whom
FOB arm of the BCSP. The average ADR is 8.4% (range 6.1-12.1%), lower than 60,581 (79.0%) responded to the questionnaire. Nearly all patients felt they
in the UK flexible sigmoidoscopy screening trial (12.1%, range 8.6-15.9%1) understood the risks (95.7%) and benefits (98.2%) of the test, and 97.8% felt
although the age range studied in the trial differs from this cohort. the preparation instructions were clear. Comparison by gender and deprivation
Further work will be required to investigate the variation in uptake rates and to did not yield clinically meaningful (3%) differences. In terms of the hospital
improve these rates. ADR variations may also need to be addressed in future experience, virtually all patients felt they were treated with respect (98.5%) and
work. had privacy (98.0%), but 20.8% experienced more discomfort than expected
REFERENCES (although only 5.2% asked for the test to be stopped/paused). Procedural dis-
1. Atkin W, et al. Once-only flexible sigmoidoscopy screening in prevention of comfort was moderated by gender, with more women than men reporting higher-
colorectal cancer: a multicentre randomised controlled trial. Lancet 2010; 375: than-expected discomfort (25.4% vs. 17.9%; p5.0005), and requesting that the
1624-1633. test be stopped/paused (7.1% vs. 3.9%; p5.0005). Use of sedation showed only a
Disclosure of Interest: None declared weak association with patient experience: 22.2% of sedated vs. 20.2% of non-
sedated patients reported unexpected discomfort; 6.4% vs. 4.8% asked for the
test to be stopped/paused; both p-values 5.0005). Post-test, 14.3% of patients
P0753 PATIENT-REPORTED EXPERIENCE OF COMFORT AND reported pain and 6.9% reported rectal bleeding. Pain was more common in
DIGNITY IN FLEXIBLE SIGMOIDOSCOPY: DATA FROM THE NHS women (18.0% vs. 11.9%; p5.0005) but there were no other clinically mean-
BOWEL SCOPE SCREENING PILOT ingful differences post-test related to gender or deprivation level.
C.Von Wagner1, H. Bowyer1, R. Bevan2,3,*, C. Rees3,4, W. Atkin5, J. Wardle1 CONCLUSION: Most patients referred for colonoscopy as part of the Bowel
1
Epidemiology and Public Health, UCL, London, 2Northern Region Endoscopy Cancer Screening Programme have a positive colonoscopy experience. The most
Group, Newcastle, 3South of Tyne Bowel Cancer Screening Centre, Gateshead, negative aspect of the experience was the test being unexpectedly uncomfortable.
4
School of Pharmacy and Health, Durham University, Stockton on Tees, Patients are extensively counselled pre-procedure but more emphasis on mana-
5
Department of Surgery and Cancer, Imperial College, London, United Kingdom ging expectations, along with continued measures to reduce discomfort and pain
are required, particularly for women.
INTRODUCTION: The NHS Bowel Cancer Screening Programme started flex- Disclosure of Interest: None declared
ible sigmoidoscopy (FS) screening (also known as Bowel Scope Screening, BSS)
at six centres across England (Gateshead, Guildford, London, Medway,
Norwich, Wolverhampton) in March 2013. The aim of this analysis was to P0755 ENDOSCOPIC RESECTION OF GIANT COLONIC POLYPS
investigate the extent to which high levels of patient satisfaction recorded in SIZE MATTERS!
previous UK trials can be replicated in the early stages of a routine screening R. Bhattacharyya1,*, G. Longcroft-Wheaton1, P. Bhandari1 on behalf of
programme. Portsmouth, UK
AIMS & METHODS: We used data from an ongoing study monitoring patient- 1
Gastroenterology, Portsmouth Hospitals NHS Trust, Portsmouth, United
reported experience in the pilot phase of the BSS Programme. We report data Kingdom
from the post-AM questionnaire which is given to patients at the end of their FS
appointment and supposed to be completed on the following day. INTRODUCTION: Colonic polyps sized 50mm and above are traditionally
RESULTS: As of January 2014, we had received 2,324 questionnaires. treated by surgical resection. Endoscopic resection has now become increasingly
Satisfaction with the test was high with 98.8% of patients being either satisfied common as the expertise of western endoscopists improves. There is very little
(21.1%) or very satisfied (77.7%). Nonetheless, 43% of patients reported mod- published literature on endoscopic resection of these giant polyps.
erate (34%) or severe pain (9%) which was high compared with the St Marks AIMS & METHODS: The aim of the study was to evaluate the feasibility, safety
demonstration programme1 and the UK Flexible Sigmoidoscopy Trial2. Women and efficacy of endoscopic resection of giant polyps 50mm in size.
were three times as likely to report severe pain during the test than men (14.3% vs This was a prospective cohort study. All patients who underwent endoscopic
4.6%), and twice as likely to find the test as more painful than they had expected resection of colonic polyps 50mm from 2007-2013 were prospectively entered
(39.9% vs 20.1% respectively). Only about 1 in 10 patients reported being mod- into a database. We excluded all polyps with fibrosis related to previous inter-
erately (9.8%) or severely (1.4%) embarrassed during the test, with women being vention. All patients were tertiary referrals from experienced gastroenterologists.
slightly more likely than men to fall into these categories (13.4 vs. 8.9%). Women All procedures were performed by a single experienced endoscopist.
also had a much stronger preference for the test to be carried out by a female RESULTS: N 124 polyps in 122 patients. Mean polyp size 71mm. Range 50-
practitioner than men (41.2% vs 7.1% respectively). 170mm. 27(22%) in right colon and 97 (78%) in left colon. M:F ratio 1.1:1. All
CONCLUSION: The vast majority of patients were satisfied with their experi- polyps were resected in a piecemeal fashion. The mean procedure time was 120
ence of FS screening. However, levels of pain appear high when compared with minutes (range 90 to 240).
previous trials. Emphasis should be placed on ensuring that patients have as The complication rate was 11/124(8.9%). All these patients required inpatient
comfortable a procedure as possible. Additional consideration should be given stay. There were 9 bleeds (3 immediate and 6 delayed), 1 post polypectomy
to women being able to choose the sex of the practitioner performing the test. syndrome and 1 case of split muscle fibres (clipped endoscopically). 1 case of
REFERENCES immediate bleeding required surgery to control the bleeding. All the others were
1 Robb K, Lo S, Power E, et al. Patient-reported outcomes following flexible managed conservatively. 4 of the 9 bleeds required blood transfusion. The com-
sigmoidoscopy screening for colorectal cancer in a demonstration screening pro- plication rate was independent of polyp size, resection technique or site of the
gramme in the UK. J Med Screen 2012; 19: 171-176. lesion.
2 Taylor T, Williamson S, Wardle J, et al Acceptability of flexible sigmoidoscopy Follow up data was available for 90 polyps. The recurrence rate was 21/
screening in older adults in the United Kingdom. J Med Screen 2000; 7: 38-45. 90(23.3%). Of the 21 recurrences, 16/21(76%) patients achieved complete clear-
Disclosure of Interest: None declared ance with a further 1 to 2 endoscopic procedures. The recurrence rate was sig-
nificantly dependent on polyp size and was not dependent on the resection
technique or the site of the lesion. Recurrence gradually increased with an
increase in polyp size up to 70mm. Recurrence was seen in 3/34(8.8%) polyps
55mm, in 7/54(12.9%) polyps 60mm and in 9/63(14.2%) polyps 70mm.
However, in polyps 470mm, the recurrence rate greatly increased to 12/
27(44%) (p 0.002).
A340
Size
Recurrence 55mm 60mm 70mm 470mm
21/90 (23.3%) 3/34 (8.8%) 7/54 (12.9%) 9/63 (14.2%) 12/27 (44.4%)
p 0.002
CONCLUSION: 1) It is safe and feasible to endoscopically resect polyps 50-
170mm in size.
2) Recurrence is significantly dependent on polyp size.
3) Giant polyps resected endoscopically have a significant recurrence rate. The
majority of these can be cleared by further endoscopic procedures. However, we
believe that the recurrence rate in polyps above 70mm is very high and surgery
should be considered in these cases.
4) Complication rates are independent of size.
Disclosure of Interest: None declared
P0756 ADVISABILITY OF COLORECTAL ENDOSCOPIC
SUBMUCOSAL DISSECTION IN ELDERLY: TREATMENT AND
LONG-TERM OUTCOMES
R. Kobayashi1,*, K. HIRASAWA1, H. KANEKO1, M. MAKAZU1, C. SATO1,
A. KOKAWA1, S. MAEDA2
1
Division of Endoscopy, Yokohama City University Medical Center, 2Department
of gastroenterology, Yokohama City University Graduate School of Medicine,
Yokohama city, Japan
Contact E-mail Address: ryo_1001@yokohama-cu.ac.jp
INTRODUCTION: Endoscopic submucosal dissection (ESD) is becoming wide-
spread as a treatment of superficial colorectal neoplasm; however, the efficacy
and safety of colorectal ESD in elderly patients has not been fully evaluated.
AIMS & METHODS: In the present study, we assessed the treatment and long-
term outcomes of colorectal ESD in elderly patients.
Between April 2008 and March 2014, 285 consecutive superficial colorectal
tumors in 267 patients were treated using ESD. Patients were divided into two
groups; elderly (75 years of age or older) and non-elderly (less than 75 years of
age), then were retrospectively compared to patient and tumor characteristics
and treatment outcome.
Long-term outcomes in elderly patients were also evaluated.
RESULTS: The elderly group comprised 93 lesions in 83 patients and non-
elderly group comprised 192 lesions in 184 patients.
No significant differences were observed between the two groups with respect to
patient and tumor characteristics as the following factors: sex, tumor location,
tumor depth, tumor size, tumor morphology.
In all patients, the rates of en bloc resection, R0 resection and curative resection
were 98.9% (282/285), 90.2% (257/285) and 82.5% (235/285) respectively. Mean
procedure time was 67.2 minutes (range 10-273 minutes), the rate of delayed
bleeding was 3.9% (11/285) and the rate of perforation was 9.5% (27/285).
There were no significant differences between the two groups in the rates of en
bloc resection, R0 resection, curative resection, delayed bleeding, perforation,
and procedure time.
In 83 elderly patients, during a median follow-up period of 20.2 months (range
1.4-63 months), 6 patients were excluded from the long-term prognosis analysis
because of missing follow-up. Four of 16 patients who judged as non-curative
resection underwent additional surgery, and the others requested only observa-
tion. Two of 77 patients (2.6%) died of infection of unknown cause (n 1) and
heart failure (n 1). The 3- and 5-year overall survival rates were 96.4% and
87.7%, respectively. However, we did not observe local or distant recurrences in
any of the patients were followed up. Therefore, the 3- and 5-year disease-specific
survival rates were 100%.
CONCLUSION: Because there was no significant difference in treatment out-
come between in elderly and non-elderly group, colorectal ESD could be used as
a treatment choice for superficial colorectal tumors in elderly patients. However,
many of the elderly non-curative cases were observed without additional surgical
treatment, implying that such patients are necessary for careful follow-up by
computed tomography (CT) or measuring tumor markers.
Disclosure of Interest: None declared
P0757 A COMPARATIVE STUDY OF TWO DIFFERENT SNARES FOR
THE COMPLETENESS OF POLYP EXCISION
S. Din1,*, A. Ball1, S. Riley1, P. Kitsanta2, S. Johal1
1
Gastroenterology, 2Histopathology, Sheffield Teaching Hospitals NHS
Foundation Trust, Sheffield, United Kingdom
INTRODUCTION: Polypectomy with cold snare is a frequently used technique
for the removal of small colorectal polyps. The influence of snare type on com-
pleteness of excision is unknown. We have therefore compared the effectiveness
of two different snares.
AIMS & METHODS: Patients attending for colonoscopy at Sheffield Teaching
Hospitals, England were prospectively included in the study. We assessed the
endoscopic and histological completeness of excision following cold snare of 3-
7mm polyps using the Exacto mini-snare (diameter 0.30mm) and Olympus mini-
snare (diameter 0.47mm). Prior to the study, consensus regarding the endoscopic
completeness of excision was standardised to complete, incomplete or uncertain
using the Delphi method. Completeness of excision was aided by chromoendo-
scopy (indigo carmine 0.1%). The primary outcome was endoscopic complete-
ness of excision. Secondary outcome measures included: completeness of
United European Gastroenterology Journal 2(5S)
histologic excision, polyp fly away, retrieval rate, early bleeding (48 hours),
delayed bleeding (2 weeks) and perforation.
RESULTS: A total of 157 polyps were removed. Median (range) polyp size was
4.0mm (3-7mm). There was no significant difference in the patients demographic
details or polyp characteristics between the two groups. Endoscopic completeness
of excision was significantly higher with the Exacto snare compared to the
Olympus snare (90.2% vs. 73.3%, p 5 0.05). There was also a trend towards a
higher complete histological excision rate with the Exacto snare (71.9% vs. 64.4%),
but this did not reach statistical significance (p 0.4). Polyp fly away occurred
less often with the Exacto snare (14.6% vs. 35.3%, p50.05), but there was no
significant difference in the polyp retrieval rate (84.3% vs. 83.8%, p 0.9). There
were no significant complications with either snare. Where the completeness of
excision was assessable (complete or incomplete), there was a fair level of agree-
ment (kappa 0.36) between endoscopic and histological assessment.
CONCLUSION: This is the first study we are aware of that compares complete-
ness of excision with different snares. Our findings suggest that snare type may be
an important factor determining completeness of excision when removing small
polyps by the cold snare techniques.
Disclosure of Interest: None declared
P0758 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
MANAGEMENT OF PATIENTS WITH COLORECTAL LESIONS: A
CONSENSUS REPORT BASED ON CLINICAL EVIDENCE
S.K. Singh1,*, R. Arsenescu2, H. Bertani3, F. Caillol4, D. Carr-Locke5,
K. Chang6, A. Dlugosz7, J.-P. Galmiche8, S.-I. Gan9, K.Y. Ho10, V. Konda11,
H. Neumann12, F. Prat13, P. Sharma14, K. Wang15, A. Zfass16
1
Gastroenterology / Endoscopy, Boston University / VA Boston, Boston, MA, 2The
Ohio State University, Columbus, United States, 3Nuovo Ospedale Civile
SantAgostino Estense, Modena, Italy, 4CLCC Institut Paoli-Calmettes, Marseille,
France, 5Beth Israel Medical Center, New York, 6University of California Irvine
Medical Center, Orange, United States, 7Karolinska University Hospital
Huddinge, Stockholm, Sweden, 8CHU Nantes, Nantes, France, 9Virginia Mason
Medical Center, Seattle, United States, 10National University Hospital, Singapore,
Singapore, 11University of Chicago Medical Center, Chicago, United States,
12
Universitaetsklinikum Erlangen, Erlangen, Germany, 13Hopital Cochin, Paris,
France, 14VA Kansas City Medical Center, Kansas City, 15Mayo Clinic Rochester,
Rochester, 16VA Richmond Medical Center, Richmond, United States
Contact E-mail Address: singhsk@bu.edu
INTRODUCTION: Recent studies have highlighted the role of Confocal Laser
Endomicroscopy (CLE) for the characterization of colorectal lesions in vivo,
specifically for the real time characterization of polyps and endoscopic mucosal
resection (EMR) sites.
AIMS & METHODS: We sought to develop consensus recommendations for the
role of CLE in the management of patients with colorectal lesions. To this end, a
single CLE expert developed a series of preliminary statements on the use of CLE
for the characterization of colorectal lesions based on the available clinical evi-
dence. Twenty statements were submitted for external review by a group of 16
gastrointestinal CLE experts using a modified Delphi approach. After two
rounds of votes to assess the quality of evidence and strength of recommenda-
tions based on relevant studies, statements were adopted if the threshold of
agreement exceeded 75%.
RESULTS: 15 of 20 statements achieved consensus and were adopted: CLE has
been shown to be highly accurate for real-time histopathological classification of
colonic neoplasia in situ. CLE criteria can be used to accurately and reliably
identify normal, hyperplastic, adenomatous (dysplastic), and cancerous
mucosa; criteria for serrated neoplasia require further validation. CLE criteria
characterize colonic tissue accurately both in real time during endoscopy as well
as off-line. CLE can be used to define the extent of flat lesions. The combination
of CLE and virtual chromoendoscopy (VCE) is highly accurate for classifying
colonic polyps 55 mm both in real time and offline and should undergo further
study toward enabling a resect-and-discard approach. A diagnosis of intramu-
cosal carcinoma and/or high-grade dysplasia by CLE alone is sufficient to trigger
an appropriate therapeutic resection. CLE can be used to classify lesions and
define margins for EMR/ESD. CLE has a role in resurveillance 3-12 months
following EMR/ESD of advanced colonic neoplasia. Absence of residual neo-
plasia by CLE and VCE at 3-12 months obviates the need for re-EMR/ablation.
The extent of therapy for residual neoplasia post-EMR can be guided in real time
by the combination of CLE and VCE.
CONCLUSION: According to a panel of 16 gastrointestinal endoscopy experts
in Confocal Laser Endomicroscopy, CLE is an important adjunct to current
endoscopic practice for the management of colorectal lesions. Standardized
guidelines are in development to serve as an educational resource for physicians
to provide increasingly personalized, state-of-the-art care for their patients.
Disclosure of Interest: None declared
P0759 IMMEDIATE AND DELAYED BLEEDING AFTER ERCP:
RESULTS FROM SINGLE CENTRE EXPERIENCE AT A DISTRICT
GENERAL HOSPITAL IN JAPAN
H. Hisai1,*, T. Hirako1, Y. Ikeda1, S. Miura1, Y. Koshiba1, E. Miyazaki1
1
Department of Gastroenterology, Japanese Red Cross Date General Hospital,
Date, Japan
INTRODUCTION: Bleeding following endoscopic retrograde cholangiopan-
creatography (ERCP) including endoscopic sphincterotomy (ES) is one of the
most frequent complications, and has been reported in 1-10% of patients.
Haemorrhage that cannot be controlled by conservative management needs to
be controlled endoscopically, radiologically, or surgically. However, there are few
reports about the incidence and the outcomes at a district hospital.
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: The aim of this study was to assess the incidence of
ERCP-related haemorrhage and the clinical outcomes in the district general
hospital setting. A review of all patients undergoing ERCP at our institution
from April 1996 and March 2014 was performed to assess the ERCP-related
haemorrhage. ERCP-related haemorrhage was classified according to the
timing of bleeding. Immediate bleeding was defined as any haemorrhage
during ERCP and warranting endoscopic haemostasis within the procedure fol-
lowing epinephrine spray. A diagnosis and severity of delayed bleeding was made
according to Cottons classification (GIE 1991).
RESULTS: Out of 6002 ERCPs, we performed ES in 975 patients, needle knife
sphincterotomy (NKS) in 195 patients, NKS followed by ES in 22 patients,
endoscopic papillectomy in 12 patients and endoscopic large balloon dilatation
in 47 patients. No patients were taking anticoagulants at the time of ERCP.
During ERCP, 48 patients (0.80%) experienced immediate bleeding. All patients
underwent endoscopic haemostatic method including balloon tanponade, dilute
epinephrine (1:10000), heater probe, clipping, covered metallic stent and com-
bined hemostatic procedures. Initial haemostasis was achieved in all patients.
However, delayed bleeding occurred in 3 patients (6%). By definition, delayed
bleeding occurred in 26 patients (0.43%). There were 14, 5 and 7 cases of mild,
moderate and severe bleeding, respectively. The time period between ERCP and
haemorrhage ranged from 1 d to 14 d (median 4 d). The time to onset of delayed
bleeding was not significantly different between patients with or without immedi-
ate bleeding. Seventeen out of 26 (65%) were managed endoscopically with
various haemostatic methods including dilute epinephrine, heater probe, argon
plasma coagulation, clipping, fibrin glue, covered metallic stent and combined
procedures. Initial haemostasis was successfully attained in all patients. The re-
bleeding rate was 15% (4 of 26). The treatment for the 4 patients with re-bleeding
was as follows: 1 underwent 1 session, 1 underwent 2 sessions and 2 underwent 3
sessions of endoscopic combined procedures (2 patients required fibrin glue) and
the bleeding was finally controlled. No patients required angiographic embolisa-
tion and surgery. No complications of the hemostatic procedure occurred in any
patients. There was no bleeding-related death.
CONCLUSION: Early recognition and appropriate management of ERCP-
related haemorrhage is crucial for optimal results.
Disclosure of Interest: None declared
P0760 USEFULNESS OF CAP-ASSISTED ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH
DIFFICULT CANNULATION DUE TO PERIAMPULLARY
DIVERTICULUM
H. Yoon1,*, J.H. Cho1, H.M. Kim2, Y.J. Kim1, Y.S. Kim1
1
Internal Medicine, Gachon University Gil Medical Center, Incheon, 2Internal
Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea, Republic
Of
Contact E-mail Address: hwa9620@naver.com
INTRODUCTION: Successful biliary cannulation is an essential for therapeutic
retrograde cholangiopancreatography (ERCP). In special cases of difficult can-
nulation due to anatomy, diverticulum, lack of space or bulky papilla other
methods are needed. Various methods depending on the practices of the endos-
copist have been developed to overcome difficult cannulation.
AIMS & METHODS: We report a retrospective case series of patients with
difficult cannulation due to periampullary diverticulum and assess the utility
and safety of cap-assisted ERCP for biliary cannulation.
From November 2013 to March 2014, inclusion criteria were: (a) documented
periampullary diverticulum; and (b) use of cap-assisted ERCP as a rescue method
on the first endoscopic encounter after failed attempts to perform ERCP with a
standard side-viewing endoscope. Among 73 patients with periampullary diver-
ticulum, 5 consecutive patients (6.8%) underwent therapeutic ERCP using a cap-
fitted forward-viewing endoscope as a rescue method due to difficult biliary
cannulation.
RESULTS: There were three men and two women, with median age of 69 years
(range 5390 years). The indications for ERCP were bile duct stones (n 4) and
common bile duct stricture (n 1). All of the ampulla is located at 6 oclock. The
causes of difficult biliary cannulation were tangential approach in two patients and
hidden papilla in three patients. A selective biliary cannulation was achieved with
needle knife fistulotomy in four patients. The mean number of ERCP sessions was
1.8 per patient and the mean procedure time was thirty eight minutes. Therapeutic
ERCP was successfully performed in all patients. In four patients, the therapeutic
ERCP was completed with a cap-fitted forward-viewing endoscope. But in the only
one patient who had a pyloric stenosis with bulbar deformity due to duodenal ulcer
scar, CBD stones were successfully removed by percutaneous procedure combined
with rendezvous method although we performed endoscopic balloon dilation of
the stenosis. The one patient undergoing biopsy was pathologically confirmed to
carcinoma of ampulla of Vater. This patient was managed previously with biliary
stent insertion due to biliary stricture.
Two patients experienced complications; post-ERCP pancreatitis and hyperamy-
lasemia. But their complications were not clinically significant and self limitied.
CONCLUSION: As a rescue method, cap-assisted ERCP is effective and safe
technique in patients with difficult cannulation due to periampullary
diverticulum.
REFERENCES
1. Myung DS, Park CH, Koh HR, et al. Cap-assisted ERCP in patients with
difficult cannulation due to periampullary diverticulum. Endoscopy 2014; 46:
352355.
2. Park CH, Lee WS, Joo YE, et al. Cap-assisted ERCP in patients with a
Billroth II gastrectomy. Gastrointest Endosc 2007; 66: 612615.
3. Udd M, Kylanpaa L and Halttunen J. Management of difficult bile duct
cannulation in ERCP. World J Gastrointest Endosc 2010; 2: 97103.
Disclosure of Interest: None declared
A341
P0761 SEQUENTIAL PERFORMANCE OF DOUBLE GUIDEWIRE
TECHNIQUE AND TRANSPANCREATIC PRECUT
SPHINCTEROTOMY IN DIFFICULT BILIARY CANNULATION
J. Park 1,*, J.H. Chang1,2, C.W. Kim1, S.W. Han1
1
The Catholic University of Korea, Seoul, 2Internal Medicine, The Catholic
University of Korea, Bucheon, Korea, Republic Of
INTRODUCTION: Double guidewire technique (DTG) and transpancreatic
precut sphincterotomy (TPS) are alternative techniques in failed standard biliary
cannulation during endoscopic retrograde cholangiopancreatography (ERCP)
when a guidewire proceeds into the pancreatic duct. However, the sequential
performance of TPS after DTG has not been evaluated.
AIMS & METHODS: We aimed to investigate the usefulness and complications
of seqeuntial DTG-TPS in comparison with needle knife precut (NK). We con-
secutively enrolled 612 patients with na ve papilla undergoing ERCP for biliary
cannulation between March 2010 and April 2014. In cases of unsuccessful stan-
dard technique, DTG or NK was performed according to the guidewire passage
through the pancreatic duct. TPS was sequentially performed when DTG had
failed. Patients demographics, laboratory, and procedure-related data were ana-
lyzed retrospectively.
RESULTS: During 612 ERCPs, DTG and NK was attempted in 67 and 58
patients, respectively. Sequential DTG-TPS were performed in 38 patients.
Successful biliary cannulation was performed in 42%, 74%, and 66% of the
DTG, TPS, and NK group, respectively (P 0.002). The cannulation rate was
higher in the sequential DTG-TPS group (85%) than in the NK group
(P 0.014). Post-ERCP pancreatitis (PEP) occurred in 37% of the sequential
DTG-TPS group and in 10% of the NK group (P 0.002). In the sequential
DTG-TPS group, PEP developed in 24% patients with pancreatic duct (PD)
stent, but in 62% patients without PD stent (P 0.023). Among them, one
patient without PD stent expired due to severe pancreatitis.
CONCLUSION: The sequential DTG-TPS is a useful alternative technique for
biliary cannulation compared with NK in patients who have failed standard
technique. Their rate of PEP was higher than that in the NK group, but PD
stent had a protective role over PEP.
Disclosure of Interest: None declared
P0762 ENDOSCOPIC RETROGRADE
CHOLANGIOPANCREATOGRAPHY FOR SUSPECTED
CHOLEDOCHOLITHIASIS FROM GUIDELINES TO CLINICAL
PRACTICE
J. Magalhaes1,*, B. Rosa1, J. Cotter1,2
1
Gastroenterology Department, Centro Hospitalar do Alto Ave, Guimaraes, 2Life
and Health Sciences Research Institute (ICVS), School of Health Sciences,
University of Minho, Braga/Guimaraes, Portugal
Contact E-mail Address: joanaltmagalhaes@gmail.com
INTRODUCTION: Patients suspected of having choledocholithiasis are diag-
nosed with a combination of laboratory tests and/or imaging studies. The
American Society for Gastrointestinal Endoscopy (ASGE) proposes a stratifica-
tion of patients according to the risk for choledocholithiasis, influencing subse-
quent management.
AIMS & METHODS: The aim of this study was to assess the practical applic-
ability and to validate the current ASGE guidelines in our population. This was a
retrospective single center study, covering a 4-year period, from January 2010 to
December 2013. All patients who underwent endoscopic retrograde cholangio-
pancreatography (ERCP) for suspected choledocholithiasis were included. Based
on the presence or absence of predictors of choledocholithiasis (clinical ascending
cholangitis, common bile duct (CBD) stones on ultrasonography (US), total
bilirubin 44mg/dL, dilated CBD on US, total bilirubin 1,8-4mg/dL, abnormal
liver function test, age 455 years and gallstone pancreatitis), patients were stra-
tified in low, intermediate or high risk for choledocholithiasis. For each predictor
and risk group we used the Chi-square to evaluate the statistical associations with
the presence of choledocolithiasis at ERCP. Statistical analysis was performed
using SPSS version 21.0. A p value of less than 0.05 was considered statistically
significant.
RESULTS: A total of 268 ERCPs were performed for suspected choledocho-
lithiasis. Except for gallstone pancreatitis (p 0.063), all other predictors of
choledocholitiasis (clinical ascending cholangitis, p 0.001; CBD stones on
US, p50.001; total bilirubin 44mg/dL, p 0.035; total bilirubin 1,8-4mg/dL,
p 0.001; dilated CBD on US, p50.001; abnormal liver function test, p 0.012;
age 455 years, p 0.002) showed a statistically significant association with the
presence of choledocholithiasis at ERCP. Approximately four fifths of patients in
the high risk group (79.8%, 154/193) had confirmed choledocholithiasis on
ERCP, versus 34.2% (25/73) and 0 (0/2) in the intermediate and low risk
groups, respectively. The definition of high risk group had a sensitivity of
86%, positive predictive value 79,8% and specificity 56.2% for the presence of
choledocholithiasis at ERCP.
CONCLUSION: The use of clinical, analytical and imaging predictors, as well as
risk stratification according to ASGE guidelines, may improve risk estimation of
choledocholithiasis and should be considered to optimize patients selection for
ERCP. However, even in the high risk group the specificity was low (56.2%),
meaning that a significant proportion of patients (20%) will still perform ERCP
unnecessarily. Thus, at this point, it seems advisable that also high risk
patients undergo further testing before being submitted to ERCP, similarly to
those patients with intermediate risk, while for patients with low-risk of
choledocholithiasis a watchful waiting strategy seems adequate.
Disclosure of Interest: None declared
A342
P0763 THE EFFECT OF RECTAL KETOPROFEN IN THE PREVENTION
OF POST ERCP ACUTE PANCREATITIS
J. Amara1,*, C. Cellier 1, E. Samaha1, G. Rahmi1, M. Barret 1, J.M. Canard 1,
A. Vienne1, B. Hotayt2
1
Hopital Europeen Georges Pompidou, Paris, France, 2Belle Vue Medical Center,
Beyrouth, Lebanon
Contact E-mail Address: jph.amara@gmail.com
INTRODUCTION: Acute pancreatitis is the most common and the most fearful
complication of endoscopic retrograde cholangiopancreatography (ERCP). A
recently published meta-analysis reported that a single dose of indomethacin
or diclofenac (100 mg) administred rectally before or immediately after ERCP
decreases the incidence of post ERCP pancreatitis (PEP).
AIMS & METHODS: A retrospective single-center non randomized study was
conducted with 304 patients who underwent a primary ERCP. Patients were
divided into 2 groups. The patients in the first group had a single dose of keto-
profen 100mg administred rectally immediately after ERCP. The 2nd group was a
control group.
The aim of this study was to determine whether prophylactic rectal ketoprofen
will reduce the incidence of PEP and to determine the risk factors of this
complication.
RESULTS: Three hundred and four patients (M/F 197/107, Mean age 62.4
y.o) were included. 107 patients (35.2%) were in the first group. The groups were
similar with regard to patient demographics and to patient and procedure risk
factors for PEP. The overall incidence of PEP was 6.9%: 4.6% (5/107) in the
group 1 versus 8.1% (16/197) in the placebo group (p 0.34, IC 95%). The
pancreatitis was graded as severe in 33% of the patients. There was no significant
difference between the groups in the frequency or severity of PEP. Two risk
factors were associated with a higher incidence of PEP:a difficult cannulation
of the common bile duct (52.4 vs 16%, p 0.0004. IC 95%) and contrast
injection into the pancreatic duct (47.62 vs 24.38 %, p 0.008, IC 95%).
CONCLUSION: Prophylactic rectally administered ketoprofen (100mg) did not
affect the frequency or severity of PEP. Prospective randomized studies with a
higher number of patients are needed.
REFERENCES
1-Dumonceau JM, Andriulli A, Deviere J, et al. European Society of
Gastrointestinal Endoscopy (ESGE) Guideline: Prophylaxis of post-ERCP pan-
creatitis. Endoscopy 2010; 42: 503515.
2-Feurer ME and Adler DG. Post ERCP pancreatitis: Review of current pre-
ventive strategies. Curr Opin Gastroenterol 2012; 28: 280-286.
3- Elmunzer BJ, Waljee AK, Elta GH, et al. A metaanalysis of rectal NSAIDS in
the prevention of post-ERCP pancreatitis. Gut 2008; 57: 12621267.
4- Cheon YK, Cho KB, Watkins JL, et al. Efficacy of diclofenac in the preven-
tion of post-ERCP pancreatitis in predominantly high-risk patients: a rando-
mized double-blind prospective trial. Gastrointest Endosc 2007; 66: 1126-1132.
5- Elmunzer BJ, Scheiman JM, Lehman GA, et al. A randomized trial of rectal
indomethacin to prevent post-ERCP pancreatitis. N Engl J Med 2012; 366: 1414
1422.
6- Elmunzer BJ, Higgins PDR, Saini SD, et al. Does rectal indomethacin elim-
inate the need for prophylactic pancreatic stent placement in patients undergoing
high-risk ERCP? Post hoc efficacy and cost-benefit analyses using prospective
clinical trial data. Am J Gastroenterol 2013; 108: 410415.
Disclosure of Interest: None declared
P0764 ANALYSIS OF THE ROLE OF PANCREATIC DUCTAL FUSION
ANOMALIES AS A RISK FACTOR FOR DEVELOPMENT OF POST-
ERCP PANCREATITIS
J.J. Vila1,2,*, G.D. L. H. Belen1, D. Ruiz-Clavijo1, C. Prieto1, F. Bolado1,
J. Urman1, M.A. Casi1, I. Fernandez-Urien2, F.J. Jimenez2
1
Biliary and Pancreatic Diseases Unit., 2Endoscopy Unit., Complejo Hospitalario
de Navarra, Pamplona, Spain
Contact E-mail Address: juanjvila@gmail.com
INTRODUCTION: Pancreatic ductal fusion occurs in the early weeks of gesta-
tion. It has been suggested the possible association between pancreatic ductal
morphology and the incidence of post-ERCP pancreatitis.
AIMS & METHODS: Our aim was to evaluate the possible association between
abnormal fusion of the pancreatic duct and the development of post- ERCP
pancreatitis. We reviewed the pancreatic ERCPs (PERCP) performed in our
center from June 2009 to June 2013. The wirsungrafies were blindly reviewed
by one ERCPist who classified the pancreatic ductal fusion unaware of the
identity and evolution of patients after PERCP. The ductal fusion was classified
into four groups: Normal (Group I), when the dorsal duct joined the upper
branch of the ventral duct and Santorini duct; Ansa Pancreatica (Group II),
when the dorsal duct was fused to the upper branch of the ventral duct but
the Santorini duct was fused to the lower branch of the ventral duct;
Pancreatic Loop (Group III), when the dorsal duct was fused to the lower
branch of the ventral duct; and Pancreas Divisum (Group IV), when there was
no fusion between dorsal and ventral duct. Incomplete wirsungrafies which could
not be classified in either group were considered indeterminate and not analyzed.
Groups II, III and IV were considered together as Fusion Anomalies Group
(FA). We compared the incidence of post-ERCP pancreatitis in each of the
groups with respect to the rest and the AF group with Group I.
RESULTS: We performed 134 PERCPs in 68 patients during the inclusion
period. We were able to determine with certainty the type of ductal fusion in
56 patients (40 men). Twenty-seven patients suffered a previous acute pancreatitis
bout and 28 had chronic pancreatitis. Women had significantly more FA (69 %
vs 37 %, p 0.04). Thirty patients were included in Group I; 10 in Group II; 3 in
Group III and 13 in Group IV. Thus, 26 patients were included in FA Group.
United European Gastroenterology Journal 2(5S)
Complications occurred in 8 patients (14 %), pancreatitis in 5 of them (8.9%).
Only Group III was significantly associated with a higher rate of post-ERCP
pancreatitis (67%vs11.3%,p 0.019). The incidence of post-ERCP pancreatitis
in Group II and IV was 10 % and 15.4 % respectively. FA Group showed a
significantly higher incidence of post-ERCP pancreatitis compared with Group I
(19.2%vs0%,p 0.017) and this comparison remained significant after adjusting
for sex (p 0.017). Variables such previous acute or chronic pancreatitis, sex and
placement of pancreatic stent did not influenced post-ERCP pancreatitis inci-
dence (p40.05).
CONCLUSION: Pancreatic ductal fusion anomalies are a risk factor for devel-
opment of post-ERCP pancreatitis. This association should be confirmed by
means of prospective comparative studies.
Disclosure of Interest: None declared
P0765 RETROPERITONEAL DUODENAL PERFORATION (TYPE II)
AFTER ERCP IS A RARE BUT SEVERE COMPLICATION. A
SINGLE - CENTER REVIEW OF TEN - YEAR EXPERIENCE
K.C. Thomopoulos1,*, G. I. Theocharis1, C. Konstantakis1, V. Theopistos1,
C.K. Triantos1
1
GASTROENTEROLOGY, UNIVERSITY HOSPITAL OF PATRAS,
PATRAS, Greece
Contact E-mail Address: kxthomo@hotmail.com
INTRODUCTION: Duodenal perforation in the periampullary region due to
sphincterotomy (Type II) is a rare post - ERCP complication with significant
mortality. The aim of this study was to determine the incidence of retroperitoneal
duodenal perforations after periampullary interventions, management options,
and clinical outcome.
AIMS & METHODS: All cases of retroperitoneal duodenal perforation (Type
II) after ERCP during a ten year period (1/2004 - 12/2013) in our Department
were retrospectivelly reviewed. All patients were initially treated with broad-
spectrum antibiotics, nasogastric aspiration and parental nutrition and/or CT-
guided drainage when needed.
RESULTS: A total of 19 patients with retroperitoneal duodenal perforation
(Type II) after 3428 ERCPs (0.55%) were managed. Indications for performing
a periampullary procedure were known or suspected choledocholithiasis in 15
(79%) and biliary stricture in 4 patients. Diagnosis was made during the first 12h,
(during the procedure in 3 cases). Radiological drainage was performed in 7
patients (36%) and were successful in all patients except one who eventually
required surgery. Surgical intervention was required in 4 patients (21%). Total
parental nutrition was given to 4 patients (21%). Three patients died (two post -
postoperatively) giving an overall mortality of 15.8%.
CONCLUSION: Retroperitoneal duodenal perforation (Type II) is a rare com-
plication after ERCP with high morbidity and mortality but aggressive conser-
vative management seems effective for the majority of cases.
Disclosure of Interest: None declared
P0766 USEFULNESS OF ENDOSCOPIC PAPILLARY LARGE BALLOON
DILATION IN THE TREATMENT OF LARGE OR MULTIPLE
COMMON BILE DUCT STONES: COMPARISON WITH
ENDOSCOPIC SPHINCTEROTOMY ALONE
K. Tsuchida1,*, M. Iwasaki1, M. Tsubouchi1, C. Tsuchida1, N. Yoshitake1,
T. Koike1, K. Tominaga1, T. Sasai1, M. Iijima1, H. Hiraishi1
1
Gastroenterology, Dokkyo medical university, Simotsugagunn Mibumachi, Japan
Contact E-mail Address: tsuchida@dokkyomed.ac.jp
INTRODUCTION: Endoscopic sphincterotomy (EST) is currently recognized as
the main treatment for choledocholithiasis. However, the treatment of large
common bile duct stones (15 mm in diameter) or multiple common bile duct
stones (3 or more stones) by EST alone is difficult, and a new therapeutic pro-
cedure to supplant EST is needed. Sporadic reports have shown the usefulness of
endoscopic papillary large balloon dilation (EPLBD) in the treatment of
common bile duct stones, and this technique is anticipated to replace use of
EST alone. This study aimed to comparatively assess the therapeutic outcomes
and short-term complications of EST versus EPLBD in cases of biliary tract
stones 15 mm in diameter or multiple (3 or more) stones presumed to be
rather refractory to EST alone.
AIMS & METHODS: Data from 70 cases of choledocholithiasis (15 mm in
diameter or 3 stones) that were treated (EPLBD, n 34; EST, n 36) in our
department between April 2010 and March 2013 were comparatively reviewed
and analysed with respect to stone removal success rate, success rate of complete
stone removal in 1st session, procedure time, concomitant mechanical lithotripsy
(ML) application status, and short-term complications. Stone size and number
were checked by endoscopic cholangiography, and the patients treated using
EPLBD underwent EST before balloon dilation. EPLBD was performed using
1218-mm-diameter balloons, and stone collection was performed using a
Dormia basket or retrieval balloon. ML was added to the procedure in case of
difficulty in expelling the stones.
RESULTS: The stone removal success rate was comparable between groups
(EPLBD 100% vs. EST 89%, p 0.115). The EPLBD group exhibited a signifi-
cantly higher success rate of a complete stone removal in 1st session (EPLBD
88% vs. EST 56%, p 0.03). Further, the procedure time was significantly
shorter for the EPLBD group (EPLBD 42 min vs. EST 67 min, p 0.011), and
the concomitant ML application rate was significantly lower for the EPLBD
group (EPLBD 50% vs. EST 94%, p 5 0.001). Short-term complication included
pancreatitis in 2 patients and haemorrhage in 1 patient of the EPLBD group and
pancreatitis in 8 patients and haemorrhage in 2 patients of the EST group
(EPLBD 9% vs. EST 25%, p 0.112), but there was no statistically significant
intergroup difference.
United European Gastroenterology Journal 2(5S)
CONCLUSION: We successfully treated large moulded (15-mm diameter)
stone or multiple stone choledocholithiasis by EPLBD with fewer sessions and
a shorter procedure time compared to EST alone. Our findings suggest the
usefulness of EPLBD for difficult cases. However, it is necessary to accumulate
further experience of cases and examine long-term complications.
Disclosure of Interest: None declared
P0767 PER ENDOSCOPIC MANAGEMENT OF ALVEOLAR
ECHINOCCOSIS BILIARY COMPLICATIONS: A EUROPEAN
SURVEY
S. Ambregna1, L. Vuitton1,*, S. Koch1, M.C. Sulz 2, J.-B. Chevaux3,
D. Moradpour 4, P. Bichard5, F. Prat6, G. Vanbiervliet7, E. Kull8, C. Richou9,
D.A. Vuitton10, S. Bresson-Hadni10
1
gastroenterology, Besancon university hospital, Besancon, France, 2Kantonsspital,
St. Gallen, Switzerland, 3University hospital, Nancy, France, 4University hospital,
Lausanne, 5University hospital, Geneva, Switzerland, 6aphp, Paris, 7University
hospital, Nice, 8CHR, Metz, 9University hospital, 10France & WHO-Collaborating
Centre for Prevention and Treatment of Human Echinococcosis, Besancon, France
Contact E-mail Address: lvuitton@chu-besancon.fr
INTRODUCTION: Cholestasis and cholangitis are among the most common
and life-threatening complications of Alveolar Echinococcosis (AE) of the
liver, because of the liver invasion by the metacestode associated with extensive
fibro-inflammatory host reaction. Biliary complications of AE are usually treated
by surgery or radiological percutaneous biliary drainage. During the last decade
the indication of per-endoscopic biliary drainage following endoscopic retro-
grade cholangio-pancreatography (ERCP) has markedly increased in various
benign or malignant biliary tree obstructions, because of its less invasive
nature and better outcome. AE is an emerging indication in this field; only
little is known about its efficacy and safety.
AIMS & METHODS: Our aim was to collect and analyse the European experi-
ence in per-endoscopic management of AE biliary complications. All European
physicians practicing ERCP and/or in charge of AE patients were recruited
directly or through various professional/scientific associations to participate in
the retrospective survey. Data were collected from May, 2013 to January, 2014.
Physicians were asked to report any AE case with ERCP. Data on patients and
disease characteristics, endoscopic techniques and follow-up filled-out through
an online questionnaire were analysed. Ethical Committee of Franche-Comte
Hospitals approved this study.
RESULTS: Between 1986 and 2014, 12 centres performed ERCP for AE in
Europe. Detailed data available for 23 patients (18 men and 5 women) in 8
centres were analysed. Sixty-one ERCP were performed (median: 2 {1-9}
ERCP per patient). Patients were 55-years-old at the time of AE diagnosis and
60-years-old at the time of the first ERCP. Indications for ERCP were: biliary
pain, 14 (23%), cholangitis, 24 (39%), jaundice or chronic cholestasis, 22 (36%).
Seventy-four plastic stents and 7 fully (5) or partially (2) covered self expandable
metallic stents (SEMS) were placed in the biliary tree. The average time between
two stenting procedures was 19.5 weeks (1-98). Two patients needed surgical
intervention or radiological drainage because of endoscopic treatment failure.
There were 11 adverse events (18%): 1 perforation, 1 hepatic collection, 4
acute pancreatitis, and 5 cholangitis. Resolution of cholestasis was obtained in
42/44 therapeutic ERCP (95.4 %). Biliary duct calibration was obtained by stent
placement in 8 patients after an average of 2 procedures; definitive stent removal
was possible after a median time of 45 weeks of treatment. Among them, recur-
rence of stenosis led to a new stent placement 4 years later in 1 patient and
gallstones extraction in 2 patients.
CONCLUSION: Endoscopic retrograde drainage is efficient in AE with biliary
obstruction. ERCP and stenting, which are less invasive than surgery and avoid
long-term external drainage, may be proposed as a valid alternative to radiolo-
gical and surgical drainage. Several procedures with stenting are usually needed
to ensure long-term efficacy and using of antibiotics are necessary during and
after the ERCP.
Disclosure of Interest: None declared
P0768 A STUDY TO INVESTIGATE RISK FACTORS FOR ASPIRATION
PNEUMONIA AFTER ERCP
M. Yamagami1,*, N. Toda1, S. Kawamura1, Y. Karasawa1, Y. Hayata1, D. Ito1,
T. Yamada1, K. Kawanishi1, K. Sato1, K. Kojima1, T. Ohki1, T. Arizumi1,
M. Seki1, K. Tagawa1
1 1
Department of Gastroenterology, Mitsui Memorial Hospital, Tokyo, Japan
Contact E-mail Address: mari.umin.tjo@gmail.com
INTRODUCTION: Aspiration pneumonia is the one of complications of various
Endoscopic procedures. But there have been few reports of that complication
after Endoscopic retrograde cholangiopancreatography (ERCP).
AIMS & METHODS: The aim of this study is to identify the rate and risk
factors for aspiration pneumonia after ERCP.
978 consecutive patients who underwent ERCP between January 2011 and
December 2013 were included. The cumulative rate and potential risk factors
for aspiration pneumonia, such as patient attributes (Age, sex, underlying con-
ditions, and medication) and ERCP procedures were retrospectively investigated.
RESULTS: Of the 978 patients 673 patients were male (68.8%). The median age
was 71.4 years (29-99y.o). 55 patients (5.62%) were diagnosed with aspiration
pneumonia after ERCP. Age over 75years (OR:5.11 P50.0001), a procedure
time of 430min (OR2.31 P50.0059), the infusion of naloxone (OR :3.68
p 0.0151), history of heart disease (OR: 2.24 p 0.0083), eGFR530 (OR
:5.45 P50.001), hemodialysis (OR :5.95 P50.0001), cancer-bearing (OR :1.96
p 0.03 ), diabetes (OR :2.08 p 0.0213), history of cerebral infarction (OR:3.68
P50.0001) and serum Alb53.5mg/dl (OR:5.76 P50.0001)were identified as the
A343
risk factors for the pneumonia by the univariate analysis. Multivariate analysis
showed age over 75years (OR:3.26 p 0.0018), a procedure time of 430min
(OR:2.55 p 0.0062), history of cerebral infarction (OR:3.06 p 0.0063),
serum Alb53.5mg/dl (OR:3.11 p 0.00016)and hemodialysis (OR:2.59
p 0.048)were revealed to be the significant risk factors for aspiration pneumo-
nia after ERCP.
CONCLUSION: Age over 75years, a procedure time of 430min, history of
cerebral infarction, serum Alb53.5mg/dl and hemodialysis are the independent
risk factor for the aspiration pneumonia after ERCP. Careful attention should be
taken when managing patients with these attributes.
Disclosure of Interest: None declared
P0769 EVALUATION FOR ERCP USING A BALLOON ASSISTED
ENDOSCOPY IN PATIENTS WITH ALTERED
GASTROINTESTINAL ANATOMY: COMPARISON OF A SHORT
TYPE DOUBLE BALLOON ENDOSCOPE AND A NEWLY
DEVELOPED SHORT TYPE SINGLE BALLOON ENDOSCOPE
M. Shimatani1,*, M. Takaoka1, T. Mitsuyama1, H. Miyoshi1, T. Ikeura1,
K. Okazaki1
1
The Third Department of Internal Medicine, Kansai Medical University,
Hirakata, Japan
INTRODUCTION: The advent of the short type double balloon endoscope (s-
DBE) and the short type single balloon endoscope (s-SBE) radically made the
endoscopic approaches feasible for pancreatobiliary diseases in patients with
altered gastrointestinal anatomy, which had been considered unpractical.
Recently many papers are published to report the efficacy of using these techni-
ques, however, there are so far few studies regarding the comparison of s-DBE
and s-SBE.
AIMS & METHODS: This present study aimed to evaluate the usefulness of a
newly developed s-SBE for therapeutic ERCP in patients with gastrointestinal
anatomy, and also to make a comparative assessment of the respective features
and the distinctions of s-DBE and s-SBE. From March 2013 to November 2013,
ERCP using a s-SBE (s-SB-ERCP) was performed in 26 postoperative patients
who had a reconstructed intestine in our hospital. We retrospectively evaluated
the success rate of reaching the blind end, the mean time required to reach the
blind end, the diagnostic success rate, the therapeutic success rate, the mean
procedure time, and complications. Among 26 patients, the s-SB- ERCP was
applied to those 18 patients who previously had undergone s-DB-ERCP and
required the recurrent procedure. It allowed us the unique comparison of the
s-DBE and the s-SBE in the same patients analyzing the data of the mean time
required to reach the blind end and the mean procedure time.
RESULTS: The success rate of reaching the blind end was 92.3% (24/26
patients). As for 2 patients in whom s-SBE failed to reach the blind end, the
procedure was successfully accomplished after switching the scope to s-DBE. The
mean time required to reach the blind end was 28.6 min. (range, 558 min). The
diagnostic success rate was 91.7% (22/24 patients). Regarding 2 patients in whom
cholangiography failed using s-SBE, they were the cases with Roux-en-Y gas-
trectomy and with na ve papilla. Switching the scope to s-DBE, the procedure
was successfully accomplished subsequently in both cases. Therapeutic success
rate was 100% (24/24 patients). Complication occurred in 1 patient (3.8%; 1/26
patients). Regarding the 18 patients who had previously undergone s-DB-ERCP,
s-SB-ERCP was successfully completed in 17 patients. The mean required time of
s-SBE to reach the blind end was 24.7 min. (range, 7-50 min.), whereas that of s-
DBE was 13.5 min. (range, 3-31 min.). The mean procedure time of s-SB-ERCP
was 52.3 min. (range, 16-107min.), whereas that of s-DB-ERCP was 70.4min.
(range, 21-168min.).
CONCLUSION: ERCP using a newly developed s-SBE for patients with gastro-
intestinal anatomy is safe and effective. In comparison with s-DBE, for the
present, we conclude that a newly developed s-SBE is advantageous in the
point of efficiency of performing ERCP-related interventions.
Disclosure of Interest: None declared
P0770 IMPACT OF PREOPERATIVE ENDOSCOPIC BILIARY
DRAINAGE ON POSTOPERATIVE COMPLICATIONS AFTER
PANCREATICODUODENOSTOMY FOR PERIAMPULLARY
CANCER
M. Chiba1,*, H. Imazu1, K. Kanazawa1, N. Mori1, H. Toyoizumi1,
N. Shimamoto1, H. Tajiri2
Department of Endoscopy, 2Division of Gastroenterology and Hepatology,
Department of Internal Medicine, The Jikei University School of Medicine, Tokyo,
Japan
Contact E-mail Address: ccl09720@yahoo.co.jp
INTRODUCTION: The clinical impact of preoperative endoscopic biliary drai-
nage (P-EBD) on the outcome after pancreaticoduodenostomy (PD) for periam-
pullary cancer with obstructive jaundice is not well known.
AIMS & METHODS: The present study was aimed to investigate whether P-
EBD was associated with increased morbidity after PD in patients with periam-
pullary cancer. Patients with periampullary cancer, including pancreatic carci-
noma, cholangiocarcinoma, and ampullary cancer, who underwent PD from
October 2003 to September 2013 were analyzed retrospectively. At our institu-
tion, P-EBD was routinely performed with a 7 Fr or 8.5 Fr plastic stent. In
addition, endoscopic nasobiliary drainage (ENBD) or switching to a larger cali-
ber stent was done if biliary drainage was insufficient after P-EBD.
RESULTS: One hundred and sixty-seven patients who underwent PD (85 with
pancreatic carcinoma, 47 with cholangiocarcinoma, and 35 with ampullary car-
cinoma) were analyzed. 98 patients received P-EBD before PD and their mean
bilirubin level before P-EBD was 7.78 mg/dl. The other 69 patients underwent
A344
PD without preoperative biliary drainage and their mean bilirubin level before
PD was 1.59 mg/dl. Complications of P-EBD occurred in 34 patients (mild post-
ERCP pancreatitis in 10, minor bile duct perforation by the guidewire in 1, stent
occlusion in 7, and insufficient biliary drainage in 16). There was no significant
difference in the time from the diagnosis of periampullary cancer until PD
between the patients with and without complications of P-EBD. Multivariate
regression analysis was performed to clarify the influence of P-EBD on post-
operative complications, including pancreatic fistula. This analysis showed that
cholangiocarcinoma and ampullary carcinoma, but not pancreatic carcinoma,
were independent risk factors for postoperative complications (p 0.002,
OR 4.9), while P-EBD had no influence on postoperative complications.
Insufficient biliary drainage was also associated with postoperative complica-
tions, but not significantly (p 0.06, OR 4.1).
CONCLUSION: P-EBD was not associated with a higher incidence of post-
operative complications. However, insufficient biliary drainage after P-EBD
was associated with postoperative complications, so the development of more
effective P-EBD might be useful to prevent such complications. The present
findings showed that P-EBD is a safe and effective procedure for distal malignant
biliary stricture due to periampullary cancer.
Disclosure of Interest: None declared
P0771 TECHNICAL SUCCESS WITH WIRE-GUIDED CANNULATION
FOR CHOLANGIOGRAPHY USING EARLY PANCREATIC GUIDE
WIRE PLACEMENT WITHOUT PRECUT SPHINCTEROTOMY
M. Murata1,*, O. Inatomi1, H. Hasegawa1, H. Ban1, M. Shioya1, S. Bamba1,
A. Andoh1
1
Division of Gastroenterology, SHIGA UNIVERSITY OF MEDICAL
SCIENCE, Otsu, Japan
INTRODUCTION: Wire-guided cannulation (WGC) and pancreatic guidewire
(P-GW) placement may increase the success rate of deep cannulation of the
common bile duct (CBD) and reduce the risk of complications compared with
contrast-assisted cannulation (CC); however, the data is still unclear. Previous
studies have suggested that repeated and unintentional injections or P-GW inser-
tions may cause post-ERCP pancreatitis due to mechanical trauma or an increase
in the hydrostatic pressure of the main pancreatic duct. Therefore, we compared
the effect of early P-GW placement on the success of deep cannulations and the
risk of post-ERCP pancreatitis with the outcomes of WGC or CC procedures.
AIMS & METHODS: We retrospectively assessed 143 patients who required
ERCP because of known or suspected biliary duct disease; we excluded patients
who had previously undergone endoscopic manipulations. Early P-GW place-
ment was defined as placing a guidewire after one or two attempts into the main
pancreatic duct without accomplishing cannulation of CBD. We performed
ERCP with CC as the initial option for CBD cannulation in the early period
and utilized WGC during the late period. The success rate of bile duct cannula-
tion, the frequency and risk of post-ERCP pancreatitis and the frequency of
requiring a pre-cut sphincterotomy were evaluated.
RESULTS: Conventional cannulation was attempted in 47 patients and WGC in
80 patients. The success rate of CBD cannulation was 96.0% in all cases, with
91.4% in the CC group and 97.5% in the WGC group. The frequency of early P-
GW placement was 20.4% in all cases, with 10.9% in the CC group and 27.5% in
the WGC group. Pre-cut sphincterotomy was performed in only one patient in
the CC group. The frequency of post-ERCP pancreatitis was 7.6% in all cases
and was 9.2% in the CC group and 7.9% in the WGC group. There were no
significant differences among the groups with regard to each cannulation, the
surgeon, actual pancreatic guide wire placement and IDUS.
CONCLUSION: Early P-GW placement can lead to a high success rate for CBD
cannulation without the use of pre-cut sphincterotomy, and it does not increase
the incidence of post-ERCP pancreatitis. In addition, WGC may be more suita-
ble for early P-GW placement when compared with CC. WGC with early P-GW
placement may be an ideal option for CBD cannulation in difficult cases and may
involve a low rate of pre-cut sphincterotomy.
Disclosure of Interest: None declared
P0772 DOWNSTREAM REVENUE GENERATED BY PROBE-BASED
CONFOCAL LASER ENDOMICROSCOPY (PCLE) IN
UNDETERMINED PANCREATICO-BILIARY LESIONS
S. Bharmal1, R. Sharaiha1, P. Kedia1, N. Kumta1, H. Umrania1, M. Gaidhane1,
M. Kahaleh1,*
1
Gastroenterology & Hepatology, Weill Cornell Medical College, New York,
United States
Contact E-mail Address: mkahaleh@gmail.com
INTRODUCTION: Probe-based Confocal Laser Endomicroscopy (pCLE)
increases diagnostic accuracy via targeted biopsies and greatly impacts manage-
ment decisions, with accuracy rates above 80%. The improved diagnostic cap-
ability of pCLE may result in high post-procedure health resource utilization
with increases in subsequent surgical and interventional procedures. Our aim
was to examine downstream revenue and profit generated from surgical and
interventional radiology procedures after pCLE.
AIMS & METHODS: A retrospective chart review was performed in a tertiary
care institution. We identified patients who underwent diagnostic pCLE between
August 2011 and December 2012 for indeterminate pancreaticobiliary lesions.
Revenue data was generated using AllScripts EPSi and billing information to
generate financial estimates.
RESULTS: 67 patients underwent diagnostic pCLE for indeterminate pancrea-
ticobiliary lesions during the study period. Of these, 12 (18%) patients had sub-
sequent procedures related to their diagnosis. Diagnoses included
adenocarcinoma (n 8), intraductal papillary mucinous neoplasm (n 1) and
United European Gastroenterology Journal 2(5S)
benign disease (n 3). Major post pCLE procedures included pancreaticoduo-
denectomy (n 4), exploratory laparotomy (n 2) and orthotopic liver trans-
plant (n 1). Average revenue generated from procedures was 100,512 dollars
while the average net profit was 25,592 dollars per person.
CONCLUSION: For indeterminate pancreaticobiliary lesions, PCLE has major
economic implications. Profit generated from surgical and interventional radiol-
ogy procedures after pCLE is significant and negates the cost of the procedure
itself. A large scale study examining the downstream financial impact of pCLE in
otherpathologic settings may be useful for further analysis.
Disclosure of Interest: None declared
P0773 EUS-GUIDED DRAINAGE OF PERI-PANCREATIC
COLLECTIONS USING A FULLY COVERED SELF EXPANDING
METAL STENT WITH DOUBLE WALLED LUMEN APPOSING
FLANGES IN AN ELECTROCAUTERY ENHANCED DELIVERY
SYSTEM
E. Rinninella1,*, M. Dollhopf 2, A.Y. Sanchez 3, U. Will4, R. Kunda 5, S. Ullrich6,
A. Meining 7, J.M. Esteban 8, J.G. Soler 9, T. Enz 10, G. Vanbiervliet 11,
F. Vleggaar 12, A. Larghi13
1
INTERNAL MEDICINE AND GASTROENTEROLOGY, CATHOLIC
UNIVERSITY OF ROME, ROME, Italy, 2Gastroenterology, Klinikum
Neuperlach, Munchen, Germany, 3Gastroenterology, Agencia Sanitaria Costa del
Sol, Marbella, Spain, 4Gastroenterology, SRH_Wald Klinkum, Gera, 5Surgical
Gastroenterology, Aarhus University Hospital, Aarhus, 6Gastroenterology,
Asklepios Klinik Altona, Hamburg, 7Gastroenterology, Technical University of
Munich, Munich, Germany, 8Gastroenterology, Hospital Clinico San Carlos,
Madrid, 9Gastroenterology, Hospital Universitario de Bellvitge, Barcelona, Spain,
10
Gastroenterology, Kliniken Nagold, Nagold, Germany, 11Gastroenterology,
Hopital LArchet, Nice, France, 12Gastroenterology, University Medical Center
Utrecht, Utrecht, Netherlands, 13Digestive endoscopy, Catholic University, Gemelli
Hospital, Rome, Italy
Contact E-mail Address: emanurinni@yahoo.it
INTRODUCTION: To analyze the safety and clinical effectiveness of EUS
guided drainage of peri-pancreatic collections (PPCs) using a fully covered self-
expanding stent incorporated in an electrocautery enhanced delivery system, the
Hot-AXIOS system (Xlumena Inc. Mountain View, Ca, USA).
AIMS & METHODS: Retrospective analysis of consecutive patients with PPCs
who underwent EUS guided drainage using the Hot-AXIOS system in 12
European Endoscopy Centers.
RESULTS: From March 2013 to April 2014, 72 patients (median age 60 yrs; 55
male) with PPCs underwent drainage using the Hot AXIOS system. Median
diameter of PPCs was 100 mm (range 38-246). 18 were pseudocysts, 35
WOPN, 15 abscesses, and 4 were acute PPCs. 41/72 PPCs were infected. In 57/
72 cases (79%) the Hot-AXIOS system was used to enter the PPCs, while in the
remaining 15 cases (21%) a 19G needle was utilized. The main approach was
transgastric (68/72), and all were technically successful with all but one procedure
described as easy to be performed. Early complications were mild fever in 2 cases
and self-limiting bleeding in 2 other cases. Late complications were: Infection (1);
self-limiting pneumoperitoneum (1); perforation (1); massive bleeding (1). Both
last two complications were related to the naso-cystic drainage placement. 3 out
of these 4 patients required surgery. Direct necrosectomy was performed in 29
cases. Overall, resolution of PPCs was achieved in 69/72 cases (95.8%). Stent
removal was done after a median of 61 days. Recurrence was seen in only two of
69 cases (2.9%), one of which was treated with repeat EUS-guided drainage while
the other did not require treatment. At the end of follow up 69 patients are alive
and asymptomatic. Complications of the PPCs was the cause of the death in two
out of the three patients who died.
CONCLUSION: EUS guided drainage with the Hot AXIOS system is a safe,
easy to use, and highly effective minimally invasive treatment modality for peri-
pancreatic collections.
Disclosure of Interest: None declared
P0774 CRYPTOGLANDULAR ANAL FISTULA OR CROHNS ANAL
FISTULA: THE ROLE OF ULTRASONOGRAPHY IN
DIFFERENTIAL DIAGNOSIS
F. Dias De Castro1,*, P. Boal Carvalho1, J. Magalhaes1, S. Leite1, M.J. Moreira1,
J. Cotter1,2
1
Gastroenterology, Centro Hospitalar do Alto Ave Guimaraes, Portugal, 2Life
and Health Sciences Research Institute (ICVS), School of Health Sciences,
University of Minho, Guimaraes, Portugal
Contact E-mail Address: franciscadcastro@gmail.com
INTRODUCTION: Endoanal ultrasonography shows good accuracy in defini-
tion of the anatomy of perianal fistulae, including those associated with Crohns
disease (CD). Several studies have been proposed ultrasonographic features to
discriminate anal fistulae associated with CD in relation to cryptoglandular
fistulae.
AIMS & METHODS: Our aim was to evaluate several ultrasonographic features
that may distinguish these two types of fistulae.
Retrospective study including fifty-eight patients who underwent endoanal ultra-
sonography 2D between 2008 and 2013. The perianal fistulae variables studied
were the complexity, transversal diameter, presence of secondary tracks and
fistulous debris. For patients with CD was also calculated the adapted perianal
disease activity index (PDAI excluding the influence in sexual activity).
Statistical analysis was performed using the SPSS program vs20.0 and a p value
of less than 0.05 was considered statistically significant.
RESULTS: Fifty-eight patients were included, 48% with CD with a mean PDAI
of 7.63.2. In CD patients a higher PDAI was statistically associated to more
United European Gastroenterology Journal 2(5S)
complex fistulae (8.5 vs 5.5, p 0.028). 38% of all patients had been previously
submitted to a surgery intervention for fistula resolution. The ultrasonographic
features that correlated with the presence of fistulae associated with CD were the
complexity (OR:5; IC95% 1.6-15.3; p 0.004), the presence of secondary tracks
(OR:3.2; IC95% 1.1-9.5; p 0.036) and the presence of fistulous debris (OR:5.9;
IC95% 1.6-15.3; p 0.002). There was no statistical difference between crypto-
glandular fistulae and fistulae associated with CD with respect to dimensions
(4.1mm vs 4.9mm, p 0.24).
CONCLUSION: In our study, the complexity of the perianal fistulae and also
the presence of secondary tracks and debris revealed to be strong predictors of
Crohns related perianal fistulae.
Disclosure of Interest: None declared
P0776 NOVEL COMPUTER-AIDED QUANTITATIVE ANALYSIS OF
THE DISTRIBUTION OF CONTRAST IN CONTRAST-ENHANCED
EUS FOR DIFFERENTIAL DIAGNOSIS OF PANCREATIC TUMORS
H. Imazu1,*, T. Kato1, M. Chiba1, S. Koyama1, T.L. Ang2, H. Tajiri3
1
Department of Endoscopy, THE JIKEI UNIVERSITY SCHOOL OF
MEDICINE, Tokyo, Japan, 2Department of Gastroenterology and Hepatology,
Changi General Hospital, Singapore, Singapore, 3Division of Gastroenterology and
Hepatology, Department of Internal Medicine, THE JIKEI UNIVERSITY
SCHOOL OF MEDICINE, Tokyo, Japan
Contact E-mail Address: himazu21@aol.com
INTRODUCTION: Differentiating between pancreatic carcinoma (PC) and
chronic pancreatitis (CP) with pseudotumor is still challenging, even with con-
trast-enhanced EUS (CE-EUS) or EUS-FNA. We developed the novel compu-
ter-aided diagnostic software (Madara, Inspeedia Inc., Kariya, Japan) to
quantify the pattern of contrast distribution in CE-EUS.
AIMS & METHODS: The aim of this study was to evaluate the utility of CE-
EUS with Madara for differential diagnosis of PC and CP with pseudotumor.
Consecutive patients who had PC or CP with pseudotumor and underwent CE-
EUS from January 2011 to December 2013 were retrospectively analyzed. A
curvilinear echoendoscope (GF-UCT260), Aloka Prosound 10 processor and
intravenous administration of 0.015ml/kg of Sonazoid were used for CE-EUS.
Using our software, a region of interest (ROI) which divided into 100 cells was
placed to cover an area within pancreatic mass. Differences of grade of gray scale
levels between the adjoining cells within the ROI were detected, and the number
of adjoining cells which showed a difference of the gray scale level was automa-
tically calculated in each frame rate of CE-EUS (heterogeneity index). A hetero-
geneity index curve was also automatically generated to depict the changes of the
heterogeneity index over time, and the mean heterogeneity index from start to
one minute after injection of Sonazoid was calculated. Moreover, using a con-
ventional software to quantify the degree of enhancement, in which time inten-
sity curve (TIC: Hitachi/Aloka Co., Ltd., Tokyo, Japan) was generated to
depict the changes in the signal intensity, maximum intensity gain (MIG: peak
intensity base intensity) was also calculated. The final diagnosis of PC was
based on the results of surgery or EUS-FNA, while CP was diagnosed from
EUS-FNA, the clinical course and other imaging tests.
RESULTS: Fifty-nine patients (39 with PC and 20 with CP) were analyzed. The
heterogeneity index curve showed bell and flat curve type in 9 patients with
CP, irregular curve type in 11 patients with CP and 37 with PC, and flat curve Inc, Limerick Ireland). The impact of the type of scope, location and size of the
type in 2 with PC. Thus, bell and flat curve type was specific to CP, while lesion, on-site cytopathological evaluation, number of needle passes and type of
flat curve type were specific to PC. The mean heterogeneity index in PC
patients was significantly higher than CP patients (15.6 vs. 6.1, p50.0001).
Flat curve type of heterogeneity index curve and the mean value of heterogeneity
index showed sensitivity of 92.3% and specificity of 90% for differentiating
between PC and CP with pseudotumor. On the other hand, MIG in CP patients
was significantly higher than PC patients (21.1 vs. 15.7, p 0.01), and showed
sensitivity of 71.8% and specificity of 65%. Combined assessment of heteroge-
neity index curve and MIG with time intensity curve, using the cut-off value of
heterogeneity index of 10.3 and MIG of 14.3, yielded sensitivity of 94.3% and
specificity of 95% to differentiate between PC and CP with pseudotumor.
CONCLUSION: CE-EUS with Madara diagnostic software to quantify the
pattern of contrast distribution might be useful for making a differential diag-
nosis between PC and CP with pseudotumor.
Disclosure of Interest: None declared
P0777 TRANSMURAL STENT PLACEMENT AS THE DOMINANT
STRATEGY FOR ENDOSCOPIC ULTRASOUND-GUIDED BILIARY
DRAINAGE
I. Penas Herrero1,*, N. Alcaide1, R. Sanchez-Ocana1, P. Gil-Simon1, C. De la
Serna-Higuera1, M. Perez-Miranda1
1
Gastroenterology, Hospital Universitario Ro Hortega, Valladolid, Spain
Contact E-mail Address: mpmiranda5@hotmail.com
INTRODUCTION: There are several ways to perform endoscopic ultrasound-
guided biliary drainage (EUSBD): transductal (rendezvous [RV] and direct ante-
grade [DAG] options) or transmural (intrahepatic [hepaticogastrostomy, HGS]
and extrahepatic [choledochoduodenostomy, CDS] options). Best approach
remains contentious, while patient selection and case-volume confound evidence
from limited available comparative data.
AIMS & METHODS: To identify current dominant strategy for EUSBD at
high-volume Unit. Data from 44 patients (male 25, mean age [SD] 75 [13],
malignant/benign 77% / 33%) undergoing EUSBD from Jan-Dec 2012 at
single Unit were prospectively captured. Standardized techniques (single-punc-
ture following comprehensive target choice, minimal needle-guidewire interplay,
graded-dilation with salvage-only 6.5F cystotome use) and algorithms for access
(intrahepatic for hilar strictures and/or altered GI anatomy; extrahepatic for the
A345
opposite when stable scope) and drainage (transductal if early guidewire passage
or if failed cannulation of native papilla in benign obstruction, transmural if
otherwise) were used. Caliber of access duct was 9.1 mm (IQR 6.3-15.6) for
extrahepatic (27%) and 5.5 mm (IQR 4.0-7.9) for intrahepatic access (73%).
Number of ERCP/PTBD over study period was 1048/5 (EUSBD 4.2% of
ERCP; PTBD 11% of EUSBD). Clinical success was defined as bilirubin 5
80% baseline values, symptom disappearance and hospital discharge. Adverse
events as per consensus. Follow-up through chart review and phone contact.
RESULTS: Technical success was achieved in 43 patients (97.7%) and clinical
success in 70%. There were adverse events in 6 patients (13.6%): 5 mild (3 mild
bleedings, 1 acute pancreatitis, 1 hypoxemia) and 1 fatal case of cholecystitis.
Transductal EUSBD was performed in 11 patients (7 DAG and 4 RV techni-
ques), and transmural EUSBD in 36 (26 HGS/hepaticojejunostomy and 10 CDS/
choledocogastrostomy, including dual DAG-HGS in 4). Fully covered metal
stents were used in 90.6% for transmural EUS-guided biliary drainage (22
Hanaro stent, 7 Wallflex stents). A variety of stent-anchorage techniques were
employed in 65% of these patients (hemoclips, flaps, double pig-tails, balloon
expansion or more than one anchorage technique). Accurate follow-up was
obtained in 35 patients. After a mean of 146 days (SD 141), 5 dysfunctions
occurred (2 patients with plastic stents [1 migration, 1 occlusion], 3 with metal
stents [2 angulation, 1 late migration]).
CONCLUSION: After a decade-long usage, the dominant strategy for EUSBD
was transmural fully covered metal stents with ancillary anchorage. No short-
term migration, minimal late dysfunction and comparable adverse event rate to
purported less invasive RV were found. Intriguing higher rate of intrahepatic Vs
extrahepatic possibly explained by patient selection/PTBD use patterns warrants
clarification.
Disclosure of Interest: None declared
P0779 FACTORS ASSOCIATED WITH THE ACCURACY OF EUS-
GUIDED FINE NEEDLE ASPIRATION FOR THE DIAGNOSIS OF
SOLID PANCREATIC MASSES
J. Iglesias-Garc a1,*, D.de la Iglesia-Garc a1, N. Vallejo-Senra1, J. Larino-Noia1,
I. Abdulkader2, L. Uribarri-Gonzalez1, J.E. Dominguez-Munoz1
1
Gastroenterology, University Hospital of Santiago de Compostela. Foundation for
Research in Digestive Diseases, 2Pathology, University Hospital of Santiago de
Compostela, Santiago de Compostela, Spain
INTRODUCTION: Endoscopic ultrasound (EUS)-guided fine needle aspiration
(FNA) and biopsy (FNB) are accurate techniques for sampling pancreatic solid
lesions. Diagnostic yield of FNA/FNB may be influenced by different factors,
but information on this regard is lacking.
AIMS & METHODS: Aim of our study was to evaluate potential factors asso-
ciated with the diagnostic accuracy of EUS-FNA/FNB for the differential diag-
nosis of solid pancreatic masses.
447 consecutive patients (mean age 66.4 years, range 17-92, 262 male), who
underwent EUS-FNA/FNB for the evaluation of solid pancreatic lesions over
the last 4 years were identified from a prospectively collected endoscopy data-
base, and included in the study. EUS was performed using a convex array
echoendoscope (Pentax EG-3870UTK and EG-3270UK). FNA/FNB was per-
formed with standard cytology and ProcoreTM histology needles (Cook Medical
needle on the diagnostic accuracy of FNA/FNB was evaluated. Overall diagnos-
tic accuracy was calculated by using surgical histopathology in operated cases
and global clinical and radiological assessment and follow-up in non-operated
cases as gold standard. Data were analyzed by multivariate stepwise logistic
regression.
RESULTS: Mean size of solid pancreatic masses was 36.116.4 mm. 283 tumors
were located in the head of the pancreas, 124 in the body, and 40 in the tail. Final
diagnosis was pancreatic adenocarcinoma in 294 cases, inflammatory lesions in
74 cases, neuroendocrine tumor in 23 cases, pancreatic metastasis in 17 cases,
cystic lesions with solid components in 36 cases and pancreatic lymphoma in 3
cases. Overall diagnostic accuracy was 87.5% (95%CI 84.1-90.2). Size of the
lesion (OR 1.03; 95%CI 1.00-1.06; p 0.014), onsite evaluation of the FNA/
FNB sample (OR 4.36; 95%CI 1.3-14.9; p 0.019), and the use of ProcoreTM
needles (OR 3.02; 95%CI 1.4-6.5; p 0.005) were independently associated with
a correct diagnosis after FNA/FNB.
CONCLUSION: EUS-guided FNA/FNB is an accurate technique. Factors asso-
ciated with a higher diagnostic yield are large lesions, onsite cytopathological
evaluation and the use of the ProcoreTM needles.
Disclosure of Interest: J. Iglesias-Garc a Lecture fee(s) from: Cook-Medical,
Consultancy for: Cook-Medical, D. de la Iglesia-Garc a: None declared, N.
Vallejo-Senra: None declared, J. Larino-Noia: None declared, I. Abdulkader:
None declared, L. Uribarri-Gonzalez: None declared, J. E. Dominguez-
Munoz: None declared
P0780 DOES EUS-BASED CHRONIC PANCREATITIS PROGRESS TO
OBVIOUS CHRONIC PANCREATITIS? - THE FOLLOW-UP STUDY
USING EUS
K. Imbe1,*, A. Irisawa1, G. Shibukawa1, Y. Abe1, A. Saito1, K. Hoshi1,
A. Yamabe1, R. Igarashi1
1
Department of Gastroenterology, Fukushima Medical University Aizu Medical
Center, Fukushima, Japan
Contact E-mail Address: kohimbe@hotmail.com
INTRODUCTION: Endoscopic ultrasonography (EUS) has been commonly
used for diagnosis of chronic pancreatitis (CP) and assessment of its severity.
In 2009, Rosemont criteria was proposed as EUS-based criteria for CP. EUS
A346
can detect minimal changes in the pancreatic duct and parenchyma, and may
reveal early pancreatic abnormalities. However, it is not clear whether the patho-
logical condition revealed by EUS will progress to obvious CP or not.
AIMS & METHODS: The aim of this study is to clarify a clinical significance of
EUS-based CP.
We retrospectively reviewed all the medical records and EUS images of the
patients who had underwent EUS for pancreas from April 2010 to March
2012 in our center. The study patients were picked-up fulfilling criteria as follows;
1) the patients who had pancreatic abnormalities (Hyperechoic foci with/without
shadowing, Lobularity with/without honeycombing, Cysts, Strands, MPD cal-
culi, Irregular MPD contour, Dilated side branches, MPD dilation, Hyperechoic
MPD margin) on the initial EUS, 2) the patients who were followed by EUS
more than twice until April 2014. These patients were classified into 4 categories
by Rosemont criteria; Consistent with CP (C-CP), Suggestive of CP (S-CP),
Indeterminate for CP (I-CP), and Normal (N). We assessed the progression of
pancreatic condition in each patient.
RESULTS: 10 of 22 patients who had pancreatic abnormalities on initial EUS
had undergone EUS more than twice (M/F:8/2, mean age: 73.5 (58-82)). Initial
diagnosis was C-CP in 1, S-CP in 2, I-CP in 3 and N in 4, respectively. In 10
patients, 5 were aggressively intervened (abstinence, taking orally protease inhi-
bitor), and the other 5 were not taken medical intervention. In intervention
group, the number of EUS criteria increased in 2 patients. However, there was
no patient who changed the category of Rosemont classification between initial
and follow-up EUS. On the other hand, in no intervention group, the number of
EUS criteria increased in 4 patients. Moreover, 3 patients got worse the category
of Rosemont classification from N to I-CP.
CONCLUSION: It was considered that early medical intervention might be
necessary in patient with pancreatic abnormalities on EUS, even if Rosemont
classification indicated Normal.
REFERENCES
Catalano MF, Sahai A, Levy M, et al. EUS$ based criteria for the diagnosis of
chronic pancreatitis: the Rosemont classification. Gastrointest Endosc 2009; 69:
1251-1261.
Disclosure of Interest: None declared
P0781 DIFFERENT SITES OF ASPIRATION IN EUS-FNA OF
PANCREATIC ADENOCARCINOMA: A PROSPECTIVE,
MULTICENTER, SINGLE-BLINDED STUDY
Y. Di1, K. Tanaka2, Q. Zhu3,4, S.-J. Hao1, C. Jin1, L. Zhong5,*, T.-T. Gong3, T.-
J. Ye6
1
Pancreatic Surgery and Pancreatic Disease Institute, Huashan Hospital, Fudan
University, Shanghai, China, 2Department of Gastroenterology, Kyoto Second Red
Cross Hospital, Kyoto, Japan, 3Department of Gastroenterology, Rui jin Hospital,
Shanghai Jiao tong University School of Medicine, 4Shanghai Gleneagles Clinic,
ParkwayHealth, 5Department of Gastroenterology and Digestive Endoscopy,
Huashan Hospital, Fudan University, 6Department of Cytopathology, Rui jin
Hospital, Shanghai Jiao tong University School of Medicine, Shanghai, China
Contact E-mail Address: zhongniping@163.com
INTRODUCTION: EUS-FNA is widely used to diagnose pancreatic malignan-
cies. Few studies have compared different sites of aspiration when performing
EUS-FNA of pancreatic lesions.
AIMS & METHODS: to evaluate the diagnostic accuracy between center and
margin of pancreatic adenocarcinoma. 69 consecutive patients with a solid pan-
creatic lesion, with long axis 2cm, were included in this study between January
2012 and December 2013 in 3 hospitals. All FNA procedures were performed
using a 22G needle with 5ml suction, 7-8 uniform to-and-fro movements with
2cm depth of insertion were made within the lesion. The first puncture was
performed within the central part of the lesion and the second was along the
edge of lesion closed to unaffected tissue. A liquid-based cytologic (LBC) pre-
paration was used to rinse the aspiration needle and fix the cytologic specimen
after every puncture and specimens were evaluated by expert cytotechnologists.
An expert cytopathologist, blinded for the sites of aspiration, reviewed the slides
for diagnosis and assessed sampling quality. The final diagnosis was based on
pathological examination of tissues obtained either surgically or by EUS-FNA,
pathological negative cases need at least 6 months follow-up to rule out benign
diseases. Data were analyzed with Students t-test and chi squared test, assuming
a significant p-value of 0.05.
RESULTS: 64 patients were confirmed with pancreatic adenocarcinoma. The
sensitivity of central site is 71.9%(46/64) and 48.4%(31/64) in marginal site
(p 0.039).
CONCLUSION: Our study shows EUS-FNA in center of tumor is more sensi-
tive for the diagnosis of pancreatic adenocarcinoma.
Disclosure of Interest: None declared
P0782 PREDICTIVE VALUE OF PRE-OPERATIVE STAGING AND
GRADING IN PANCREATIC NEUROENDOCRINE NEOPLASMS
M.C. Petrone1,*, M.C. Mariani2, M. Manzoni2, S. Testoni1, M. Traini1,
P.A. Testoni1, P.G. Arcidiacono1
1
Gastroenterology and Digestive Endoscopy Unit, 2 Endocrine Tumors Unit, San
Raffaele Scientific Institute, Vita Salute San Raffaele University, Milan, Italy
Contact E-mail Address: petrone.mariachiara@hsr.it
INTRODUCTION: Pancreatic NeuroEndocrine Tumors (P-NETs) are a hetero-
geneous group of neoplasms with highly variable clinical behavior. In the attempt
to assess a better prognostic description, The European Neuroendocrine Tumors
Society (ENETS) proposed a new grading and TNM-based staging system.
AIMS & METHODS: To compare pre-operative and post-operative Staging and
Grading in P-NETs and their prognostic significance; secondary to determine if a
United European Gastroenterology Journal 2(5S)
new cut-off value of Ki-67 proliferative index for P-NETs Grading can improve
the accuracy of prognostic stratification.
Our retrospective long-term survival case study is composed of 285 patients with
P-NETs observed at San Raffaele Scientific Institute from 1988 to 2012. 274
neoplasms were classified according to ENETS classification models; out of
these, 90 and 42, respectively, were classified according to a new pre-surgical
classification, composed of pre-operative Staging (CT, MRI, EUS) and
Grading (EUS-guided fine needle aspiration and cytological Ki-67 evaluation).
Comparison between pre- and post-operative models (Pre-Stage vs. Stage e Pre-
Grade vs. Grade) was possible for 88 and 33 neoplasms, respectively. Ki-67
proliferative index was evaluated through immunocytochemical (Pre-Grade)
and immunohistochemical (Grade) analyses. Agreement between pre-operative
and post-operative models was performed through k-statistics (Cohen). A p-
value50.05 was considered significant.
RESULTS: Among all pre-operative and post-operative models, Pre-Grade
shows the highest Harrells C (0.97), resulting the best tool for a proper prog-
nostic stratification. When comparing pre-operative and post-operative models,
percent agreement between Pre-Stage and Stage was good (83%, k 0.74), other-
wise agreement between Pre-Grade and Grade was moderate (70%, k 0.42),
when used a 2% cut-off for Grade 1 tumor definition; contrarily, when used a
5% cut-off, Pre-Grade and Grade showed a good agreement (88%, k 0.66).
The definition of a new 5% cut-off for cytological and histological Ki-67 index
improved the accuracy of patients prognostic stratification, being not significant
the difference between patients 10-year survival for Ki-67 levels within 5%
(93.75% vs. 90%).
CONCLUSION: The new proposed pre-surgical classification, based on Pre-
Stage and Pre-Grade, is comparable to post-surgical models. This system
shows a good agreement with post-surgical one, being efficient in pre-surgical
diseases biology evaluation.
Disclosure of Interest: None declared
P0783 DUPLICATION CYSTS: THE ROLE OF ENDOSCOPIC
ULTRASONOGRAPHY
M.J. Magalhaes1,*, F. Castro-Pocas1, T. Araujo1, P. Lago1, T. Moreira1,
I. Pedroto1
1
Gastroenterology, Centro Hospitalar do Porto - Hospital de Santo Antonio, Porto,
Portugal
Contact E-mail Address: mj.magalhaes@gmail.com
INTRODUCTION: The duplication cysts are uncommon congenital anomalies
and rarely diagnosed in adults. They can be found in any part of the digestive
tract. The cysts are typically discovered incidentally on endoscopy or radiologic
imaging since they are usually asymptomatic. However complications such as
infection, bleeding, perforation, ulceration, obstruction and malignant transfor-
mation can occur. Their management can be challenging and increased availabil-
ity of new diagnostic modalities such as endoscopic ultrasonography (EUS) may
change their approach.
AIMS & METHODS: To describe the experience of a center in the diagnosis of
duplication cysts by EUS.
We performed a retrospective analysis to the upper EUS performed between 2000
and 2013, with the diagnosis of duplication cyst. The patient characteristics and
the endoscopic/imaging findings were analyzed. The contribution to the diagno-
sis of fine needle aspiration (FNA) was also evaluated.
RESULTS: Between 2000 and 2013, 23 patients (16 men (69.6 %)) with a mean
age of 51.9  15.9 years underwent EUS, whose final diagnosis was duplication
cyst. Prior to EUS: 19 underwent gastrointestinal endoscopy (EGD), 13 of them
by symptoms such as dyspepsia (n 9) and dysphagia (n 4). Of the 19 EGD
performed, 3 had no endoscopic abnormalities and 16 had suspection of sube-
pithelial lesions (10 esophageal); Four patients had previous imaging study by
computed tomography (CT), 2 with suspected esophageal duplication cysts. EUS
detected 16 anechoic lesions with endosonographic criteria of duplication cyst in
the esophagus (average size 24.2 x14, 2 mm; 7 with echogenic material inside) and
7 in the stomach (average size 23.6 x14, 1 mm, 2 with fluid levels and septae).
There were 8 cases where EUS FNA was performed (5 esophagus); in 75% of
cases one pass FNA was done using a 22 Gauge needle. There was cytological
confirmation in 3 cases, and in 3 other cases other entities besides cysts were
excluded. A CT scan was performed in four patients after EUS, with diagnostic
agreement in one case. Annual EUS follow up was performed in 9 patients, with
no changes in the lesions characteristics.
CONCLUSION: EUS plays a central role in the diagnosis and monitoring of an
entity which, although rare, has potential serious risks and complications
associated.
Disclosure of Interest: None declared
P0784 DECISION TREE ANALYSIS OF THE DIAGNOSTIC VALUE OF
EUS IN DETERMINING ESD INDICATION IN EGC
N. Indo1,*, A. Watanabe1, T. Fujita1
1
Digestive disease center,Department of gastroenterology, Yodogawa Christian
Hospital, Osaka, Japan
Contact E-mail Address: inchan0701@gmail.com
INTRODUCTION: In recent years, due to the spread of endoscopic submucosal
dissection (ESD) for early gastric cancer (EGC), preoperative determination of
ESD indication has become increasingly important.
AIMS & METHODS: In determining the ESD indication for EGC, we diagnose
the depth of invasion by endoscopic ultrasonography (EUS) in all cases as much
as possible in our hospital. We investigated its efficacy by decision tree analysis.
We performed EUS in 179 cases from January 2011 to March 2014. We per-
formed EUS using 20MHz small-diameter probe. The average age was 69 years
United European Gastroenterology Journal 2(5S)
old. Male-to-female ratio was 142:37. We classified the invasion depth into M,
M-SM and SM. We evaluated the accuracy of the invasion depth by area, mor-
phological type, histological grading and UL according to the pathology speci-
men after resection.
RESULTS: The accuracy of all 179 cases was 89 %. It was 91 % in the 150 cases
that ESD was performed, and 75% in the 29 cases that surgery was performed.
Total cases and accuracy according to area was 83% in 42 U area cases, 93% in
80 M area cases, and 88% in 57 L area cases. According to the macroscopic type,
accuracy was 91% in 89 0-IIc type cases, 88% in 60 0-IIa type cases, 92% in 13 0-
IIb type cases, 60% in 10 0-IIaIIc type cases, and 100% in 7 0-I type cases.
Accuracy was 68% in 32 UL () cases. According to histological type, accuracy
was 92% in 155 differentiated type cases, 75% in 24 undifferentiated type cases.
164 cases were diagnosed as M or M-SM, which are indications for ESD, and
correct diagnostic rate was 91%. 15 cases were diagnosed as SM, in which
surgical treatment is indicated, and accuracy was 67%. In decision tree analysis,
accuracy was 69% in UL() cases, and as low as 84% in undifferentiated UL (-)
cases, and 97% in other cases.
CONCLUSION: In ESD cases, decision tree analysis enabled differentiation
between high and low accuracy groups in diagnosis of the depth of invasion.
Disclosure of Interest: None declared
P0785 EUS-FNA OF NON MASS-FORMING CHOLANGIOCARCINOMA
WITH A 25 G PROCORE NEEDLE. A CASE SERIES
N. Pagano1,*, C. Luigiano2, L.H. Eusebi1, G. Rando3, R.M. Zagari1, F. Bazzoli1
1
Gastroenterology and Endoscopy Unit, Policlinico S. Orsola, University of
Bologna, Bologna, 2Gastroenterology Unit, ARNAS Garibaldi, Catania, 3UOC.
Chirurgia e diagnostica endoscopica, Az. ospedaliera S. Salvatore, LAquila, Italy
Contact E-mail Address: nicopagano@gmail.com
INTRODUCTION: Preoperative pathological diagnosis in patients with biliary
strictures suspected for malignancy is often difficult. The diagnostic yield of
endoscopic retrograde cholangio-pancreatography (ERCP) guided brushing is
low and endoscopic ultrasound fine needle aspiration (EUS-FNA) may be diffi-
cult to perform in non-mass forming lesions. We report a case series of patients
affected with suspected cholangiocarcinoma in which a cytological diagnosis was
attempted by EUS-FNA.
AIMS & METHODS: All the cases of EUS-FNA performed in patients with
biliary strictures suspected for malignancy from June 2012 to October 2013 were
reviewed. Patients were excluded if the EUS examination showed a mass lesion.
Only patients in whom an EUS-FNA was attempted were included in the
analysis.
RESULTS: During the study period 12 patients (8 males, mean age of 75, range
60 to 85) diagnosed with a non mass forming biliary stricture underwent EUS-
FNA. The stenosis was distal from the cystic duct insertion in 8 cases. Aspirates
were carried out using a 25 G core needle with the capillary suction technique.
The material was put on smears and processed in the standard fashion. The
results were definite for malignancy in 9 patients and suspected in 2 patients.
In one patient the cytological results were inconclusive. All the patients were
resected. The surgical pathology results showed a cholangiocarcinoma in all
these patients. The sensitivity of EUS-FNA was 75% considering only the posi-
tive cytology and 91% considering also the suspected ones. No complications
were reported.
CONCLUSION: Our results suggest that EUS-FNA is a safe and useful proce-
dure for investigating biliary strictures suspected of malignancy even without a
mass. Although false-negative diagnosis can still occur, core biopsy needle seems
to improve the diagnostic yield of cytology.
Disclosure of Interest: None declared
P0786 LIMITATIONS OF CAPSULE ENDOSCOPY - A SINGLE CENTER
STUDY ON 1193 CONSECUTIVE EXAMINATIONS
E. Dulic-Lakovic1,*, M. Schleicher1, M. Dulic1, B. Blaha1, A. Halmetschleger1,
P. Ordubadi1, M. Gschwantler1
1
Department of Internal Medicine IV, Wilhelminenspital, Vienna, Austria
Contact E-mail Address: michael.gschwantler@wienkav.at
INTRODUCTION: Over the past years, capsule endoscopy (CE) has been estab-
lished as an imaging technique in the diagnosis of small bowel diseases. The aim
of this study was to examine the limitations of this method by analysing a large
number of consecutive CEs.
AIMS & METHODS: This was a retrospective study, including 1193 consecutive
examinations performed at our centre in 1091 patients (male/female 517/574,
mean age  SD: 61.83  17.46a, range: 9-93a) between 2002 and 2012. In 1061
examinations the system of Given (Yoqneam, Israel) was used. In 132 exam-
inations the capsule endoscope MiroCam (IntroMedic, Seoul, South Korea)
was used.
RESULTS: Complications requiring an endoscopic or surgical intervention
occurred in 0.34% (4/1193) of examinations: In two patients the capsule was
retained in a duodenal diverticulum or a hiatal hernia, respectively. In both
cases the capsule could be removed endoscopically. In one patient with
Crohns disease (CD) the capsule was retained in a stenosis of the terminal
ileum and was removed during colonoscopy after dilation of the stricture. One
patient underwent surgery after the capsule was retained in a stenosis caused by
CD.
Technical defects of the capsule or the data recorder occurred in 16 (1.34%) CEs:
Hence the passage through the small intestine was not completely recorded
(n 12) or the pictures could not be used for further evaluation (n 4).
Transit abnormalities: In 1017 examinations (85.25%) the cecum was reached
within the recording period.
A347
Visibility conditions were classified as very good 54.41%, as partly limited in
32.05% and as severely limited during the most part of recording in 13.54% of
examinations.
CONCLUSION: Complications of CE requiring endoscopic or surgical interven-
tion are very rare (0.34%). However, technical defects as well as transit abnorm-
alities and limited visibility may decrease the diagnostic yield of CE in some
cases.
Disclosure of Interest: None declared
P0787 OESOPHAGEAL CAPSULE ENDOSCOPY VERSUS STANDARD
OESOGASTRODUODENOSCOPY FOR THE SCREENING OF
OESOPHAGEAL VARICES. RESULTS OF A PROSPECTIVE TRIAL
IN PATIENTS WITH LIVER CIRRHOSIS
S. Sacher Huvelin1,*, P. cales2, C. bureau3, D. valla4, J.P. Vinel3, C. duburque5,
A. attar4, I. Archambeaud1, R. benamouzig6, M. gaudric7, D. LUET2,
P. Couzigou8, L. Planche1, J.P. galmiche1, E. Coron1
1
University Hospital, Nantes cedex 01, 2University Hospital, Angers, 3University
Hospital, toulouse, 4University Hospital, beaujon, PARIS, 5University Hospital,
lomme, 6University Hospital, Avicennes Bobigny, 7University Hospital, Cochin-
PARIS, 8University Hospital, Bordeaux, France
Contact E-mail Address: sylvie.sacherhuvelin@chu-nantes.fr
INTRODUCTION: Oesophageal capsule endoscopy (OCE) is a non-invasive
technology that allows the investigation of the oesophagus. Our aim was to
evaluate prospectively the diagnostic yield of OCE in patients with cirrhosis
and suspected portal hypertension (PHT).
AIMS & METHODS: 330 patients with cirrhosis and without known oesopha-
geal variz (OV) were enrolled. Patients first underwent OCE, then OGD; endos-
copists who performed OGD were blind to OCE result. In case of discrepancy for
the presence of VO, a second exploration by OGD was immediately performed.
Patients satisfaction was assessed by an VAS (visual analogic scale, maximal
score 100).
RESULTS: Thirty patients were not included in the analysis because neither
OCE nor OGD were performed. Patients (216 male, mean age 56 years) had
mainly alcoholic (45%) or viral (22%) cirrhosis. The diagnostic yields of OCE
to detect, and to adequately classify, OV were as follows: sensitivity 76% [95%
CI, 69% - 83%] and 64% [95% CI, 50% - 78%], specificity 91% [95% CI, 86% -
95%] and 93% [95% CI, 87% - 100%], positive predictive value 88% [95% CI,
82% - 93%] and 88% [95% CI, 77% - 99%] and negative predictive value 81%
[95% CI, 75% - 87%] and 78% [95% CI, 68% - 87%] respectively. OCE patient
satisfaction scored significantly higher than OGD (8722 vs. 5835; p50.0001).
CONCLUSION: OCE was well tolerated and safe in patients with liver cirrhosis
and suspicion of PHT. The sensitivity of OCE is not currently sufficient to
replace OGD as a first exploration in these patients. However, due to its excellent
specificity and PPV, OCE may have a role in cases of refusal or contra-indication
to OGD. OCE might also improve compliance to endoscopic follow-up and help
in making important therapeutic decisions in the prophylaxis of bleeding.
Disclosure of Interest: S. Sacher Huvelin Financial support for research from:
given imaging, Consultancy for: given imaging, P. cales Consultancy for: bioli-
vescale, C. bureau: None declared, D. valla: None declared, J. P. Vinel: None
declared, C. duburque: None declared, A. attar: None declared, I. Archambeaud:
None declared, R. benamouzig: None declared, M. gaudric: None declared, D.
LUET: None declared, P. Couzigou: None declared, L. Planche: None declared,
J. P. galmiche: None declared, E. Coron: None declared
P0788 ARE NON-INVASIVE MARKERS OF GASTRO-INTESTINAL
DISEASE PREDICTORS OF ENTEROPATHY AT SMALL BOWEL
CAPSULE ENDOSCOPY?
R. Caccaro1, G. Lollo1,*, G. Hatem1, A. Ugoni1, A. Buda2, A. DOdorico1,
F. Galeazzi1, R. DInca`1, E. V. Savarino1, G.C. Sturniolo1
1
Department of Surgery, Oncology and Gastroenterology, University of Padua,
Padua, 2Department of Oncology, Gastroenterology Unit, Santa Maria del Prato
Hospital, Feltre, Italy
Contact E-mail Address: roberta.caccaro@gmail.com
INTRODUCTION: Small bowel capsule endoscopy (SBCE) represents the gold
standard diagnostic technique in case of obscure gastrointestinal bleeding.
Moreover, its use is gaining acceptance also as diagnostic procedure when an
organic disease of the small bowel (i.e. duodenum/jejunum/ileum) is suspected.
On the other hand, SBCE is an expensive, invasive tool and data about its cost/
effectiveness are lacking. Thus, non-invasive markers of small bowel disease are
desirable in order to increase the rate of positive SBCE examinations.
AIMS & METHODS: We aimed to evaluate the role fecal markers of inflamma-
tion (i.e. fecal calprotectin and lactoferrin) and intestinal permeability test (i.e.
lactulose-mannitol ratio, L/M) in predicting the presence of enteropathy at
SBCE. We included consecutive patients who underwent SBCE because of symp-
toms suggestive of small bowel disease (i.e. chronic diarrhea, chronic anemia,
signs of malabsorption) and with negative upper and lower endoscopy. Patients
dosed levels either of fecal calprotectin (normal values, n.v., 0-50 ug/g) or lacto-
ferrin (n.v. 0-7 ug/ml) and performed L/M test (n.v.50.030) at the time of SBCE.
Erosions, aftous lesions, ulcers and vascular abnormalities at SBCE were con-
sidered positive for small bowel disease presence.
RESULTS: In this retrospective analysis of prospective collected data, 101 con-
secutive patients (66F/35M; mean age 40 years) with dosed levels either of fecal
calprotectin or lactoferrin were included. In 51 (50%) patients, SBCE detected
the presence of small bowel disease. Sixty-three (62%) patients had increased
levels of fecal markers, whereas in 38 (38%) patients these markers were
normal. The diagnostic accuracy of fecal markers for the detection of small
bowel disease was 62.4%, with 75% sensitivity and 46% specificity, a positive
A348
likelihood ratio (PLR) of 1.49 and a negative likelihood ratio (NLR) of 0.51.
Sixty-seven out of 101 patients performed also L/M test. This was abnormal in 46
(69%) patients and normal in 21 (31%). In 36/67 (54%) patients, SBCE was
positive for small bowel disease. The diagnostic accuracy of L/M test for the
detection of small intestine disease was 76%, with 75% sensitivity and 56%
specificity, a PLR of 1.7 and a NLR of 0.45. The alteration of at least one
between fecal markers and L/M test has a diagnostic accuracy of 56.7%, whereas
having both fecal markers and L/M test abnormal had a diagnostic accuracy of
64.6%.
N Sensitivity % Specificity % PLR NLR
patients (95%CI) (95%CI) (95%CI) (95%CI)
Fecal markers 101 75 (60-86) 50 (34-64) 1.36 (1.08-2.05) 0.57
L/M test 67 75 (58-88) 56 (40-71) 1.70 (1.15-2.50) 0.45
At least 1 abnormal 67 83 (67-94) 26 (12-45) 1.12 (0.87-1.45) 0.65
Both abnormal 48 79 (60-92) 42 (20-66) 1.37 (0.89-2.10) 0.49
CONCLUSION: Although fecal calprotectin and lactoferrin are established mar-
kers of colonic inflammation, their diagnostic yield in detecting small intestinal
disease through SBCE seems suboptimal. Their combination with L/M test mini-
mally improves this diagnostic accuracy, whereas that of L/M test alone appears
the most satisfactory. It remains to establish whether performing either fecal
markers or L/M test (or both) might be cost-effective in the selection of patients
to address for SBCE when a small bowel disease is suspected.
Disclosure of Interest: None declared
P0789 A THERAPEUTIC WIRELESS ROBOTIC ENDOSCOPE
CONTROLLED VIA THE INTERNET REMOTELY
H. Ohta1,*, S. Katsuki2
1
Gastroenterology, Sapporo Orthopedics and Cardiovascular Hospital, Sapporo,
2
Gastroenterology center, Otaru Ekisaikai, Otaru, Japan
Contact E-mail Address: hideohta@true.ocn.ne.jp
INTRODUCTION: A few researchers have tried to make the paradigm shift
from diagnosis to treatment with the capsule endoscopy (CE) application.
Though technical innovation is rapidly spreading throughout the CE field,
there are still several crucial problems with both the hardware and software
which were highlighted by the system we presented at the last UEGW in
Berlin. This report presents a wirelessly controlled robotic endoscope equipped
with some newly developed tools; a syringe for injecting or spraying drugs or
contrast medium, a scalpel for cutting and a rubber band for suturing.
AIMS & METHODS: Our goal is to realize a patient-friendly, swallowable,
therapeutic and wirelessly controlled robotic endoscope. We tested three newly
developed therapeutic tools in a phantom, which had part of its inner wall
covered with a patch of porcine stomach. 1) A 0.3ml syringe for injecting or
spraying was driven by a spring and switched on electrically. The amount used
was dependent on the drug, dye or contrast medium. 2) The rubber band (similar
to a variceal ligater) was held between two cylinders and released by a spring.
When the spring was released the outer cylinder pushed the band over the
mucosa. 3) The scalpel blade was vibrated by a motor similar to a harmonic
scalpel. All the tools were triggered by signals originating from a controller in the
hospital via a smartphone next to the phantom. In addition, similar to the pre-
vious version the tools were controlled via the Internet.
RESULTS: It was possible to control all the new tools in the phantom both
locally (Bluetooth) and via the Internet. However, the cuts made by the scalpel in
the mucosa were a little bit jagged. In retrospect, it would have been better to
move the robotic endoscope slowly backwards during cutting to improve the
operators view of the lesion, so that they could have made a cleaner cut. The
tools occupied a large volume and therefore it was difficult to fit all the tools in a
single robotic endoscope. To enable the robotic endoscope to be swallowed, it
will be necessary to equip it with only one or two tools. The best approach might
be to build several specialized robotic endoscopes and the number of endoscopes
that a patient would swallow would be determined by their circumstances.
CONCLUSION: This study has built on the previous study by increasing the
number of therapeutic tools from two to five and hopefully, it has brought
treatment by a robotic endoscope, a little bit closer. However, the current pro-
totype has a number of limitations (e.g. too large to be swallowed and the tools
could only be used once) and these will need to be addressed if treatment by
robotic endoscope is to become a reality.
Disclosure of Interest: H. Ohta: None, S. Katsuki: None
P0790 KINETICS OF COLON CAPSULE ENDOSCOPY: A NEW MODEL
OF PREPARATION
I. GUTIERREZ-DOMINGO1,*, C. GUTIERREZ-GONZALEZ1 on behalf of
Instituto de Patolog a Digestiva de Sevilla, A. GUTIERREZ-DOMINGO1,
I. MORENO-GARCIA1
1
Digestive Diseases, Instituto de Patologa Digestiva de Sevilla, Sevilla, Spain
Contact E-mail Address: ignaciogutierrezdomingo@hotmail.com
INTRODUCTION: Up until now, the use of colon capsule endoscopy (CCE)
has been limited by the inabilities to achieve a complete examination. A pilot
study was conducted to determine the efficacy of a new preparation based on
associating Prucalopride (Resolor) and polyethylene glycol plus ascorbic acid
(Moviprep). Prucalopride is a highly selective serotonin 5HT4 receptor agonist
which stimulate the release of acetylcholine necessary for smooth bowel muscle
contraction and therefore peristalsis. After observing its benefits on the treatment
United European Gastroenterology Journal 2(5S)
for constipation, we believe that Prucalopride could be useful in the preparation
of colon capsule endoscopy, speeding up intestinal transit and therefore making
the examination shorter, increasing the excretion rate. This article presents the
results obtained in terms of transit times, total examination time and expulsion
rates.
AIMS & METHODS: Pilot study with 50 patients (cases) with the new pre-
paration compared with 50 control patients with the standard preparation (PEG/
Fosfosoda/). Each video is read by two researchers.
Preparation protocol: - Two days of residue-free diet - Day before the test, liquid
diet - Resolor 2 mg, 1 on each day of the diet and 2 on the examination day -
Moviprep, 1 liter in the evening prior to the examination and 1 liter in the
morning of the examination Then 2 boosters of half a liter each in alarms 1
and 2.
(0.30-0.88) RESULTS: A cohort with 41 men and 59 women, mean age of 54.6 years old
(0.24-0.84) (10-90). Expulsion rate over time of 87% in the cases with respect to 55.5% in the
(0.25-1.66) controls (p 0.188). The mean gastric transit time (75 vs. 49.5 minutes; p 0.12),
(0.20-1.19) intestinal transit time (81.4 vs. 44 minutes; p 0.001) and colon transit time (252
vs. 232 minutes; p 0.79) were shorten.
CONCLUSION: The higher excretion rate as well as the shortened gastric and
intestinal transits, without modifying the colon transit, with the new preparation
(PrucalopridePolyethylene glycol plus ascorbic acid), allow conducting a higher
quality study of the colon over time and with less adverse effects and better
tolerance as a result of excluding sodium phosphate.
This procedure may be considered as an alternative, particularly for patients in
whom sodium phosphate-based preparations are contraindicated.
REFERENCES
1. Spada C, et al. Meta-analysis shows colon capsule endoscopy is effective in
detecting colorectal polyps. Clin Gastroenterol Hepatol 2010; 8: 516522.
2. Hansen MB. Small intestinal manometry. Physiol Res 2002; 51: 541-556.
3. Fireman Z, Paz D and Kopelman Y. Capsule endoscopy: improving transit
time and image view. World J Gastroenterol 2005; 11: 5863-5866.
4. Manabe N, et al. New-generation 5-HT4 receptor agonists: potential for treat-
ment of gastrointestinal motility disorders. Expert Opin Investig Drugs 2010; 19:
765-775.
5. Tack, et al. Diagnosis and treatment of chronic constipation a European
perspective. Neurogastroenterol Motil 2011; 23: 697-710.
7. Quigley, et al. Clinical trial: the efficacy, impact on quality of life, and safety
and tolerability of prucalopride in severe chronic constipation a 12-week, ran-
domized, double-blind, placebo-controlled study. Aliment Pharmacol Ther 2009;
29: 315-328.
8. Gu a Europea Spada C, Hassan C, Galmiche JP, et al. Colon capsule endo-
scopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline
Endoscopy, 2012.
Disclosure of Interest: None declared
P0791 COMPARATIVE STUDY OF SMALL BOWEL TRANSIT TIME IN
TWO SMALL-BOWEL CAPSULE ENDOSCOPY SYSTEMS
I. Ribeiro1,*, R. Pinho1, A. Rodrigues1, T. Pais1, C. Fernandes1, J. Silva1,
A. Ponte1, S. Leite1, J. Carvalho1
1
Centro Hospitalar Vila Nova Gaia, Vila Nova Gaia, Portugal
Contact E-mail Address: iolandacribeiro@gmail.com
INTRODUCTION: Some studies1 suggest that the MiroCam endoscopy cap-
sule (CE) has a small bowel transit time (SBTT) greater than Given CE, which
may result in greater detection of positive lesions.
AIMS & METHODS: Aims: To compare the SBTT, the detection of positive
lesions and percentage of complete studies between Mirocam and Given .
Methods: retrospective study of 429 patients who underwent CE between 2005-
2013. Lesions were considered positive according to the indication of CE:
obscure gastrointestinal bleeding (OGIB) - multiple erosions/ ulcers, typical
angiodysplasias, tumor and blood; suspected Crohns disease (CD)/ evaluation
of the extension of CD - multiple erosions/ ulcers and blood; abdominal pain -
tumor, multiple erosions / ulcers and blood. Statistical tests: t-student; X2
RESULTS: The mean age was 54.2 years. MiroCam CE was performed in
48.7% of patients and Given CE in 51.3% patients. Indications for performing
CE: OGIB 62.5%, suspected CD/ evaluation of the extension of CD - 21.2%,
polyposis 5%, abdominal pain 4.4% and others 6.8%.
The mean gastric transit time (GTT) in MiroCam and Given CE was
identical (38min vs 41min, p 0.52). The mean SBTT of MiroCam CE
was superior to Given CE - 5h17min vs 4h45min, p 0.004. We did not find
any differences between the two CE with respect to mean age (MiroCam - 54.9
years; Given - 53.6 years, p 0.46), sex (Mirocam - female sex 57%; Given -
female sex - 61.3%, p 0.35), percentage of diabetic patients (10.1% MiroCam
- 10.1%; Given - 14.5%, p 0.2), percentage of complete exams (MiroCam -
90%; Given - 89%, p 0.63) and positive lesions (MiroCam - 38.2%, -
Given - 39.5%, p 0.78). There were also no differences regarding the indica-
tions for CE (p 0.051).
CONCLUSION: Our study suggests that the SBTT of MiroCam CE was
superior to Given CE, but it does not influence the positive findings or com-
plete examination rate. However, a longer SBTT is associated with a longer
reading time, an important aspect in daily clinical practice.
REFERENCES
1 - Pioche M, et al. Prospective, randomized comparison of two small-bowel
capsule endoscopy systems in patients with obscure GI bleeding. Gastrointest
Endosc 2011; 73: 1181-1188.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0792 THE USE OF SMALL BOWEL CAPSULE ENDOSCOPY IN
OCTOGENARIANS; THE EDINBURGH EXPERIENCE
L. Bartzis1, A. Koulaouzidis1,*
1
Centre for Liver & Digestive Disorders, The Royal Infirmary OF Edinburgh,
Edinburgh, United Kingdom
INTRODUCTION: Over the last 13 years, the clinical use of capsule endoscopy
(CE) has revolutionised the investigation pathways for the small-bowel.
Although (as procedure) non-invasive, there are reports of capsule aspiration
in certain patient-groups.[1] Moreover, CE video sequence review is a time-con-
suming process and on occasions with limited diagnostic yield (DY). There is
scarcity of data on the use of CE in octogenarians.[2-4]
AIMS & METHODS: Aim: We aim to report our centres experience in using CE
in octogenarians. Setting: University hospital & tertiary referral centre for CE for
the South East of Scotland. Retrospective study; the small-bowel CE database of
our unit was interrogated for patients480 years of age who underwent CE.
Categorical data are reported as mean SD (range). The Fischers exact, the
chi-square and the t (unpaired) tests were used to compare datasets. A two-
tailed P value of 50.05 was considered statistically significant.
RESULTS: 1,477 patients underwent small-bowel CE between 2005 and 2013. 93
CE were performed in 84 (35M/59F) octogenarians; mean age 84 2.9 years.
PillCamSB1/SB2 & MiroCam were used in 61 & 32 CE examinations, respec-
tively. Ten (11.9%) patients had more than 1 CE. One patient was unable to
swallow the capsule, and in another the capsule was retained in the stomach. The
CE report was unavailable in one case. Indications for small-bowel CE were iron
deficiency anaemia (IDA): 44, obscure gastrointestinal bleeding (OGIB): 29,
OBIGIDA: 6, diarrhoea: 4,?small-bowel varices:1. Forty-five (53.6%) patients
subsequently died. The mean time from small-bowel CE to death was 23 20.9
months, (range: 0.13-83 months). The DY (all findings) of CE in our octogenar-
ian cohort was 56.8%. Vascular lesions (any P class)/active bleeding were found
in 33, inflammatory pathology in 9, and other findings in 4 CE. No neoplastic
pathology was identified. The DY was independent to the indications for the
procedure (P 0.166), the small-bowel CE system used (P 0.068), the patient
final outcome i.e. deceased/alive (P 0.051) and/or the time from CE to death
(P 0.053).
CONCLUSION: CE in patients 480 years of age has high DY, but sinister
pathology in this cohort is rare. Furthermore, small-bowel CE has limited
impact on the final patient outcome in this patient-group.
REFERENCES
1. Koulaouzidis A, et al. Small-bowel capsule endoscopy: a ten-point contem-
porary review. World J Gastroenterol 2013; 19: 3726-3746.
2. Koulaouzidis A, et al. The use of small-bowel capsule endoscopy in iron-
deficiency anemia alone; be aware of the young anemic patient. Scand J
Gastroenterol 2012; 47: 1094-1100.
3. Tsibouris P, et al. Capsule endoscopy findings in patients with occult or overt
bleeding older than 80 years. Dig Endosc 2012; 24: 154-158.
4. Sidhu R and McAlindon ME. Age should not be a barrier to performing
capsule endoscopy in the elderly with anaemia. Dig Dis Sci 2011; 56: 2497-2498.
Disclosure of Interest: L. Bartzis Financial support for research from: Grant from
the Hellenic Society of Gastroenterology, A. Koulaouzidis Financial support for
research from: ESGE-Given Imaging research grant 2011, Lecture fee(s) from:
Dr Falk Pharma, Other: Travel support: Dr FalkPharma, Abbott,MSD
P0793 USEFULNESS OF FLEXIBLE SPECTRAL IMAGING COLOR
ENHANCEMENT (FICE) IN DIFFICULT TO INTERPRET MUCOSAL
ULCERATIVE LESIONS OF THE SMALL BOWEL
M. Rimbas1,2,*, L. Negreanu2,3, L. Ciobanu4, C. Spada5, A. Bengus2,
C.R. Baicus2,6, G. Costamagna5
1
Gastroenterology Department, Colentina Clinical Hospital, 2Internal Medicine
Department, Carol Davila University of Medicine and Pharmacy, 3Internal
Medicine Department, Emergency University Hospital, Bucharest, 4Regional
Institute of Gastroenterology and Hepatology, Iuliu Hatieganu University of
Medicine and Pharmacy, Cluj-Napoca, Romania, 5Digestive Endoscopy Unit,
Universita Cattolica del Sacro Cuore, Rome, Italy, 6Clinical Research Unit
RECIF, Reseau dEpidemiologie Clinique International Francophone, Bucharest,
Romania
Contact E-mail Address: mrimbas@gmail.com
INTRODUCTION: Identification of subtle small bowel mucosal lesions can
sometimes be challenging, as small differences in mucosal hue or pattern are
difficult to detect. To overcome this problem, chromoendoscopy virtual techni-
ques based on narrowing the bandwidth of the conventional white light endo-
scopy (WLE) image were imagined, possibly allowing for contrast-enhanced
assessment of the nature of small-bowel mucosal lesions. However, data on the
already implemented FICE (Flexible spectral Imaging Color Enhancement) soft-
ware application in videocapsule endoscopy (VCE) are limited.[1-3]
AIMS & METHODS: This is a multicenter study involving a selection of mixed
de-identified images of 250 difficult to interpret small bowel ulcerative lesions
(selected as the least representative visualization of an unequivocally confirmed
erosion from a succession of images, comprising small or shallow mucosal
defects, erosions lacking a clear rim of erythema or located marginally in the
field of view, or lesions with a poor image quality due to luminal content), and 50
artifacts mimicking ulcerative lesions, all selected from the 64 VCE recordings in
a prospective study (ClinicalTrials.gov ID NCT00768950). The evaluation was
performed by three blinded experienced VCE readers in two steps, initially as
white light images, then with the addition of all available FICE settings (1,2,3
and Blue), labeling them as real or faked lesions and rating each FICE setting as
useful or not. The comparison of accuracies in correctly categorizing the images
was performed between the two readings (McNemars test).
A349
RESULTS: Between the first (WLE only) and the second (FICE aided) reading,
in terms of accuracy, there was a 19.5% [95% CI:15.7% to 23%] improvement
(from 52% to 71.5%) in the global evaluation of all images (p50.001), coming
from a 26% [95% CI: 22% to 30%] improvement (from 47% to 73%) in the
evaluation of true ulcerative images (p50.001), and a 12% [95% CI: 3.5% to
22%] decrease (from 75% to 63%) in the evaluation of faked ulcerative images
(p50.01), results reproduced for all three readers. FICE 1 and 2 settings were
rated as most useful.
CONCLUSION: This study demonstrates that FICE virtual chromoendoscopy
(mostly settings 1 and 2) applied for VCE is useful to enhance surface patterns
and color differences and to better categorize difficult to interpret small bowel
mucosal ulcerative lesions. However, care must be taken, and individual images
should only be evaluated as part of a succession in a recording, as the technology
could also misguide the interpretation of artifacts as ulcerative lesions.
REFERENCES
1. Gupta T, et al. Evaluation of Fujinon intelligent chromo endoscopy-assisted
capsule endoscopy in patients with obscure gastroenterology bleeding. World J
Gastroenterol 2011; 17: 4590-4595.
2. Imagawa H, et al. Improved detectability of small-bowel lesions via capsule
endoscopy with computed virtual chromoendoscopy: a pilot study. Scand J
Gastroenterol 2011; 46: 1133-1137.
3. Duque G, et al. Virtual chromoendoscopy can be a useful software tool in
capsule endoscopy. Rev Esp Enferm Dig 2012; 104: 231-236.
Disclosure of Interest: None declared
P0794 THE CORRELATION OF WIRELESS VIDEO CAPSULE
ENDOSCOPY AND OTHER RADIOLOGICAL IMAGING IN THE
INVESTIGATION OF SUSPECTED AND ESTABLISHED SMALL
BOWEL CROHNS DISEASE
P. Moore1,*, G. Holleran1, B. Hall1, D. McNamara1
1
Tallaght Hospital, Tallaght, Ireland
Contact E-mail Address: moorepe@tcd.ie
INTRODUCTION: Background: In recent times there have been significant
advances in both the radiological, CT and MRI Enterocolysis (CTE / MRE)
and the endoscopic, video capsule endoscopy (CE) investigation of small bowel
disease. The optimal complimentary and appropriate use of various new evolving
and standard diagnostic modalities remains to be established. In particular, their
role in identifying small bowel Crohns disease remains unclear. Early identifica-
tion of ileal Crohns disease is desirable to guide treatment and impact on long-
term outcome.
AIMS & METHODS: Aim: To compare the diagnostic performance of CE and
radiological imaging in detecting small bowel Crohns disease in the local popu-
lation and to correlate the findings of CE with other various imaging modalities.
Method: A retrospective analysis was undertaken of a database of patients who
underwent capsule endoscopy from 2009 to 2013 at Tallaght Hospital. Those
patients who underwent CE for known histologically-confirmed or suspected
Crohns disease were identified. This cohort was cross-referenced with the
Hospital Radiology Report system Keogh for the same period. Patient demo-
graphics, radiological procedures, CE and radiology findings were recorded. The
diagnostic yield and correlation coefficient was calculated for radiological tests
compared to CE.
RESULTS: Results: In all, 263 patients, 155 female (59%), mean age 41 years,
had a CE for known (n 29, 11%) or suspected (n 234, 89%) Crohns disease.
In all 110 (42%) had active disease on CE. In only 96 (37%) patients additional
radiological tests were available for comparison, 73 (76%) and 23 (24%) in
positive and negative CE cases. Of 28 CTEs, 28 SBFTs and 17 Abdominal
CTs performed in positive CE subjects only 37 (51%) also reported evidence
of active Crohns disease, overall correlation coefficient k 0.49, 95% CI 0.37-
0.61. SBFT was the least sensitive test, 32% (9/28), while CTE and Abdominal
CTs had similar diagnostic yields of 64% (11/17) and 61% (17/28). Correlation
was better among patients without active Crohns disease, with 20 of 23 radi-
ological tests, 7 CTEs, 7 SBFTs and 9 Abdominal CTs also being reported as
normal, correlation coefficient k 0.87, 95% CI 0.72-1.0. The incremental diag-
nostic yield for CE in patients with suspected or known Crohns disease in our
cohort compared to radiological investigations was 34%, CE 76% and all
Radiology 42%. Table 1: Diagnostic yield according to test.
Number (%) CE CTE CT-Abd SBFT
Positive 73 (76%) 18 (51%) 11 (42%) 11 (31%)
Negative 23 (24%) 17 (49%) 15 (58%) 24 (69%)
Total 96 35 (36%) 26 (27%) 35 (36%)
CONCLUSION: Despite its poor diagnostic yield and the advent of new diag-
nostic modalities SBFT remains a frequently employed test in CD.
Notwithstanding the inherent bias in our study, the findings suggest the correla-
tion between CE and standard and targeted small bowel radiology is at best
moderate, with CE having a higher diagnostic yield. CE should be considered
in all subjects with suspected Crohns disease.
Disclosure of Interest: None declared
A350
P0795 PROSPECTIVE FOLLOW-UP OF MESENTERIC PANNICULITIS
IN A FRENCH UNIVERSITY HOSPITAL; SHOULD WE GO ON WITH
CLOSED FOLLOW UP OF PATIENTS?
1,* 1 2 3 1 4
C. Briquez , L. Vuitton , F. Mauny , S. Valmary , S. Koch , N. Badet ,
E. Delabrousse4
1
gastroenterology, 2centre de methodologie clinique, 3Pathology, 4Radiology,
Besancon university hospital, Besancon, France
Contact E-mail Address: lvuitton@chu-besancon.fr
INTRODUCTION: Mesenteric panniculitis (MP) is a rare, non-specific inflam-
matory process affecting the adipose tissue of the mesentery. Symptoms may be
absent or there may be fever, abdominal pain, vomiting or diarrhea. MP is
characterised on computed tomography (CT) scan by an increased mesenteric
fat density called misty mesentery and the presence of lymph nodes within the
fatty mass; and sometimes the presence of a hypodense halo surrounding blood
vessels and nodes called fat ring sign, and/or a hyperdense pseudocapsule
surrounding the mesenteric fat. Prior studies suggested an association of MP
with malignancy and also with acute abdominal disorders, infectious or inflam-
matory diseases. However data are heterogeneous and mainly retrospective and
patients care and follow-up remain unclear.
AIMS & METHODS: We aimed to evaluate the prevalence of cancer in patients
with MP on abdominopelvic CT scans, and to study clinical and radiological
course of patients. A prospective and descriptive study was performed in a
French University hospital. All CT scans performed in the Radiology department
between January 2012 and February 2013 with a diagnosis of MP were recorded.
The diagnosis of MP was defined as the presence of misty mesentery, infra-
centimetric nodes, and the absence of invasion of the adjacent small-bowel loops
and vascular structures. Clinical and radiological characteristics of patients with
MP were recorded, and patients with isolated MP were followed-up in the
Gastroenterology department. An initial search for associated disease, especially
for cancer, was performed and prospective 1-year follow-up was proposed.
RESULTS: MP was diagnosed based on CT findings in 100 consecutive patients
among 9027 abdominopelvic CT scans (1.1%) over the study period; 54 patients
(54%) had cancer, of which 12 (22 %) were melanomas and 11 (20 %) were
lymphomas. MP was present at the time of diagnosis (35/54), or appeared within
the subsequent months (7/54). Twenty-two patients had MP associated with
acute abdominal disorders, and 24 patients had isolated MP. Among those
patients and during the prospective follow-up only one cancer was diagnosed,
and it was a basal cell carcinoma. Regarding radiological aspects of MP: a
pseudocapsule was found in 58 % of cases, a fat ring sign in 63 % of cases
and a left-sided location in 88 % of cases. There were no significant difference
between the radiological characteristics of MP according to the associated dis-
eases, especially cancer.
CONCLUSION: This study is one of the largest to describe MP diagnosed at CT
scan and the first to propose prospective evaluation of patients. MP is frequently
associated with cancer, mainly melanoma and lymphoma, already documented at
the time of MP diagnosis. However data from follow-up suggest that when PM is
isolated, or associated with other disease there does not appear to be underlying
or incidental cancer.
Disclosure of Interest: None declared
P0796 CT RADIOLOGICAL MODELLING OF THE UPPER GI TRACT
ANATOMY; ESSENTIAL CLUES TO PERFORMING MAGNETIC
ASSISTED CAPSULE ENDOSCOPY (MACE)
I. Rahman1,*, M. Kay1, T. Bryant1, S. Pelitari1, P. Patel1
1
University Hospital Southampton, Southampton, United Kingdom
Contact E-mail Address: imdi81@hotmail.com
INTRODUCTION: Capsule endoscopy, employed to investigate the small
bowel, is now being further developed to visualise the upper GI tract. In a pig
model, using a hand held magnet, we have demonstrated that magnetic assisted
capsule endoscopy (MACE) in the stomach is feasible. However, it is unclear
what the best methodology is to achieve complete gastric luminal views in
humans. Our aim was to utilise CT modelling of the abdomen to determine
the optimal placements of a capsule endoscope in the stomach to allow complete
mucosal visualisation and to determine the optimal placement of the hand held
magnet to aid pyloric traversing.
AIMS & METHODS: Using multiplanar reformatting, 100 good quality con-
trast abdominal CT scans were analysed to assess luminal visualisation by a
magnetic capsule endoscope from 5 fixed stations throughout the stomach.
From each station, we assessed the ability of a capsule endoscope to visualise
6 anatomical landmarks (cardia, fundus, body, incisura, antrum and pylorus).
Success of visualisation of an anatomical area was only accepted when 490%
mucosal visualisation was achieved from a particular station. The pyloric canal
angles were calculated to create a vector. We mapped the position of this vector
on the patients skin (pyloric canal vector surface point) to determine the optimal
placement of the magnet that would allow traversing of the capsule endoscope
through the pylorus.
RESULTS: There were 65 female and 35 male patients. Mean age of patients was
53 years (s.d/-18 years). Best mucosal visualisation of the stomach landmarks
was achieved from 3 stations; fundal dependant, antral dependent and opposite
the antral dependent points. Maximal visualisation of the whole of the stomach,
required combining 2 stations as shown in Table 1
United European Gastroenterology Journal 2(5S)
Cardia Fundus Body Incisura Antrum Pylorus
Station (%) (%) (%) (%) (%) (%)
Station 1 Station 3 87 99 99 100 100 45
Station 1 Station 4 92 99 99 100 100 86
The optimal positioning of the magnet to aid pyloric traversing was posteriorly
between vertebrae T5 to L2, in an area 10cm to the left and 18cm to the right
(83% cases). Age455yrs (p 0.03) and the ability to view the pylorus from
station 3 (p 0.04) was associated with an extreme pyloric canal vector.
CONCLUSION: CT modelling has provided important data regarding the opti-
mal stations in the stomach to position a magnetic capsule endoscope to allow
maximal luminal mucosal visualisation and traversing the pylorus. Although
there is some extreme variation in the upper GI anatomy, the majority of cases
will allow the use of a single standard method in performing MACE which may
be very useful for screening purposes.
Disclosure of Interest: None declared
P0797 INVESTIGATION OF URGENT REFERRALS WITH
UNEXPLAINED IRON DEFICIENCY ANAEMIA: IS A CT SCAN
RELEVANT?
J. Iqbal1,*, G. Kaur1
1
Surgery, SCUNTHORPE GENERAL HOSPITAL, Scunthorpe, United
Kingdom
Contact E-mail Address: gkaur@email.com
INTRODUCTION: Anaemia is a common medical problem and can be due to
deficiency of one or more nutrients, blood loss or a variety of medical problems.
Generally, anaemia of almost any degree requires medical assessment so that the
correct cause can be ascertained and appropriate treatment given. The patients
symptoms and initial FBC findings will influence both the urgency and direction
of initial clinical investigation. Upper and lower GI investigations should be
considered in all males and post-menopausal females with iron deficiency anae-
mia unless there is an obvious alternative cause. NICE guidelines for referral for
suspected colorectal/ Upper GI cancer includes referral of patients with unex-
plained iron deficiency anaemia who are men of any age with a haemoglobin of
11 g/100 ml or below and who are non-menstruating women with a haemoglobin
of 10 g/100 ml or below. Unexplained iron deficiency anaemia does not usually
prompt a referral to chest physicians, gynaecologists nor the urologists.
AIMS & METHODS: All our urgent referral patients with iron deficiency anae-
mia are investigated with upper and lower GI endoscopy where possible and a
CT scan of the chest abdomen and pelvis. We aimed to evaluate our management
of these patients with respect to investigations performed, especially the cost
effectiveness of a adding on a CT scan to the upper and lower GI scopes that
are always part of this investigation.
All Urgent referrals to the Colorectal unit over a 3 month period were retro-
spectively analysed. CT scan, Colonoscopy and Flexible sigmoidoscopy data was
collected as well as any histology obtained from biopsies taken.
Of 73 urgent referrals, 54 were referred with Iron deficiency anaemia. Of these, 46
(85%) underwent a Lower GI scope (37 Colonoscopy and 9 Flexible sigmoido-
scopy); 8 did not undergo any scope - 1 failure, 1 refusal (both underwent CT
pneumocolon) and 6 patients who were considered too frail, poor mobility etc.
43% patients undergoing colonoscopy were reported normal; of the 57% with
findings, 28% were found to have bowel cancer. 98% patients referred urgently
with unexplained iron deficiency anaemia underwent a CT scan; of these, 15
(28%) were normal. Of the remaining 38 patients, 47% had significant findings
with respect to malignancy (half of which were bowel related) and the remaining
53% had other relevant non-cancer pathology (40% of which was bowel related).
Hence, CT scans picked up non bowel related pathology that would not have
been found on colonoscopy alone in 39% patients referred urgently with iron
deficiency anaemia, 17% of which was significant with respect to malignancy.
CONCLUSION: Patients with iron deficiency anaemia are generally referred to
gastroenterology / colorectal surgery for further investigations, with appropriate
urgency. These patients are usually investigated with a gastroscopy and colono-
scopy. We found our routine use of an addition of a CT scan chest, abdomen and
pelvis yielded useful results, both related to malignant and non malignant non-
bowel related pathology. This helped us guide further management appropri-
ately, with an urgency dependent on the causative pathology. We would therefore
recommend the routine use of a CT scan in the investigation of a patient referred
urgently with iron deficiency anaemia, unless contraindicated for any reason.
Disclosure of Interest: None declared
P0798 PATIENT-RELATED FACTORS AFFECTING PATIENT
ACCEPTANCE FOR REDUCED-LAXATIVE CT COLONOGRAPHY:
WHO DOES PREFER TO CT COLONOGRAPHY?
K. Nagata1,2,*, A. Iyama3, H. Kanazawa2, T. Mikami3, H. Sugimoto2
1
Department of Gastroenterology, Tokyo International Clinic, Chiyoda-ku,
2
Department of Radiology, Jichi Medical University, Shimotsuke, 3Department of
Radiology, Sakakibara Sapia-tower Clinic, Chiyoda-ku, Japan
Contact E-mail Address: Nagata7@aol.com
INTRODUCTION: Although CT colonography (CTC) is minimal invasive pro-
cedure, the actual patient acceptance for CTC varies between patients.
AIMS & METHODS: The aim of this prospective study was to assess patient
tolerance and to identify the patient-related factors affecting the patient
United European Gastroenterology Journal 2(5S)
acceptance of reduced-laxative CTC in screening purpose. A total of 1242 out-
patients at average risk for colorectal cancer were consecutively enrolled in this
study. All patients underwent reduced-laxative fecal-tagging CTC with 64-detec-
tor row CT using carbon dioxide insufflation. Patients age, gender, height,
weight, and the bowel habits were recorded before the procedure. After the
procedure, acceptance and preference were evaluated using self-assessed ques-
tionnaires regarding tolerance assessment for overall procedure and preference
for future testing.
RESULTS: Percentages of patients in good tolerance category for CTC were
83.9% (897/1069). Sixty percent (641/1062) of patients were willing to accept
CTC as a future method of examination. Discomfort factors during CTC were
abdominal distention (64.8%) and abdominal pain (4.9%). Among the patient
factors, only the older age affected the degree of discomfort during CTC (over 60
vs. under 60, odds ratio 1.59, p 0.006). Patient factors of gender, BMI, con-
stipation/laxative use, history of abdominal surgery, and previous colonoscopy
or barium enema experiences were not related to patient tolerance during CTC.
CONCLUSION: An uncomfortable CTC procedure may be expected in elder
patients. Overall, reduced-laxative CTC has excellent patient tolerance.
Disclosure of Interest: None declared
P0799 INCIDENTAL SLIDING HIATAL HERNIA: FINDINGS AND
RELATIONSHIP WITH CT WITH WATER ENEMA AND CT
COLONOGRAPHY
M. Revelli1, M. Furnari2,*, L. Bacigalupo3, F. Paparo3, D. Astengo1,
E. Savarino4, G.A. Rollandi3
1
E. O. Ospedali Galliera, Unit of Radiology, 2Di. M. I., Gastroenterology Unit,
UNIVERSITY OF GENOA, 3Unit of Radiology, E. O. Ospedali Galliera, genoa,
4
Division of Gastroenterology, Department of Surgery, Oncology and
Gastroenterology, University of Padua, Padua, Italy
Contact E-mail Address: matteorevelli@gmail.com
INTRODUCTION: Barium-contrast radiography originally constituted the first
development in diagnosing hiatal hernia (HH) and reflux disease however, con-
ventional radiology is no more a gold standard investigation for their assessment.
We observed in clinical practice a worrisome rate of HH type I reported as extra-
colonic finding during CT with water enema (CT-WE) and CT colonography
(CTC), likely induced by increased intra-abdominal pressure due to colon dis-
tension. HH has been positively related with the incidence and severity of reflux
disease and with the risk of its complications. Although HH is not a life-threa-
tening condition it is our opinion that erroneous reporting of HH may trigger
consecutive diagnostic unnecessary processes that induce unmotivated anxiety
and expensive and time-consuming for the patient and the socio-sanitary system.
AIMS & METHODS: To determine whether colonic distension at CT-WE and
CTC can induce a small incidental physiologic sliding hiatal hernia and whether
exist differences between water and gas distension achieved with the two different
techniques. We retrospectively evaluated 400 consecutive patients, 200 under-
going CT with water enema and 200 undergoing CT colonography, including
59 subjects who also underwent a routine abdominal CT evaluation at a different
time, used as internal control, while a separate group of 200 consecutive patients
who underwent abdominal CT evaluation was used as external control. Two
abdominal radiologists assessed the CT exams for the presence of a sliding
HH, grading the size as small, moderate, or large; the internal control groups
were directly compared with the corresponding CT-WE or CTC study looking
for a change in hernia size. We used the Fisher exact test applying a size-specific
correction factor, in order to account for the effect of colonic distention: these
corrected values were then individually compared with the external control stage gastric or colorectal tumor indicated for endoscopic resection. Patient
group.
RESULTS: Sliding HH was present in 51% (102/200) of the CT-WE patients and
in 48.5% (97/200) of the CTC patients. Internal control CT of the 31 patients
with a hernia at CT-WE showed resolution of the hernia in 58.1% (18/31) of
patients, including 76.5% (13/17) and 45.5% (5/11) of small and moderate HH.
Comparison CT of the 28 patients with HH at CTC showed absence of the it in
57.1% (16/28) patients, including 68.8% (11/16) and 50% (5/10) of small and
moderate HH. Its prevalence in the external control group was 22% (44/200),
lower than the CT-WE and CTC cohorts prevalence of 51% (p 5 0.0001) and
48.5% (p 5 0.0001). After applying the correction factors for the CT-WE and
the CTC groups, the estimated residual prevalences (16% and 18.5%, respec-
tively) were much closer to that of the external control patients (p 0.160 for CT-
WE and p 0.455 for CTC).
CONCLUSION: Incidental findings at CT-WE and CTC should be considered
according to the clinical background. Small sliding HH should not be reported in
patients with unrelated symptoms undergoing CT-WE or CTC: when encounter-
ing these findings, accurate anamnesis and review of medical history looking for
GERD-related symptoms are essential, in order to address these patients to a
correct diagnostic iter, taking advantage from appropriate techniques such as GI
endoscopy or esophageal manometry.
Disclosure of Interest: None declared
P0800 THE POTENTIAL OF MR COLONOGRAPHY AS A SCREENING
TOOL FOR COLORECTAL CANCER: A COST-EFFECTIVENESS
ANALYSIS
M. Greuter1,*, E. Demirel1, J. Berkhof1, R. Fijneman1, J. Stoker2, G. Meijer1,
V. Coupe1
1
VU University Medical Center, 2Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: mj.greuter@vumc.nl
INTRODUCTION: For colorectal cancer (CRC), a range of screening modalities
is available. Based on diagnostic accuracy, colonoscopy is the preferred test but
A351
there is a low risk on serious complications and, due to the burdensome proce-
dure, the population uptake is low. MR colonography may have potential as a
CRC screening tool since it has comparable test characteristics as colonoscopy
but is less invasive. Furthermore, innovators in the field of MR technology are
striving to develop a targeted contrast agent that specifically detects adenomas at
high risk of progressing to CRC. This might even further increase the potential of
MR colonography for CRC screening.
AIMS & METHODS: To explore the potential of conventional and targeted MR
colonography in terms of (cost-)effectiveness using the Adenoma and Serrated
pathway to Colorectal CAncer (ASCCA) model.
Thirteen screening strategies were evaluated, differing in primary screening
instrument and number of screening rounds. The strategies under consideration
were conventional MR colonography, targeted MR colonography, colonoscopy
and CT colonography with two, three and four screening rounds at a ten year
screening interval. In addition, eleven rounds of biennial faecal immunochemical
test (FIT) screening were evaluated because this is the current Dutch screening
programme. For each strategy, both realistic and perfect participation rates were
taken into account. Incremental costs and effects were estimated from a societal
perspective with an ICER less than the Dutch GDP per capita in 2012, i.e.
E35,823/LYG, considered as cost-effective.
RESULTS: All screening strategies were cost-effective compared to no screening.
For conventional MR colonography, the ICER ranged between E1,271/LYG to
E3,003/LYG for two to four screening rounds at a participation rate of 34%. For
participation rates of 62% and 100%, this range was respectively E1,576/LYG to
E3,777/LYG and E1,971/LYG to E4,577/LYG. However, conventional MR
colonography screening was more expensive than other screening strategies at
comparable LYG, for all participation rates. For example, colonoscopy at two to
four screening rounds at realistic participation (22%) led to cost-savings of E71
to E87 at 0.025 to 0.035 LYG per person. The effectiveness of targeted MR
colonography was only slightly higher than of conventional MR colonography
but it was considerably more costly, even under the most favourable assumptions
regarding test characteristics and costs per test.
CONCLUSION: This is the first study to evaluate the cost-effectiveness of MR
colonography screening for CRC. Although conventional and targeted MR colo-
nography are cost-effective compared to no screening, at the moment they cannot
compete with more established screening tests because of the high costs per test.
Disclosure of Interest: None declared
P0801 PRELIMINARY STUDY OF PHOTODYNAMIC DIAGNOSIS
USING 5-AMINOLEVULINIC ACID IN GASTRIC AND
COLORECTAL TUMORS
M. Nakamura1,*, J. Nishikawa1, K. Hamabe1, A. Goto1, J. Nishimura1,
H. Shibata1, M. Nagao1, S. Hashimoto1, T. Okamoto1, I. Sakaida1
1
Department of Gastroenterology and Hepatology, Yamaguchi University
Graduate School of Medicine, Ube, Yamaguchi, Japan
INTRODUCTION: Photodynamic diagnosis (PDD) using 5-aminolevulinic acid
(5-ALA), has been performed to detect the accumulation of fluorescent proto-
porphyrin IX (PpIX) in tumors. 5-ALA is a precursor of the fluorescence-emit-
ting PpIX, and PpIX accumulates specifically in tumor cells and emits
fluorescence when the excitation light irradiated on them. This property of 5-
ALA may improve the endoscopic diagnosis of gastric and colorectal tumors.
AIMS & METHODS: In this preliminary study, we investigated the utility of 5-
ALA using PDD in the detection of gastric and colorectal tumors. This prospec-
tive single-center study investigated inter-subject variability in patients with early
selection criteria were age 2080 years, either sex, and provision of informed
consent. After oral administration of 5-ALA, endoscopic resection of gastric
or colorectal tumors was performed, then the resected specimens were subjected
to fluorescence endoscopy to examine for red fluorescence. Endoscopic, macro-
scopic, and histopathologic findings of the tumors were assessed.
RESULTS: Ten patients (7 men and 3 women) with a total of 13 lesions (10
gastric and 3 colorectal tumors) were enrolled in this study. Fluorescence was
detected in 7 (53.8%) of the 13 lesions. No significant differences were observed
in sex, age, color of the tumor, tumor diameter, macroscopic type, histological
type, invasion depth, lymph node metastasis, or procedure time between the cases
with and without fluorescence. The detection rate of fluorescence tended to be
high for elevated lesions. Liver dysfunction developed in 4 (40.0%) of the 10
patients.
CONCLUSION: The results of this preliminary study suggest the utility of PDD
using 5-ALA for screening gastric and colorectal cancers.
Disclosure of Interest: None declared
P0802 INCREASED VISCERAL TO SUBCUTANEOUS FAT RATIO IS
ASSOCIATED WITH LOWER RISK OF IBD RELATED SURGERY
IN PATIENTS WITH CROHNS DISEASE ON INFLIXIMAB
P. Brown1,*, D. Tolan2, L. Warren3, T. Clark3, G. Dowson3, J. Hamlin3,
V. Subramanian1
1
Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, St James
University hopsital, Universityof Leeds, 2Radiology, 3Gastroenterology, St James
University Hospital, Leeds Teaching Hospital NHS Trust, Leeds, Leeds, United
Kingdom
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: Fat wrapping and mesenteric hypertrophy are characteris-
tics of Crohns disease (CD). In patients with CD, mesenteric adipose tissue
releases higher levels of adiponectin, which could up-regulate production of
tumor necrosis factor- and increase the risk for aggressive disease. We have
A352
previously shown that a higher visceral to subcutaneous fat ratio was associated
with complicated (stricturing or fistuling) CD (reference).
AIMS & METHODS: The aim of this study was to investigate the effect of
visceral fat accumulation on clinical outcomes in patients with CD on
Infliximab. We identified patients with a confirmed diagnosis of CD on
Infiximab who had computed tomography or magnetic resonance imaging
scans of their abdomens within 12 weeks of starting infliximab, from the biolo-
gics database of Leeds Teaching Hospital NHS Trust. Areas of subcutaneous and
visceral fat were measured in 1 cross-sectional scan, taken at the level of the
umbilicus using a previously validated method. All measurements were made
using AdodeTM CS3 with magic wand function. The outcomes of interest were
1) IBD related flare (defined as increase in dose or steroid use or need for IBD
related hospitalization or surgery), 2. Any IBD related surgery and 3) IBD
related resectional surgery.
RESULTS: 150 patients with CD on Infliximab met our predefined inclusion
criteria. The mean age of the patients was 37.2  13.9 years. On multivariate
analysis a higher visceral to subcutaneous fat ratio was associated with a lower
risk of all IBD related surgery (HR 0.125 and 95% CI 0.02 0 0.81) and a lower
risk of an IBD related flare that almost reached significance (HR 0.39, 95% CI
0.13-1.14). Females were less likely to need IBD related surgery (p 0.03) and
ileal and ileo-colonic disease was associated with a higher risk of surgery com-
pared to colonic disease (p 0.03). Only structuring and fistulating disease phe-
notype was significantly associated with a higher risk of resectional surgery
(p 0.0.2).
CONCLUSION: Higher visceral to subcutaneous fat on cross sectional imaging
at baseline is associated with better clinical outcomes in patients with CD on
Infliximab. This could imply that mesenteric fat hypertrophy has a protective
role in CD.
REFERENCES
Erhayiem B, Dhingsa R, Hawkey CJ, et al. The ratio of visceral to subcutaneous
fat area is a biomarker of complicated Crohns disease. Clin Gastroenterol
Hepatol 2011; 9: 684-687.
Disclosure of Interest: None declared
P0803 "DOUBLE-DUCT" SIGN - WHAT IS THE CLINICAL
SIGNIFICANCE?
K. Padala1,*, T. Gardner1, R. Sinha2, O. Elneima1, S. Niaz1, J.R. Greenaway2,
D. Joy2
1
Gastroenterology, 2Endoscopy, South Tees NHS Foundation Trust,
Middlesbrough, United Kingdom
Contact E-mail Address: rohits78@gmail.com
INTRODUCTION: Double-duct sign on endoscopic retrograde cholangio-
pancreatography (ERCP) is considered suggestive of pancreatic or biliary malig-
nancy [1]. This sign is frequently encountered in radiological imaging. We wish to
investigate the prognostic value of the double-duct sign in patients who undergo
magnetic resonance cholangio-pancreatogram (MRCP), attempting to define the
associated features, which would predict underlying malignant disease [1,2].
AIMS & METHODS: An analysis of retrospectively collected database of all
patients (n 2,741) who had MRCP over a four-year period; January 2010 to
December 2013 was performed. All the radiological reports showing both a
dilated common bile duct (CBD) and pancreatic duct (PD) or the double-
duct sign were included. These were all interpreted and reported by specialist
gastrointestinal radiologist. The demographics, liver biochemistry, final diagnosis
and outcome for all patients with the double duct sign were accessed using the
radiology PACS system, biochemical results WebICE, hospital letters and
case notes. Follow up information was available for a mean of 36 months
(range 12-48 months).
RESULTS: 81 patients (annual incidence 2.2% - 3.3% incidence) had double-
duct sign with a mean age of 71 years. The ratio of male to female patients was
(F: M) 1.2:1. The commonest cause of double duct sign was choledo-cholithiasis
(27.2%) followed by malignancy (20%). Patients with jaundice in the context of
double-duct sign had a higher incidence of malignancy (48%). More than half
of the patients, (48/81; 59%) with double-duct sign were anicteric. None of the
anicteric patients were found to have malignancy (p 0.002). Of the anicteric
patients, 25% (12/48) had completely normal liver test and the remaining 75%
(36/48) had some abnormality of the liver enzymes (raised GGT and/or Alkaline
phosphatase). Four patients in the anicteric group had benign tumours (1 case of
benign IPMN [Intra-ductal papillary mucinous neoplasm] and 3 cases of benign
ampullary tumour, histology confirming low grade and high grade dysplasia
without evidence of invasive malignancy on resection specimens). The benign
nature was confirmed on clinical, pathological and radiological follow-up. All
four patients remained anicteric over the period of follow-up (mean 24 months;
and one unrelated death at 18 months). Our results show that double duct sign
in the absence of jaundice makes a malignant aetiology unlikely.
CONCLUSION: In patients with cross-sectional imaging evidence of double-
duct sign, the absence of jaundice makes a malignant aetiology unlikely.
Conversely, in jaundiced patient a malignant cause is much more likely.
REFERENCES
1. Baillie J, et al. Biliary imaging: a review. Gastroenterology 2003; 125: 1565.
2. Ahualli J. The double duct sign. Radiology 2007; 244: 314-315.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0804 QUANTITATIVE ASSESSMENT OF GLOBAL SMALL BOWEL
MOTILITY IN CHRONIC INTESTINAL PSEUDO-OBSTRUCTION
AND CONTROLS: A PRELIMINARY STUDY
S.K. Butt1,*, A. Menys2, D. Atkinson2, A. Plumb2, S.A. Taylor2, N. Zarate-
Lopez1, A. Emmanuel1
1
Gastroenterology, 2Centre for medical imaging, UCLH, London, United Kingdom
Contact E-mail Address: s.butt@ucl.ac.uk
INTRODUCTION: In this preliminary report, we present the initial results of a
prospective investigation comparing MRI quantified global small bowel motility in
healthy controls and patients with proven clinical and radiological Chronic Intestinal
pseudo-obstruction (CIPO). Diagnosis is initially difficult and often delayed, many
patients undergoing unnecessary surgical intervention prior to final diagnosis. MRI
offers a potential non-invasive modality of diagnosis and monitoring, employing
post-processing quantitation of global metrics describing small bowel motility1.
AIMS & METHODS: Subject selection: 11 healthy non-smoking volunteers (7
Male, mean age 33[22 to 48]) and 5 CIPO patients (3 Male, mean age 53[32 to 82])
were recruited. CIPO patients stopped any medications that influenced small bowel
motility for one week prior to scan including opioids, anti-emetics & anti-diarrhoeals.
Study overview: Participants underwent a single MRI motility scan before and
immediately after an injection of 0.5mg IV neostigmine, a cholinomimetic with
potent prokinetic action.
MR Protocol: The motility scan protocol used a 3D Balanced Turbo Field Echo
(BTFE) motility sequence capturing one coronal volume through the abdomen
and pelvis per second over a 20 second breath hold (2.5x2.5x10 in mm resolution,
FA 20, TE 1.7ms, TR 3.5ms, 15cm thickness in 15 reconstructed slices)
Motility Analysis: Dynamic time-series data was registered using a modified 2D
optic-flow technique for each slice through the abdominal volume2. The deforma-
tion fields generated by the registration process were used to provide a motility
metric (arbitrary unit, AU) expressed as the standard deviation of pixels Jacobian
(a measure of local area change) and averaged across a user defined ROI.
ROI Placement: A radiologist, with 5 years experience reading MRE, placed
regions of interest (ROIs) around the small bowel in each coronal slice over
the 15-slice volume. The radiologist was blinded both to subject group and
whether the scan was pre-
RESULTS: 1) Mean baseline small bowel motility scores in CIPO patients was
0.19AU (range 0.1 to 0.25) and in controls 0.35AU (range 0.275 to 0.37) with a
statistically significant difference of 0.17AU, p 0.0026 (CI 0.09 to 0.23).
2) The mean percent increase in small bowel motility scores in CIPO patients
following noestigmine was 29% (95% CI from 19 to 50%) and in controls 10%
(range 0 to 34) with a statistically significant difference in groups response to
neostigmine of 19%, p 0.029 (95% CI from 4 to 40%).
CONCLUSION: This study demonstrated significant differences in both resting
and cholinomimetic-induced global motility between CIPO patients and healthy
controls. Despite marked bowel distension in the CIPO patients, motility
appeared present but reduced compared to controls, and responded to provoca-
tion with neostigmine suggesting the bowel still exhibits the expected pro-kinetic
effects following pharmacological stimulation. With just five patients this is a
preliminary study, nevertheless initial results appear promising and support our
ongoing investigation program.
REFERENCES
1) Menys, et al. Radiol 2013; 269: 443-450.
2) Odille, et al. MRM 2012; 68: 783-793.
Disclosure of Interest: None declared
P0805 MALIGNANT GASTRODUODENAL OBSTRUCTION
TREATMENT WITH SELF-EXPANDABLE METALLIC STENTS IN A
SINGLE REFERRAL CENTRE
L.C. R. Freitas1,*, L. Meireles1, P. Sousa1, J. Lopes1, L.C. Ribeiro1, J. Velosa1
1
Gastrenterology and Hepatology Department, Hospital de Santa Maria, Lisbon,
Portugal
Contact E-mail Address: luisfreitas29@gmail.com
INTRODUCTION: Endoscopic treatment is a valid choice in treating malignant
gastroduodenal obstruction, when patients are not candidates to surgery. Self-
expandable metallic stents (SEMS) have been increasingly used in this context.
AIMS & METHODS: To retrospectively analyze the use of SEMS in malignant
gastroduodenal obstructions, in one referral centre, over a period of 8 consecutive
years.
RESULTS: SEMS were successfully inserted in 43 patients in this period (male sex
21 (48.8%); mean age 70.67/-13.46 years), all of them complaining with stasis
symptoms. Primary tumor was gastric adenocarcinoma in 26 patients (60.5%),
pancreatic adenocarcinoma in 12 patients (27.9%), and cholangiocarcinoma, gall-
bladder and colon cancer in 5 patients (11.6%). The median time between tumor
diagnosis and stent placement was 27.5 days (range 0-980). Complications to the
procedure occurred in 3 patients (7%): hypovolemic shock, perforation and aspira-
tion pneumonia. Clear clinical improvement (tolerance to oral intake) was seen in
26 patients (60.5%). In 10 patients (23.3%), reintervention due to stent occlusion
was necessary, including stent-in-stent placement in 6 patients, balloon dilation in 2
and argon plasma coagulation in 2. Median survival after sent insertion was 42
days (range 1-420), with 15 patients (34.9%) dying within less than 30 days after
the procedure, with no statistical significant differences between different ages and
different types of primary tumor.
CONCLUSION: When feasible, SEMS placement is a safe and efficient therapy
for malignant gastroduodenal obstruction. The relatively high percentage of
patients that were dead one month after stent placement, in our series, may
reflect an over-selection of patients that had too advanced a disease to benefit
from this technique.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0806 SELF EXPANDIBLE METAL STENTS IN VARICEAL BLEEDING
AS THE BLAKEMORE-SENGSTAKEN TUBE OF NOWADAYS? A
SINGLE INSTITUTION EXPERIENCE
M. Muller1,*, T. Seufferlein1, M. Wagner1, A. Kleger1
1
Department of Gastroenterology, Universitatsklinikum Ulm, Ulm, Germany
Contact E-mail Address: martin.mueller@uniklinik-ulm.de
INTRODUCTION: Despite a dramatic reduction of lethality rates due to upper
gastrointestinal bleeding, esophageal variceal bleeding remains a challenge and
still accounts for a mortality rate of up to 50 % within the first 6 weeks. Rapid
and efficient varical ligations in combination with vasoactive terlipressin are key
requirements for the initial patients stabilization. However, a relevant proportion
of esophageal varical bleeding remains refractory, thus, making a call for addi-
tional tools to achieve hemostasis. Self expandible metal stents (SEMS) incorpo-
rate such a tool.
AIMS & METHODS: We report 12 cases of stent application in patients with
variceal bleeding between 2011 and 2014. A retrospective analysis reporting a
series of clinically relevant parameters in combination with bleeding control rates
and adverse events was performed.
RESULTS: The initial bleeding control rate was 100 %. Despite this success, we
observed a 30% mortality within the first 42 days due to non-hemorrhage asso-
ciated reasons in the cirrhotic patients. Interestingly, we found in 7 out of 12
patients stent dislocation even after a proven correct position 24 h after hemos-
tasis. The stent removal procedure appeared to be safe with slight reactivation of
bleeding in only one of our patients. Of note, our study cohort required an
extensive amount of hospital care.
CONCLUSION: Self expandible metal stents seem to be safe and efficient in
patients with therapy refractory variceal bleeding. Despite high rates of stent
migration no serious adverse events were observed in short term observation.
This contrasts strongly with the formerly used Blakemore-Sengstaken tubes.
Thus, SEMS should be considered as the new Gold standard in case of refractory
esophageal bleeding.
Disclosure of Interest: None declared
P0807 SAFETY AND EFFICACY OF COLONIC STENTING: 7 YEAR
EXPERIENCE FROM A DISTRICT GENERAL HOSPITAL IN THE UK
M. Hu1,*, V. Mitra1, V. Krishnan1, D. Majumdar1, B. Chaudhury1, J. Hancock1,
D. Dwarakanath1
1
Department of Gastroenterology, University Hospital of North Tees, Stockton-on-
Tees, United Kingdom
Contact E-mail Address: deepak.dwarakanath@nth.nhs.uk
INTRODUCTION: A significant proportion of patients with colon cancer pre-
sent with partial or complete bowel obstruction. Emergency decompression sur-
gery may be associated with up to 25% mortality1. Self expandable metal stents
(SEMS) provide an alternative low-risk option for managing these patients2 and
have been routinely used as the first line of treatment of these patients in our
hospital. The aim of this study was to assess the safety and efficacy of SEMS in
malignant colonic obstruction (MCO) in a district general hospital (DGH)
setting.
AIMS & METHODS: A retrospective study of patients presenting with MCO
and treated with uncovered SEMS between 2007 and 2013 was carried out. All
stents were deployed by experienced gastroenterologists. Data including patient
demographics, indication and treatment intent, site of lesion, stent type, proce-
dure outcome, adverse events, and outcome at six months were obtained using
the endoscopy reporting software and hospital patient record.
RESULTS: 78 patients were included. 53 (68%) had elective and 25 (32%) had
emergency stenting. Median age was 77 years (range 47-96 years). 53 (68%)
patients were male. 4 (16%) out of 25 patients who underwent emergency stent-
ing subsequently had curative surgery. 6 (11.3%) patients in the elective stenting
group (n 53) had curative surgery. Overall, SEMS was used as a bridge to
surgery in 10 (12.8%) patients while 68 (87.2%) underwent palliative stenting.
The sites of malignancy were as follows: sigmoid colon 40 (51.3%), descending
colon 15 (19.2%), rectum 14 (17.9%), transverse colon 7 (9.0%) and anastomotic
recurrence post left hemicolectomy 2 (2.6%). Procedure related serious compli-
cations included one case of stent related perforation (proceeded to palliative
rescue Hartmanns procedure) and one of contrast extravasation (successfully
managed conservatively). 3 patients presented with early stent failure from
blocked stent patency was restored in one with endoscopy, one underwent
Hartmanns procedure and the third patient chose to be palliated. The stents
did not adequately restore luminal patency in 2 patients despite optimal position-
ing. Stent migration was discovered in 2 patients who represented with partial
obstruction. 2 patients with rectal stents complained of discomfort and were
managed conservatively. The technical success rate was 98.7% (n 77) and the
clinical success rate (functional stent without complication) was 88.5%. The 30-
day all-cause mortality was 10.3% (n 8) with none being attributable to the
procedure.
CONCLUSION: Our study shows that a safe and effective colonic stenting
service can be delivered in a DGH setting. There was no procedure related
mortality compared to emergency decompression surgery which has a higher
mortality rate1. This relates to service delivery by experienced operators. We
suggest that all DGH with acute surgical admissions should provide this service
to reduce the morbidity and mortality related to emergency decompression
surgery.
REFERENCES
1 Tekkis PP, et al. The Association of Coloproctology of Great Britain and
Ireland study of large bowel obstruction caused by colorectal cancer. Ann Surg
2004; 240: 76-81.
A353
2 Small AJ, et al. Endoscopic placement of self-expandable metal stents for
malignant colonic obstruction: long-term outcomes and complication factors.
Gastrointest Endosc 2010; 71: 560-572.
Disclosure of Interest: None declared
P0808 ENDOSCOPIC STENT PLACEMENT OR SURGICAL
GASTROJEJUNOSTOMY FOR THE PALLIATION OF MALIGNANT
GASTRIC OUTLET OBSTRUCTION CAUSED BY UNRESECTABLE
OR METASTATIC GASTRIC CANCER
M. Murakami1,*, R. Takenaka1, C. Sakaguchi1, S. Oka1, Y. Baba1, N. Okazaki1,
D. Kawai1, H. Tsugeno1, K. Takemoto1, S. Fujiki1
1
Gastroenterology, Tsuyama, Japan
INTRODUCTION: Malignant gastric outlet obstruction (GOO) is traditionally
treated with gastrojejunostomy (GJJ). Recently, endoscopic placement of a self-
expanding metal stent (SEMS) to the GOO was covered by insurance and spread
widely in Japan because it was a minimally invasive and effective method. The
aim of this study was to verify the usefulness of SEMS compared with GJJ.
AIMS & METHODS: We conducted a retrospective study comparing the
patients treated with endoscopic SEMS placement from April in 2010 to
December 2013 with those treated with GJJ from April in 2000 to December
2013 in the management of malignant GOO caused by gastric cancer. Endoscopic
SEMS placement was performed by using WallFlex duodenal stent (Boston
Scientific, Tokyo, Japan). Following variables were evaluated between the
SEMS group and the GJJ group; age, gender, clinical stage of gastric cancer,
procedure time, Gastric Outlet Obstruction Scoring System (GOOSS) score,
fasting period after placement, period of hospitalization after placement, survival
period after placement, and complications.
RESULTS: The study subjects consisted of 16 patients in the SEMS group and
28 patients in the GJJ group. Between the 2 groups, there were no significant
differences in median age (70 years vs. 72 years), percentage of women (31% vs.
18%), percentage of clinical stage at IV (81% vs. 89%), median GOOSS score (1
vs. 1). The technical success rates were 100% both in the SEMS group and the
GJJ group. Median procedure time for SEMS stent placement was shorter than
that for GJJ (25 minutes vs. 128 minutes; P 5 0.0001). The clinical success rates
were 88% in the SEMS group and 71% in the GJJ group (p 0.28). The median
GOOSS score after SEMS placement was similar to that after GJJ (3 vs. 3).
However, the time to oral intake was significantly less in the SEMS group
than in the GJJ group (2 days vs. 7 days; p 5 0.0001). Early adverse event
(occurring 5 1 week) rates did not differ significantly between the 2 groups:
(6% in the SEMS vs. 7% in the GJJ group). The median postprocedure length
of hospital stay was shorter in the SEMS group than in the GJJ group, but not
significant (17 days vs. 26 days; p 0.13). Median postprocedure survival periods
was similar in 2 treatment groups (68 days vs. 109 days; p 0.85). Late adverse
event (occurring  1 week) occurred in 2 patient in the SEMS group and 3
patients in GJJ group.
CONCLUSION: Endoscopic stent placement is preferable to GJJ in terms of
shorter treatment time and more rapid improvement of food intake. Endoscopic
stent placement seems to contribute to improve quality of life for the palliation of
malignant GOO cause by gastric cancer.
Disclosure of Interest: None declared
P0809 ESOPHAGEAL COVERED STENTS FIXATION USING
ENDOSCOPIC OVER-THE SCOPE CLIPS VERSUS ENDOSCOPIC
SUTURING SYSTEM (WITH VIDEO)
M. Diana1,2,*, L. Swanstrom2, P. Halvax2, A. Le`gner2, Y.-Y. Liu2, S. Cho2,
A. Alzaga2, N. Demartines1, J. Marescaux2
1
Visceral Surgery, University Hospital of Lausanne, Lausanne, Switzerland,
2
General, Digestive and Endocrine Surgery, IRCAD/IHU UNIVERSITY
HOSPITAL STRASBOURG, Strasbourg, France
Contact E-mail Address: michele.diana@ircad.fr
INTRODUCTION: Endoscopic prosthesis migration from the originally stented
area occurs in up to 40% of cases and may lead to serious life-threatening
complications. Endoscopic suture fixation of the stent using the OverStitchTM
Suturing System (Apollo Endosurgery, Inc.) significantly reduces migration.
However, suturing with the OverStitchTM has a steep learning curve and is
time-consuming. A novel memory shape over-the-scope endoscopic clip, the
PadlockTM clip, has been developed recently by Aponos Medical. The device is
a preloaded point & shoot single-use instrument.
AIMS & METHODS: The aim of this study was to demonstrate that the anchor-
ing of a covered Self-Expandable Metallic Stent using the PadlockTM clip is as
effective as endoscopic suturing by means of the OverStitchTM and that
PadlockTM fixation can be faster and user-friendly. Eleven pigs were involved
in this experimental study. A fully covered esophageal stent (Wall-Flex, Boston
Scientific) of 12.3cm in length, 18mm in diameter, was placed under endoscopic
guidance at the esophagogastric junction. Five pigs underwent stent fixation with
1 figure-of-eight suture using the OverStitchTM. In 4 pigs, the stent was fixed by
firing the Aponos Clip over a loop of Vicryl 0, which was attached to the upper
edge of the stent. In two pigs, the stent was placed but not fixed and was used as a
control. A laparotomy was performed and a specifically designed pulling device
made of 4 fishing hooks attached to a plastic ring was anchored to the distal part
of the stent at 4 cardinal points after performing a gastrotomy. A suture attached
to the plastic ring was passed over the holding hook of a Digital Dynamometer
(Chatillon II, Ametek, Inc.). Constant traction was applied on the sutures until
full stent mobilization was achieved. The force required to remove the stent was
recorded.
RESULTS: Mean force to mobilize the stent was higher in the OverStitchTM
group when compared to the PadlockTM group (23.99N; SD 14.91 vs. 19.97N;
A354
SD 7.62), but the difference was not statistically significant. In the 2 control pigs,
the force required was 7 and 11 Newtons respectively. Mean suturing time was
statistically significantly higher when compared to the time required to apply the
PadlockTM clip (455.4sec; SD 144.83 vs. 155sec; SD 12.9; p 0.002).
CONCLUSION: Full-thickness PadlockTM clip application is faster and may
achieve a comparable stent fixation when compared to endoscopic suturing
with the OverStitchTM.
Disclosure of Interest: M. Diana: None declared, L. Swanstrom Consultancy for:
Unpaid consultant for Apollo Endosurgery and Aponos, P. Halvax: None
declared, A. Le`gner: None declared, Y.-Y. Liu: None declared, S. Cho: None
declared, A. Alzaga: None declared, N. Demartines: None declared, J.
Marescaux: None declared
P0810 ENDOSCOPIC DILATATION OF BENIGN PYLORIC STENOSIS:
IS IT A GOOD ALTERNATIVE TO SURGERY?
M. Acharki1,*, M. Bakkar2, N. Kabbaj2
1
EFD hepato gastro enterology, 2EFD hepato gastro enterology, Ibn Sina Hospital,
Rabat, Morocco
INTRODUCTION: Pyloric stenosis is a common complication of ulcerative
disease which requires surgery. The endoscopic dilatation is now a good
alternative.
AIMS & METHODS: Aim: evaluate the efficiency of the endoscopic dilatation
in the managment of benign pyloric stenosis due to ulcer diseases.
It is a prospective study from January 2009 to January 2014 including 21
patients. The dilatation was performed using a hydrostatic balloon.
RESULTS: There were 13 men and 8 women. Mean age was 48 years (35-70
years). 58 dilations were performed. In 11 cases (52 %), patients had ulcer disease
and in 6 cases (29 %) non steroidal anti -inflammatory medication. The duration
of symptoms was 13 months (3 months - 3 years). Vomiting and epigastric pain
were the predominant clinical signs (90%). All patients underwent an upper
endoscopy and had pyloric stenosis and / or pyloro - bulbar stenosis. 12 cases
(57%) had impassable strictures. The average number of dilatations was three per
patient (1-5). 17 patients (81%) had favorable response. The average follow-up
time was 30 months (3-60 months).
CONCLUSION: Through this prospective study, we identified factors of success
and failure of endoscopic dilation in benign pyloro-bulbar stenosis: the passable
nature of the stenosis, the extent of the stenosis, the distance between the pylorus
and the dental arches reflecting gastric distension and food stasis.
Disclosure of Interest: None declared
P0811 PREVIOUS BILIARY STENTING IS NOT REQUIRED BEFORE
ENDOSCOPIC PLACEMENT OF DUODENAL COVERED SELF
EXPANDABLE METAL STENTS
F. Goutorbe1, O. Rouquette1,*, A. Mulliez2, M. Goutte1, A. Abergel1,
M. Dapoigny1, G. Bommelaer1, L. Poincloux1
1
Gastroenterology and Hepatology department, 2Clinical research and innovation
department, CHU ESTAING, Clermont Ferrand, France
Contact E-mail Address: fgoutorbe@chu-clermontferrand.fr
INTRODUCTION: Gastroduodenal uncovered Self Expandable Metal Stent
(SEMS) placement is the first line treatment in advanced malignant gastroduo-
denal obstruction. The main disadvantage of uncovered stents is recurrent
obstruction, mainly due to tumor ingrowth. Covered SEMS (cSEMS) reduce
the re-obstruction rate. As cSEMS are removable they could represent an alter-
native to surgery or endoscopic dilation in benign stricture. However, cSEMS
placement covering the major papilla has been suspected to be responsible of
mechanical occlusion the ampullary of Vater, which could lead to cholangitis or
pancreatitis. Despite the lack of data, some authors recommend concomitant
biliary stenting to guarantee the adequate bile outflow before duodenal cSEMS
placement. Nevertheless, the need for biliary stenting in patient without conco-
mitant biliary stricture before cSEMS placement remains unknown.
AIMS & METHODS: The aim of our study is to compare the occurrence of
jaundice or pancreatitis after duodenal cSEMS placement in patients with biliary
stenting vs patients with no biliary stenting.
All consecutive patients who underwent endoscopic duodenal cSEMS placement
in the second duodenum area between June 2005 and March 2014, because of
obstructive symptoms were assessed. Biliary stenting was performed when
patients presented with associated biliary stricture. Patients with previous or
concomitant biliary stenting (cSEMSBS group) were compared to patients
with no biliary stent (cSEMS group). The primary end point was the occurrence
of jaundice during an observation period of 90 days. Secondary end points were
bilirubinemia at baseline compared to day 10, technical success, clinical effecti-
venes and complications rates, during a follow-up period of 90 days.
RESULTS: 106 patients were included: 53 patients in the cSEMS group (58%
male, mean 66.4/-13.3 y/o) and 53 patients in cSEMSBS group (60% male,
mean 70.4/-11.6y/o). The obstruction was due to cancer in 45% in cSEMS
group and 87% in cSEMSBS group. No case of jaundice was reported in the
cSEMS group or in the cSEMSBS group. We report one case (2%) of edema-
tous pancreatitis after stent removal 90 days after stent placement in the cSEMS
group (p 1). In cSEMS group the mean bilirubin level (mmol/L  SD) was 9.3
5.8 at baseline and 8.4 4.5 at day 10, while in the cSEMS-BS group it was
90.3106.9 at baseline and 34.7 39 at day 10. No significant difference was
observed between the two groups in term of technical success, clinical effective-
ness, migration and other complications. In all patients, endoscopic duodenal
stenting was successful. The global clinical effectiveness was 90%. The overall
migration rate was 25% and the symptomatic migration rate, defined as obstruc-
tive symptoms recurrence, was 16%. Other reported complications were gastro-
intestinal bleeding (2% in cSEMS group vs 4 % in cSEMS-BS group), Duodenal
United European Gastroenterology Journal 2(5S)
perforation (0% in cSEMS group vs 4% in cSEMS-BS group), death from all
causes (13% in cSEms group vs 28% in cSEMS-BS group, p 0.06). We report
3% of stent obstruction due tumor ingrowth.
CONCLUSION: Concomitant biliary stenting is not recommended before cov-
ered duodenal SEMS placement in patients with no concomitant biliary
obstruction.
Disclosure of Interest: None declared
P0812 ENDOSCOPIC THERAPY OF ESOPHAGEAL LEAKS WITH
STENTS: EXPERIENCE IN A REFERRAL CENTER
P. Sousa1,1,*, L. Meireles1, L.C. Freitas1, J. Lopes1, C. Noronha Ferreira1,
R. Palma1, L. Carrilho Ribeiro1, J. Velosa1
1
Gastrenterologia, Centro Hospitalar Lisboa Norte, Hospital de Santa Maria,
Lisboa, Portugal
Contact E-mail Address: patlizbms@gmail.com
INTRODUCTION: Esophageal leaks have an important morbi-mortality. The
best approach is still unclear; some studies show a potential benefit of stents.
Randomized controlled trials are difficult in this area.
AIMS & METHODS: The aim of this study was to evaluate the efficacy of
esophageal stents for the treatment of esophageal leaks.
Retrospective analysis of stent use for esophageal leaks. In a period of 60 months
demographic data, leak etiology, endoscopic procedures, time until closure and
fistulas relapse were analyzed.
RESULTS: 45 consecutive patients were included (29 males; mean age 63 years).
42% had post-operative leaks (10 after gastric sleeve, 6 after Y-Roux and 3 after
subtotal esophagectomy), 42% had malignant esophagopulmonary fistulas (16
esophageal and 3 bronchogenic), 7% had boerhaave syndrome and 9% had
iatrogenic perforation (2 foreign body and 2 after esophageal dilation). The
median time for post-operative fistula detection was 16 days (4-145).
In 36 of the 45 patients the initial approach was using a stent. Of these, in 16
patients this was the only endoscopic therapy done. Metallic stents were inserted
in 40 (13 partially covered, 27 fully covered) and plastic in 5. The rest of patients
had another therapeutic endoscopic procedure - another stent (n 10), through-
the-scope (TTS) clip (n 3), nasoenteric tube (n 10), over-the-scope clip (n 2)
and argon-plasma coagulation (n 6).
The median time for leak closure was 48.5 days (13-308). In 6 cases the fistulas
closure wasnt documented.
In 4 patients there was relapse of the leak in a median of 125 days after the initial
closure. All cases were managed endoscopically - metallic stent (n 3), argon-
plasma coagulation (n 6), nasoenteric tube (n 3) and TTS clip (n 1). In 3
cases there was closure in a median of 27 days after the diagnosis.
In 12 patients the overall endoscopic approach failed and surgery was needed in 8
patients and percutaneous drainage in 4.
The observed complications were: stent migration (n 10), upper GI bleeding
(n 2). There was no need for surgery in any case or death for a procedure
related complication.
CONCLUSION: The use of esophageal stents seems to be a safe and effective
therapy for esophageal leaks.
Disclosure of Interest: None declared
P0813 TREATMENT OF POSTOPERATIVE LEAKS OF THE UPPER
GASTROINTESTINAL TRACT WITH COLONIC SELF-
EXPANDABLE METAL STENTS: SINGLE CENTRE EXPERIENCE
P.R. Sousa1,*, A. Castanheira1, P. Ministro1, R. Araujo1, E. Cancela1,
L.F. Pinheiro2, R. Simao2, J. Castro3, A. Silva1
1
Gastroenterology, 2Surgery 1, 3Surgery 2, Centro Hospitalar Tondela-Viseu,
Viseu, Portugal
Contact E-mail Address: paulacrfsousa@gmail.com
INTRODUCTION: The use of self-expandable metal stents (SEMS) for the
treatment of postoperative leaks of the upper gastrointestinal tract is already
established. However, there are discrepancies between the relatively small caliber
of the esophageal stents available in our center and the post-surgical luminal size,
which may determine an inadequate juxtaposition. As colonic stents have a
bigger diameter, they might be more adequate. Additionally, stents with a
larger diameter might have a lower risk of migration.
AIMS & METHODS: The aim of this study was to evaluate the efficacy and
complications associated with the use of colonic SEMS in the treatment of post-
operative leaks in critical patients. All patients with postoperative leaks of the
upper gastrointestinal tract treated with colonic stents (Hanarostent CCI)
between 2010 and 2013 were retrospectively included.
RESULTS: Four patients with postoperative leaks treated with colonic SEMS
were identified (3 men, 1 woman) with a mean age of 63. The underlying surgeries
were a gastric bypass, an esophagogastrectomy for Boerhaave syndrome, a pri-
mary repair of esophagopleural fistula due to Boerhaave syndrome and an eso-
phagectomy due to squamous cell cancer of esophagus. The leaks were detected
on average 17 days after the initial surgery, and surgical resolution wasnt pos-
sible. In this way, the four cases were of difficult management, and in need of
urgent care. They were all admitted to the intensive care unit.
Stent placement was technically feasible in all patients. There were no cases of
stent dislocation. The median residence time of the stent was 7 weeks, and no
complications were verified when they were removed. The treatment was success-
ful in all patients, with complete healing of the leaks. On follow-up, one of the
patients needs periodic endoscopic dilation due to esophagogastric stenosis.
Another patient died 15 days after stent removal, due to septic shock not related
to the procedure.
CONCLUSION: The placement of colonic SEMS seems to be successful and safe
in the treatment of postoperative leaks of the upper gastrointestinal tract.
United European Gastroenterology Journal 2(5S)
Disclosure of Interest: P. Sousa: None declared, A. Castanheira: None declared, P.
Ministro Consultancy for: MSD, Abbott, Abbvie, Hospira, Ferring Portugal, R.
Araujo: None declared, E. Cancela: None declared, L. Pinheiro: None declared, R.
Simao: None declared, J. Castro: None declared, A. Silva: None declared
P0814 TIPS BEYOND THE CLASSICALLY RECOMMENDED: IN
SEVERE HYPERTENSIVE GASTROPATHY
S. Campos1,*, A. Oliveira1, A. Agostinho2, V. Carvalheira2, D. Gomes1, C. Sofia1
1
Gastroenterology, 2Imagiology, Centro Hospitalar Universitario de Coimbra,
Coimbra, Portugal
Contact E-mail Address: saratcampos@gmail.com
INTRODUCTION: In addition to variceal hemorrhage, upper gastrointestinal
bleeding due to hypertensive gastropathy may also occur in liver cirrhosis with
portal hypertension, contributing to the poor prognosis of these patients. The
portal decompression achieved by transjugular intrahepatic portosystemic shunts
(TIPS) has shown positive results in the treatment/secondary prophylaxis of
variceal hemorrhage, and in that sense, the analysis of their value in other com-
plications of portal hypertension becomes relevant.
AIMS & METHODS: The aim of this study was to evaluate the efficacy and
safety of TIPS in patients with severe hypertensive gastropathy.
Retrospective study including patients undergoing TIPS for severe hypertensive
gastropathy in a hospital in the period between 2000 and 2013, evaluating: demo-
graphic characteristics (age, gender), liver disease (cirrhosis etiology, prior ther-
apy, Child-Pugh, MELD), episode of decompensation (clinical and analytical
parameters) and outcome (effectiveness, complications after TIPS, liver trans-
plantation, death at 30 days and at 1 year).
RESULTS: Of the 8 patients with severe hypertensive gastropathy with recurrent
medical therapy undergoing TIPS, 62.5% were male with a mean age of 53  15
years. In terms of the underlying liver disease: 37.5 % had alcoholic cirrhosis,
average MELD of 17 and Child-Pugh stage C in 50%. TIPS has proved effective
in only 28.6% of the patients. Portosystemic encephalopathy was recorded in
57.4% of the cases. Mortality: 1 case at 30 days and 28.6% at year, both Child-
Pugh C. No other feature was implicated in the prognosis of patients after TIPS
placement. Two patients underwent liver transplantation. The mean follow-up
was 773 days (0-3534 days).
CONCLUSION: Given the low rates of efficacy and high morbidity and mor-
tality rates, TIPS should be carefully weighed in patients with severe hypertensive
gastropathy, especially in those with more advanced liver disease.
Disclosure of Interest: None declared
P0815 TIPS IN REFRACTORY HYDROTHORAX A CONTRIBUTION
TO AN INCREASED RELEVANCE
S. Campos1,*, A. Oliveira1, A. Agostinho2, V. Carvalheira2, D. Gomes1, C. Sofia1
1
Gastroenterology, 2Imagiology, Centro Hospitalar Universitario de Coimbra,
Coimbra, Portugal
Contact E-mail Address: saratcampos@gmail.com
INTRODUCTION: Hepatic hydrothorax (HHT) is a relatively rare complication
of portal hypertension, but potentially severe. Although conservative therapy
may be effective, it is not without risk and refractory cases are not rare. The
portal decompression achieved by transjugular intrahepatic portosystemic shunts
(TIPS) have shown positive results in the treatment of refractory ascites, and in
that sense, the analysis of their value in other complications of portal hyperten-
sion becomes relevant.
AIMS & METHODS: The aim of this study was to evaluate the efficacy and
safety of TIPS in patients with HHT.
Retrospective study including patients with HHT undergoing TIPS in a hospital
in the period between 2000 and 2013, evaluating: demographic characteristics
(age, gender), liver disease (cirrhosis etiology, prior therapy, Child-Pugh,
MELD) episode of decompensation (clinical and analytical parameters) and out-
come (effectiveness, complications after TIPS, liver transplantation, death at 30
days and 1 year).
RESULTS: 15 patients with HHT underwent TIPS, most previously underwent
multiple thoracenteses and all with hypoalbuminemia, 60%4male, mean age 63 
9years, 73% with cirrhosis of alcoholic etiology, mean MELD-16 and 53% with
Child-Pugh B. TIPS was effective in 50% of cases. Portosystemic encephalopathy
was recorded in 66.6% of the cases. Mortality: 20% at 30 days and 40% at year
with septic complications or progression of liver disease. Two cases underwent
liver transplantation. In the univariate analysis, only the hematocrit value had
prognostic value (p 0.016). The mean follow-up was 443 days (1-2250 days).
CONCLUSION: TIPS appears to be a relatively efficient method of control
HHT, making it a valid option in refractory cases despite the high risk of porto-
systemic encephalopathy and mortality. Low hematocrit levels seem to imply a
worse prognosis of patients to be considered for TIPS for refractory HHT.
Disclosure of Interest: None declared
A355
TUESDAY, OCTOBER 21, 2014 9:0017:00
SURGERY II POSTER EXHIBITION HALL XL_____________________
P0816 DIFFERENCES IN MORTALITY BETWEEN ARTERIAL, VENOUS
AND NON-OCCLUSIVE MESENTERIC INFARCTION. A
SYSTEMATIC REVIEW AND META-ANALYSIS OF
OBSERVATIONAL STUDIES
F. Adaba1,*, A. Askari2, S. Gabe2, C. Vaizey2, J. Nightingale2, J. Warusavitarne2
1
Intestinal Failure, 2St Marks Hospital, Harrow, United Kingdom, London, United
Kingdom
Contact E-mail Address: f.adaba@nhs.net
INTRODUCTION: Acute mesenteric infarction is a rare but often lethal event.
Primary vascular aetiology can be of arterial, venous or a Non-occlusive mechan-
ism. Mortality from acute mesenteric infarction may vary with aetiology. The
aim of this study is to determine whether there are differences in mortality
between arterial, venous and non-occlusive mesenteric infarction.
AIMS & METHODS: A literature search was performed via PubMed, Ovid and
Google Scholar. Studies that had reported comparative mortality between arter-
ial, venous and Non-occlusive mesenteric infarction (NOMI) were included.
Odds ratios of mortality were calculated using a Mantel-Haenszel, random
effect model. Meta-regression was attempted, however due to lack of adequate
information in studies, it was not possible.
RESULTS: A total of 1,207 articles were screened. Of which, 20 were suitable for
data synthesis for arterial vs. venous infarction, 16 for NOMI vs. venous infarc-
tion and 15 for Arterial vs. NOMI. When compared with venous infarction,
patients who had arterial infarction were significantly more likely to die during
primary hospital admission (OR 3.47, CI 2.43-4.96, p 50.001). Similarly,
patients with NOMI were over three times more likely to die during hospital
admission compared with those with venous infarction (OR 3.2, CI 1.83-5.6,
p 50.001). There was no difference in mortality rates between arterial infarc-
tion and NOMI (OR 1.08, CI 0.57-2.03, p 0.82)
CONCLUSION: Patients with arterial infarction or NOMI are over three times
more likely to die from mesenteric infarction during primary hospital admission.
Disclosure of Interest: None declared
P0817 A SCORING SYSTEM TO DISTINGUISH SIMPLE FROM
PERFORATED APPENDICITIS BASED ON CLINICAL PLUS
IMAGING FEATURES
J. Atema1,*, M. Leeuwenburgh1, C.Van Rossem2, J. Stoker3, M. Boermeester1 on
behalf of On behalf of the OPTIMA and OPTIMAP study groups
1
Surgery, Academic Medical Center, Amsterdam, 2Surgery, Tergooi Hospital,
Hilversum, 3Radiology, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: j.j.atema@amc.nl
INTRODUCTION: During the last decade, conservative management is sug-
gested to be a safe and effective alternative to appendectomy for selected patients
with non-perforated (simple) appendicitis. However, preoperative selection of
patients with uncomplicated appendicitis is proven to be a challenge.
Computed tomography (CT) is generally accepted as the most accurate test for
the diagnosis of acute appendicitis, but the performance of CT in distinguishing
simple from perforated appendicitis is by far not accurate enough.
AIMS & METHODS: The aim of this study was to analyse clinical and CT
features associated with perforation and to develop a scoring system for the
selection of patients with simple appendicitis.
All patients with a final diagnosis of acute appendicitis were selected from a
prospective database including adult patients with acute abdominal pain. The
final diagnosis was assigned by an expert panel based on perioperative data,
histopathology and at least 3-months of follow-up. Predefined clinical and ima-
ging features were recorded in a structured online case record form. Only patients
in whom CT was performed were included in the present analysis. Medical
literature was searched and several clinical and imaging features suggested to
be associated with perforated appendicitis were selected. Stepwise backward
elimination (p50.05) was used to construct a multivariable regression model
with independent predictors of perforation. The discriminatory capacity of the
model was expressed as the area under the curve (AUC). The model was trans-
formed into a clinically applicable scoring system and a cut-off analysis was
performed to illustrate the consequences in our cohort.
RESULTS: A total of 333 patients with a final diagnosis of acute appendicitis
were identified. A CT was performed in 281 patients of whom 65 (23%) had
perforated appendicitis. The final model for clinical and CT features included;
age 4 45 years (OR 2.726; 95%CI 1.363-5.452), temperature 437.2 (OR 6.066;
95%CI 2.632-13.978), white blood cell count 4 10 x 109/L (OR 4.786; 95%CI
1.532-14.952), c-reactive protein 45 4 mg/L (OR 4.761; 95%CI 2.263-10.016),
appendicolith on CT (OR 2.309; 95%CI 1.142-4.661), destruction of appendiceal
wall on CT (OR 2.370; 95%CI 1.028-5.467) and free extraluminal air on CT (OR
4.026; 95%CI 1.172-13.829). The model had a discriminative value of 0.850
(95%CI 0.801-0.898). A scoring system was constructed and points were assigned
for every variable, with a maximum score of 27 points. Using this score in the
study cohort, 134 (48%) patients were identified with a score of 12 or less of
whom 7 (5%) had perforated appendicitis, resulting in a negative predictive value
of 95%.
CONCLUSION: Using this simple scoring system, a subgroup of patients with
simple appendicitis can be identified based on clinical and CT features with a low
percentage (5%) of false negatives (i.e. patients with perforated appendicitis).
These patients can be considered for treatment options other than
appendectomy.
Disclosure of Interest: None declared
A356
P0818 SURGICAL META-EVIDENCE AND ITS CURRENT
CHALLENGES
J. Delaney1,*, P. Laws2, Y. Salama3, J. Evans3, A. Engel3
1
Northern Clinical School, University of Sydney, 2Prince of Wales Hospital,
3
Department of Colorectal Surgery, Royal North Shore Hospital, Sydney,
Australia
Contact E-mail Address: jdel2642@uni.sydney.edu.au
INTRODUCTION: The aim of this study was to compare the methodological
quality and input paper characteristics of systematic reviews and meta-analyses
done in the medical and surgical literature by performing a systematic "overview
of reviews". Ulcerative colitis (UC) and Crohns disease (CD) were used as the
framework for this comparison as they are relatively common, serious conditions
with medical and surgical therapy options.
AIMS & METHODS: MEDLINE, Embase, CINHAL and the Cochrane
Database were searched to November 2013. Eligible papers were systematic
reviews or meta-analyses that considered a question of therapy in either CD or
UC. Two independent reviewers selected the papers, extracted the data and
scored their methodology using the AMSTAR scoring system. The papers
were categorized into medical therapy (M), surgical therapy (S), or surgical
and medical therapy (MS) groups.
Following retrieval of the sample of meta-evidence papers, the original input
studies used in their creation were identified and a search of MEDLINE,
Embase, CINHAL and the Cochrane Database was performed. A team of
researchers then examined this collection of papers for bibliographic and finan-
cial information.
RESULTS: 500 papers were identified in the meta-evidence search. 114 were
deemed eligible. There was a significant difference in the AMSTAR-rated aver-
age quality of the papers (S 7.36, M 8.87, MS 8.11, ANOVA p 0.016). On
average S papers were published in journals with a lower impact factor (S
3.26, M 5.13, MS 5.32, p50.001). S papers also showed more heterogeneity
(I2: S 37%, M 24%, MS 10%, p50.001). Some 25% of S meta-analyses used
data-sets with significant heterogeneity (I2 4 75%), compared to 8% of M meta-
analyses and 3% of the MS group. Some 5% of S papers were done on data sets
that had I2 values 4 90%.
There was no significant difference in the average number of papers assessed in
each group (S 15.5, M 12.33, MS 15.2, p 0.38), the average number of patients per
meta-paper (S 1,304, M 1,757, MS 2,576, p 0.2), the average time over which
the reviews covered (S 16.1yrs, M 15.2yrs, MS 14.8yrs, p 0.93), the average
number of papers considered within each meta-analysis (S 5.7, M 5, MS 3.8,
p 0.45), or the average number of patients considered within each meta-analysis
(S 632, M 689, MS 473, p 0.12). Considering the conclusions of each meta-
analysis, S meta-evidence was 50% more likely than M meta-evidence to be
unable to make recommendations for practice.
1,443 original input papers were identified, of which 469 were duplicates. Within
the non-duplicate papers (n 974) the average impact factor within the S group
was lower than that of the M and the MS groups (3.805 vs 10.241 & 7.062,
ANOVA p50.001). When compared with S papers, M papers had higher rates
of pharmaceutical sponsorship (M 51% vs S 1%) and twice the level of govern-
ment support (M 14% vs S 7%). Of note, 21% of M papers had corporate
sponsorship but did not list any conflict of interest.
CONCLUSION: Compared to medical meta-analyses, surgical meta-analyses, in
the UC and CD domain, are more likely to be of poorer methodological quality,
are of a greater degree of heterogeneity, and less often offer a positive conclusion.
The input papers used to generate meta-evidence in medical papers have a greater
degree of corporate and government sponsorship, and are more likely to come
from journals with higher impact factors.
Disclosure of Interest: None declared
P0819 ALTERED CORTICAL PROCESSING IN RESPONSE TO RECTAL
STIMULI IN PATIENTS SUFFERING FROM IDIOPATHIC FECAL
INCONTINENCE
S. Haas1,*, C. Brock2,3, K. Krogh4, M. Gram3, L. Lundby1, A.M. Drewes2,3,
S. Laurberg1
1
Department of Surgery P, Aarhus University Hospital, Aarhus C, 2Center for
Sensory-Motor Interaction (SMI), Department of Health Science and Technology,
Aalborg University Hospital, 3Department of Gastroenterology and hepatology,
Mech-Sense, Aalborg University Hospital, Aalborg, 4Neurogastroenterology Unit,
Department of Hepatology and Gastroenterology, Aarhus University Hospital,
Aarhus C, Denmark
Contact E-mail Address: susahaas@rm.dk
INTRODUCTION: The role of intact sensory function of both the rectum and
the anal canal has been recognized to be essential for fecal continence. We
hypothesized that a cause of idiopathic fecal incontinence is related to changes
in the afferent sensory pathways and that this would be reflected in cortical
potentials evoked by mechanical stimulation of the rectum.
AIMS & METHODS: Nineteen healthy women (mean age 5412, mean Wexner
score 1.5) and 20 women suffering from ideopathic fecal incontinence (mean
6113, mean Wexner score 14.5) underwent repeated rapid balloon distensions
of the rectum at the level of discomfort/ urge to defecate under simultaneous
recording of cortical evoked potentials. Single sweep spectral band analysis was
conducted to obtain the relative EEG amplitude within each frequency band.
RESULTS: The latency of the cortical evoked potentials generated in the vertex
electrode of idiopathic fecal incontinence patients was longer than in healthy
subjects (p50.001), but there were no differences in location or strength of
electrical sources in areas involved in the cerebral processing (insula, secondary
somatosensory cortex and mid-cingulate gyrus bilaterally).
United European Gastroenterology Journal 2(5S)
Analysing spectral contents of single sweeps, we found a significant increase in
the alpha (8 - 12 Hz) and beta (12-32 Hz) bands (p50.001) and a significant
decrease in the gamma (32-70 Hz) band (p50.0001) whereas low frequency
bands did not differ. The changes in the gamma band were negatively correlated
to the anal resting- and squeeze pressure as well as the first urge to defecate.
CONCLUSION: Our study indicates that idiopathic fecal incontinence is asso-
ciated with abnormal rectal sensory perception and cortical processing of the
afferent activity.
Disclosure of Interest: None declared
P0820 ENDOSCOPIC INTERNAL DRAINAGE FOR TREATMENT OF
LEAKS FOLLOWING SLEEVE GASTRECTOMY
G. Donatelli1,*, B.M. Vergeau1, J.-L. Dumont1, T. Tuszynski1, P. Dhumane2,
B. Meduri1
1
Unite dEndoscopie Interventionnelle, Hopital Prive des Peupliers, Generale de
Sante, Paris, France, 2General and Laparoscopic Surgery, Lilavati Hospital and
Research Center, Mumbai, India
Contact E-mail Address: donatelligianfranco@gmail.com
INTRODUCTION: The most common complications of sleeve gastrectomy (SG)
are gastric line leaks (GLL). Standard management protocol for GLL is not yet
established. We report our experience about endoscopic internal drainage (EID)
using double plastic pigtails stent changed between 4 and 6 weeks until healing.
AIMS & METHODS: 34 pts (26 F), 43.6 y (23 70) presented GLL 12.8 days (1
97) from surgery. 8 patients underwent single port and 26 laparoscopic SG. 25
patients underwent a second surgery at 10.6 (0 97) days from SG. 9 out 34
patients presented peri-gastric collections and fever. One, two or three plastic
pigtail stents (AdvanixO`, Boston Scientific), according to orifices size and
collection, were delivered with the one end in the collection and the other one
in the stomach. In 26 patients a naso-jejunal feeding tube was inserted and kept
NPO. 2 presented jejunostomy, and 4 kept to eat normal. Endoscopic control
was performed systematically between 4 - 6 weeks, with either re-stenting (if the
leak was still present), or removal (if no extravasation of contrast medium in the
peritoneal cavity was detected), or closure with an OTSC (if contrast material
passed through the crossing stent without concomitant detection in the peritoneal
cavity).
RESULTS: EID was possible in 97% (33/34) of patient. 1 (3%) was perforated
during stenting deliver. 13 patients were healed at first control, 32.3 days (26 54)
from stenting, 2 needed OTSC. At a second control, 61.6 days (48 87) by first
EID, 10 patients respected criteria of good outcome, 4 presented a sealed fistula,
6 needed OTSC. Three patients healed as follows: three changes at 84 days,
fourth change at 135 days, and at 180 days follows 7 changes respectively. 1
patient died, 24h later EID for pulmonary embolism. Overall, 6 out 32 patients
(18.8 %) are still under treatment, and 26/32 (81.2 %) were healed with an
average time of EID treatment of 57.4 days (26 180), they are now symp-
tom-free, on a normal diet at a median follow up of 129 days (2 276).
CONCLUSION: EID is a promising therapeutic mini invasive approach for the
treatment of leaks following SG, well tolerated by patients, despite the need of
multiple endoscopic sessions. It allows draining peri-gastric collections and pro-
motes tissue regrow, permitting to avoid re-surgery.
Disclosure of Interest: None declared
P0821 PERINEAL WOUND PROBLEMS AFTER ABDOMINOPERINEAL
RESECTION FOR RECTAL CANCER; A TWO-INSTITUTIONAL
EXPERIENCE IN THE ERA OF INTENSIFIED ONCOLOGICAL
TREATMENT
G.D. Musters1,*, D.A. Sloothaak1, S. Roodbeen1, A.A. van Geloven2,
W.A. Bemelman1, P.J. Tanis1
1
Surgery, Academic Medical Center, Amsterdam, 2Surgery, Tergooi ziekenhuizen,
Hilversum, Netherlands
Contact E-mail Address: G. D. Musters@amc.nl
INTRODUCTION: Intensified treatment for distal rectal cancer has improved
oncological outcome but at the cost of more perineal wound problems in patients
undergoing an abdominoperineal resection (APR). The aim of this study was to
analyse perineal wound healing after APR with primary perineal wound closure
over time.
AIMS & METHODS: All patients undergoing APR for primary rectal cancer
with primary wound closure between 2000 and 2013 were included and analysed
in three consecutive time periods. Both early (530 days postoperatively) and late
perineal wound complications were determined. Independent risk factors of peri-
neal wound complications were identified using multivariable analysis.
RESULTS: In total 136 patients were identified, of whom 129 patients under-
went primary perineal wound closure. The use of neo-adjuvant (chemo)ra-
diotherapy increased from 58% to 91% and the use of an extralevator
approach increased from 9% to 19%. The rate of complicated perineal wound
healing increased from 18% to 31%. An extralevator approach (OR 3.17; 95%
CI 1.16-8.66) and intra-operative perforation (OR 3.35; 95% CI 1.06-10.57) were
independent predictors for perineal wound complications. No differences in
oncological outcome were found in patients with and without perineal wound
complications. During a median follow-up of 28 months (IQR 14-56), 3% devel-
oped a perineal fistula, in 8% a persistent presacral sinus was diagnosed, and in
8% of the patients a perineal hernia occurred.
CONCLUSION: The increased use of an extralevator approach significantly
increased the perineal wound complication rate over time. Intra-operative per-
foration was also an independent predictor of perineal wound problems.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0822 SEALING BOWEL DEFECTS WITH TISSUE ADHESIVES: A
COMPARATIVE ANALYSIS OF THE CLINICAL, MECHANICAL
AND HISTOPATHOLOGICAL EFFECTS OF 7 SURGICAL
ADHESIVES
K. Vakalopoulos1,*, Z. Wu1, L. Kroese1, K. Lam2, G.-J. Kleinrensink3,
H. Jeekel1, J. Lange1
1
Surgery, 2Pathology, 3Neurosciences, Erasmus MC, Rotterdam, Netherlands
Contact E-mail Address: k.a.vakalopoulos@gmail.com
INTRODUCTION: The use of tissue adhesives (TA) in bowel surgery is gaining
popularity. Sealing bowel defects with TA may be a quick and safe alternative to
suture closure. This study provides information on the sealing capability of
several TA, as well as their histopathological effects on colonic tissue, providing
a tool for the selection of the optimal TA.
AIMS & METHODS: 160 rats received a 0.5 cm incision in the proximal and
distal colon which was then sealed with 1 of the following TA: Histoacryl Flex,
Bioglue, Dermabond, Evicel, Duraseal Xact, Gelatin-Resorcinol-Formaldehyde
and Glubran 2. A control group without TA was also included. Follow-up was 3
or 10 days. Leakage related complications were noted, bursting pressure (BP) and
histopathological analysis were performed.
RESULTS: At 3 days leakage rates were highest in the control group and for
Bioglue, Duraseal Xact and Tissucol. Glubran 2 and Tissucol showed the lowest
Leakage rates. BP was highest in Duraseal Xact, Tissucol and Omnex.
Histopathologically Tissucol, Omnex and the control group showed highest
inflammation scores. At day 10 Controls, Bioglue and Duraseal showed the
highest leakage rates and Tissucol and Omnex the lowest. BP was highest in
Tissucol, Glubran 2 and Histoacryl Flex. Histopathological analysis showed
highest inflammation for Bioglue, Omnex and Tissucol.
CONCLUSION: Sealing of colonic defects with TA is a safe and effective way to
prevent leakage-related complications while maintaining high mechanical
strength. However, large differences exist between the safety and effectiveness
of the available TA. In this study, the cyanoacrylates Histoacryl Flex, Omnex
and Glubran 2 as well as the fibrin glue Tissucol showed lowest leakage rates and
the most inert histopathological profile while maintaining sufficient mechanical
strength.
REFERENCES
1. Vakalopoulos KA, Daams F, Wu Z, et al. Tissue adhesives in gastrointestinal
anastomosis: a systematic review. J Surg Res 2013; 180: 290-300.
2. Vakalopoulos KA, Wu Z, Kroese L, et al. Mechanical strength and rheological
properties of tissue adhesives with regard to colorectal anastomosis: an ex vivo
study. Ann Surg. Epub ahead of print 25 March 2014.
3. Kingham TP and Pachter HL. Colonic anastomotic leak: risk factors, diag-
nosis, and treatment. J Am Coll Surg 2009; 208: 269-278.
4. Pommergaard HC, Achiam MP and Rosenberg J. External coating of colonic
anastomoses: a systematic review. Int J Colorectal Dis 2012; 27: 1247-1258.
5. Spotnitz WD and Burks S. State-of-the-art review: Hemostats, sealants, and
adhesives II: Update as well as how and when to use the components of the
surgical toolbox. Clin Appl Thromb Hemost 2010; 16: 497-514.
6. Reece TB, Maxey TS and Kron IL. A prospectus on tissue adhesives. Am J
Surg 2001; 182(Suppl.): 40S-44S.
Disclosure of Interest: None declared
P0823 CASE CONTROL STUDY OF USEFULNESS OF INTRA-GASTRIC
BALLOON BEFORE BARIATRIC SURGERY IN MORBID OBESITY
A. Ortega1, L.R. Rabago1,*, C. Vicente2, A. Olivares1, M.L. Arias1, A. Castillo1,
A. Alonso1, J. Vazquez Echarri3, N. Herrera3
1
gastroenterology, 2internal Medicine, 3Surgical Department, HOSPITAL
SEVERO OCHOA, Leganes, Spain
Contact E-mail Address: lrabagot@gmail.com
INTRODUCTION: Bariatric surgery has an important morbidity with a scarce
number of reports using intragastric- balloons (IGB-BIB) before surgery trying
to lose weight and subsequently to reduce postoperative complications.
AIMS & METHODS: In the setting of an on-going randomized study of (IGB-
BIB for 6 months before Bariatric surgery [sleeve resection (SR) or gastric
bypass (GB)]) to reduce postoperative complications. We present an interim
case-control study comparing with patients came from our historic surgical
group "gr2" and operated by the same surgical team. We matched cases, by
gender, age ( 5 years) and type of surgery (1:1). The study protocol was
approved by the H. Ethical Committee. All patients provided their informed
consent OBJECTIVE: to evaluate if morbidity (medical and surgical) and hospi-
tal stay will decrease after IGB-BIB treatment, and to check if there was any
relationship between patient (pt) weight before surgery and morbidity
RESULTS: The historic group included 47 pts, 21.7% were male, with a mean
age of 45.9 y-o (SD 10.33), a weight before surgery of 125.05 kg (SD 21.25) and
BMI of 47.42 (SD 6.77). 50% of pts were ASA III. 61% of these pts were
operated with GB. All in all the surgical complications rate was 32.6% (57.1%
of them severe,15pts). The hospital stay was 8 days (P25-75: 6-9). The case-con-
trol study included 48 pts, 24 in each group matched by sex (58.3% women), type
of surgery (66.7% GB and 33.3% SR) and age (gr1, 41.5 y-o, SD 10.04, gr2, 44.4
y-o,SD 10.04, p 0.261). When we compared the age, sex, weight before surgery,
surgical morbidity, hospital stay and ASA score between gr2 and the pts left in
the historic group, we did not find statistical differences. The rate of IGB-BIB
failure was 20,9% in gr1. The gr1 had a lower ASA score than the gr2 (ASA III,
25% vs. 54.2%, p 0.04). The mean weight loss before surgery was greater in gr1
than gr2: 16.7 kg (SD 9.7) vs. 1.6 (SD 6.1), p 0.0001. the morbidity related to the
balloon was 8,3% in gr1. Surgical complications rate was 29.2% in gr1 (38,5% of
them severe) vs 33.3% in gr2(58.8% severe). The reoperation rate was 8,3% in
both groups. The hospital stay was 7 days (p25-75: 5.2-8) in gr1 and 8 d (p25-75:
A357
7-9.2) in gr2, p 0.061. One patient died in gr2 representing a 2.1% rate of mor-
tality in the historic group. We did not find any significative differences either in
surgical morbidity (p 0.781) or in total morbidity [surgical plus balloon morbidity
(p 1)] in the case-control analysis. There was also not difference in morbidity
classified as severe (p 1) in this case control-study. Multivariable logistic
Regression Analysis in all the cohort patients of the study (gr1historic group)
did not find that weight before surgery,type of surgical procedure, age of sex were
predictors of morbidity.
CONCLUSION: 20.9% of pt with IGB-BIB failed to lose weight. It has not been
found yet a decrease in morbidity or hospital stay in the IGB-BIB group
compared with their matched control group in spite of the fact that that the
case group had a lower ASA score. Case control and Multivariate analysis
have not proven any relationship between patient weight before surgery and
morbidity.
Disclosure of Interest: None declared
P0824 ROUTINELY CRP QUANTIFICATION AFTER APPENDECTOMY
DUE TO ACUTE APPENDICITIS A WASTE OF MONEY?
M. Tachezy1,*, I. Anusic1, F. Gebauer1, J.R. Izbicki1, M. Bockhorn1
1
General, Visceral and Thoracic Surgery, University Medical Center Hamburg-
Eppendorf, Hamburg, Germany
Contact E-mail Address: m.tachezy@uke.de
INTRODUCTION: Appendectomy is the most frequent non elective surgical
procedure in general surgery. Until now, indication is generally based on clinical
findings. However, laboratory results such as leukocyte count and C-related
Protein (CrP) are usually determined before and after the surgical procedure,
and clinicians are not infrequently confronted with the question, if a patient can
be discharged with an increasing inflammatory laboratory parameter. A clear
evidence for a prospective value of the parameters and their trend regarding
complications is missing.
AIMS & METHODS: Between November 2004 and April 2010, nine hundred
sixty-nine patients underwent a surgical procedure due to clinically suspected
acute appendicitis. All clinical, laboratory and histopathological data were
obtained from the clinical and pathological records and a quality control data
base containing information 0 (n 243). Laboratory results were correlated with
clinical and histopathological data (t-test, Chi-square test, regression analysis,
ROC curve, respectively).
RESULTS: Eight hundred ninety-two (92%) patients had a histological con-
firmed acute appendicitis; median hospitalisation was 3 days (range 1-38 days).
Overall morbidity was 6.2%; 60 (5.7%) patients suffered from infectious com-
plications. Strongest predictive parameter for complications was a CrP value of
more than 108 mg/l on the first postoperative day with an odds ratio of 16.6
(96% CI 6.4/42.8, p50.001). ROC analysis revealed an AUC of 0.821 with a
Specificity of 88% and Sensitivity of 69%. Patients with below the threshold
suffered from complications in 1.1% in contrast to the patients above with
16.8% (p50.001). In patients without acute appendicitis Operative trauma
causes a CrP increase from less than 5 mg/l up to a median of 30 mg/l (25th
percentile: 8mg/l and 75th percentile 100mg/l) on POD 1 to 47 mg/dl (25th per-
centile: 23mg/l and 75th percentile 125mg/l) on POD 2.
CONCLUSION: Operative trauma due to a non-acute inflamed appendectomy
causes a significant increase of serum CrP, which must be taken into account for
clinical assessment after appendectomy. Therefore, a moderate elevation of CrP
values postoperatively is no general contraindication for discharge. However,
postoperative determination of CrP serum values after appendectomy seems to
be an effective predictor for complications and should therefore be measured in
the clinical routine.
Disclosure of Interest: None declared
P0825 ENDOSCOPIC ELECTROCAUTERY IN PATIENTS WITH
IMPLANTABLE CARDIAC DEVICES
M.K. Baeg1,*, S.-W. Kim1, S.H. Ko1, C.-H. Lim1, H.H. Kim1, J.S. Kim1,
Y.K. Cho1, J.M. Park1, B.-I. Lee1, I.-S. Lee1, M.-G. Choi1
1
Internal Medicine, College of Medicine, the Catholic University of Korea, Seoul,
Korea, Republic Of
Contact E-mail Address: baegmk@catholic.ac.kr
INTRODUCTION: Patients with implantable cardiac devices who undergo
endoscopic electrosurgery are at risk of potentially harmful electromagnetic
interference (EMI). However, few reports on the association between the two
exist.
AIMS & METHODS: We aimed to analyze the effects of endoscopic electro-
surgery in patients with implantable cardiac devices. The medical records of
patients who underwent endoscopic procedures requiring the use of electrosur-
gery, such as snare polypectomy, endoscopic submucosal dissection (ESD), and
endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic
sphincterotomy (EST), were analyzed retrospectively. Patients with implantable
cardiac devices had their medical records reviewed, which included postproce-
dural patient symptoms, demographic data, and outpatient follow-up data.
Electrical data, including preprocedural and postprocedural arrhythmia records,
such as pacemaker interrogation, 24 h Holter monitoring, and electrocardio-
gram, were also reviewed.
RESULTS: Forty-nine patients who underwent 59 procedures were analyzed.
Fifty procedures were performed in 43 patients with pacemakers, and nine pro-
cedures were performed in six patients with implantable cardioverter-defibrilla-
tors. There were 44 colon snare polypectomies, one colon ESD, one gastric snare
polypectomy, five gastric ESDs, and eight ERCPs with EST. Fifty-five cases of
electrical follow-up were observed, with two postprocedure changes noted that
were not caused by electrosurgical EMI. Thirty-one pacemaker interrogations
A358 United European Gastroenterology Journal 2(5S)
had recordings of the procedure, with two cases of asymptomatic tachycardia have shown significantly decreased leak rates in diverted patients with less
events. All patients were asymptomatic, and no adverse events after the proce- severe clinical consequences. The last decade, a trend has been seen towards
dure were reported. more extensive medical treatment in IBD patients, leaving refractory patients
CONCLUSION: Our study reported no adverse events from endoscopic electro- in a worse condition when it comes to surgery. Since timely identification of
surgery in patients with implantable cardiac devices, which suggests that this high-risk patients could influence surgical decision-making and diminish the
procedure is safe. However, because of the possibility of EMI, recommendations risk for complications, the aim of our study is to identify clinical and surgical
regarding endoscopic electrosurgery should be followed. parameters associated with AL and to analyse whether a defunctioning ileostomy
Disclosure of Interest: None declared should be considered as standard care in patients undergoing IPAA.
AIMS & METHODS: In a retrospective study, 691 patients undergoing IPAA
for IBD, dysplasia, or FAP were identified from prospectively maintained data-
P0826 RISE IN TROPONIN T AFTER MAJOR GASTROINTESTINAL bases of three large IBD centres. The creation of an ileostomy was left at the
SURGERY IS ASSOCIATED WITH OCCURRENCE OF NEW discretion of the surgeon. AL was defined as any leak confirmed by either con-
MAJOR CARDIOVASCULAR EVENTS trast extravasation on imaging or by re-laparotomy. Multivariable regression
P.W. Chiu1,*, M.T. Chan2, S.S. Ng1, A.Y. Teoh1, S.K. Wong1, E.K. Ng1 models were developed to identify risk factors for AL.
1
Department of Surgery, 2Department of Anesthesia and Intensive Care, THE RESULTS: In 305 IBD patients (49.1%), an ileostomy was created during IPAA.
CHINESE UNIVERSITY OF HONG KONG, Hong Kong, China A comparable overall leak rate was found in the stoma group when compared to
Contact E-mail Address: philipchiu@surgery.cuhk.edu.hk non-diverted patients (16.7% vs 17.1%, p 0.92). This unexpected finding of
high leak rates despite stoma formation could probably be explained by the
INTRODUCTION: A risk in Troponin T is associated with myocardial infarc- increased use of anti-TNF (12.6% versus 4.6%, p50.001), steroids (33.0% vs
tion, cardiovascular death and heart failure. Recently, an international prospec- 12.1%, p50.001), and weightloss (45% of bodyweight) (14.6% vs 8.5%,
tive cohort study recently suggested a significant association between peak p 0.02) when compared to non-diverted patients. Despite having a stoma, a
postoperative Troponin T (TnT) within three days after surgery and 30-day high leak rate (40.0% vs 15.1%, p 0.02) was found in patients treated with a
mortality. However, there is no study to investigate the long term risk of cardi- combination of anti-TNF and steroids. This was also emphasized by the fact that
ovascular events among those with elevated troponin T level after surgery. This patients undergoing subtotal colectomy with IPAA at a later stage (weaned of
study aimed to investigate elevated Troponin after gastrointestinal surgery and 3 medication) had a significantly decreased leak rate when compared to patients
year outcomes. undergoing primary IPAA (11.6% vs 20.7%, p 0.003). Multivariable regression
AIMS & METHODS: This is a prospective cohort study including patients age models demonstrated, long-term disease course (OR 2.01, 95%CI 1.273.19),
above 45 years who underwent either elective or emergency upper or lower GI high ASA score (OR 1.94, 95%CI 1.093.47) and a combination of anti-TNF
surgery under general anesthesia. Those recruited had measurement of peak and steroid treatment (OR 5.61, 95%CI 1.7118.48) as independent risk factors
troponin T (TnT) levels by fourth generation TnT assay. The data for assessing for AL.
perioperative mortality and cardiovascular diseases were collected, including CONCLUSION: These results imply that in daily practice surgeons perform
baseline demographics, smoking status, history of cardiovascular disease, type ileostomy in more fragile and disease affected patients. This strategy seems inef-
of surgery performed as well as clinical outcomes. The primary outcome was 3 fective in the prevention of AL in these series implicating that a staged procedure,
year mortality after surgery. Secondary outcomes included new major cardiovas- that is subtotal colectomy followed by completion proctectomy and IPAA after
cular events (which were defined as myocardial infarction, stroke, deep vein weaning of the medication, is more appropriate when preoperative risk factors
thrombosis and pulmonary embolism), new use of anti-platelet medication (e.g. are identified. Long-term disease course, high ASA score, and a combination of
aspirin, clopidogrel) and new use of anti-coagulation drugs (e.g. warfarin) within anti-TNF and steroid treatment within 3 months before IPAA were all indepen-
3 years after surgery. dent risk factors for AL.
RESULTS: A total of 213 patients were recruited including 128 male and 85 Disclosure of Interest: None declared
female. 53 patients underwent upper gastrointestinal surgery and 152 underwent
lower gastrointestinal surgery. 28 patients (13.1%) had elevated peak troponin T
level (40.01ng/mL) in at least one measurement within 3 days after surgery. 5 TUESDAY, OCTOBER 21, 2014 9:0017:00
out of 213 patients drop out of the study with 97.7% of patients completed 3-year IBD II POSTER EXHIBITION HALL XL_____________________
follow-up. There was no difference in 3 year mortality between those with and
without elevation of TnT after surgery. Those in the elevated TnT group sus- P0828 DIFFERENTIAL EXPRESSION OF TRPM6 AND TRPM7
tained significantly higher rate of cardiovascular events (57.1% vs 10.4%; p 5 FOLLOWING INTESTINAL INFLAMMATION EMERGING NEW
0.001) and also higher use of anti-platelets agents (30% vs8.2%; p 0.009) within PATHWAYS OF CHRONIC INFLAMMATION AND DIARRHEA
3 years after surgery when compared to the normal TnT group. There was no F. Scaldaferri1,*, V. Petito1, V. Trapani2, L. Lopetuso1, D. Scannone2,
difference in 3 year cancer recurrence between the two groups. A. Boninsegna2, A. Sgambato2, F. Wolf2, A. Gasbarrini1
1
Internal Medicine Department, Gastroenterology division, 2Pathology
Non-elevated Department, Catholic University of Sacred Heart of Rome, Rome, Italy
Elevated Troponin Troponin T
T group (TnT) group (non-TnT) INTRODUCTION: IBD patients display a variety of nutritional deficiencies
(n 28) (n 185) P value because of decreased nutrient intake or absorption and/or increased losses.
Magnesium (Mg) is a critical cofactor for numerous enzyme systems and its
Age 75 (51-99) 68 (45-90) 0.002y deficiency may result in several clinical manifestations. Recent evidence
showed that Mg participates in immune system regulation. Intestinal mucosa
BMI 22.70 (15.36-30.03) 22.10 (14.91-29.29) 0.426 and kidneys, are the natural access routes for magnesium into the blood
Gender M:F 15/13 113/72 0.450 stream which involves cation channels and transporters, like TRPM-6 and -7.
Upper GI Surgery 6 (22.2%) 47 (26.4%) 0.644 Few information exist on Mg in IBD pathogenesis.
Lower GI Surgery 21 (77.8%) 131 (73.6%) AIMS & METHODS: The aim of the study is to assess whether Mg receptors
TRPM-6 and -7 are involved in an experimental model of colitis. DSS colitis was
History of coronary 8 (28.6%) 7 (3.8%) 50.001y induced in C57BL/6 mice. 5 Mice received 2.5% DSS in tap water for 5 days and
artery disease then sacrificed, while controls received only water. 5 further mice received 2.5%
History of Diabetes 8 (28.6%) 41 (22.2%) 0.453 DSS for 5 days and then exposed to water for further 7 days to observe recovery.
Occurrence of new 16 (57.1%) 19 (10.4%) 50.001y At the sacrifice plasma was collected from each animal, stored at -80 C and then
cardiovascular assessed for Mg content by atomic absorption spectroscopy; a first section of
events in 3 years liver, kidney and bowel were snap frozen and then analized by Real Time (RT)-
New use of aspirin / 6 (30%) 14 (8.2%) 0.009y PCR for TRPM-6 and -7; a second section of each was fixed in 4% formalin and
Clopidogrel in 3 years embedded in paraffin for immunohistochemistry (IHC).
RESULTS: As expected mice exposed to DSS for 5 days developed a mild colitis,
which was associated to lower Mg plasma concentration (mean value 0.64mM)
compared to healthy controls (mean value 0.77 mM). At IHC and RT-PCR
CONCLUSION: Patients with elevated TnT after major gastrointestinal surgery analysis TRPM-6 and -7 expression did not differ in liver and kidney among
had significantly higher risk of cardiovascular events in 3 years after surgery. healthy and colitic mice. On the contrary, their expression in bowel decreased
Disclosure of Interest: None declared drastically in colitic mice. By IHC, we observed a decrease of TRPM6 expression
and a change of localization of TRPM7 within enterocytes from apical to baso-
lateral position. In recovered mice, the intestinal expression of
P0827 DEFUNCTIONING ILEOSTOMY DOES NOT PREVENT TRPM-6 and -7 was restored.
ANASTOMOTIC LEAKS AFTER RESTORATIVE CONCLUSION: Mg plasma concentration decrease during active colitis. This
PROCTOCOLECTOMY; A MULTICENTER EVALUATION OF observation paralleled the decrease of intestinal TRPM-6 and -7 expression.
CLINICAL AND SURGICAL RISK FACTORS Further experiments are required to show the immunological consequences of
S. Sahami1,*, C. Buskens1, P. Tanis1, T. Young Fadok2, A. De Buck van this observation.
Overstraeten3, A. DHoore3, W. Bemelman1 Disclosure of Interest: None declared
1
Surgery, AMC, Amsterdam, Netherlands, 2Surgery, Mayo Clinic, Phoenix,
United States, 3Surgery, UZ Leuven, Leuven, Belgium
Contact E-mail Address: s.sahami@amc.uva.nl
INTRODUCTION: Anastomotic leakage (AL) is a serious complication after
restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) that
could lead to pelvic sepsis and ultimately to pouch failure. Previous studies
United European Gastroenterology Journal 2(5S)
P0829 HIRSUTENONE AMELIORATES EPITHELIAL BARRIER
DISRUPTION THROUGH CONVERGENCE OF EGFR/AKT AND
ERK1/2 PATHWAYS ON HEME OXIDASE-1 INDUCTION IN HUMAN
INTESTINAL EPITHELIAL CELLS
W.-Y. Jiang1,2, H. Jin1,2, G.S. Seo3, S.H. Lee1,2,*
1
College of Pharmacy, Wonkwang University, 2BK21plus program & Department
of Smart Life-Care Convergence, Wonkwang University, Graduate School,
3
Digestive Disease Research Institute, Wonkwang University College of Medicine,
Iksan, Korea, Republic Of
Contact E-mail Address: gsseo@wku.ac.kr
INTRODUCTION: Oxidative stress-induced disruption of epithelial tight junc-
tions (TJ) plays a critical role in the pathogenesis of intestinal disorders, includ-
ing inflammatory bowel disease (IBD).
AIMS & METHODS: The current study investigated the protective effect of
diarylheptanoid hirsutenone against disruption of the intestinal barrier in vitro
and in a mouse model of colitis. Caco-2 cells were stimulated with tert-butyl
hydroperoxide (t-BH). Monolayer permeability was assessed by measuring the
transepithelial electrical resistance and inulin flux. Colitis was induced in mice by
intrarectal administration of trinitrobenzene sulfonic acid (TNBS). The mRNA
and protein levels were analyzed by real-time polymerase chain reaction (PCR)
and immunoblotting, respectively.
RESULTS: Hirsutenone prevented the t-BH-induced increase in permeability by
inhibiting the reduction in zonula occludens-1 (ZO-1) expression, and rapidly
stimulated tyrosine phosphorylation of the epidermal growth factor receptor
(EGFR). Hirsutenone-mediated protection against the loss of ZO-1 depends
on the activation of both ERK1/2 and Akt signaling pathways. Interestingly,
hirsutenone-mediated activation of Akt, but not ERK1/2, signaling was EGFR-
dependent. Hirsutenone increased heme oxygenase-1 (HO-1) expression through
both EGFR/Akt- and ERK1/2-dependent pathways, contributing to the protec-
tive effects against TJ dysfunction. Hirsutenone administration improved the
clinical parameters and tissue histological appearance, stimulated HO-1 expres-
sion, attenuated reduction of ZO-1 and occludin mRNA, and promoted BrdU
incorporation in the colonic epithelium of TNBS-treated mice.
CONCLUSION: Hirsutenone reversed disordered intestinal permeability by acti-
vating EGFR/Akt and ERK1/2 pathways, which are involved in HO-1 expres-
sion regulation. These findings highlight the potential of hirsutenone for clinical
applications in the treatment of IBD.
Disclosure of Interest: None declared
P0830 DIFFERENTIAL EXPRESSION IN ALPHA7 NICOTINIC
RECEPTOR IN MUCOSAL MACROPHAGES OF IBD PATIENTS: A
ROLE FOR NICOTINE MODULATION OF INFLAMMATION?
L. Spagnol1,2, G. Girardin1,*, P. Brun2, M. Scarpa2,3, M. Scarpa3, R. DInca`1,
G.C. Sturniolo1, I. Castagliuolo2, F. Galeazzi1
1
Dpt of Surgical, Oncologicall and Gastroenterological Science, Section of
Gastroenterology, Padova University-Hospital, 2Dpt of molecular medicine,
Microbiology and clinical microbiology, 3Dpt of Surgical, Oncologicall and
Gastroenterological Science, Surgical Oncology Unit, Veneto Institute of
Oncology, Padova, Italy
Contact E-mail Address: giulia.girardin@gmail.com
INTRODUCTION: It is well accepted that in animal models of intestinal inflam-
mation nicotine activates a cholinergic counter-inflammatory mechanism
through the alpha7 nicotinic acetylcholine receptors (7nAChR). However in
inflammatory bowel diseases (IBD) nicotine shows opposing effects on intestinal
inflammation: its beneficial in ulcerative colitis (UC) while it increases risk of
surgery and relapse in Crohns disease (CD).
AIMS & METHODS: In this study we measured 7nACh expression on periph-
eral and intestinal mucosa-derived macrophages from patients with UC, CD and
healthy controls (HV) and evaluated the effect of nicotine on LPS-induced cyto-
kines production in macrophages. Peripheral blood derived macrophages (Mc)
were obtained by supplementing blood monocytes from UC and CD patients (in
clinical remission) and HV with M-CSF (7 days). 7nAChR mRNA and protein
levels were evaluated by qRT-PCR and FACS analysis using -bungarotoxin
(Bgt)-FITC. Mc were pre-incubated with nicotine (1mg/ml 30min) and then
stimulated with LPS (1mg/ml 24 hrs). TNF levels were measured on supernatant
using ELISA. Colonic mucosa macrophages (Mi) were isolated from biopsies
of UC (n 12), CD (n 11) and HV (n 17) and 7nAchR expression was PPAR during UC remains challenging and of therapeutic interest. Mucosal
evaluated by FACS analysis using Bgt-FITC. Macrophages were incubated
for 24 hrs with LPS (1mg/ml) in presence or absence of nicotine (1mg/ml) and
TNF and IFN assessed by staining with specific antibodies and cytofluori-
metric analysis.
RESULTS: Mc from UC showed greater 7nAchR mRNA levels then cells
from CD (p 0.006), while no differences were found with HV. FACS analysis
confirmed greater 7AChR expression in UC patients than in CD (90.75 Gmean
in UC Vs 15.62 Gmean in CD, p 0.031) but not in HV. Although nicotine
significantly decreased LPS-stimulated TNF release in Mc from HV, CD
and UC, no differences were observed among groups. Indeed, in UC derived
Mi 7nAChR levels were significantly higher than in CD and HV cells
(p50.01 vs both). Furthermore, nicotine significantly specifically reduced LPS-
induced TNF upregulation in Mi from UC patients (from 18.912.57 to
10.811.99 %fluorescence, p 0.013) but not in CD and HV whereas nicotine
had no effect on LPS-induced IFN upregulation in Mi in the different experi-
mental groups.
CONCLUSION: The selective 7nAchR upregulation in Mi from UC patients
and their responsiveness to the anti-inflammatory effects of nicotine may explain
nicotines protective effects in UC but not in CD patients.
Disclosure of Interest: None declared
A359
P0831 NOTCH SIGNALING AND TNF-A SYNERGISTICALLY
PROMOTES INTRACELLULAR PROTEIN ACCUMULATION OF
OLFM4 IN THE INFLAMED MUCOSA OF ULCERATIVE COLITIS
G. Ito1,*, R. Okamoto1,2, H. Shimizu1, S. Fujii1, T. Nakata1, K. Suzuki1,
K. Tsuchiya1, T. Nakamura1, M. Watanabe1
1
Gastroenterology and Hepatology, 2Center for Stem Cell and Regenerative
Medicine, Tokyo medical and dental university, Tokyo, Japan
Contact E-mail Address: rokamed2@tmd.ac.jp
INTRODUCTION: The intestinal epithelium is maintained by the stem cell
residing at the bottom of the crypt. Olfactomedin-4 (OLFM4) is one of the
specific marker genes of the human intestinal stem cell. The gene encodes secre-
tory-type, as well as intracellular-type, OLFM4 proteins. Reports have shown
that secretory-type OLFM4 facilitates cell adhesion and may take part in muco-
sal defense, whereas intracellular-type OLFM4 can exhibit anti-apoptotic prop-
erty. Also, it has been shown that the expression and secretion of OLFM4 is
upregulated in the inflamed mucosa of ulcerative colitis (UC), where Notch
signaling is highly activated. However, the expression of the intracellular-type
OLFM4 protein in the inflamed mucosa, or the mechanism regulating its expres-
sion, remains unclear.
AIMS & METHODS: We aimed to identify the expression of intracellular-type
OLFM4 in the normal and inflamed mucosa of the human colonic tissue, and
also to clarify the molecular mechanism regulating its expression in the inflamed
mucosa. Expression of intracellular-type OLFM4 in colonic tissues of normal
and UC patients was analyzed by immunohistochemistry (IHC). Human colonic
epithelial cell lines, Ls174T and DLD1, were employed to analyze the expression
of OLFM4 in response to various inflammatory stimuli. Involvement of Notch
signaling in OLFM4 protein expression was examined by using a sub-line of
Ls174T cells (Ls174T-NICD cells) in which Doxycycline-dependent activation
of Notch signaling can be induced. Using those cell-lines, the expression of
secretory-type OLFM4 protein was quantified by ELISA, whereas that of intra-
cellular-type OLFM4 protein was examined either by immunoblot analysis or by
immunocytochemistry.
RESULTS: IHC analysis of the normal human colon tissues showed that
OLFM4 is expressed mostly at the apical surface of epithelial cells residing at
the lower crypt, indicating dominant expression of secretory-type OLFM4.
However, in the inflamed mucosa of UC patients, an increased number of colonic
epithelial cells clearly expressed OLFM4 in their cytoplasm, indicating high-level
expression of intracellular-type OLFM4. In vitro analysis using human colonic
epithelial cell-lines showed that, among various pro-inflammatory cytokines,
TNF- significantly upregulates secretion of OLFM4, but do not promote accu-
mulation of the intracellular-type OLFM4. In contrast, forced activation of
Notch signaling never induced secretion of OLFM4, but induced accumulation
of intracellular-type OLFM4. Upon addition of TNF- under forced activation
of Notch signaling, those stimuli synergistically up-regulated the accumulation of
intracellular-type OLFM4 protein to a remarkably high-level, but did not give
any additional change to secretion of the OLFM4 protein.
Immunocytochemistry clearly confirmed the cytoplasmic accumulation of
OLFM4 protein by the synergistic effect of TNF- and Notch activation.
CONCLUSION: Notch signaling and TNF- synergistically promotes accumu-
lation of intracellular-type OLFM4 protein in human colonic epithelial cells. As
it has been suggested that those type of OLFM4 protein can exhibit anti-apop-
totic function, such an accumulation may contribute to protect human colonic
epithelial cells in the inflammatory environment.
Disclosure of Interest: None declared
P0832 PPAR-GAMMA EXPRESSION IN THE COLON IS REGULATED
BY THE MIR27A UNDER HYPOXEMIC CONDITION
G. Bouguen1,2,*, J.-B. Delobel1, C. Rauch1, B. Clement1, L. Dubuquoy3,
A. Corlu1, L. Siproudhis1,2
1
INSERM U991, Universite de Rennes 1, 2Service des maladies de lAppareil
Digestif, CHU Pontchaillou, Rennes, 3INSERM U995, Universite de Lille 2, Lille,
France
Contact E-mail Address: guillaume.bouguen@chu-rennes.fr
INTRODUCTION: The peroxisome proliferator-activated receptor- (PPAR)
is a key factor of mucosal homeostasis and the pharmaceutical target of 5-ami-
nosalycilates. Thus, understanding of the primarily decrease expression of
hypoxemia has been well described during UC. The aim of the study was to
assess and to study the link between hypoxia and PPAR expression in intesintal
epithelial cell during UC.
AIMS & METHODS: In Vitro, PPAR mRNA and protein were quantified in
various epithelial cell lines 1) during exposure to hypoxia (1%O2) at several time
points 2) after chemical induction of HIF-1 3) after transfection of miR-27a or
knockout of miR-27a (a microRNA induced by hypoxia and with high affinity to
PPAR in silico) and 4) after stimulation by sildenafil (a phosphodiesterase type
5 inhibitor used for blood vessel dysfunction). Ex vivo, PPAR and miR27a
expressions were quantified from mucosal biopsies of surgical specimens from
controls or patients with UC.
RESULTS: In vitro, exposure of Caco-2 and HT29 cells to hypoxia (1% O2)
decreased significantly mRNA and protein expression of PPAR (at least 50%)
as compared to normoxic condition (21% O2) at days 2. To assess the link
between hypoxia and the decreased expression of PPAR, we first induced
HIF-1 expression, a key factor of cells response under hypoxic condition, by
chemical treatment of cultured cells lineages (deferoxamine, cobalt chloride and
dimethyloxaloylglycine). No effect was observed either on PPAR expression
neither on miR27a expression. Regarding this result suggesting an independent
HIF-1 way that controls PPAR expression during hypoxia, we focused on
A360
miR-27a. MiR-27a was induced by hypoxia in epithelial cells. When miR-27a
was overexpressed by transfection in caco-2 cells during normoxic condition,
PPAR expression was decreased. Conversely, PPAR was not affected by
hypoxia after knockout for miR27a of caco-2 cells by transfection of miR-27a
inhibitors. Ex vivo, we confirmed a decreased of PPAR expression in colonic
mucosa of patients with UC and higher miR-27a expression as compared to
controls. In order to affect the variation of PPAR expression during hypoxia
we used the sildenafil. The sildenafil raised PPAR expression in caco-2 cells
exposed to hypoxia. Furthermore the use of sildenafil resulted in the absence of
overeexpression of miR-27a expression during hypoxia.
CONCLUSION: A direct relationship was observed between hypoxia and
PPAR expression. Mir-27a which is overexpressed during hypoxia and in
patients with UC might be the key factor involved during hypoxia to control
PPAR expression. These results open new insight into the pathophysiology of
UC and the role of hypoxia as well as new therapeutic strategy such as the use of
sildenafil.
Disclosure of Interest: None declared
P0833 MECHANISMS UNDERLYING THE EFFECTS OF CALCITONIN
GENE-RELATED PEPTIDE IN A RAT COLITIS MODEL
H. Yamasaki1,*, R. Yamauchi1, K. Kuwaki1, S. Yoshioka1, H. Takedatsu1,
K. Mitsuyma1,2, T. Torimura1
1
Department of Medicine, 2Infllamatory Bowel Disease Center, KURUME
UNIVERSITY SCHOOL OF MEDICINE, Kurume, Japan
INTRODUCTION: Calcitonin gene-related peptide (CGRP), a vasodilative neu-
ropeptide, is involved in potent tissue repair and anti-inflammatory actions.
Previous studies have shown that the administration of CGRP prevents colonic
injury. However, the mechanism of action responsible for the effect of CGRP on
colitis remains unknown.
AIMS & METHODS: Colitis was induced by the oral feeding of 3% dextran
sulfate sodium to rats for up to 7 days. After the induction of colitis, CGRP (200
g/L/day) was administered via the tail vein twice a day for 7 consecutive days.
Disease severity was assessed by clinical and endoscopic evaluation, and histo-
logic scoring. The tissue levels of pro-inflammatory cytokines (interleukin [IL]-
1, IL-6, and tumor necrosis factor [TNF]-) and CGRP receptors (receptor
activity-modifying protein-1 [RAMP1] and calcitonin receptor-like receptor)
were determined using real time-PCR. Bone marrow cell induction and colonic
blood flow were also investigated. Additionally, the cytokine response in periph-
eral blood mononuclear cells stimulated by lipopolysaccharide with or without
CGRP was examined in vitro.
RESULTS: The administration of CGRP, but not a control vehicle, improved
the clinical disease activity (P 0.009) and the endoscopic disease activity
(P 0.009). CGRP decreased the mRNA levels of IL-1 (P 0.032), IL-6
(P 0.032) and TNF- (P 0.016) and increased the mRNA level of RAMP1
(P 0.001). CGRP increased the colonies of CFU-GM in the bone marrow
(P 0.016) and the number of endothelial progenitor cells in the peripheral
blood (P 0.040) and enhanced the colonic blood flow (P 0.032). The
mRNA and protein levels of the inflammatory cytokines in lipopolysaccharide-
stimulated peripheral blood mononuclear cells were significantly reduced after
the addition of CGRP in vitro.
CONCLUSION: The administration of CGRP effectively suppresses colonic
injury through the down-regulation of pro-inflammatory cytokines and the up-
regulation of protective events, including bone marrow-derived cell induction, in
addition to promoting colonic blood flow. Consequently, CGRP is an attractive
and novel therapeutic target for the treatment of inflammatory bowel disease.
Disclosure of Interest: None declared
P0834 SERUM IL-23 DIFFERENTLY CORRELATES WITH COLONIC
MMP-9/TIMP-1 AND MMP-9/TIMP-2 IN CROHNS DISEASE, BUT
NOT ULCERATIVE COLITIS PATIENTS
A. Piechota-Polanczyk1, M. Jonakowski1, A. Pilarczyk1, M. Wlodarczyk2,
A. Sobolewska2, M. Wis niewska-Jarosinska2, J. Fichna1,*
1
Department of Biochemistry, 2Department of Gastroenterology, MEDICAL
UNIVERSITY OF LODZ, Lodz, Poland
Contact E-mail Address: jakub.fichna@umed.lodz.pl
INTRODUCTION: Intestinal alterations in IBD are triggered and sustained by
over-expression of pro-inflammatory cytokines. Cytokine quantification may
become a non-invasive tool to monitor the disease progression and effectiveness
of therapy, or assist in understanding disease etiology. Currently, there are lim-
ited non-invasive biomarkers for monitoring IBD progression; however, the role
of selected cytokines like IL-23 and IL-17, or proteolytic proteins like matrix
metaloproteinases (MMP) or their tissue inhibitors (TIMP), is under
consideration.
AIMS & METHODS: The aim of this study was to evaluate if IL-17 and IL-23
correlate with MMP-9/TIMP complexes in IBD and if those parameters differ in
affected and unaffected colon mucosa.
Serum and biopsy specimens from affected and unaffected colonic mucosa of 19
patients with IBD (9 with ulcerative colitis, UC and 10 with Crohns disease, CD)
and 8 controls were included in our study. Serum and tissue cytokines, and tissue
MMP-9/TIMP-1 and MMP-9/TIMP-2 were quantified at the protein level by
ELISA.
RESULTS: The UC subjects had significantly lower serum IL-23 (p 0.002) and
slightly higher serum IL-17 level (p 0.09) compared with control. In unaffected
tissues, there was a significant decrease in IL-23 content (p 0.002 vs. control).
In CD patients no difference in serum IL-23 or IL-17 content was measured;
however, both IL-23 and IL-17 were significantly decreased in unaffected colon
United European Gastroenterology Journal 2(5S)
tissues (p 0.00003 and p 000002 vs. control). The levels of IL-23 or IL-17 in
affected tissues from UC and CD groups were comparable.
As IL-17/IL-23 axis directly influences MMP-9 activity, we measured the con-
centration of MMP-9 in complex with TIMP-1 or TIMP-2. The UC group had
significantly higher MMP-9/TIMP-1 level in unaffected tissue compared with
control (p 0.001), while in CD an opposite tendency was observed.
Regarding MMP-9/TIMP-2, there was a decrease in unaffected tissue in both
UC and CD groups compared with control (p 0.07 and p 0.08, respectively).
Further analysis revealed that IL-23 correlates with MMP-9/TIMP-1 in UC and
with MMP-9/TIMP-2 in CD. In the UC group serum IL-23 negatively correlated
with MMP-9/TIMP-1 in unaffected tissue (r -0.903), but positively in affected
colon sections (r 0.72). In CD subjects, there was a strong negative correlation
between serum IL-23 and MMP-9/TIMP-2 in unaffected tissue (r -0.94); and
positive correlations between tissue IL-23 and MMP-9/TIMP-2 in both unaf-
fected and affected areas (r 0.66 and r 0.62, respectively).
CONCLUSION: It is believed that higher IL-23 levels decrease the content of
MMP-9/TIMP complexes, which in turn may lead to elevated MMP-9 levels and
MMP-9-induced tissue damage. The correlations between serum and tissue IL-23
and MMP-9/TIMP-1 in UC or MMP-9/TIMP-2 in CD, in particular in unaf-
fected mucosa, may therefore be an indicator of an ongoing inflammatory pro-
cess. However, further studies are necessary to explain the interaction between
cytokines, especially IL-23 and pro- and anti-proteolytic proteins in inflamed and
non-inflamed areas in IBD subjects.
Disclosure of Interest: None declared
P0835 CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE E.
COLI INDUCE SECRETION OF EXOSOMES WITH PRO-
INFLAMMATORY ACTIVITY BY INTESTINAL EPITHELIAL CELLS
J. Carriere1,*, H. Nguyen1, A. Darfeuille-Michaud1
1
UMR 1071 Inserm, University of Auvergne, Clermont-Ferrand, France
INTRODUCTION: Crohns disease (CD) is a chronic inflammatory bowel dis-
ease of which the etiology involves environmental, genetic and microbial factors.
Our group and others have shown a high prevalence of the invasive E. coli
strains, designated adherent-invasive E. coli (AIEC), in the intestinal mucosa
of CD patients. Exosomes are small endosomal-derived vesicles involved in cell
to cell communication and have been implicated in various diseases including
cancer and infectious disorders. It has been reported that mammalian cells
infected with pathogens can release exosomes containing microbial compounds.
AIMS & METHODS: Here, we investigated the capacity of CD-associated
AIEC bacteria to induce secretion of exosomes by intestinal epithelial cells and
to determine the inflammatory characteristics of the released exosomes. Human
intestinal epithelial T84 cells cultured on transwell filters were infected with an
AIEC reference strain LF82. Exosomes were purified using the ExoQuick exo-
some precipitation reagent. Exosomes released into the apical or basolateral
compartments of LF82-infected T84 cells were tested for their ability to promote
a pro-inflammatory response in na ve macrophagic cells.
RESULTS: Electron microscopy and immunogold-labeling for an exosomal
marker, CD63, analyses showed that differentiated T84 cells infected with
AIEC LF82 secreted an increased amount of exosome compared to uninfected
cells. This was confirmed by increased levels of four exosomal markers (CD63,
CD81, CD9 and Hsp70) as assessed by Western blot. Exosomes apically secreted
by infected T84 cells but not from uninfected cells significantly induced produc-
tion of the pro-inflammatory cytokines TNF- and IL-6 in human macrophages,
and this was not due to the presence of lipopolysaccharide, known to induce a
pro-inflammatory response.
CONCLUSION: In conclusion, our study shows that upon infection with CD-
associated AIEC bacteria, differentiated intestinal epithelial cells release exo-
somes that can trigger pro-inflammatory responses in na ve macrophagic recipi-
ent cells.
Disclosure of Interest: None declared
P0836 DIAGNOSIS AND PERSISTENCE OF HISTOLOGICAL CHANGES
IN LYMPHOCYTIC COLITIS
J. Rasmussen1,*, P. Engel2, L.K. Munck3,4
1
Department of medicin, Kge Sygehus, Kge, 2Department of pathology, Roskilde
Hospital, Roskilde, 3Department of medicin, Kge Hospital, Kge, 4Faculty of
Health and medical sciences, University of copenhagen, copenhagen, Denmark
Contact E-mail Address: jul.rasmussen@gmail.com
INTRODUCTION: The topographic distribution of histological changes in
microscopic colitis (MC) remains controversial. The main conception has been
that in order to detect or rule out MC, biopsies from the right colon is necessary.
However this has to some extent been proposed on the basis of a selected popu-
lation of patients included in randomised trials with collagenous colitis (CC). A
sigmoideoscopy is more gentle with the patient, cheaper and often more acces-
sible and thus would be preferred if sufficient in detecting MC.
AIMS & METHODS: Aims: To access the topography of histological changes in
the colon diagnostic of lymphocytic colitis (LC) in a complete series of consecu-
tive, non-selected patients and to provide the sensitivity of left- and right-side
biopsies respectively. Furthermore to analyse the persistence of changes in
repeated endoscopies.
Methods: Retrospective review of the pathologic descriptions in the Danish
National Pathology Database in patients diagnosed with lymphocytic colitis in
the coverage area of Kge Hospital from 2000 through March 2014. Biopsies
from the rectum were excluded.
RESULTS: LC was diagnosed in 238 patients; in 81 (34%) by sigmoideosopy
and in 136 (57%) by colonoscopy. A medical history of watery diarrhoea could
be retrieved in 196, 1 did not have diarrhoea. The median number of biopsies
United European Gastroenterology Journal 2(5S)
taken was 6 (mean 7.6). Biopsies were taken from both right and left colon in 122
(51%) and showed LC in both left and right colon of 119 (98%). At the diag-
nostic endoscopy 3 patients (2%) had changes in the left colon only and no one
had changes in the right colon only. The histological diagnosis in the right colon
were: normal (1), chronic inflammation (1) and incomplete LC (1). The sensitiv-
ity of left sided biopsies for the primary diagnosis of LC were 100% (95% CI: 97-
100%) and right sided 98% (94-100%). A second endoscopy following the diag-
nostic one was performed in 50 (21%) of the 238 patients after a median of 13.5
months (mean 27.2) with a median of 6.5 biopsies (mean 7.1). LC was recon-
firmed in 28 (56%). Other histological changes found were: normal (4), chronic
inflammation (2), incomplete LC (2), CC (2) and non specific changes (10). In 3
patients histological changes diagnostic of collagenous colitis were found in one
or more of the endoscopies following the diagnostic one. Looking at the total
number (161) of colonoscopies diagnostic of LC (with biopsies from both right
and left colon) done in the population, 1 patient (1%) had changes in the right
colon only and 3 patients (2%) had changes in the left colon only. Prior non-
diagnostic endoscopies were performed in 22 patients (9%) with a median of 4
(mean 5) biopsies. In these histological changes were: normal (4), chronic inflam-
mation (10), incomplete LC (4) and non specific changes (4).
CONCLUSION: While a full colonoscopy can be necessary in order to exclude
other diagnoses, biopsies from the left colon are suffice for diagnosing or exclud-
ing LC in patients with chronic watery diarrhoea. The histological findings are
not permanent and can change from one type of microscopic colitis to another
suggesting that the different types of microscopic colitis are closely related.
Disclosure of Interest: None declared
P0837 METABOLIC PROFILING OF FECAL VOLATILE ORGANIC
COMPOUNDS IN ULCERATIVE COLITIS PATIENTS
L. Boesmans1,*, K. Windey1, G. Vandermeulen1, V. De Preter1, K. Verbeke1
1
Translational Research for Gastrointestinal Disorders, Leuven Food Science and
Nutrition Research Centre, KU Leuven, Leuven, Belgium
Contact E-mail Address: leen.boesmans@med.kuleuven.be
INTRODUCTION: Ulcerative colitis (UC) is an inflammatory bowel disease
characterized by chronic inflammation of the colonic epithelium. The exact etiol-
ogy of the disease is not fully understood, but the microbiota is implicated in the
initiation and the propagation of the disease. Through bacterial fermentation of
carbohydrates and proteins a plethora of luminal compounds is produced in the
colon, which might interact with the hosts physiology. In the present study, the
metabolic activity of the microbiota was compared between healthy controls and
UC patients with both active and quiescent disease.
AIMS & METHODS: Fecal samples were collected from healthy control subjects
(HC; n 19, 11 female/8 male, age range 20-61 years) and UC patients with active
disease (UC-A; n 45, 14 female/31 male, age range 20-84 years) and during
remission (UC-R; n 40, 15 female/25 male, age range 19-78 years). Active disease
was defined as a partial Mayo score 3. Fecal water (FW) was derived from these
samples by ultracentrifugation at 50.000 x g at 4 C for 2h and was sterile filtered.
Profiles of volatile organic compounds (VOCs) were determined in the FW sam-
ples using GC-MS (single quadrupole), coupled on line to a purge-and-trap sample
preparation system. All VOCs were relatively quantified versus an internal stan-
dard and classified according to chemical class. Partial least squares (PLS) analysis
was applied to cluster samples with similar metabolite profiles and to identify
VOCs accounting for discrimination between HC and UC patients.
RESULTS: A total of 201 different VOCs were identified in the FW samples,
with an average of 618 VOCs per sample. Cluster analysis of the metabolite
profiles revealed complete separate clustering between HC and UC patients.
Samples from UC-A and UC-R patients were not completely separated. FW
samples from UC patients were associated with a higher prevalence of alcohols,
phenols and benzene-like VOCs. The two latter groups are suggested to arise
from protein fermentation. UC-A patient samples were associated with the pre-
sence of primary alcohols (ethanol, 1-propanol and 1-butanol) and low levels of
short and medium chain fatty acids (SCFA and MCFA) and other acids. SCFA
(acetate, propionate and butyrate) are generally recognized to be beneficial for
the hosts health and mainly originate from carbohydrate fermentation. Similar
reductions of SCFA in UC patients were previously observed by the use of
proton NMR [1]. These carboxylic acids are the oxidized counterparts of the
primary alcohols, which suggests an imbalance in reduction-oxidation (redox)
reactions in the colonic lumen.
CONCLUSION: The metabolite profiles of fecal samples allowed to differentiate
HC from UC patients, partly due to the increased presence of alcohols, phenols
and benzene-derivatives in UC patient samples. We identified primary alcohols,
SCFA and MCFA as the most discriminatory metabolites in UC-A patients
compared to HC and UC-R patients. The role of the observed shift in intestinal
redox balance in UC-A patients (more primary alcohols, less SCFA) needs to be
further investigated.
REFERENCES
[1] Marchesi JR, et al. J Proteome Res 2007; 6: 546-551.
Disclosure of Interest: None declared
P0838 THE ASM MUCINASE IS INVOLVED IN ILEAL COLONIZATION
BY CROHNS DISEASE-ASSOCIATED ADHERENT-INVASIVE
ESCHERICHIA COLI
L. GIBOLD1,2,*, C. GALLUCCI1, G. DALMASSO2, D. CIA3, N. BARNICH2,
R. BONNET1,2, J. DELMAS1,2
1
Laboratoire de Bacteriologie, CHU Gabriel Montpied, 2Laboratoire M2iSH,
UMR 1071 Inserm/UdA USC INRA 2018, 3Equipe Biophysique neurosensorielle,
UMR INSERM 1107, Clermont-Ferrand, France
Contact E-mail Address: llyonne@chu-clermontferrand.fr
A361
INTRODUCTION: Mucins are secreted by the intestinal epithelium and consti-
tute an efficient component of innate immune defenses to promote homeostasis
and protect against bacteria. Enteric pathogens, such as Shigella and Vibrio
cholerae, can produce proteases designated mucinases that are capable of cleav-
ing mucins. Ileal lesions of patients with Crohns disease (CD) are abnormally
colonized by adherent-invasive Escherichia coli (AIEC).
AIMS & METHODS: Genome analysis of the AIEC strain LF82 revealed the
presence of a chromosomal gene, designated asm, similar to the Hbp gene of the
avian pathogenic E. coli strains (79% of homology). Hbp has a mucinolytic
activity. To determine whether the Asm protein cleaves mucins, we generated
the LF82asm isogenic mutant and transcomplemented this mutant with the
cloned asm gene.
RESULTS: Concentrated supernatants from LF82 strain and transcomplemen-
ted LF82Dasm/asm yielded zones of clearing on mucin gels, whereas LFDasm
did not exhibit mucinolytic activity. We showed, by using a simple column pene-
tration assay, that Asm promoted mucus penetration of LF82. No difference in
adhesion and invasion between LF82 and LF82asm was found in the colonic
epithelial HT29 cells, which are not mucin hyperproducing. However, a signifi-
cant difference between these strains was observed in the mucin hyperproducing
cell line HT29-16E, suggesting a role for Asm in mucus penetration. These results
were also obtained by confocal and electronic microscopy. To evaluate the invol-
vement of Asm in LF82 colonization in vivo, CEABAC10 transgenic mice were
orally challenged with LF82 or LF82Dasm strains. The numbers of bacteria
counted in the feces and of intestinal mucosal-associated bacteria were increased
in mice infected with LF82 compared to those infected with LF82Dasm.
Quantification of asm mRNA levels showed that bile salts act as an activator
of Asm transcription as well as ileal pH.
CONCLUSION: In conclusion, Asm has a mucinolytic activity that promotes
mucus penetration of AIEC strains and enhances adhesion and invasion to
epithelial cells. Asm contributes to gut colonization of AIEC in murine model.
Thus, mucinases could be one of the key factors of AIEC implantation in CD
patients.
Disclosure of Interest: None declared
P0839 HYPERBARIC OXYGEN THERAPY AMELIORATES TNBS-
INDUCED ACUTE DISTAL COLITIS IN RATS
R.S. Parra1, L.R. R. Camperoni1,*, A. Lopes2, E.U. Carreira2, F.Q. Cunha2,
S.B. Garcia3, T.M. Cunha2, J.J. R. Rocha1, O. Feres1
1
Surgery and Anatomy, 2Pharmacology, 3Pathology, University of Sao Paulo,
Ribeirao Preto, Brazil
Contact E-mail Address: rsparra@yahoo.com.br
INTRODUCTION: This study investigated the therapeutic effects of hyperbaric
oxygen (HBO) in experimental acute distal colitis focusing on its effect on cyto-
kines and HIF-1.
AIMS & METHODS: Twenty-eight Wistar rats were divided into four groups
(each group had 7 rats): I (Saline); II (Saline/HBO); III (TNBS); and IV
(TNBSHBO). Colitis was induced with a rectal infusion of 150 mg/kg of trini-
trobenzenesulfonic acidethanol (TNBS) under anesthesia with Ketamine (50
mg/kg) and Xylazine (10 mg/kg). Control animals received only rectal saline.
After induction, the colitis animals were subjected to two sessions of HBO and
were then euthanized. The distal intestine was resected for macroscopic analysis,
myeloperoxidase activity (MPO) measurements, Western-blot analyses of nitric
oxide synthase activity (iNOS) and Cicloxygenase-2 (COX-2) and immunohisto-
chemical analysis of HIF-1 and COX-2. Cytokines levels (IL-1, CINC-1, IL-10
and TNF-) in the distal intestine were measured using an enzyme-linked immu-
nosorbent assay (ELISA).
RESULTS: HBO therapy attenuated the severity of acute distal colitis, with
reduced macroscopic damage score and reduced cytokine expression. HBO ther-
apy inhibited the acute distal colitis-induced up-regulation of HIF-1 and its
downstream iNOS and myeloperoxidase activity, as well as producing diminished
COX-2 levels
CONCLUSION: The results indicate that HBO therapy attenuates the severity
of acute distal colitis through the down-regulation of the expression of HIF-1
and pro-inflammatory cytokines
REFERENCES
Podolsky DK. Inflammatory bowel disease. N Engl J Med 2002; 347: 417-429.
Iezzi LE, Feitosa MR, Medeiros BA, et al. Crohns disease and hyperbaric
oxygen therapy. Acta Cir Bras 2001; 26(Suppl. 2): 129-132.
Eltzschig HK and Carmeliet P. Hypoxia and inflammation. N Engl J Med 2011;
364: 656-665.
Disclosure of Interest: None declared
P0840 DIFFERENCES IN EXPRESSION OF G PROTEIN-COUPLED
RECEPTOR 55 IN PATIENTS WITH CROHNS DISEASE AND
ULCERATIVE COLITIS
M. Wlodarczyk1,*, A. Sobolewska1, A. I. Cygankiewicz2, P.K. Zakrzewski2,
W.M. Krajewska2, K. Stec-Michalska1, A. Piechota-Polanczyk3, J. Fichna3,
M. Wis niewska-Jarosinska1
1
Department of Gastroenterology, Medical Univeristy of Lodz, 2Department of
Cytobiochemistry, University of Lodz, 3Department of Biochemistry, Medical
Univeristy of Lodz, Lodz, Poland
Contact E-mail Address: dr.mwlodarczyk@gmail.com
INTRODUCTION: G protein-coupled receptor 55 (GPR55) is a newly discov-
ered cannabinoid (CB) receptor, which has been qualified as a part of the endo-
genous CB system along with classical receptors CB1 and CB2. There is a
growing interest in the possible use of CB receptor agonists in the treatment of
inflammation and abdominal pain. Here we attempted at establishing the levels
A362
of GPR55 expression in inflammatory bowel disease (IBD) patients and healthy
controls and potential implication in IBD treatment.
AIMS & METHODS: The study aimed at identifying whether GPR55 is
expressed in colonic tissue of IBD patients and if so, whether the GPR55 levels
differ between Crohns disease (CD) and ulcerative colitis (UC) patients and
between IBD patients and controls. Twenty five adult patients with IBD (UC:
n 11; CD: n 14) were enrolled in the study. The control group consisted of 6
healthy subjects. The GPR55 mRNA and protein expression were measured
using RT-PCR and immunoenzymatic (Western blot) assay, respectively. Each
assay was performed in triplicate.
RESULTS: GPR55 mRNA was detected in all samples tested. The level of
GPR55 mRNA was strongly (2.7 fold) increased in CD, but only moderately
in UC patients vs. controls. In CD, GPR55 mRNA expression was 3.5 fold
higher in biopsies from inflamed compared to non-inflamed tissues. In contrast,
GPR55 mRNA level in inflamed and non-inflamed tissues in UC was compar-
able. Similar results were observed for GPR55 expression at protein level. The
changes in GPR55 expression were unrelated to patient age or gender.
CONCLUSION: Different patterns of expression of GPR55 at mRNA and pro-
tein levels were observed in IBD patients. We speculate that GPR55 is crucial for
the inflammatory processes in IBD, in particular in CD and may affect disease
severity, as well as response to treatment depending on disease type. The GPR55
receptors may become an attractive target for novel therapeutic strategies in the
treatment of IBD.
Disclosure of Interest: None declared
P0841 HYPERACTIVITY OF THE ENDOGENOUS OPIOID SYSTEM
PROTECTS AGAINST ACUTE, BUT NOT CHRONIC STRESS-
INDUCED EXACERBATION OF COLITIS IN MICE
M. Sobczak1,*, M. Salaga1, A. Wasilewski1, H. Zatorski1, M. Sacharczuk2,3,
J. Fichna1,3
1
Department of Biochemistry, Medical Univesity of Lodz, Lodz, 2Department of
Molecular Cytogenetics, Institute of Genetics and Animal Breeding, Polish
Academy of Sciences, Jastrzebiec, 3Mossakowski Medical Research Center, Polish
Academy of Sciences, Warsaw, Poland
Contact E-mail Address: sobczak.mart@gmail.com
INTRODUCTION: The endogenous opioid system plays an important role in
the maintenance of homeostasis in the gastrointestinal tract. Recent studies sug-
gest that the impairment of EOS function may be crucial in the pathogenesis and
progression of inflammatory bowel diseases (IBD). However, this has not been
confirmed due to the lack of relevant models.
Recently, two mouse lines - with high (HA) and low (LA) opioid system activity
were developed based on the expression of swim stress-induced analgesia. The
aim of our study was to characterize the role of the endogenous opioid system
and stress in the development of IBD symptoms in HA and LA mouse lines.
AIMS & METHODS: Mice were bred using bidirectional selection and classified
as HA or LA line based on the measurement of analgesia with the hotplate and
tail-flick tests. Colitis was induced by instillation of trinitrobenzenesulfonic acid
(TNBS) in 30% EtOH/saline. After 3 days, the macroscopic score was assessed
and the samples for biochemical, molecular and histological studies were col-
lected. To evaluate the influence of stress on development of colitis, we used
chronic mild stress (exposure to stress stimuli for 2 and 5 weeks) and acute
stress (short restraint over 3 days) models.
RESULTS: We observed a significant difference in the development of colitis
between non-stressed HA and LA mice, as indicated by the macroscopic score
(3.080.06 vs. 6.500.79 for HA and LA, respectively) and ulcer score
(0.300.31 vs. 2.100.31 for HA and LA, respectively). Chronic mild stress
had no influence on colitis in both mouse lines. Colitis was improved in HA
mice exposed to acute stress in comparison with non-stressed animals (1.770.12
vs. 4.601.60), but did not change the inflammation score in LA line.
CONCLUSION: Our studies strongly support the hypothesis that the activity of
the endogenous opioid system may be crucial in IBD development and affect the
success rate in IBD treatment. We also evidence that acute, but not chronic stress
influence significantly the exacerbation of IBD symptoms depending on the
endogenous opioid system activity.
Disclosure of Interest: None declared
P0842 ENTERIC GLIAL CELLS FROM CROHNS DISEASE PATIENTS
MISPRODUCE 15-DEOXY-12,14-PROSTAGLANDIN J2: DEFECT IN
INTESTINAL EPITHELIAL BARRIER RESISTANCE
S. Coquenlorge1, N. Cenac2, M. Biraud1, J. Jaulin1, N. Vergnolle2, M. neunlist1,*,
M. Rolli-Derkinderen1
1
Inserm UMR913, Nantes, 2INSERM UMR-1043 CNRS UMR-5282, Toulouse,
France
Contact E-mail Address: malvyne.derkinderen@univ-nantes.fr
INTRODUCTION: Enteric glia, the major constituent of the enteric nervous
system, plays a key role in the control of intestinal epithelial barrier (IEB) func-
tions. Under physiological conditions, enteric glial cells (EGC) inhibit intestinal
epithelial cells (IEC) proliferation, enhance IEB repair and increase its resistance
to pathogens. All these mechanisms are altered during inflammatory bowel dis-
ease (IBD), such as Crohns Disease (CD). EGC lesions have also been observed
in this pathological context, and we investigated here the possible link between
CD EGC and IEB dysfunctions.
AIMS & METHODS: First, we have characterised EGC isolated from CD and
cancer patients (considered as control EGC) by real time Q-PCR and immunos-
taining. Next, we studied EGC functional impact on IEB using an indirect co-
culture model with human intestinal epithelial cell (IEC; Caco-2) cell line seeded
on Transwell filters, measuring transepithelial resistance (EVOM), IEC spreading
United European Gastroenterology Journal 2(5S)
(ZO1 immunostaining) and IEC proliferation (DAPI cell counting). EGC-
derived soluble factors (IL6, TGF, proEGF, GSH) and thirty polyunsaturated
fatty acid (PUFA) metabolites were quantified in EGC supernatants. 15dPGJ2,
PPAR agonist (Rosiglitazone) and PPAR antagonist (GW9662) functional
impacts were then measured on IEC spreading and IEB resistance.
RESULTS: EGC isolated from CD and cancer patients (considered as control
EGC) expressed the same level of glial markers (GFAP, S100beta, Sox10).
Whereas control EGC increased significantly IEC transepithelial resistance,
IEC spreading and decreased IEC proliferation, CD EGC had no significant
effect. EGC supernatants showed a severe decrease in 15dPGJ2 and
11betaPGF1alpha production but no change in others EGC-derived soluble
factor expression. 15dPGJ2 also induced a decrease in IEC proliferation but
also an increase in IEC spreading and IEB resistance. In addition, PPAR ago-
nist reproduced these effects and PPAR antagonist abrogated them.
CONCLUSION: All together, these results show that human EGC from Crohns
disease patients have lost their protective properties on IEB integrity among the
regulation of IEB resistance, IEC spreading and proliferation. This could be due
to a defect in the 15dPGJ2 pathway in CD EGC.
Disclosure of Interest: None declared
P0843 HOMOCYSTEINE EXACERBATED DSS-INDUCED COLITIS BY
ACTIVATION OF TH17 CELLS VIA P38 SIGNALING PATHWAY
S. Zhu1, J. Li1, W. Yan1, M. Chen1,*, B. Xia1
1
Department of gastroenterology, Zhongnan hospital, Wuhan, China
Contact E-mail Address: chenmin8106@aliyun.com
INTRODUCTION: It is well knownz that homosysteine is a pro-inflammatory
molecule and contributes to the chronic inflammation of cardiovascular and
cerebral disorders. Hyperhomocysteinemia (HHcy) is a common phenomenon
observed in patients with inflammatory bowel disease (IBD). The influence of
HHcy on the colonic inflammation of IBD has never been explored.
AIMS & METHODS: The aim of this study is to investigate the effect of HHcy
on Dextran sulfate sodium (DSS) induced-colitis. Rats were randomly divided
into 5 groups (n 6 per group): control, HHcy, DSS, HHcyDSS and
HHcyDSSp38 inhibitor. HHcy was induced by giving rats rodent food con-
taining 1.7% methionine for three weeks. Colitis was induced by giving water
containing 5% DSS. The p38 inhibitor (5mmol SB203508/kg) was given twice
daily beginning 60h after DSS treatment. The plasmatic concentration of IL-17
was measured by ELISA. The mRNA and protein expressions of inflammatory
mediators were detected by RT-PCR and Western-blot, respectively.
RESULTS: The rats of HHcyDSS group had scientifically higher body weight
loss, MPO activity, DAI score, and histological score compared to the rats of
DSS group. HHcy significantly increased the plasmatic concentration, the colo-
nic mRNA and protein levels of IL-17, as well as the protein levels of phosphory-
lated-p38 MAP kinase, phosphorylated cytosolic phospolipaseA2,
cyclooxygenases 2 and RORt. The increased protein expressions of these
inflammatory mediators were suppressed by p38 inhibitor.
CONCLUSION: HHcy aggravated DSS-induced colitis by the activation of
Th17 cells via p38 signaling pathway. The p38 inhibitor may represent a novel
approach to treatment the chronic intestinal inflammation exacerbated by HHcy
in patients with IBD.
REFERENCES
1. Oussalah A, Gueant JL and Peyrin-Biroulet L. Meta-analysis: hyperhomocys-
teinaemia in inflammatory bowel diseases. Aliment Pharmacol Ther 2011; 34:
1173-1184.
2. Peyrin-Biroulet L, Rodriguez-Gueant RM, Chamaillard M, et al. Vascular and
cellular stress in inflammatory bowel disease: revisiting the role of homocysteine.
Am J Gastroenterol 2007; 102: 1108-1115.
3. Chen M, Peyrin-Biroulet L, George A, et al. Methyl deficient diet aggravates
experimental colitis in rats. J Cell Mol Med 2011; 15: 2486-2497.
4. Danese S, Sgambato A, Papa A, et al. Homocysteine triggers mucosal micro-
vascular activation in inflammatory bowel disease. Am J Gastroenterol 2005; 100:
886-895.
Disclosure of Interest: None declared
P0844 MICRORNA-612 REGULATES AQUAPORIN 8 EXPRESSION AND
IS UP-REGULATED IN PATIENTS WITH ULCERATIVE COLITIS
M. Min1,*, Y. Yang2, Y. Liu1
1
Dept. of Gastroenterology and Hepatology, Affiliated Hospital of Academy of
Military Medical Sciences, 2Dept. of Gastroenterology and Hepatology, Chinese
PLA general hospital, Beijing, China
INTRODUCTION: MicroRNA (miRNA) plays an important role in the patho-
genesis of many diseases by regulating the gene expression at the post-transcrip-
tional level and control crucial physiological processes. Altered levels and
functions of miRNAs have been associated with ulcerative colitis (UC), although
little is known about their roles in UC.
AIMS & METHODS: We screened different genes from UC tissues and healthy
subjects by using genome-wide and miRNA microarray in colon samples from 20
patients with UC and 16 healthy subjects undergoing diagnostic colonoscopy.
AQP8 expression and miR-612 were measured by real-time polymerase chain
reaction analysis. Regulation of gene expression by miRNAs was assessed by
luciferase reporter construct assays and transfection of specific miRNA mimics
and inhibitor.
RESULTS: We identified that 1596 genes and 33 miRNAs were increased, 1301
genes and 35 miRNAs were decreased in UC patients compared to healthy sub-
jects. Among them, aquaporin 8 (AQP8) was decreased in patients with UC
compared with control tissues (P 50.01). We searched candidate target
miRNAs of AQP8 through bioformatics and the luciferase report assay analysis
United European Gastroenterology Journal 2(5S)
indicated that miR-612 which has complementary site in the 3-untranslated
region (UTR) of AQP8 could decrease the relative luciferase activities by 45%
and transfection of HT29 cells with the miR-612 mimic resulted in inhibition of
the basal AQP8 protein.
CONCLUSION: miR-612 appears to regulate the expression of AQP8. Increased
levels of miR-612 in colon tissues of active UC appear to decrease expression of
AQP8, which could involved in the pathogenesis of UC.
Disclosure of Interest: None declared
P0845 HEPATOBILIARY, PANCREATIC AND RENAL
MANIFESTATIONS IN GREEK INFLAMMATORY BOWEL
DISEASE PATIENTS
K. Karmiris1,1, A. Avgerinos2, A. Tavernaraki1, C. Zeglinas3, P. Karatzas4,
T. Koukouratos4, K. Oikonomou5, A. Kostas6, E. Zampeli7, V. Papadopoulos8,
A. Theodoropoulou1,*, N. Viazis4, D. Polymeros8, S. Michopoulos7, G. Bamias6,
A. Kapsoritakis5, D.G. Karamanolis4, G. Mantzaris4, C. Tzathas3,
I.E. Koutroubakis2
1
Gastroenterology, Venizeleio General Hospital, 2Gastroenterology, University
Hospital, Heraklion, Crete, 3Gastroenterology, Tzaneio General Hospital, Pireus,
4
Gastroenterology, Evangelismos Hospital, Athens, 5Gastroenterology, University
Hospital, Larissa, 6Gastroenterology, Laiko Hospital, 7Gastroenterology,
Alexandra General Hospital, 8Gastroenterology, Attikon University Hospital,
Athens, Greece
Contact E-mail Address: kkarmiris@gmail.com
INTRODUCTION: Inflammatory bowel disease (IBD) patients often exhibit
common manifestations, which are not characterized as classic extra-intestinal 1
manifestations, posing clinical dilemmas.
AIMS & METHODS: The aim of our study was to investigate the prevalence
and characteristics of certain common manifestations from the liver, biliary tree,
pancreas and kidneys in IBD patients followed-up in tertiary centers. Data from
1741 IBD patients (females: 43.5%, Crohns disease: 53.9%, median [IQR] age at
IBD diagnosis: 32.9 [23.0-48.4] and IBD duration until 1st EIM diagnosis: 3.0
[0.2-8.0] years) have been retrospectively retrieved and registered according to a
pre-defined protocol. Positive results were based on imaging findings and/or pre-
existing compatible clinical diagnosis. The impact of certain demographic and
IBD characteristics on results was studied.
RESULTS: Cholelithiasis was present in 113/1489 (7.6%) patients mainly in
females (p50.0001) with Crohns disease ileitis or extensive ulcerative colitis
(p 0.042), concomitant nephrolithiasis (p50.0001) and those having undergone
a major IBD surgery (p 0.031), appendectomy or tonsillectomy (p50.0001).
Non-alcoholic fatty liver disease was detected in 159/1489 (10.7%) patients
mainly in females (p50.0001) with ulcerative colitis (p 0.014) and concomitant
nephrolithiasis (p50.0001). Pancreatitis was diagnosed in 46/1656 (2.8%)
patients. In particular, autoimmune IgG4-related pancreatitis was observed in
5/46 (10.9%), drug-induced in 34/46 (73.9%) and lithiasic in 6/46 (13%) patients.
Pancreatitis was more frequent in smokers (p 0.004) with concomitant nephro-
lithiasis (p 0.002) and in patients with an ileal-anal pouch anastomosis
(p 0.049). Nephrolithiasis was present in 140/1592 (8.8%) patients less fre-
quently in those with perianal Crohns disease (p 0.019).
CONCLUSION: One tenth or less of our IBD patients exhibited at least one
hepatobiliary, pancreatic or renal manifestation. A different pattern of appear-
ance was observed between Crohns disease and ulcerative colitis patients.
Nephrolithiasis often accompanies the other manifestations.
Disclosure of Interest: None declared
P0846 RENAL CELL CARCINOMA PATIENTS HAVE A BETTER
SURVIVAL IN A NATIONWIDE INFLAMMATORY BOWEL
DISEASE COHORT COMPARED WITH THE GENERAL
POPULATION
L.A. Derikx1,*, C.M. van Herpen2, J.P. Drenth1, W. Kievit3, L. Nissen1,
P.F. Mulders4, I.D. Nagtegaal5, F. Hoentjen1 on behalf of Dutch Initiative on
Crohn and Colitis
1
Department of Gastroenterology and Hepatology, 2Department of Oncology,
3
Department for Health Evidence, 4Department of Urology, 5Department of
Pathology, Radboud university medical centre, Nijmegen, Netherlands
Contact E-mail Address: Lauranne. Derikx@radboudumc.nl
INTRODUCTION: Patients with inflammatory bowel disease (IBD) frequently
undergo abdominal imaging. This may result in an increased number of inciden-
talomas including renal cell carcinoma (RCC). A high percentage of incidentally
found RCCs might improve cancer outcome; however, immunomodulators and
biological agents, as used in the treatment of IBD, may also impact cancer out-
come. In this study we aimed to compare the outcome of RCC between IBD
patients and the general population. Next we evaluated the impact of IBD ther-
apy on RCC outcome.
AIMS & METHODS: Using the Dutch National Pathology Registry (PALGA)
we identified all IBD patients diagnosed with RCC in The Netherlands from
January 1991 until May 2013. Cases were confirmed using anonymized medical
records and clinical and demographic variables were collected. The control group
was derived from the Eindhoven Cancer Registry (1991-2010) which provided the
cancer registration for approximately 2.3 million people in The Netherlands.
RCC characteristics like TNM stage, age at RCC diagnosis and treatment
were compared univariately between cases and controls. Survival analyses were
made with Kaplan Meier curves and confounder correction was performed with
Cox regression.
RESULTS: We included 160 patients from 69 academic and non-academic hos-
pitals with a confirmed IBD diagnosis who developed RCC. 64/160 (45.1%) IBD
patients used thiopurines or biologicals during their disease course of IBD. 73/
A363
160 (51.8%) RCC cases in IBD patients concerned incidentalomas. The control
group consisted of 4388 patients with RCC. Upon comparison, IBD patients had
a statistically significant lower age at RCC diagnosis (median 62.0 versus 66.0;
p50.005), lower N-stage (5.8% N versus 11.4% N; p 0.030) and lower M-
stage (10.7% M1 versus 20.0% M1; p50.005). Furthermore IBD patients under-
went more frequently surgical treatment for RCC (96.2% versus 75.6%;
p50.005). A Kaplan Meier curve showed better overall survival in IBD patients
(log rank p50.005). Age at RCC diagnosis, T, and M-stage, and surgical treat-
ment emerged as confounders. Adjusted for these confounders, a protective effect
of IBD on overall survival was still present (p 0.015; hazard ratio 0.690; 95%
CI 0.512-0.932). Comparing IBD patients with and without thiopurines and/or
biologicals, overall survival was significantly better in the group who did use
immunosuppression (log rank p 0.012). However, a Cox model adjusted for
TNM stage and age at RCC diagnosis completely abolished the protective effect
of immunosuppression (p 0.949).
CONCLUSION: Patients with IBD who develop RCC have a significantly better
overall survival compared to the general population with RCC, which may par-
tially be explained by an earlier diagnosis of RCC with a subsequent lower
disease stage. Immunosuppression does not adversely affect overall survival.
Disclosure of Interest: None declared
P0847 INFLUENCE OF COPING ON THE CLINICAL COURSE OF
PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A
PROSPECTIVE COHORT STUDY
M. Barreiro-de Acosta1,*, R. Ferreiro-Iglesias2, A. Lorenzo-Gonzalez3,
J.E. Dominguez-Munoz2
University Hospital of Santiago de Compostela. Foundation for Research in
Digestive Diseases, Santiago de Compostela, Spain, 2Gastroenterology, University
Hospital of Santiago de Compostela. Foundation for Research in Digestive
Diseases, 3Gastroenterology, University Hospital of Santiago de Compostela,
Santiago de Compostela, Spain
INTRODUCTION: Coping strategies are used to manage conflicts and illnesses,
and may have both adaptative or maladaptative effects on health status. Coping
strategies have not been well studied in patients with Inflammatory Bowel
Disease (IBD), and their influence on the clinical course of the disease and the
use of health resources is unknown
AIMS & METHODS: The aim of the study was to evaluate the influence of the
use of different coping strategies on the number of emergency or unscheduled
visits and hospitalisations in IBD patients.
Methods: A prospective observational cohort study was designed. The cohort
consisted of consecutive out-patients with IBD (Crohns disease (CD) and ulcera-
tive colitis (UC)) who attended our monographic IBD Unit. A basal demo-
graphic and clinical questionnaire was completed by all patients. Coping
strategies were assessed with the Spanish version of the COPE scale. It consists
of 60 items that participants rated themselves using the dispositional response
format, and indicating how frequently they engaged in each coping behaviour on
a 4-point Likert scale. The scale had 3 different global strategies: Problem-
focused coping, avoidance coping and emotion-focused coping. All emergency
and unscheduled visits and hospitalisations related to IBD over a follow-up
period of 18 months were recorded. The influence of coping on clinical course
was analysed by Multiple Regression analysis.
RESULTS: 776 patients were included (364 male (46.9%), mean age 45 years,
age ranging from 18 to 86 years). 317 (40.9%) patients had CD and 459 (59.1%)
UC. At the baseline evaluation, the most frequently used coping strategies by
IBD patients were problem-focused coping (mean: 2.72 standard deviation, SD:
0.45) and avoidance coping (mean: 2.60, SD: 0.37), and the least frequently used
was emotion-focused coping (mean: 2.36, SD: 0.57). The mean number of
unscheduled or emergency visits was 1.05 (SD: 1.68, range 0-14) and the mean
number of hospitalizations was 0.35 (SD: 0.94, range 0-9). After a follow up of 18
months, the use of avoidance coping strategies was a risk factor for a higher
number of emergency or unscheduled visits in the multivariate analysis
(B 0.027, CI95%: 0.009-0.045; p50.005). However, coping strategies did not
influence the need of hospitalisations.
CONCLUSION: The coping strategies mostly used by IBD patients are the
problem-focused coping and avoidance coping. A frequent use of avoidance
coping strategies appears to be a risk factor for requiring a higher number of
emergency visits in the following months. Therefore, these patients would prob-
ably benefit from psychological support.
Disclosure of Interest: None declared
P0848 SEXUAL DYSFUNCTION IN INFLAMMATORY BOWEL
DISEASE: DO GASTROENTEROLOGISTS OVERLOOK THIS ISSUE?
M.J. Arguero1,*, M.J. Etchevers1, M.J. Sobrero1, N.S. Causada Calo1,
M. Mahler1, P.R. Daffra1, R.C. Gonzalez Sueyro1, D.C. Madrid1,
D. Manazzoni1, J.A. De Paula1
1
Gastroenterology, Hospital Italiano de Buenos de Aires, Ciudad Autonoma de
Buenos Aires, Argentina
Contact E-mail Address: maria.arguero@hiba.org.ar
INTRODUCTION: Inflammatory bowel disease (IBD) is a condition associated
with high morbidity and poor quality of life (QoL). This population is usually
young and sexually active. Studies addressing sexual dysfunction (SD) in IBD
patients are scarce and their results are controversial. Moreover, little is known
about how often gastroenterologists discuss this matter with IBD patients.
AIMS & METHODS: Our primary objective was to estimate SD frequency
among IBD patients in the ambulatory setting. Secondary objective was to esti-
mate how often SD is addressed by gastroenterologists. A self-administered
anonymous questionnaire was delivered to adult ( 18 years) IBD patients
A364
who assisted the IBD ambulatory clinic between August and September 2013.
The survey had two parts. The first one assessed QoL by the EuroQol scale and
SD by the Female Sexual Function Index (FSFI) and the International Index of
Erectile Function (IIEF-15) in women and men, respectively. Patients were asked
about whether gastroenterologists inquiry about their sexual function and if they
considered this to be relevant. The second part was filled out by the gastroenter-
ologist who was blinded to the first one. It included the Mayo and Harvey-
Bradshaw Scores, IBD treatment in the previous month and IBD phenotype
according to the Montreal Classification.
RESULTS: Response rate was 74.5%. Seventy five patients were recruited, 61%
(n 46) had ulcerative colitis, 37% (n 28) had Crohns disease and one had
undetermined colitis. Median age was 37 years (IQR 30-55) and 56% (n 42)
were women. SD prevalence in women was 69.7% (n 30). In men, the most
affected domains were overall satisfaction 64.5% (n 20), sexual desire 38%
(n 12) and intercourse satisfaction 35% (n 11). SD was not addressed in
84% (n 63) of IBD patients. In this subgroup, 57% (n 36) answered that
the main reason was that the gastroenterologist did not ask them and 41%
(n 26) answered that it would had been important to be asked about it. QoL
was good or very good in 97% (n 73) of the subjects. None of the patients was
consuming antidepressants.
CONCLUSION: SD was very frequent in both genders. Above 50% of our IBD
patients had impaired sexuality, whereas in the general population SD is consid-
ered to be lower, around 35%. Notably, men had lower overall satisfaction and
sexual desire rather than orgasmic and erectile dysfunction. Gastroenterologists
did not assess SD in the majority of IBD patients, while a considerable proportion
of them found discussing this topic with their physician to be relevant. Therefore,
this issue should be addressed. Even though QoL was satisfactory in the vast
majority, SD was prevalent and it should be included in the assessment of QoL
in this population. The small sample size did not allow us to estimate associations.
This is the first study in Latin America that addresses SD in IBD patients.
REFERENCES
Gut 2005; 54: 364-368./Inflamm Bowel Dis 2006; 12(Suppl. 1): S3-S9./
Gastroenterology 2009; 136: 361-362./J Gastroenterol 2013; 48: 713-720./
Gastroenterol Hepatol 2009; 32: 50-54./Clin Gastroenterol Hepatol 2007; 5: 87-
94./Sexualidad y Salud Mental, ed. Glosa 2003./Gu a GETECCU 2012./
Gastroenterology 2009; 136: A-361-A-362.
Disclosure of Interest: None declared
P0849 INCREASED RISK OF WORK DISABILITY IN INFLAMMATORY
BOWEL DISEASE PATIENTS AFTER SEVEN YEARS OF FOLLOW-
UP A POPULATION-BASED COHORT STUDY
M.K. Vester-Andersen1, M. V. Prosberg1, I. Vind1, M. Andersson2, T. Jess2,*,
F. Bendtsen1
1
Gastro unit, medical section, Hvidovre Hospital, University of Copenhagen,
Hvidovre, 2Department of Epidemiological Research, National Health Surveillance
and Research, Copenhagen, Denmark
Contact E-mail Address: marianne@kajbaek.dk
INTRODUCTION: Inflammatory bowel disease (IBD) often affects younger
persons and may have considerable impact on the ability to maintain connected
to the labour market.
AIMS & METHODS: We aimed to evaluate the occurrence and risk of sick leave
(SL) and work disability (WD) in incident patients with IBD after 7 years of
follow-up compared to a population-based control group and look for associa-
tions of social, phenotypic and clinical characteristics.
A subgroup of 379 IBD patients aged 18-67 years from an IBD-inception cohort
(513 patients) registered Jan 1 2003 to Dec 31 2004 in a well-defined Copenhagen
area were our IBD study population. Clinical data were collected from the med-
ical records. Data on eucational level, sick leave and work disability was retrieved
from national registers. A random subset of the general population (n 1435)
were matched on sex, age and residency to IBD cases. Survival curves displaying
the cumulative probabilities of work disability and sick leave were derived with
the Kaplan-Meier method. Cox proportional hazard regression analyses were
performed to identify possible independently associated predictive factors.
RESULTS: After 7 years of follow-up the cumulative risk of SL and WD was
47.8% and 5.8% in UC respectively and 55.8% and 6.3% in CD respectively.
The overall hazard of SL was 2.01 (95% CI 1.66-2.43) and 2.03 (95% CI 1.18-
3.49) of WD in IBD patients. Male IBD patients (HR 2.38 (95% CI 1.10-5.14))
and patients aged 55-67 years at diagnosis (HR 4.36 (1.65-11.53)) were at
increased risk of receiving WD compared to the general population. Both
women (HR 1.83 (1.43-2.35)) and men (HR 2.29 (1.71-3.08)) were at increased
risk of SL as well as patients aged 18 to 55 had a significantly higher risk of SL
compared to the background population. Age above 55 years increased the risk
of WD in patients with CD (HR 17.49 (95% CI 1.92-159.01) but WD in CD was
not explained by sex, educational level, behaviour and localisation of disease,
smoking or surgery after mutually adjustment. Educational level (HR4 13 years of
schooling 1.79 (95% CI 1.02-3.15)), stricturing disease behaviour (HRB2 0.33 (95%
CI 0.14-0.83) and surgery (HR1 resection 4.09 (95% CI 2.17-7.71), HR2 resections
8.96 (95% CI 2.86-28.03)) were predictors of SL in CD. Smoking ((former (HR
0.22 (95% CI 0.02-2.16) or current (HR 6.02 (95% CI 0.95-37.99)) compared to
never (p .04)) was a predictor of WD in UC and female gender (HR 1.73 (95%
CI 1.10-2.72)) and surgery (HR 4.19 (95% CI 2.09-8.38)) were predictors of SL in
UC.
CONCLUSION: In this population-based study of incident Danish IBD patients
we found that after 7 years of follow-up IBD patients are at increased risk of WD
and SL compared to the background population and that educational level, dis-
ease behaviour and surgery were predictors of SL in CD, while high age was a
predictor of WD in CD. Female gender and surgery were predictors of SL in UC,
while smoking status was a predictor of WD in UC. Continuous attention early
after diagnosis should be made on reducing the risk of WD in IBD patients.
United European Gastroenterology Journal 2(5S)
Disclosure of Interest: M. Vester-Andersen: None declared, M. Prosberg: None
declared, I. Vind: None declared, M. Andersson: None declared, T. Jess: None
declared, F. Bendtsen Financial support for research from: MSD, Ferring
Pharmaceuticals, The Research Council of Hvidovre Hospital and The
Research Council of the Capital Region of Denmark.
P0850 PHENOTYPIC CHARACTERISTICS AND USE OF
THERAPEUTIC RESOURCES IN ELDERLY-ONSET
INFLAMMATORY BOWEL DISEASE: A MULTICENTRE, CASE-
CONTROL STUDY
M. Manosa1,2,*, M. Calafat2, R.de Francisco3, C. Garcia4, M.J. Casanova5,6,
P. Huelin7, M. Calvo8, J. Tosca9, A. Ruiz-Cerulla10, Y. Zabana1,11 on behalf of
on behalf of GETECCU
1
CIBEREHD, Barcelona, 2Gastroenterology, Hospital Universitari Germans Trias
i Pujol, Badalona, 3Gastroenterology, Hospital Central de Asturias, Oviedo,
4
Gastroenterology, Hospital reina Sofa, Cordoba, 5CIBEREHD,
6
Gastroenterology, Hospital La Princesa, Madrid, 7Hospital Santa Creu i Sant
Pau, Barcelona, 8Hospital Puerta de Hierro, Madrid, 9Hospital Clnic de Valencia,
Vale`ncia, 10Hospital de Bellvitge, LHospitalet de Llobregat, 11Gastroenterology,
Hospital Mutua de Terrassa, Terrassa, Spain
Contact E-mail Address: mmanosa.germanstrias@gencat.cat
INTRODUCTION: It has been reported that IBD onset occurs at old age in up
to 10% of cases. Elderly patients have more comorbidities and, therefore, a
potential increased risk of drug adverse effects, increased likelihood of hospital
admissions and postoperative complications.
AIMS & METHODS: To evaluate the phenotypic characteristics and use of
therapeutic resources in patients with elderlyonset IBD.
Methods: Retrospective, case-control, multicentre study. All those patients diag-
nosed with IBD over the age of 60 years (cases) since 2000 and with a follow-up
412 months were identified from the IBD databases of each centre. Cases were
compared with controls, who were diagnosed with IBD between 18 and 40 years
of age, and matched by year of diagnosis, gender, and type of IBD.
RESULTS: A total of 1,374 cases and 1,374 matched controls were included, of
whom 43% women, 62% ulcerative colitis (UC), 36% Crohns disease (CD) and
2% unclassified IBD. The mean age at diagnosis was 68 years (range, 60-87) within
cases and 28 years (range, 18-45) within controls. 59% of the cases (but only 3% of
controls) had at least one cardiovascular risk factor (arterial hypertension, dysli-
pidemia or diabetes). The proportion of active smokers at the time of IBD diag-
nosis was 25% among controls and 13% among cases. Phenotypically, elderly-
onset patients had a lower proportion of extensive UC (p50.0001), and a higher
proportion of stenosing and a lower proportion of penetrating pattern (p50.0001)
and exclusive colonic location (p50.0001). Elderly-onset patients had a lower rate
of IBD-related complications (p 0.009) but a higher prevalence of thrombotic
events (p50.0001). Regarding the use of therapeutic resources, there was a sig-
nificantly lower use of corticosteroids (p50.0001), immunomodulators
(p50.0001) and biological agents (p50.0001) in elderly-onset patients as com-
pared to controls, but a similar rate of surgeries. Finally, elderly-onset patients had
a higher rate of hospitalizations (p50.0001), neoplasms (p50.0001) and deaths
(p50.0001). In the multivariate analysis, elderly-onset of IBD was independently
associated to a decreased need of immunomodulators and biological agents, and
an increased need of hospital admissions.
CONCLUSION: Elderly-onset IBD is associated to a less severe/complicated
phenotype and the lesser use of immunosuppressive therapies, which probably
accounts for a non-increased IBD-related morbidity. Age at diagnosis might
explain the increase in the rate of hospitalizations among elderly patients.
Disclosure of Interest: None declared
P0851 C. DIFFICILE COLONISATION AND INFECTION RATES ARE
NO LONGER RAISED IN INFLAMMATORY BOWEL DISEASE
N.M. Joshi1,*, M. Adelson1, D. Ball2, D.S. Rampton1
1
Centre for Digestive Diseases, Blizard Instuite, Barts and The London School of
Medicine and Dentistry, 2Department of Medical Microbiology, Barts Health NHS
Trust, London, United Kingdom
Contact E-mail Address: n.m.joshi@qmul.ac.uk
INTRODUCTION: While several studies in the last 10 years have reported
higher rates of C. difficile colonisation (CDC) and C. difficile infection (CDI)
in IBD than in non-IBD patients, the overall incidence of CDI in the UK is now
falling. We have therefore reassessed the incidence of CDC and CDI in diar-
rhoeal patients with and without IBD.
AIMS & METHODS: All stool samples tested for C. difficile by our laboratory
in the 3-month period ending October 2012 were identified using the microbiol-
ogy database (Barts Health NHS Trust). A 2-step, ELISA algorithm for
C. difficile testing was applied to liquid stools only: the first was a test for
CDC (presence of glutamate dehydrogenase[GDH] a C. difficile-specific
enzyme); if GDH was positive, a second step was performed to look for CDI
(presence of toxin in stool). Electronic patient records (EPR) were then reviewed
to see if patients whose stool was tested had a known diagnosis of IBD (Crohns
or ulcerative colitis) when the sample was sent.
RESULTS: 927 stool samples were tested, EPR data was not available for 22
(2%) cases (excluded from analysis). 88 (10%) patients had IBD. Mean age
(SEM) in years was 42.1 (2.1) for IBD and 58.2 (0.8) for non-IBD patients,
respectively (p50.0001). With the groups combined: 109 (11%) patients had
CDC and 27 (3%) had CDI. CDC was found in 4 (5%) IBD and 105 (12%)
non-IBD patients (p 0.02). There were no CDI cases in IBD patients and 27
(3%) in non-IBD samples (p 0.1). None of the non-IBD CDC patients went on
to develop IBD (EPR review to March 2014) after their samples were analysed.
United European Gastroenterology Journal 2(5S)
CONCLUSION: In our diarrhoeal patients, CDC is now less common in IBD
than in non-IBD patients. We also found no CDI in our 88 IBD samples.
Although the period studied was short and the numbers of samples limited,
our results suggest that the recent epidemic of CDI in IBD patients may now
be on the wane.
Disclosure of Interest: None declared
P0852 RECENTLY-DIAGNOSED CROHNS DISEASE PATIENTS
DEMONSTRATE MIXED COPING SKILLS TO CONTROL THEIR
PSYCHOLOGICAL DISTRESS
O. Sarid1,*, V. Slonim-Nevo1, D. Schwartz2, V. Dizengof2, N. Abu Freha2,
L. Eidelman2, N. Gaspar2, A. Moshkelo2, A. Rozental2, G. Ben Yaakov2,
D. Munteau2, P. Krugliak2, A. Fich2, M. Friger3, H. Vardi3, D. Greenberg4,
S. Odes5 on behalf of Israel IBD Research Nucleus
1
Social Work, Ben Gurion University of the Negev, 2Gastroenterology and
Hepatology, Soroka University Hospital, 3Public Health, 4Health Systems
Management, Ben Gurion University of the Negev, Beer Sheva, 5Gastroenterology
and Hepatology, Ben Gurion University of the Negev, Metar, Israel
Contact E-mail Address: odes@bgu.ac.il
INTRODUCTION: The general psychopathology and coping processes of
Crohns disease (CD) patients are incompletely understood. Since these elements
are expected to impact on quality of life, it is necessary to define their relation-
ships precisely. The social constructionist perspective has become a useful frame-
work for understanding coping strategies of men and women. This study
examines emotional distress and coping strategies between the genders.
AIMS & METHODS: 158 consecutive CD patients undergoing clinical assess-
ment at the IBD Clinic completed a series of questionnaires: Brief Symptom
Inventory (BSI) which measures psychological distress (range: 0 "not at all"
to 4 "extremely distressed"), Ways of Coping (WAYS) that measures thoughts
and actions that people use to handle stressful encounters (range: 1-8, greater
value higher use), and IBDQ (disease-specific quality of life). Appropriate uni-
variate analysis was performed. Data given as mean  SD.
RESULTS: 135 patients (85%) completed the questionnaires, 62 men (age 39.1 
14.9 years, Harvey-Bradshaw Index (HBI) 7.1  3.7, disease duration 2.2  0.3
years) and 73 women (age 43.5  17.2, HBI 7.9  4.4, disease duration 2.4  0.8).
BSI scores for somatization (1.15), obsessive-compulsive behavior (1.10), inter-
personal sensitivity (0.83), depression (0.81), anxiety (1.08), hostility (0.79),
phobic anxiety (0.65), paranoid ideation (0.81) and psychoticism (0.59) revealed
low levels of psychological distress and did not differ significantly between men
and women. WAYS scores without gender differences were: range 46: accep-
tance, self-blame, active coping; range 5-6: self-distraction, planning, positive
reframing; range 2-4.9: humor, religion, denial, behavioral disengagement, sub-
stance use. WAYS scores with gender differences were: use of emotional support
(men 4.03, women 4.80, p50.02), use of instrumental support (3.92, 4.64,
p50.03), venting (3.48, 4.32, p50.005). BSI depression correlated with WAYS
instrumental support (p 0.01), behavioral disengagement (p50.03), and self-
blame (p50.02). IBDQ scores were men 49.2  14.9; women 48.6  12.6.
Significant correlations were found between IBDQ and the WAYS scores of
self-distraction, denial, behavioral disengagement, venting, self-blame and reli-
gion; and HBI with the BSI scores of somatization, positive symptom total and
positive symptom distress index. IBDQ correlated with HBI (p50.001).
CONCLUSION: In this recently-diagnosed CD cohort, men and women had
similar levels of disease activity and psychological distress. The most prominent
positive coping mechanisms were acceptance and active coping, and negative
trends of self-blame and self-distraction. Women practiced more emotional sup-
port, instrumental support and venting. These findings need attention in clinical
practice. [Supported by a generous grant from the Leona M. and Harry B.
Helmsley Charitable Trust].
Disclosure of Interest: None declared
P0853 PREVALENCE OF ALCOHOL CONSUMPTION AND ITS
INFLUENCE ON DISEASE COURSE IN SWISS IBD PATIENTS
F. Brunner1, R.von Kanel2, S. Begre3, C. Clair4, A. Macpherson1, P. Juillerat1,*
1
Visceral Surgery and Medicine, Gastroenterology, 2Department of General
Internal Medicine, Division Psychosomatic Medicine, Inselspital Bern, Bern,
3
Psychiatric Service, Spital Burgdorf, Burgdorf, 4Policlinique medicale universi-
taire, University Hospital Lausanne, Lausanne, Switzerland
INTRODUCTION: Little is known about the prevalence and influence of alco-
hol consumption on the disease course in patients with IBD.
Pathophysiologically alcohol might have an impact on disease course by increas-
ing intestinal permeability, disrupting gut barrier function, inhibiting intestinal
immune system and favouring bacterial overgrowth. Otherwise, low to moderate
alcohol consumption might have an anti-inflammatory effect by lowering IL-6
and TNF- levels.
AIMS & METHODS: We aimed to estimate the prevalence of alcohol consump-
tion and its influence on disease course within the Swiss IBD cohort. Frequency
of alcohol consumption was assessed in a screening question provided in the
enrolment questionnaire of the Swiss IBD cohort. According to the given
answers patients were distributed in 3 categories: non-drinkers (abstainers or
rarely), light-to-moderate drinkers (1-2x per week to daily alcohol consumption),
heavy drinkers (4 2x daily). At enrolment socio-demographic variables and
disease characteristics were compared cross-sectionally to identify risk factors for
increased alcohol consumption and to evaluate a possible influence of alcohol
consumption on disease course. During follow-up need for surgeries and occur-
rence of abscesses and fistulas were compared prospectively between the 3
groups.
A365
RESULTS: 2019 patients, who had answered the question about alcohol con-
sumption at enrolment in the Swiss IBD cohort between July 2006 and May
2013, were included in the analysis. 870 patients (43%) drank regularly alcohol:
818 low-to-moderately, 52 heavily. Drinkers were older, by the majority male,
had a higher body mass index and smoked more often. The proportion of
Crohns disease patients was lower in non-drinkers (59%) compared to low-to-
moderate drinkers (52%). Drinkers reported less extraintestinal manifestations
than non-drinkers (32% vs. 39%, P50.01). Low-to moderate drinkers (31%)
with ulcerative colitis have a lower (p 0.03) proportion of pancolitis than non-
drinkers (41%). However heavy drinkers with ulcerative colitis had to be hospi-
talized less often before enrolment,which, after stratification, seems to be due to
the known protective effect of smoking. Generally heavy drinkers received sig-
nificantly less immunomodulators (AZA, MTX) and anti-TNF-inhibitors.
During follow-up (6925 patient-years) the need for surgery was similar among
non-drinkers and low-to-moderate drinkers. However heavy drinkers with
Crohns disease had to undergo less surgeries and developed fewer abscesses
and fistulas.
CONCLUSION: The prevalence of regular alcohol consumption within the
Swiss IBD cohort was 43%, whereof 94% drank low-to-moderately. Patients
with higher alcohol consumption were older, preferably males with a higher
body mass index and more often smokers. Heavy drinkers received less treatment
with immunosupressants. In ulcerative colitis low-to-moderate drinking seemed
to favour a shorter extent and heavy drinkers were less hospitalized. In Crohns
disease heavy drinking seemed to reduce the development of abscesses and fis-
tulas and the need for surgeries during follow-up. A prospective project nested
within the Swiss IBD cohort for a better understanding of alcohol on disease
course is ongoing.
Disclosure of Interest: F. Brunner: None declared, R. von Kanel: None declared,
S. Begre: None declared, C. Clair: None declared, A. Macpherson: None
declared, P. Juillerat Lecture fee(s) from: AbbVie, UCB, MSD and Vifor
P0854 IS HOSPITALIZATION PREDICTING THE DISEASE COURSE IN
UC? PREVALENCE AND PREDICTORS OF HOSPITALIZATION
AND RE-HOSPITALIZATION IN ULCERATIVE COLITIS IN A
POPULATION-BASED INCEPTION COHORT BETWEEN 2000-2012
P.L. Lakatos1,*, P.A. Golovics1, M. Mandel1, Z. Kurti1, I. Szita2, Z. Vegh1,
L.S. Kiss1, A. Horvath3, T. Pandur2, M. Balogh4, A. Mohas1, B.D. Lovasz1,
L. Lakatos2
1
1st Department of Medicine, Semmelweis University, Budapest, 2Department of
Medicine, 3Department of Pediatrics, Csolnoky F. Province Hospital, Veszprem,
4
Department of Medicine, Grof Eszterhazy Hospital, Papa, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: Limited data are available on the hospitalization rates in
population-based studies. This is a very important outcome measure.
AIMS & METHODS: The aim of this study was to analyze prospectively if early
hospitalization is associated with the later disease course as well as to determine
the prevalence and predictors of hospitalization and re-hospitalization in the
population-based UC inception cohort in the Veszprem province database
between 2000 and 2012. Data of 347 incident UC patients diagnosed between
January 1, 2000 and December 31, 2010 were analyzed (m/f: 200/147, median age
at diagnosis: 36, IQR: 26-50 years, duration: 7, IQR 4-10 years). Both in- and
outpatient records were collected and comprehensively reviewed.
RESULTS: Probabilities of first UC-related hospitalization and first re-hospita-
lization were 28.6%, 53.7%, 66.2% and 23.7%, 55.8% and 74.6% after 1, 5 and
10 years of follow-up in Kaplan-Meier analysis. Main reasons for first hospita-
lization were diagnostic procedures (26.7%), disease activity (22.4%) or UC
related surgery (4.8%), but the majority of the hospitalizations were unrelated
to UC (44.8%). In Kaplan-Meier and Cox-regression analysis disease extent at
diagnosis (HR: 1.35, p 0.018, HRextensive: 1.79, p 0.02 vs. proctitis) or at last
follow-up (HR: 1.56, p 0.001), need for steroids (HR: 1.98, p50.001),
azathioprine (HR: 1.55, p 0.038) and anti-TNF (HR: 2.28, p50.001) were
associated with the risk of UC-related hospitalization. Early hospitalization
was not associated with a specific disease phenotype, however 46.2% of all
colectomies were performed in the year of diagnosis.
CONCLUSION: Hospitalization and re-hospitalization rates are relatively high
in this population-based UC cohort. Early hospitalization was not predictive for
the later disease course.
Disclosure of Interest: None declared
P0855 FAECAL CALPROTECTIN IS AN ACCURATE PREDICTOR OF
ENDOSCOPIC AND HISTOLOGICAL DISEASE ACTIVITY IN IBD
G. Chung-Faye1,*, A. Rahman2, J. Tumova2, B. Hayee2, R. Sherwood2
1
Gastroenterology, Kings College Hospital, 2Kings College Hospital, London,
United Kingdom
Contact E-mail Address: guycf1@gmail.com
INTRODUCTION: Assessment of disease activity in Inflammatory Bowel
Disease (IBD) is challenging as the gold standards of endoscopy and histology
are invasive, expensive and impractical for regular use. Faecal calprotectin (FC)
is increasingly being used as a biomarker of intestinal inflammation but its role in
predicting endoscopic and histological changes in IBD is limited. We explore the
role of FC to assess histological disease in IBD patients, in comparison to C-
reactive protein (CRP), in the largest series of IBD patients to date.
AIMS & METHODS: Retrospective analyses of 407 IBD patients who had a
colonoscopy with FC (mg/g) and CRP (mg/L) measurements. The most severe
histological inflammation found was graded according to the simplified histology
score (0-normal, 1-mild, 2-moderate, 3-severe). Spearmans correlation coeffi-
cient (r) was used to measure correlation between the groups. Receiver operating
A366
characteristic (ROC) curves were used to differentiate patients with normal/mild
disease (histology scores 0-1) from patients with moderate/severe disease (his-
tology scores 2-3).
RESULTS: In 203 Crohns disease (CD) patients, the median FC values for the
histology scores; 0, 1, 2, 3 were; 113, 238, 645 and 3075, respectively (graph). The
corresponding medians for CRP were; 2.5, 9.8, 14.6 and 54.6. Both FC ( 0.59,
p50.0001) and CRP ( 0.30, p50.0001) showed very strong correlations to
histology scores. Using a cut-off value of 250g/g, FC showed an 88% sensitivity
and 62% specificity for predicting moderate / severe disease (AUC 0.82). CRP
46 mg/L was less sensitive and specific (70%, 44%, respectively, AUC 0.64).
In 204 ulcerative colitis (UC) patients, the median FC values for the histology
scores; 0, 1, 2, 3 were; 38, 296, 520 and 1468, respectively (graph). The corre-
sponding values for CRP were; 2.5, 5.4, 8.2 and 9.7. There was a very strong
correlation between the FC values to histology scores ( 0.37, p50.0001), com-
pared to CRP ( 0.21, p 0.003). Using a cut off value of 222 g/g, FC had a
71% sensitivity and 51% specificity (AUC 0.66) for predicting moderate / severe
histological disease. The corresponding figures for CRP46 mg/L were 54% and
59%, respectively (AUC 0.59).
Histology n CD - Calpro 95% n UC - Calpro
score (CD) (Median) CI (UC) (Median) 95% CI
0 42 113.0 53.0 to 161.0 25 38.0 25.0 to 66.0
1 87 238.0 175.0 to 330.0 94 295.5 205.0 to 481.0
2 65 645.0 517.0 to 955.0 73 520.0 280.0 to 770.0
3 9 3075.0 452.0 to 5575.0 12 1468.0 122.0 to 4655.0
CONCLUSION: In the largest IBD series to date, FC was strongly predictive of
histological disease activity in both CD and UC patients, and with a cut off level
of 220-250g/g gave high sensitivity and moderate specificity for predicting
moderate to severe disease activity. FC showed greater accuracy in CD than in
UC and also performed better than CRP. This study highlights the importance of
FC as a valuable, non-invasive biomarker of disease activity in IBD, which can
help direct treatment and reduce the need for invasive endoscopic procedures.
Disclosure of Interest: None declared
P0856 THE ROLE OF CONFOCAL LASER ENDOMICROSCOPY IN THE
MANAGEMENT OF PATIENTS WITH INFLAMMATORY BOWEL
DISEASES: A CONSENSUS REPORT BASED ON LITERATURE
H. Neumann1,*, R. Arsenescu2, H. Bertani3, E. Coron4, A. Dlugosz5,
J. Galmiche4, K. Ho6, S. Singh7
1
Universitatsklinikum Erlangen, Erlangen, Germany, 2Ohio State University
Medical Center, Columbus, United States, 3Nuovo Ospedale Civile SantAgostino
Estense, Modena, Italy, 4CHU Nantes, Nantes, France, 5Karolinska University
Hospital Huddinge, Stockholm, Sweden, 6National University Hospital, Singapore,
Singapore, 7VA Boston Healthcare System- West Roxbury, Jamaica Plain, United
States
Contact E-mail Address: helmut.neumann@uk-erlangen.de
INTRODUCTION: Confocal Laser Endomicroscopy (CLE) allows microscopic
imaging of the colonic mucosal layer during endoscopy. Clinical studies pub-
lished during the past years have enhanced the potential of this technique to
accurately assess the mucosa at the microscopic level and to provide accurate
information either for the assessment of inflammation or for the detection of
neoplasia. Those findings have the potential to improve patient management by
tailoring both diagnostic and treatment approaches.
AIMS & METHODS: The aim of this study is to develop evidence-based con-
sensus statements for the assessment of the role of CLE in the management of
patients with IBD.
Initial statements on the use of CLE in the assessment of IBD were developed by
a single CLE expert based on the available clinical literature. Those preliminary
statements were edited and submitted by an external group of 8 GI physicians
experts in CLE, using a modified Delphi approach. After two rounds of votes
based on current literature and strength of recommendation, statements were
adopted if the threshold of agreement was higher than 75%.
RESULTS: Out of 17 proposed statements, 11 were adopted and 6 rejected. CLE
can identify Crohns disease (CD) and ulcerative colitis (UC) associated histolo-
gical changes in vivo. CLE can be used to acquire targeted biopsies for surveil-
lance of IBD patients. Targeted biopsies should be preferably used instead of
random four quadrant biopsies for surveillance in IBD. CLE can identify IBD
associated histological changes in macroscopically non-inflamed mucosa. CLE
provides dynamic in vivo live information about intestinal barrier function and
vascular permeability. CLE provides dynamic in vivo live information about
intestinal barrier function and vascular permeability. Surveillance in IBD by
using CLE should be performed in macroscopically non-inflamed mucosa.
CLE can redefine the term mucosal healing in vivo. The ultimate goal of in patients aged 26-30 years: 6/7 (86%) were HSV1 (), 5/7 (71%) HSV2 (), 4/7
CLE for IBD patients is to predict response to anti-tumour Necrosis Factor
(anti-TNF) antibody therapy and may help to initiate an individualised therapy
of IBD patients to reduce drug associated side effects, morbidity and costs for the
health care system. Step-down and step-up approaches should be replaced by an
individualized, adapted approach, including microscopic evaluation of the
mucosa.
CONCLUSION: 11 consensus statements on the use of Confocal Laser
Endomicroscopy for the management of IBD were adopted by a panel of 8
clinical experts. These statements were established based on published literature
and consensus opinions, suggesting that Confocal Laser Endomicroscopy has the
potential to play an important role in the management of IBD patients by
United European Gastroenterology Journal 2(5S)
assessing mucosal healing and individualizing approach with biologics. Further
clinical studies are necessary to support these ideas.
Disclosure of Interest: H. Neumann: None declared, R. Arsenescu: None
declared, H. Bertani: None declared, E. Coron Consultancy for: Has been a
consultancy for Mauna Kea Technologies, A. Dlugosz: None declared, J.
Galmiche Consultancy for: Mauna Kea Technologies, K. Ho: None declared,
S. Singh: None declared
P0857 NEGATIVE PREDICTIVE VALUE OF TRANSABDOMINAL
ULTRASOUND FOR SHORT-TERM OUTCOMES OF
INFLAMMATORY BOWEL DISEASE
I. Sturdik1,*, J. Toth1, T. Hlavaty1, T. Koller1, M. Huorka1, Z. Zelinkova1
1
5th internal medicine department, University hospital Bratislava, Bratislava,
Slovakia
Contact E-mail Address: igor.sturdik@gmail.com
INTRODUCTION: Transabdominal ultrasound is considered a useful tool for
the assessment of inflammatory bowel disease (IBD) activity but its negative
predictive value for gold standards diagnostic methods, such as endoscopy, is
limited. Therefore, usefulness of transabdominal ultrasound in monitoring of
disease activity has been questioned. However, the diagnostic value of ultrasound
has not been tested with regards to short or long-term outcomes of IBD.
AIMS & METHODS: The aim of our study was to assess the negative predictive
value of transabdominal ultrasound in IBD for short term disease complica-
tions. We retrospectively evaluated all IBD patients with clinical suspicion of
disease flare who underwent an intestinal ultrasound performed by one sono-
graphist at a single tertiary IBD Center. Disease activity and the presence of
disease complications were evaluated according to standard parameters for
intestinal ultrasound. Findings of colonoscopy performed within 2 months of
the ultrasound were compared to the ultrasound findings for each respective
bowel segment. For correlation of categorical findings at ultrasound and colono-
scopy a chi-square test was used. The changes in therapy were noted as well as
clinical remission and surgical intervention at respective month 3 and 6 following
the ultrasound and negative predictive value of ultrasound was calculated for
each of the outcomes.
RESULTS: In total, sixty five ultrasounds were performed in 61 IBD patients
(mean age 39, range 18 to 94 years; 41% of males; 45/16 Crohns disease/ ulcera-
tive colitis) were evaluated. Overall, there were 45 cases (70%) of disease activity
detected by ultrasound, in 18 cases (28%) no abnormalities were found and 2
cases (3%) were inconclusive. Complications of IBD, such as abscess and fistulas
were found in 10 cases (15%). Colonoscopy was performed in 39 cases.
Ultrasound correlated well with endoscopy in assessment of disease activity in
terminal ileum (p 0.049) as well as in colonic disease (p50.0001). The positive
and negative predictive values (NPV) of ultrasound for disease activity as
assessed by endoscopy were 90% and 78%, respectively, for terminal ileum dis-
ease localisation; and 100% and 75%, respectively, for colonic disease. None out
of 18 cases with no abnormalities found on ultrasound needed a therapy adjuste-
ment nor surgery during the six months following the ultrasound; all these
patients were in remission at respective months 3 and 6 (NPV of relapse 100%).
CONCLUSION: Transabdominal intestinal ultrasound has a high negative pre-
dictive value for short-term complications of inflammatory bowel disease.
Disclosure of Interest: None declared
P0858 HERPES FAMILY VIRUSES IN PATIENTS WITH
INFLAMMATORY BOWEL DISEASE AND IMMUNOSUPPRESSION
P. Tsibouris1,1, I. Koumoutsos1, P. Apostolopoulos1, C. Kalantzis1, E. Chounta1,
E. Vlachou1,*, G. Alexandrakis1
1
GASTROENTEROLOGY, NIMTS GENERAL HOSPITAL, Athens, Greece
Contact E-mail Address: tsibofam@yahoo.com
INTRODUCTION: Herpes family viruses (herpes simplex virus 1 and 2 (HSV1
and HSV 2), Epstein Barr Virus (EBV), cytomegalovirus (CMV)) are prevalent in
the adult population.
AIMS & METHODS: Aim: Study the primary infection in an adult population
with inflammatory bowel disease and infection reactivation under
immunesuppression.
Patients-Methods: 56 patients (40 with Crohns disease, 13 with ulcerative colitis,
3 with indetermined inflammatory bowel disease) were evaluated before immu-
nosuppression initiation (infliximab 36 patients, immunosuppressant 9, inflixi-
mabimmunosuppressant: 11). Serology was evaluated before treatment (anti-
HSV IgG/IgM antibodies, anti-CMV IgG/IgM antibodies, IgG/IgM antibodies
against EBV viral capsid antigens and nuclear antigen). Patients were follow-up
for 3 years with serologic evaluation every 3 months and tissue sampling in case
of disease flare ups for PCR.
RESULTS: In patients aged 17-20 years 3/3 (100%) were HSV 1,2 (), 3/3
(100%) EBV (), 2/3 (66%) CMV (); in those aged 21-25: 6/8 (75%) were
HSV 1 (), 5/8 (63%) HSV2 (), 8/8 (100%) EBV (), 7/8 (88%) CMV ();
(58%) EBV (), 6/7 (84%) CMV (); in patients aged 31-40: 9/11 (81%) were
HSV 1,2 (), 9/11 (81%) EBV (), 9/11 (81%) CMV (); in patients aged 41-50:
11/11 (100%) were HSV 1 (), 10/11 (91%) 10/11 (91%) EBV (), 7/11 (64%)
CMV (); in patients aged over 60: 10/12 (84%) were HSV 1,2 (), 12/12 (100%)
EBV (), 9/12 CMV (). During follow-up 3 patients presented HSV2 serocon-
version, while HSV1 was positive, 3 EBV seroconversion and 3 CMV serocon-
version. All of them were reported to be asymptomatic. 3 patients presented HSV
flare-ups treated with topical and systematic treatment, while immunosuppres-
sion was temporally withheld. No flare-ups reported for EBV and CMV.
United European Gastroenterology Journal 2(5S)
CONCLUSION: Herpes family viruses are prevalent in patients with inflamma-
tory bowel disease. Flare-ups under immunosuppression are rare while serocon-
versions are rather asymptomatic.
Disclosure of Interest: None declared
P0859 ACIDITY OF INTESTINAL CONTENTS IN THE DISTAL PARTS
OF THE COLON IN PATIENTS WITH ULCERATIVE COLITIS
I. Gubonina1,*, V. Grinevich1, V. Ekimov1, N. Sherstneva2
1
2nd Therapy Department, 2Military Medical Academy, Saint-Petersburg, Russian
Federation
Contact E-mail Address: giv70@bk.ru
INTRODUCTION: It is nececcary to determine the possibility of using mesala-
zine-delivering drugs with different release mechanisms depending on the pH
value in patients with UC relapse.
AIMS & METHODS: To evaluate the acidity of intestinal contents in the distal
parts of the colon in patients with ulcerative colitis (UC) relapse. 43 patients with
left-sided UC and 24 patients with extensive UC having mild or moderate relapse
were evaluated. The evaluation of the pH of the chymus with use of a universal
indicator test strip, as well as analysis of changes in the oM of intestinal contents
depending on clinical, laboratory and endoscopic indicators of ulcerative colitis
activity, were carried out in all these patients. The control group consisted of 16
healthy volunteers.
RESULTS: On the whole, there was a trend towards acidification of chymus in
patients with left-sided UC as compared to healthy volunteers (oM 6.760.21
vs. oM 6.940.2, respectively); however, this difference was not statistically
significant. In the group of patients with extensive UC, a decrease in pH to
below 6.0 (20.8%) was noted significantly more often as compared to the patients
with left-sided UC (4.7%, o50.05) or control group subjects (0%, o50.05).
Statistically significant correlation between the pH of the intestinal contents
with ulcerative colitis activity index (correlation coefficient (CC) -0.23), fecal
calprotectin value (CC -0.25), UC duration (CC -0.21) or duration of UC
treatment (CC 0.35) was not revealed.
CONCLUSION: In patients with left-sided UC, acidity of the intestinal contents
in the distal parts of the colon did not differ from that in the healthy volunteers
and did not depend on disease activity or duration of ulcerative colitis. Decrease
in the pH of the intestinal contents to below 6.0 was noted significantly more
often in patients with extensive UC as compared to patients with left-sided UC or
healthy volunteers. In the treatment of patients with decreased intraluminal pH
levels, preference should be given to drugs with oM-independent release of active
ingredient.
Disclosure of Interest: None declared
P0860 ITS ALL IN THE STOOL. FAECAL CALPROTECTIN TO HELP
GUIDE ANTI-TNF THERAPY; A RETROSPECTIVE STUDY
J. Gulliver1,*, G. Baker1, K. Millington 1, K. Zacchariah1, R. Makins1
1
Gastroenterology, Cheltenham General Hospital, Gloucestershire Hospitals NHS
Foundation Trust, Cheltenham, United Kingdom
Contact E-mail Address: james.gulliver@glos.nhs.uk
INTRODUCTION: Faecal calprotectin (FC), a protein derived mainly from
neutrophils and monocytes, is detected in increased quantities in the stool of
patients with inflammatory bowel disease (IBD). Recently, the National
Institute of Clinical Excellence (NICE) in the United Kingdom (UK) has recom-
mended its use as a biochemical test to differentiate between IBD and functional
bowel disease; furthermore, it can also be used to evaluate disease activity or
response to treatment. We routinely assess patients symptoms and biological
markers including FC at least annually once established on anti-TNF therapy.
This assessment is brought forward if there is a suspicion of ongoing disease
activity.
AIMS & METHODS: We sought to assess the impact of FC testing on our
clinical management, specifically for our patients with Crohns disease receiving
anti-TNF therapy. We interrogated our pathology database to collect FC results
from all patients at Gloucestershire Hospitals NHS Foundation Trust who were
established on anti-TNF therapy for Crohns disease. FC samples had been
obtained either as part of annual assessment or earlier due to ongoing symptoms.
We then reviewed the patients notes to determine what actions, if any, had been
taken as a consequence of the FC results.
RESULTS: FC results were available from 28 of 31 patients collected during
2011 and 2012. Results were subdivided based on the FC level into four groups.
1) 5 50ug/g (n 9, 32.1%); 2) 50-100ug/g (n 7, 25%); 3) 100-200ug/g (n 5,
17.9%) and 4) 4200ug/g (n 7, 25%).
Across all four groups anti-TNF therapy was unaltered in 14 patients (50%) and
stopped in 3 (11%). The dose was increased but frequency of treatment main-
tained in 2 (7%), and frequency increased in a further 2 (7%). Frequency was
reduced in one patient from 8 weekly to 10 weekly (3.5%). Two patients were lost
to local follow up.
More specifically, in group 1, 34% had their anti-TNF therapy unaltered and
22% had their therapy stopped with consequent significant cost savings. In con-
trast; 43% of patients in group 4 had their anti-TNF therapy altered, either by
increasing dose or frequency of administration. Regarding further investigations
no patient with a FC result 4100ug/g went on to have a colonoscopy compared
with 33% of patients with an FC 550ug/g.
CONCLUSION: FC is a useful tool when judging clinical response to anti-TNF
therapy in patients with Crohns disease. Once treatment is established it allows
identification of patients for whom anti-TNF therapy can be further optimised or
stopped. It also helps guide the need for further investigation, if either to re-stage
disease extent and severity or if considering alternative diagnoses.
REFERENCES
A367
1. NICE. Faecal calprotectin diagnostic tests for inflammatory diseases of the
bowel, http://www.nice.org.uk/nicemedia/live/14285/65337/65337.pdf (accessed
14 April 2014).
Disclosure of Interest: None declared
P0861 INFLAMMATORY LOAD MEASURED BY SPECT-CT RELIABLY
CORRELATES WITH HISTOLOGY AND FECAL CALPROTECTIN IN
ULCERATIVE COLITIS
J.F. Brandse1,*, R. Bennink2, S.van Eeden3, P.A. Baars4, M. Lowenberg1,
C.Y. Ponsioen1, G.R. van den Brink5, G.R. DHaens1
1
Department of Gastroenterology & Hepatology, 2Nuclear Medicine, 3Pathology,
4
Experimental Immunology, Academic Medical Center, Amsterdam, 5Department
of Gastroenterology & Hepatology, Academic Medical Center, Amsterdam,
Netherlands
Contact E-mail Address: j.f.brandse@amc.uva.nl
INTRODUCTION: Assessing inflammatory activity is essential in therapeutic
decision making in Ulcerative Colitis (UC). Novel scintigraphy techniques
including SPECT-CT are promising to measure inflammatory load in chronic
inflammatory conditions such as UC. Leukocyte scintigraphy therefore needs to
be validated using other established markers of inflammation.
AIMS & METHODS: We aimed to prospectively validate leukocyte SPECT-CT
as a tool to measure and quantify inflammatory load in patients with different
extent and severity of UC.
UC patients with an indication for full colonoscopy were included. Within 1
week and without any changes in therapy both colonoscopy (Mayo score,
UCEIS) with biopsies (Geboes score) and leukocyte scintigraphy were per-
formed. In addition, serum CRP and fecal calprotectin (Buhlmann ELISA)
were measured and clinical questionnaires (CCAI, Mayo) were collected.
Patients peripheral blood leukocytes were isolated and labelled with 200 MBq
technetium-99m HMPAO. SPECT combined with a low-dose CT was performed
60 min after reinjection of labelled cells. To quantify inflammation in each colon
segment the uptake of leukocytes was calculated as a ratio to the mean uptake in
bone marrow of 4 lumbar vertebrae and expressed as SPECT inflammation score
in each colon segment and a Summed Activity Score (SAS) for the inflammatory
activity in all 5 colonic segments together.
RESULTS: Twenty-six UC patients were studied. 3/26 were using anti-TNF, 4/
26 thiopurines, 3/26 prednisone and 20/26 5-ASA at inclusion. At endoscopy 6/
26 (23%) of patients had proctitis, 8/26 (31%) left-sided and 12/26 (46%) pan-
colitis. According to endoscopic Mayo score, 1/26 (4%) of patients had inactive,
5/26 (19%) mild, 8/26 (31%) moderate and 12/26 (46%) severe disease. The
median (IQR) full Mayo score was 7 (5-10), CCAI: 6 (2-9), serum CRP 4.1
mg/L (1.7-12.5) and fecal calprotectin 449 ug/g (245-1142). According to
SPECT-CT patients were classified as having 9/26 mild, 12/26 moderate and 5/
26 severe disease in their most affected segment. At the level of individual seg-
ments, significant correlations (Spearman) were observed between the SPECT
inflammation score and endoscopic Mayo: r 0.54 (P50.01), UCEIS r 0.56
(P50.01) and histologic Geboes score r 0.59 (P50.01). The Summed Activity
Score correlated much better with fecal calprotectin r 0.55 (P50.01) than with
CRP: r 0.24 (p 0.24), CCAI: r 0.43 (P50.05) or clinical Mayo: r 0.54 (P50.01).
CONCLUSION: SPECT-CT assessment of UC disease severity in the most
inflamed colon segment is correlated with both endoscopic and histologic
scores. The total inflammatory load in UC at SPECT-CT is better reflected by
fecal calprotectin than by serum CRP.
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie and Takeda,
R. Bennink: None declared, S. van Eeden: None declared, P. Baars: None
declared, M. Lowenberg: None declared, C. Ponsioen: None declared, G. van
den Brink: None declared, G. DHaens Financial support for research from:
Abbott Inc, Jansen Biologics, Given Imaging, MSD, DrFalk Pharma,
Photopill, Lecture fee(s) from: Abbott Inc, Tillotts, Tramedico, Ferring, MSD,
UCB, Norgine, Shire, Consultancy for: Abbott Laboratories, Actogenix,
Centocor, Cosmo, Engene, Ferring Pharmaceuticals, GlaxoSmithKline, Jansen
Biologics, Millenium Pharmaceuticals, MSD, Novonordisk, PDL Biopharma,
Pfizer, SetPoint, Shire, Takeda, Teva, UCB
P0862 A COCOON IMMUNISATION STRATEGY AMONG
HOUSEHOLD CHILDREN OF ADULTS PATIENTS WITH
INFLAMMATORY BOWEL DISEASE
K. Waszczuk1,*, E. Waszczuk2, A. Mulak2, L. Szenborn1, L. Paradowski2
1
Department of Pediatric Infectious Diseases, 2Department of Gastroenterology
and Hepatology, Wroclaw Medical University, Wroclaw, Poland
Contact E-mail Address: karolkap@gmail.com
INTRODUCTION: In order to protect patients with inflammatory bowel disease
(IBD) against serious infections, vaccination of their household children is
recommended.
AIMS & METHODS: The aim of our study was to assess the not mandatory and
not reimbursed vaccination coverage including pneumococcal, rotavirus, influ-
enza, and varicella vaccines among household children of adult patients with
IBD as the Cocoon Strategy. A self-designed survey was conducted in 138
IBD patients hospitalised in the Department of Gastroenterology and
Hepatology at Wroclaw Medical University from November 2013 to March
2014. The survey comprised questions about household children vaccination
coverage and the reasons of its refusal as well as the history of infectious diseases
in the patients. Randomly, patients completed the survey with a physician pre-
sent to determine questions comprehension. In order to provide test-retest relia-
bility a group of ten patients completed it twice. Fisher exact test was used for
cross-classification tables.
A368
RESULTS: The survey data from 52 IBD patients having household children (25
women, 27 men, mean age: 36 years) were analysed. Two patients declared
refusing one obligatory vaccination of their children, while 40% of the patients
reported at least one not reimbursed vaccine administration. Most frequently,
children obtained pneumococcal (31%), rotavirus (23%), varicella (14%), and
influenza (10%) vaccines. The most common reasons for non-immunisation was
unawareness of the existing recommendations (46%), fear of adverse effects of
the vaccines (18%) and not believing in vaccines efficacy (10%). In one case a
medical health care worker discouraged from immunisation. There was statisti-
cally significant association between not reimbursed vaccines coverage and edu-
cational level of the patients (p50.001). Despite the fact that 28% of IBD
patients could not definitively recall varicella infection, none of their household
children nor they were vaccinated against chickenpox.
CONCLUSION: The use of not mandatory vaccines recommended in Poland in
IBD patients family members is insufficient. Frequently, patients have serious
doubts concerning safety and efficacy of vaccinations. Therefore, further vac-
cines promotion and education of patients as well as their health care providers
are needed. A particular concern is associated with not vaccinating against influ-
enza and varicella, which pose a high risk of infection. Non-immunised and VZV
seronegative IBD patients should be vaccinated, and in case of their immunosu-
pression, vaccination of household children is required.
Disclosure of Interest: None declared
P0863 THE ROLE OF PET-CT IN THE CHARACTERIZATION OF THE
ACTIVITY OF CROHNS DISEASE
K. Palatka1,*, L. Szilvia1, L. Davida1, I. Altorjay1, L. Galuska2
1
Gastroenterology, 2Department Of Nuclear Medicine, University Of Debrecen,
Debrecen, Hungary
Contact E-mail Address: palatka@med.unideb.hu
INTRODUCTION: Crohns disease is an immune-mediated disorder with
unknown etiology, characterized by segmental, transmural inflammation of the
gastrointestinal tract and extraintestinal inflammatory symptoms. The diagnosis
is based on endoscopy, imaging examinations, the disease activity is characterized
by Crohns disease activity index (CDAI), which includes subjective, objective
sympthoms and laboratory parameters. PET-CT is a global, non-invasive, highly
sensitive method to determine the location and activity of some malignant and
inflammatory lesions. Former studies showed 85% sensitivity and 87% specifity
of 18F-FDG-PET-CT in IBD.
AIMS & METHODS: The aim of the study was to evaluate the role of PET-CT
in patients with active Crohns disease (CDAI 4300) before and after biological
therapy and comparing with endoscopic index (SES-CD), CDAI and biochemical
parameters. Twelve patient were examined: 5M/6F, age between 18 and 39,
average age: 25 years. The evaluation of the PET-CT activity was determined
considering the activity of the small intestine and the four colon segments. The
SUVmax (Standardized Uptake Value) of the intestinal segment was correlated
to the SUVmax of the liver, which was chosen as a reference for normal tissue
activity. To get the global PET-score, the activity scores of the five intestinal
segments were summed.
RESULTS: The PET-score showed correlation with CDAI (R2 0.1441) and
CRP (R2 0.0512), but not with SES-CD (R2 0.0041). After one year biologic
therapy CDAI (R2 0.1622), CRP (R2 0.0815) and SES-CD (R2 0.1699) cor-
related well with the PET-score. In active disease, the PET-CT was more sensitive
than the endoscopy to indicate the extent of the inflammation. Examining new
patients, PET-CT was the most informative on the activity and extent of the
disease (small intestine involvement). In one case, the terminal ileum stenosis
with high CDAI score associated with negative PET-CT score, which was a
fibrotic stenosis as it turned out after the surgery. Patients with negative PET-
CT score after biological treatment remained in remission during a two year
follow-up period.
CONCLUSION: The PET-CT results correlated well with the activity of the
Crohns disease. In the future, this should be a promising, non-invasive
method in the diagnosis of Crohns disease and in the planning the treatment
and follow-up. Negative PET-CT proved to be a good indicator of deep
remission.
Disclosure of Interest: None declared
P0864 THE ROLE OF DOUBLE BALLOON ENDOSCOPY FOR CROHNS
DISEASE
K. Mitsui1,*, S. Fujimori1, A. Ehara1, J. Omori1, N. Akimoto1, K. Maki1,
M. Suzuki1, Y. Kosugi1, Y. Ensaka1, Y. Kasuga1, M. Yonezawa1, S. Tanaka1,
A. Tatsuguchi1, C. Sakamoto1
1
Gastroenterology, NIPPON MEDICAL SCHOOL, Graduate School of
Medicine, Tokyo, Japan
Contact E-mail Address: k5mitsui@gmail.com
INTRODUCTION: Deep enteroscopy has been widely used for various small
bowel diseases. One of the most common diseases that affected the small bowel is
Crohns disease. The idea is being accepted that the mucosal healing is important
parameter for the better outcome of Crohns disease. However the efficacy and
safety of the DBE is not fully understood.
AIMS & METHODS: We conducted a retrospective case series study to eluci-
date the efficacy of DBE in Crohns disease. We enrolled the consecutive 40
patient who underwent the 95 DBE examinations since 2003. Patients character-
istics, indications of the deep enteroscopy, duration of procedures, therapeutic
interventions and complications were assessed.
RESULTS: Subjects were 7 females and 33 males, mean age was 3813 years
old. The indications of DBE were mucosal evaluation for known Crohns disease,
obscure gastrointestinal bleeding, small bowel obstruction, removal of the
United European Gastroenterology Journal 2(5S)
retained small bowel capsule endoscopy (SBCE), suspicious of Crohns disease
and further evaluation of protein-losing enteropathy in 17, 10, 7, 3, 2, 1 case,
respectively. The mean number of DBE examination per patient was 2.41.4.
Types of scope were type T, type P (thin type), and type B (short type) in 49, 41
and 5 cases. The choice of the scope had depended on the therapeutic capability
or the facility of deeper insertion. The insertion roots were antegrade (from
mouth) in 31 patients and retrograde (from anus) in 64 patients. The mean
insertion time was 6531 minute. The antegrade vs. retrograde was 4525 vs.
3440 minutes (p 0.005). The mean total examination time was 8334 min.
The antegrade vs. retrograde was 8334 vs. 5626 min. (p50.0001). The mean
insertion depth was 9593 cm. The antegrade vs. retrograde was 17875 vs.
5570 minutes (p50.0001). Balloon dilation therapies were performed in 18
procedures in 8 patients. In 10 patients, the prior SBCE had been done and 6
patients were retained. All the retained SBCE were removed by double balloon
endoscopy. In only one out of 10 patients, DBE had not shown any severe
stricture and SBCE was used for the mucosal evaluation repeatedly. No compli-
cation was encountered in diagnostic and therapeutic DBE.
CONCLUSION: DBE showed that ileal lesions were more common and oral
DBE was time-consuming in Crohns disease. The evaluation with DBE also can
pick out the patient who can undergo the SBCE. The dilation therapy may delay
the timing of the surgical interventions. DBE, especially the retrograde DBE,
have a potential to improve the outcome of Crohns disease.
Disclosure of Interest: None declared
P0865 USE OF INTERVAL ULTRASOUND TO PROSPECTIVELY
MONITOR PATIENTS WITH CROHNS DISEASE ON ADALIMUMAB
K. Novak1,*, G. Kaplan1, R. Panaccione1, S. Ghosh1, E. Ehteshami Afshar1,
A. Wilson1, S. Wilson2
1
Medicine, 2Diagnostic Imaging, University of Calgary, Calgary, Canada
Contact E-mail Address: knovak@ucalgary.ca
INTRODUCTION: Accurate, non-invasive methods of evaluating treatment
response in patients with Crohns disease (CD) are important in a treat to
target paradigm. The aim of this study is to prospectively evaluate the ability
of sonography to monitor patients on adalimumab (ADA), correlated with endo-
scopy as a gold standard.
AIMS & METHODS: This is an IRB-approved, single-center, prospective study,
evaluating patients with CD treated with adalimumab for at least 6 months.
Baseline clinical score (Harvey Bradshaw/HBI), C-reactive protein (CRP), ileo-
colonoscopy and transabdominal ultrasound were completed within 2 weeks at
time zero and 12 months (if clinically indicated), with intervening scans at 4 and 8
months. Standard sonographic assessment included bowel wall thickness, color
Doppler signal, presence of inflammatory fat and lymph nodes. Endoscopy was
scored using validated simple endoscopic score (SES) and/or Rutgeerts score
(Ri) in post-operative patients. Endoscopic responsiveness was defined as muco-
sal healing (SES-CD5 and/or Ri1) and sonographic responsiveness as bowel
wall thickness (6mm) with minimal inflammatory fat and Doppler signal. The
aim of this study is to prospectively evaluate sonographic and endoscopic main-
tenance of remission in patients on adalimumab.
RESULTS: 50 patients have been recruited to date with n 34 included in this
analysis (n 16 excluded given drop out, missing data or in progress). At time
zero, 34 patients had endoscopy and 19/34 (56%) patients underwent follow-up
endoscopy at 1 year, those who did not were deemed in clinical and serologic
remission without indication for endoscopy. There were (3/34) strictures limiting
endoscopic visualization of disease at time zero, and one had proximal disease.
The agreement between the remaining US and endoscopy (n 30) at time zero
was excellent (complete agreement in 26/30), as was the correlation at twelve
months. Table 1 shows endoscopy and US findings for 17/19 at 12 months.
Final endoscopies were limited given proximal disease in 2/19 and thus were
not included. Patients with endoscopically active disease at 12 months showed
active sonographic disease as early as 4 months.
Mucosal Healing Endoscopically Active
(SES-CD3 (SES-CD43
and/or Ri1) and/or RI41)
Absence of US disease 11 0
Presence of US Disease 1 4 (1 pouch case)
CONCLUSION: US is an accurate, non-invasive modality useful in evaluating
maintenance of response to therapy, which correlates with mucosal healing on
endoscopy. Thus, US may be a surrogate for endoscopy and a repeatable, objec-
tive target for treatment.
Disclosure of Interest: None declared
P0866 QUALITY OF LIFE IN ULCERATIVE COLITIS ASSOCIATION
BETWEEN THE SHORT INFLAMMATORY BOWEL DISEASE
QUESTIONNAIRE (SIBDQ) AND THE SHORT HEALTH SCALE
(SHS) AND THEIR RELATIONSHIPS WITH CLINICAL AND
ENDOSCOPIC DISEASE ACTIVITY
K. Theede1,*, M. Kiszka-Kanowitz1, I. Nordgaard-Lassen1, A.M. Nielsen1
1
Gastrounit, Medical Division, Copenhagen University Hospital Hvidovre,
Hvidovre, Denmark
INTRODUCTION: Health Related Quality of Life (HRQoL) is an important
part of Inflammatory Bowel Disease (IBD) assessment, and is affected by both
disease activity, psychological, and social factors. Several HRQoL questionnaires
United European Gastroenterology Journal 2(5S)
have been developed, but are primarily used in the setting of clinical trials. Little
is known about the relationship between HRQoL and disease activity and
between the different HRQoL questionnaires. We aimed to assess the association
between the SIBDQ and the SHS and their associations with clinical and endo-
scopic disease activity.
AIMS & METHODS: Prospectively, 110 patients with ulcerative colitis under-
went sigmoidoscopy and completed the SIBDQ and the SHS. The SIBDQ is a
validated 10-question tool measuring physical, social, and emotional status (score
10-70, poor-good). The SHS is a four-part visual analogue scale questionnaire
measuring bowel symptoms, activities of daily life, worry, and general well-being
(score 0-40, good-poor). Clinical disease activity was assessed using the Mayo
score (0-12) and was divided into remission (2), mild (3-5), moderate (6-9), and
severe (10-12) activities. The endoscopic grade of inflammation was assessed
using Mayo Endoscopic Score (MES, 0-3).
RESULTS: The median age was 37 years (19-80), and 56 % were female. The
median disease duration was 4.5 years. 29 % had mucosal healing, 20 % active
proctitis, 16 % active proctosigmoiditis, 18 % active left-sided colitis and 18 %
pancolitis. According to the MES, 29 % had mucosal healing, 26 % had mild, 31
% moderate and 14 % severe inflammation. According to the Mayo score, 37 %
were in clinical remission, 21 % had mild, 31 % moderate and 11 % severe
disease activity.
HRQoL significantly decreased with increasing clinical disease activity (Mayo
score) when assessed with both SIBDQ (2 51.9, p50.0001) and SHS
(2 56.2, p50.0001). HRQoL also significantly decreased with increasing endo-
scopic disease severity (MES) when assessed by both SIBDQ (2 33.1,
p50.0001) and SHS (2 40.3, p50.0001). Overall, we found a significant dif-
ference in HRQoL between patients with mucosal healing (MES 0) and active
inflammation (SIBDQ, inactive/active, 59.1/45.6, p50.0001 and SHS, inactive/
active, 6.8/19.7, p50.0001). Moreover, we found a strong association between
SIBDQ and SHS using linear regression (SHS -0.73SIBDQ52.1,
p50.0001).
CONCLUSION: In this study we demonstrate that HRQoL is not only strongly
associated with clinical disease activity, but also with the endoscopic disease
severity. We also demonstrate that SIBDQ and SHS are strongly associated
with each other.
Both SIBDQ and SHS show significantly decreasing HRQoL with increasing
clinical disease activity as well as with increasing endoscopic disease severity.
The study also shows significant difference in HRQoL between patients with
mucosal healing and endoscopic active disease. Both questionnaires seem equally
adequate in determining the disease impact on HRQoL.
HRQoL is from the patients perspective one of the most important parts of IBD
management. SIBDQ and especially SHS can be completed quickly during reg-
ular visits, and can be used as an easy tool for HRQoL monitoring. Significant
changes must be followed by exploration of the possible causes including assess-
ment of disease activity.
Disclosure of Interest: K. Theede Financial support for research from: Research
grant from AbbVie Inc. and Ferring Pharmaceuticals, M. Kiszka-Kanowitz:
None declared, I. Nordgaard-Lassen Financial support for research from:
Research grant from AbbVie Inc. and Ferring Pharmaceuticals, Consultancy
for: Advisory Board AbbVie Inc., A. Nielsen Financial support for research
from: Research grant from AbbVie Inc. and Ferring Pharmaceuticals,
Consultancy for: Advisory Board AbbVie Inc.
P0867 IS THE TUBERCULIN SKIN TEST ALONE ACCURATE IN
MODEATE-TO-SEVERE BCG VACCINATED PATIENTS WITH
INFLAMMATORY BOWEL DISEASE TREATED WITH
IMMUNOSUPPRESSIVES TO TEST FOR LATENT TUBERCULOSIS?
K.B. Gecse1,*, Z. Kurti1, A. Balint2, K. Farkas2, B.D. Lovasz1, A. Szabo1,
M. Mandel1, A. Gyurcsanyi1, Z. Vegh1, A. Mohas1, T. Molnar2, L.S. Kiss1,
P.A. Golovics1, P.L. Lakatos1
1
1st Department of Medicine, Semmelweis University, Budapest, 21st Department
of Medicine, University of Szeged, Szeged, Hungary
Contact E-mail Address: lakatos.peter_laszlo@med.semmelweis-univ.hu
INTRODUCTION: There are few data available on effect of immunomodulator/
biological therapy on the accuracy of tuberculin skin test (TST, Mantoux skin
test) and interferon-gamma release assay (IGRA) in BCG vaccinated immuno-
suppressed IBD patients.
AIMS & METHODS: Our aim was to define the accuracy of the TST and IGRA
tests in a BCG vaccinated referral IBD cohort treated with immunosuppressives
and/or biologicals. Data of 135 consecutive moderate-to-severe IBD (98 CD, 37
UC) patients were analyzed (male/female: 64/71, median age at diagnosis: 24.0;
IQR: 18-31 years, duration: 7.0; IQR: 4-13 years). Patients were treated with
immunosuppressives (azathioprine, steroids) and/or anti-TNF therapy. Blood
samples for IGRA were collected during routine laboratory testing parallel
with TST. The result of TST was determined according to international guide-
lines. Both in- and outpatient records were collected and comprehensively
reviewed.
RESULTS: TST positivity rate was 21.6%, 20.1%, 13.4% or 12.7% with cut-off
values of 5, 10, 15 and 20mm. IGRA positivity rate was 7.7% with indeterminate
result in 1.2%. The correlation between TST and IGRA was significant, with
moderate-to-good kappa values if TST results were 415mm (kappa: 0.32-0.34,
p50.001). In addition, a TST of 14 and 17mm was also identified as best cut-off
value in a ROC analysis (AUC: 0.70, p 0.04). There was no association between
the type and number of immunomodulators used or any disease phenotype char-
acteristics and the TST or IGRA results. Importantly, smoking was identified as
a risk factors for TST but not IGRA positivity (OR: 3.80, 4.88, 9.87 and 8.98,
p50.002, for TSTcut-off 5, 10, 15 and 20mm).
CONCLUSION: The TST and IGRA are partly complimentary methods and
accuracy is acceptable also in BCG vaccinated and immunosuppressed IBD
A369
patients. A TST of 415mm should be used as a cut-off to identify patients at
risk for latent TB in these patients. Smoking is a risk factor for TST positivity.
Disclosure of Interest: None declared
P0868 INCREASED EXTRACELLULAR MATRIX PROTEINS TURN-
OVER IN PATIENTS WITH CROHNS DISEASE
L.E. Godskesen1, M.D. Jensen1,*, L. Klinge1, J. Mortensen2, A.-C. Bay-Jensen2,
A. Krag1, J. Kjeldsen1
1
Department of Gastroenterology, Odense University Hospital, Odense C, 2Nordic
Bioscience A/S, Herlev, Denmark
Contact E-mail Address: line@napoleon.dk
INTRODUCTION: Ongoing inflammation in Crohns disease (CD) may lead to
development of intestinal fibrosis and patients may present with stenosis.
Inflammation is a dynamic process with a permanent remodeling of the extra-
cellular matrix (ECM). Small fragments of the ECM generated during this pro-
cess, so called neoepitopes, are released into the circulation and could be used as
biochemical markers of disease activity or markers of fibrosis.
AIMS & METHODS: This study investigates a panel of these novel developed
markers in patients with suspected or known CD.
106 patients referred for evaluation of CD had serum samples drawn. Patients
were evaluated with colonoscopy, small-bowel imaging (capsule endoscopy, MR
enterography, and CT enterography), fecal calprotectin, and C-reactive protein.
35 patients had newly diagnosed CD, 26 had CD with active inflammation or
stenosis, 11 had known CD without inflammation or complication, and 34 had
no evidence of Crohns disease. The following neoepitopes were measured by
competitive ELISAs; MMP-mediated of type I, III, IV collagen (C1M, C3M,
C4M), N-terminus pro-collagen type I (P1NP), and MMP-degraded, citrulli-
nated vimentin (VICM).
Data were not normally distributed and Kruskal-Wallis one-way analysis of
variance was used for comparison. ROC-curve analysis were used to test the
biomarkers ability to discriminate CD from non-CD.
RESULTS: Serum levels of C3M were significantly elevated in patients with CD
compared to patients without CD (median 24.4 and 19.1, respectively; P 0.01).
C3M discriminated CD from non-CD with an AUC of 0.66. Concentrations of
C1M and C4M were also elevated but statistical significance was not reached
(C1M: median 68.9 and 62.9; P 0.12. C4M: median 70.5 and 67.2; P 0.15). In
patients with CD, C1M and C3M concentrations were higher in clinically active
disease (CDAI 4 150) compared to quiescent disease (C1M: median 75.0 and
63.2; P 0.02. C3M: median 24.5 and 22.7; P 0.10), and C3M concentrations
were higher in CD involving the colon compared to small bowel CD (median 26.2
and 22.1; P 0.05). C1M, C3M and C4M correlated with CRP (Spearmans rho
0.76, 0.40, and 0.45, respectively; P 5 0.001) but not with fecal calprotectin.
Concentrations of ECM degradation markers were not significantly increased in
patients with stricturing CD compared to patients without CD. In subgroup
analysis of patients with diagnosed CD and elevated CRP compared to non-
CD and normal CRP C1M, C3M and C4M discriminated CD from non-CD
(AUC of 0.95, 0.88 and 0.90).
CONCLUSION: Turnover of ECM proteins is increased in patients with CD.
These neoepitopes may distinguish between patients with CD and patients with-
out CD and between active CD and disease in remission. Further studies of these
promising markers of the ECM are warranted.
Disclosure of Interest: L. E. Godskesen: None declared, M. Jensen: None
declared, L. Klinge: None declared, J. Mortensen Other: Employee at Nordic
Bioscience, A.-C. Bay-Jensen Other: Employee at Nordic Bioscience, A. Krag:
None declared, J. Kjeldsen: None declared
P0869 INTESTINAL EPSTEIN- BARR VIRUS IS ASSOCIATED WITH
MUCOSAL LYMPHOPROLIFERATION AND SUBSEQUENT
INTESTINAL SURGERY IN INFLAMMATORY BOWEL DISEASE
PATIENTS
L. Nissen1,2,*, I. Nagtegaal2, D.de Jong1, W. Kievit1, L. Derikx1, M. Lynch2,
H.van Krieken2, F. Hoentjen1
1
Gastroenterology and Hepatology, 2Pathology, RadboudUMC Nijmegen, The
Netherlands, Nijmegen, Netherlands
Contact E-mail Address: loes.nissen@radboudumc.nl
INTRODUCTION: Thiopurine therapy increases the risk of (Epstein- Barr virus
associated) lymphomas for Inflammatory Bowel Disease (IBD) patients up to
four times. Epstein- Barr virus (EBV) can cause a wide spectrum of lymphopro-
liferative reactions, ranging from morphologically benign with normal B lym-
phocytes (BL) and lymphoplasmacytic infiltrate in the lamina propria (LI) to
aggressive lymphomas with atypical BL and LI.
EBV can be detected in colonic mucosa in up to 60 % of the IBD patients, but
there is no consensus on when to perform EBV testing on intestinal mucosa. We
hypothesized that EBV testing can be guided by histological features including
morphology of BL and LI.
AIMS & METHODS: The aim of this study was to determine the value of the
histology of the inflammation in predicting EBV presence in intestinal mucosa
and to correlate EBV positivity with clinical endpoints such as intestinal surgery
and development of lymphoma.
All IBD patients who underwent EBV testing by EBV-encoded RNA in situ
hybridization (EBER) in intestinal biopsies between January 2005 and October
2013 in our centre were identified. All biopsies were revised by a blinded, expert
gastro-intestinal pathologist and scored on three histological features: number of
EBV positive cells per high power field (HPF); normal or atypical LI and normal
or atypical BL. Demographic and clinical data were collected from patient charts.
Adverse events that were registered included intestinal surgery and lymphoma.
A370
We used the Chi square test or Fishers exact test to identify an association with
EBV positivity.
RESULTS: 58 IBD patients were included, 28 were EBV positive and 30 were
EBV negative. Ulcerative colitis was more frequent in the EBV positive group
(82,1 % versus 56,7 %; p 0.052)
EBV positive patients had significantly more frequent atypical LI (57.1 % versus
3.3 %; p 50.001). The specificity for predicting EBV presence of the atypical
LI is high (96.7 %), just as its positive predictive value (94.1 %). At time of
biopsy, EBV positive patients used more often combinations of two or more anti-
inflammatory drugs (5-aminosalicytes excluded; 50 % versus 16.7 %; p 0.007)
Eighteen EBV positive patients (64.29 %) had 20 pre-defined complications (18
colectomies, 2 lymphomas). Within the group of EBV positive patients, those
who developed complications had a significantly higher EBV load (50 % versus
10 %; p 0.048), expressed as the frequency of  10 EBV positive cells per HPF.
11 patients had atypical LI and BL, including 2 lymphomas: those were treated
with chemotherapy. In the other 9 patients at least one immunosuppressive drug
was stopped. In all patients the atypical LI showed resolution. 8 of the 9 patients
became EBV negative and 1 patient had reduction of EBV positive cells.
CONCLUSION: In the present study, atypical LI was associated with mucosal
EBV in IBD patients. A high EBV load is correlated with adverse events.
Reduction of immunosuppression may decrease intestinal EBV associated
lymphoproliferation.
Disclosure of Interest: None declared
P0870 SCREENING OF NOVEL PLASMA MICRORNAS ASSOCIATED
WITH DISEASE PROGRESSION IN ULCERATIVE COLITIS
M. Patel1,2,*, A.M. Verma1,2, M. I. Aslam1,2, K. West2, J. Jameson2,
J.H. Pringle1, B. Singh2
1
Cancer Studies & Molecular Medicine, University of Leicester, 2University
Hospitals of Leicester, Leicester, United Kingdom
Contact E-mail Address: maleene@doctors.org.uk
INTRODUCTION: New biomarkers are required to monitor patients with
Ulcerative Colitis (UC) and predict complications such as dysplasia and colitis
associated cancer (CAC). Accurate plasma based biomarkers would allow phy-
sicians to make clinical decisions, thereby avoiding unnecessary invasive tests.
AIMS & METHODS: This feasibility study aimed to identify novel microRNAs
(miRNAs) in the plasma of patients with Ulcerative Colitis related to disease
progression.
RESULTS: Primary analysis of the array data identified the differential expres-
sion of several miRNAs from which the following miRNAs 122,125b, 139-3p,
331-5p, 375, 383-3p, 409-3p, 720, 1274B were chosen for validation. Analysis of
variance was used to assess differences between groups. MiR-375 was shown to
be significantly up-regulated in the CAC cohort (p 0.002) when compared to
UC and PSC. MiR-375 was found to be an effective biomarker of disease pro-
gression over disease duration, with Cox-regression analysis showing a Cox
hazard ratio of 1.91 (p 0.01).
CONCLUSION: Peripheral plasma miRNAs have the potential to act as bio-
markers of disease progression in Ulcerative colitis. This study provides the first
evidence that miRNA-375 is up regulated in cases of CAC. This finding needs to
be extended to a larger validation cohort.
Disclosure of Interest: None declared
P0871 THE INS AND OUTS OF MRI AND ENDOSCOPY IN THE (57 582) mg/g, 52 (15 415) mg/g and 55 (9 158) mg/g using the Buhlmann-,
EVALUATION OF DISEASE ACTIVITY AND SEVERITY IN
CROHNS DISEASE
M. Serio1,*, A. Pierro2, G. Maselli2, K. Efthymakis1, A. Milano1, F. Laterza1,
A. Bonitatibus1, G. Sallustio2, M. Neri1
1
Medicine and Aging Sciences and CESI, Universita` "G. DAnnunzio", Chieti,
2
Radiology Department, Fondazione di Ricerca e Cura Giovanni Paolo II, the Buhlmann- and the Immundiagnostik assay and the Phadia- and the
Universita` Cattolica del Sacro Cuore, Campobasso, Italy
Contact E-mail Address: mneri@unich.it
INTRODUCTION: Endoscopy is the gold standard for activity assessment in
luminal Crohns disease (CD) but, due to the full thickness involvement of the
bowel wall, or presence of complications, CD activity is the result of an integra-
tion of endoscopic, clinical, laboratory, and imaging data. Recently, a radiolo-
gical score which integrates both mural and extramural involvement has been
validated for a global disease evaluation (1).
AIMS & METHODS: to examine the relationships among MRI, laboratory
inflammatory markers, clinical activity scores and endoscopy in a series of CD
patients.
45 consecutive patients with endoscopically proven CD underwent at the time of
enrollment MRI enterography, performed utilizing a 1.5 T system, for the staging
of disease at diagnosis and activity assessment. Endoscopic activity was measured
by a quantitative score (Simple Endoscopic Score for Crohns Disease, SES-CD
(2), range 0-40) with active disease being present for a 43 score and mild,
moderate ad severe disease for ranges of respectively 4-10, 11-19 and 420.
MRI activity was measured by a previously validated quantitative score
(Magnetic Resonance Enterography global score, MEGS, range 0-296), with
active disease being present for a 40 score. For all participants the Crohns
Disease Activity Index (CDAI) was completed and CRP and fecal calprotectin
(FC) were measured (positivity cut-off respectively 4 0.50 mg/dl and 4150 g/
gr).
RESULTS: We enrolled 19 males and 26 females, mean age 3714 years, mean
disease duration 5 years. According to Montreal disease classification the phe-
notype was L1 in 47%, L2 in 6% and L3 in 47%; the behavior was B1 in 24%, B2
in 56%, B3 in 20% and perianal disease in 2%; resectional surgery related to CD
was observed in 20%. According to SES-CD, 91% of patient had active disease
United European Gastroenterology Journal 2(5S)
and 9% had inactive disease (64% mild, 20% moderate and 7% severe disease).
Mean MEGS was 2018, with 82% having active disease and 18% inactive
disease (p50.01 in comparison to endoscopy, sensibility 88%, specificity 75%,
VPP 97%, VPN 38%). MEGS, was significantly higher in penetrating than in
non-penetrating and non-stricturing disease (respectively 359 vs 711, p5
0.001). MEGS was significantly correlated with SES-CD (p50.01), in particular
for the ileal (p50.01) and ceacum-ascending colon subscores (p 50.05). Severity
of the disease at endoscopy did not correlate to severity at MEGS (p 0.7). Both
MEGS and SES-CD show significant correlations with CDAI (p50.01) and
CRP (p50.05), yet SES-CD only correlated significantly with FC (p50.001).
The extramural involvement subscore, observed in half of patients, regardless of
the behavior and severity at endoscopy, was associated to CRP positivity
(p50.05), not with fecal calprotectin (p 0.67). Increasing staging of grading
at endoscopy was significantly correlated to the risk of extramural involvement
(p 0.008)
CONCLUSION: MRI is capable of identifying disease activity, although it
results less accurate in the assessment of severity as measured at endoscopy.
The presence of positive CPR suggests the need of MRI for the staging of
patients with active luminal disease.
REFERENCES
1 Makanyanga J, et al. Eur Radiol 2014.
2 Daperno M, et al. Gastrointest Endosc 2004.
Disclosure of Interest: None declared
P0872 ASSAY SPECIFIC DIFFERENCES IN CONSECUTIVELY
MEASURED F-CALPROTECTIN IN PATIENTS WITH IBD
FOLLOWED OVER TIME
K. Amcoff1, M. Lampinen2, M. Stridsberg3, J. Halfvarson1,4, M. Carlson2,*
1
School of Health and Medical Sciences, Orebro University, Orebro, 2Department
of Medical Sciences, Gastroenterology Research Group, Uppsala University,
3
Department of Clinical Chemistry and Pharmacology, Uppsala, 4Dep of Internal
Medicine, Div of Gastroenterology, Orebro University Hospital, Orebro, Sweden
Contact E-mail Address: jonas.halfvarson@orebroll.se
INTRODUCTION: Faecal calprotectin (FC), an abundant neutrophil protein,
has recently been introduced as a non-invasive marker for monitoring of disease
activity in inflammatory bowel disease (IBD). However, it has been difficult to
define a definite threshold to discriminate between remission and active disease.
AIMS & METHODS: We, aimed to compare the results of different FC-assays
in a well-characterized cohort of patients with IBD, followed over time. Patients
(n 13) with established IBD provided faecal samples and reported clinical activ-
ity every third months prospectively for a two year period. Relapse was defined
as increasing symptoms and intensified treatment. FC was measured with three
different assays; Calprotectin Elisa Buhlmann Laboratories AG, Basel,
Switzerland; Phadia Elia Calprotectin, ThermoFischer Scientific, Freiburg,
Germany; and PhiCal Calprotectin Elisa, Immundiagnostik AG, Bensheim,
Germany. Disease status, defined as clinical remission or relapse, i.e. active dis-
ease, was determined at the time of collection of each fecal sample in each
patient. Samples were grouped as corresponding to clinical remission or active
disease. However, samples collected three months after a relapse were excluded to
reduce possible bias due to prolonged intensified therapy, steroid dependent
disease or ongoing subclinical inflammation.
RESULTS: In total, the 13 patients prospectively provided 91 faecal samples
during the two year period. The median (IQR) concentration of FC was 187
Phadia- and Immundiagnostik assay, respectively (p50.0001). Based on the cut-
off provided by the manufactures, i.e. 450 mg/g, the FC assay was positive in 74
(81 %), 47 (52 %) and 50 (55 %) of the 91 samples when analyzed by the
Buhlman-, Phadia- and Immundiagnostik assay, respectively. Modest to fairly
good correlations were observed between the Buhlmann- and the Phadia assay,
Immundiagnostik assay (R2 0.70, R2 0.80 and R2 0.86, respectively).
However, Bland-Altman plots revealed overall poor agreement between the
assays. Assay specific sensitivity, specificity and predictive values for defining
clinical remission vs. active disease for each assay based on different cut-offs
are shown in table 1.
Table 1. Assay specific sensitivity, specificity and predictive values for defining
clinical remission vs. active disease for each assay based on different cut-offs
FC cut-off
(mg/g) Bu 50 Ph 50 Im 50 Bu 100 Ph 100 Im 100 Bu 150 Ph 150 Im 150
Sensitivity 86% 71% 86% 86% 64% 36% 79% 50% 14%
Specificity 26% 66% 62% 50% 72% 78% 56% 76% 80%
NPV 87% 89% 94% 93% 88% 81% 90% 84% 77%
PPV 24% 37% 39% 32% 39% 31% 33% 37% 17%
Bu; Buhlmann assay, Ph; Phadia assay, Im; Immundiagnostik assay, NPV; nega-
tive predictive value, PPV; positive predictive value
CONCLUSION: By cross-comparisons pronounced inter-assay differences were
revealed. Although moderate to fairly good correlations between the FC assays
were observed, Bland-Altman plots showed overall poor agreement.
Disclosure of Interest: None declared
United European Gastroenterology Journal 2(5S)
P0873 RESIDUAL ABNORMALITIES AFTER MAYO ENDOSCOPIC
SUBSCORE DEFINED COMPLETE MUCOSAL HEALING
DEMONSTRATED BY NOVEL ISCAN ENDOSCOPIC AND REFINED
HISTOLOGICAL GRADINGS
M. Iacucci1,*, M. Fort Gasia1, R. Panaccione1, S. Ghosh1, X. Gui2
1
IBD clinic. Division of Gastroenterology, 2Department of Pathology, University of
Calgary, Calgary, Canada
Contact E-mail Address: miacucci@ucalgary.ca
INTRODUCTION: High definition(HD)- iSCAN endoscopy can characterize in
details the mucosa in patients with ulcerative colitis (UC) and may provide more
information about inflammation and mucosal healing (MH). However, the gold
standard of mucosal healing is still histological diagnosis. More refined histologic
and high definition iSCAN endoscopic criteria may redefine mucosal healing.
AIMS & METHODS: 78 patients (40 male, median age 42y, range 19-90y)
with UC were assessed by HDiSCAN colonoscopy (Pentax EC-3490Fi; Pentax,
Japan) as well as by white light endoscopy (WLE). Mayo endoscopic subscore
and UC endoscopic index of severity (UCEIS) score were assigned to patients
according WLE findings. Mucosal pattern on iSCAN was graded as 1 normal,
2 mosaic pattern, 3 tubular-gyrus, 4 nodular rosette. The vascular pattern
was graded as 1 normal, 2 spiral isolated vessels, 3 crowded tortuous ves-
sels, 4 Irregular vessels. A histological grading and scoring system that assesses
all changes possibly seen in IBD was developed for a detailed and comprehensive
evaluation. This system (GUI-ECAP system) was designed to reflect all histologic
changes in IBD categorized as 1) Extent of inflammation (focal, multifocal,
diffuse), 2) Chronicity (crypt architectural alteration, Paneth cell metaplasia),
3) Activity (surface epithelium changes, neutrophilic cryptitis, crypt abscess,
crypt destruction, lamina propria mononuclear cellularity, lamina propria neu-
trophil infiltration, and basal plasmacytosis), and 4) Plus additional findings,
including eosinophilia and lymphoid follicles/aggregates. An established histolo-
gic grading system, New York Mount Sinai score was used to validate the grad-
ing of inflammation.
RESULTS: In this cohort of 78 patients with UC, 23 (29%) patients had Mayo
endoscopic subscore of 0. Of these 23 patients with complete MH, 18 patients
(78%) had abnormal vascular pattern on iSCAN and 7 (30%) had abnormal
mucosal pattern on iSCAN. By using ECAP histologic scoring all 23 patients
(100%) showed various histologic abnormalities including crypt architectural
alteration [19, (83%)], surface epithelium abnormality [16, (70%)], crypt destruc-
tion [3, (13%)], increase in lamina propria mononuclear cells [15, (65%)], basal
plasmacytosis [11, (48%)], lamina propria neutrophilic infiltration [5, (21%)] and
other additional findings [19, (83%)].
CONCLUSION: The subtle histologic abnormalities underlying the apparently
healed mucosa with Mayo endoscopic subscore of 0 can be detected by using
refined histological scoring system (GUI-ECAP) in combination with iSCAN.
Sensitive endoscopic techniques such as iSCAN and histologic scoring such as
ECAP can detect residual abnormalities in the majority of patients with see-
mingly complete MH in UC.
Disclosure of Interest: None declared
P0874 COLORECTAL CANCER IN IBD PATIENTS TREATED OR
UNTREATED WITH ANTI-TNFS: A RETROSPECTIVE MATCHED-
PAIR STUDY IN A 13 YEARS FOLLOW UP
M. Ascolani1,*, G. Condino1, C. Petruzziello1, S. Onali1, E. Calabrese1, E. Lolli1,
A. Ruffa1, F. Pallone1, L. Biancone1
1
Universita` Tor Vergata, Rome, Italy
Contact E-mail Address: biancone@med.uniroma2.it
INTRODUCTION: In murine models, blocking TNF-alpha showed efficacy in
colitis-associated colon cancer. Chronic inflammation in Inflammatory Bowel
Disease (IBD) colitis has been associated with colorectal cancer (CCR).
AIMS & METHODS: In a monocentric retrospective matched-pair study, the
frequency of colon cancer was compared in a cohort of IBD patients treated or
untreated with anti-TNFs. In a matched-pair study, the role played by clinical
characteristics of IBD in determining the frequency of colon cancer was also
evaluated. Clinical records of all IBD patients in follow up from 2000 to 2013
at our tertiary IBD referral center developing cancer of the lower GI tract (IBD-
K)(small intestine, appendix, CCR, anal canal) were reviewed. Each IBD-K
patient was retrospectively matched with 2 IBD patients with no cancer of the
lower GI tract (IBD-C), for IBD type (MDC/RCU), gender, age (5yrs). Anti-
TNFs (Infliximab or Adalimumab1 dose) and IMM (6mos) use was reported.
Data expressed as median (range). Students T test and Chi squared test used as
appropriate.
RESULTS: From 2000 to 2013, the study population included 2387 IBD
patients: anti-TFNs use in 384 (16%). Cancer of the lower GI tract developed
in 15/2387 (0.62%) patients (9CD,6UC), including 12 CCR, (6UC,6CD), 1 ileal
adenocarcinoma (1CD), 1 carcinoid of the appendix (1CD), 1 anal canal carci-
noma (1CD). In the 15 IBD-K patients, age at diagnosis of cancer was 51 (28-73)
yrs, IBD duration 19yrs (1-47): there were 9 CD of the ileum (I) (n 4), colon (C)
(n 2), ileum-colon (IC) (n 3) and 6 UC distal (n 3), left-sided (n 1) or total
(n 2). Among the 15 IBD-K patients, 3 (20%) received anti-TNFs and/or IMM
(combined in all 3). In these 3 patients, cancer included CCR (n 2) or carcinoid
(n 1) in 2CD (2F,age 40 and 54yrs, CD duration 28 and 26 yrs; I-C, fistulizing)
and 1UC (1F, CCR, age 30, duration 19yrs; pancolitis). Among the 384/2387
(16%) IBD patients treated with anti-TNFs, CCR developed in 3 (0.78%)(com-
bined IMM in 3). Among the 2003/2387 (84%) patients anti-TNFs na ve,
12(0.6%) developed cancer of the lower GI tract,including CCR in 10 (0.5%)
(p ns vs anti-TNFs treated patients). IBD-C included 30 patients
(18CD,12UC;14 M/16 F, age 54,range 37-75), with CD (13 I;2 C;3 I-C) or UC
(distal 11, left-sided 1). Anti-TNFs use was reported in a comparable proportion
A371
of IBD patients developing or not cancer (IBD-C n 6/30; 20% vs IBD-K n 3/
15; 20%). In IBD-C, IMM were used in 10 (33%)(combined anti-TNFs in 2;6.
7%).
CONCLUSION: In a retrospective matched-pair study, a comparable low fre-
quency of colon cancer was observed in IBD patients treated or untreated with
anti-TNFs.
Disclosure of Interest: None declared
P0875 IS THERE A ROLE FOR THE NEW SEROLOGICAL MARKERS IN
PREDICTING DISEASE COURSE IN AN IBD POPULATION
COHORT? LESSONS LEARNT FROM A PROSPECTIVE IRISH
POPULATION
M.N. Shuhaibar1,*, C. OMorain1
1
Department of Gastroenterology/ Clinical Medicine, AMNCH/Trinity College
Dublin, DUBLIN, Ireland
Contact E-mail Address: mnshuh@gmail.com
INTRODUCTION: Crohns disease and Ulcerative colitis are the two main
forms of inflammatory bowel disease. There are different disease phenotypes
within those groups and yet another 10-17% of patients may not have either
diagnosis and can be then be classified as indeterminate colitis until later on in
their disease course when they are reclassified into either main group as symp-
toms progress. Furthermore, some patient with gastrointestinal symptoms may
not have IBD initially, but develop it in future. Several antibodies have been
linked to CD and different IBD subtypes.
AIMS & METHODS: The aim of our study was to determine the prevalence of
the new anti-glycans antibody panel in a prospective homogenous IBD cohort to
help differentiating those with IBD from healthy controls. We aimed to assess
panels role in discriminating between CD and UC with their different phenotype
and their predictive value for disease course and treatment stratification in the
future.
Antibodies against a mannan epitope of Saccharomyces cerevisiae (gASCA),
laminaribioside (ALCA), Chitobioside (ACCA), mannobioside (AMCA) were
tested in serum samples of 103 IBD patients, 199 healthy matched controls.
Antibody response was matched to disease type and course. A backward step
multiple-regression analysis was performed along with 2- sample t-test for uni-
variate biomarker analysis.
RESULTS: The anti-glycans antibody panel was useful in differentiating IBD
patients from healthy matched controls. Overall, 72% of IBD patients tested
positive for anti-glycans antibodies and of those 64% were positive for
gASCA, compared to 49% for ACCA antibody. gASCA was highly sensitive
and specific in CD patients.
CONCLUSION: From applying the anti-glycans antibody panel, combination of
gASCA IgA, Anti-L and Anti-C antibodies were statistically very significant in
differentiating CD from UC (with a p 50.0001). gASCA was very specific to CD
and correlated with severe disease course requiring surgery or fistulas, requiring
anti -TNF therapy in the lateral years.
Disclosure of Interest: None declared
P0876 CLINICAL OUTCOMES IN PATIENTS WITH INTERMEDIATE
RAISED FAECAL CALPROTECTIN LEVELS
M. Mcfarlane1, A. Dhaliwal1, S. Chambers1,*, C. Nwokolo1, A. Patel1,
R. Arasaradnam1,2
1
Gastroenterology, UHCW, Coventry, 2CSRI, University of Warwick, Warwick,
United Kingdom
Contact E-mail Address: r.arasaradnam@warwick.ac.uk
INTRODUCTION: Calprotectin is a calcium binding protein of the S100 family
associated with inflammation. A recent systematic review has confirmed its value
in distinguishing between organic (inflammatory bowel disease - IBD) and non-
organic gastrointestinal disease (irritable bowel syndrome - IBS). Those with FC
levels below 50 mcg/g have a negative predictive value of 492% to exclude
organic gastrointestinal disease. Conversely, FC levels greater than 250mcg/g,
correlates with endoscopic disease activity in those with IBD; sensitivity of 90%.
The aim of our study was to determine the clinical outcome in patients presenting
with an intermediate raised level of FC between 50-250 mcg/g.
AIMS & METHODS: FC test results from July 2012 to October 2013 were
reviewed. FC testing was performed using the PhiCal ELISA method. 482
patients were identified from the UHCW pathology database: 390 normal
(550mcg/g), 51 intermediate (50-250mcg/g) and 41 high (4250mcg/g).
Excluding paediatric patients (under 16), left 47 intermediate and 35 high results.
Where possible clinical information was obtained from the UHCW Clinical
results and reporting system. If no information was found then general practi-
tioners (GPs) were contacted for further details (long term clinical data could not
be found for 5 intermediate and 9 high patients).
RESULTS: We studied a subset of 50 of the 390 normal FC values (550mcg/g)
which served as a comparator group. Of these, 9 (18%) were referred to second-
ary care gastroenterology, with 3 (6%) still in secondary care 6 months post FC.
None were diagnosed with IBD.
Of the 26 patients with high FC (4250mcg/g), 8 did not have details provided by
their GPs, 8 (31%) were known IBD patients and 3 (12%) were not investigated -
declining referral or patient mortality. 6 (23%) had a new diagnosis of IBD and 1
(4%) with post infective IBS. 15 (58%) were still in secondary care 6 months after
FC testing.
Of the 42 intermediate (50-250mcg/g) patients, 17 did not have information
provided by their GPs and 2 (5%) were known IBD patients. 8 patients (19%)
were diagnosed with colon cancer or were still under investigation. 3 (7%) had a
new diagnosis of IBD and 12 (29%) with non IBD conditions (e.g. BAM,
A372 United European Gastroenterology Journal 2(5S)
Diverticular disease and IBS). 13 (31%) patients were still in secondary care 6 REFERENCES
months after initial FC see table 1. Robinson A. Review article: inflammatory bowel diseaseempowering the
Within the intermediate group, 10 patients had FC 5 100mcg/g, none were patient and improving outcome. Aliment Pharmacol Ther 2004; 20(Suppl. 4):
diagnosed with IBD and 20% remained in secondary care 6 months post FCP. 84-87.
Of the 16 available patients with FC of 100-250, 3 (23%) had a new diagnosis of Disclosure of Interest: None declared
IBD and 7 (54%) were still in secondary care 6 months after FC.

P0878 SERUM HEPCIDIN LEVELS PREDICT INTESTINAL IRON

550mcg/g 50-250mcg/g 4250mcg/g
ABSORPTION IN IBD PATIENTS
Groups (subset n 50) (n 42) (n 26)
M. Wiesenthal1,*, F. Hartmann1, T. Iqbal2, A. Dignass1,3, J. Stein1,4
1
Managed in primary care 41(82%) 5 (12%) 3 (12%) Crohn Colitis Centre Rhein-Main, Frankfurt/Main, Germany, 2Birmingham
Undergoing investigations 9 (18%) 17 (40%) 6 (23%) University Hospital, Birmingham, United Kingdom, 3Agaplesion Markus
Krankenhaus, 4Krankenhaus Sachsenhausen, Frankfurt/Main, Germany
New diagnosis of IBD 0 3 (7%) 6 (23%) Contact E-mail Address: j.stein@em.uni-frankfurt.de
Existing diagnosis of IBD 0 2 (5%) 8 (31%)
Still under follow-up at 6 months 3 (6%) 13 (31%) 15 (58%) INTRODUCTION: Circulating hepcidin is proposed to regulate iron absorption
(from FC testing) by modulating iron export by ferroportin at the basolateral membrane of the
duodenal mucosal cells and/or uptake into the cells at the apical membrane by
DMT1. To date, no data have shown a relationship between plasma hepcidin
concentrations and iron absorption in IBD patients.
CONCLUSION: 1) The majority (81%) of FC requested were normal with a AIMS & METHODS: We used stored samples from a human iron absorption
similar proportion managed in primary care without any new diagnosis of IBD. study to further test the hypothesis that plasma hepcidin may explain interindi-
2) New diagnosis of IBD is three times more common in those with FC values 4 vidual variation in iron absorption in IBD patients. Serum ferritin (SF) and
250mcg/g and 3) A third (31%) with intermediate FC levels remain under sec- serum markers of inflammation [high-sensitivity C-reactive protein (hsCRP)
ondary/tertiary care at 6 months but still half compared with those having high and IL-6] were measured in stored samples from a human iron absorption
FC levels. study using commercially available immune-assays. Hepcidin-25 concentrations
Disclosure of Interest: None declared were determined in fasting samples from 71 adult subjects with IBD (31 UC, 40
CD) and 26 healthy controls. Hepcidin was measured by LC-MS.
RESULTS: There was a positive correlation between hepcidin (mean: 2.3; range:
P0877 LONG-TERM EFFECTIVENESS, PATIENT SATISFACTION & 0.17.8nmol/L) and hsCRP (p50.005), but not between hepcidin and serum
COST-BENEFIT ANALYSIS OF A SELF-MANAGEMENT ferritin (p40.05). Whereas iron absorption was negatively correlated with
PROGRAMME FOR PATIENTS WITH INFLAMMATORY BOWEL serum ferritin only in patients with inactive disease (hsCRP55md/dl; p5
DISEASE: A FIVE YEAR FOLLOW-UP STUDY 0.001), a negative correlation was observed with serum hepcidin in both active
S. Gethins1, M.S. Hanna1,*, B. Robinson1, T. Duckett1, P. Hunt1, and inactive disease (p 0.006), independent of IBD phenotype. Multiple linear
R.J. Robinson1 regression models showed that serum hepcidin in isolation significantly predicted
1
Department of Gastroenterology, Leicester General Hospital, Leicester, United the interindividual variation in iron absorption.
Kingdom CONCLUSION: Concentration of serum hepcidin, but not serum ferritin, was
Contact E-mail Address: minahanna@yahoo.com highly correlated with intestinal iron absorption in IBD patients.
Disclosure of Interest: None declared
INTRODUCTION: Self management programmes enable patients with
Inflammatory Bowel Disease to play a greater role in monitoring and treating
their illness, allowing them to be discharged from hospital follow up. Short-term P0879 LONG TERM OUTCOME OF CROHNS DISEASE ACTIVITY A
studies have shown reduced health service utilization, without compromising PROSPECTIVE STUDY-
health outcomes1. N. Bounab1,*, L. Kecili1, A. Balamane1, K. Belhocine1, K. Layaida1, L. Gamar1,
AIMS & METHODS: The aim of our study was to evaluate the long-term T. Boucekkine1
effectiveness of a self-management programme for patients with IBD and 1
Faculty of Medicine, Algiers, Algeria
assess patient satisfaction and health care cost benefits. Over a 12 month
period in 2007, 157 patients with IBD (122 with Ulcerative colitis (UC), 31 INTRODUCTION: Crohns Disease (CD) is a chronic and heterogeneous
Crohns disease (CD) and 4 indeterminate colitis were recruited to our IBD inflammatory bowel disease affecting the gastrointestinal tract; its etiology is
self management programme. Stable patients on first line therapy met with a unknown and its outcome is unpredictable
specialist IBD nurse and were provided with specific information about their AIMS & METHODS: To analyze the long term outcome of the disease activity,
diagnosis, relapse recognition and medication. A personalised written self man- we studied a cohort of 226 consecutive cases of CD hospitalized from 01/01/2000
agement programme was provided with an escalation plan in the event of symp- to 31/12/2004. These patients, enrolled at diagnosis, underwent initial complete
toms. The first 70 patients recruited to the study were sent a patient satisfaction investigation. CD diagnosis was based on international criteria. All patients were
questionnaire 1 year post-recruitment. A cost-saving analysis over the 5 year included in a prospective study and followed-up from 01/01/2005 to 31/12/2009
period was performed based on the premise of avoiding 2 hospital follow-up during at least 5 years or until the first surgical resection. A systematic clinical
appointments per year and the local tariff (103). After 5 years, the case notes control was performed every 6 or 12 months and on demand; complete investiga-
of all patients re-referred were reviewed to establish the reason for re-referral and tion comprising endoscopy was done when needed. Statistical study: Student
interval between discharge & re-referral. Fishers t test and Mann Withney U test.
RESULTS: Over the 5 year period 22 (14.0%) patients (22 UC, 2 CD) had RESULTS: The cohort included 103 males and 123 females (mean age was 30, 3
been re-referred to our service with a flare of their IBD. Five patients required years at diagnosis); 41 patients were smokers (18.1%). At the end of follow-up: 1/
azathioprine & one patient with Crohns disease was started on biologics. One The overall annual activity which was defined as the percentage of active disease
patient was admitted as an emergency, initially responding to cyclosporine but per year has showed a progressive decrease (from 59.3 % the first year to 46.5%
required a colectomy 1 year later. The remainder were treated with increased 5- the last year p50.05) associated with a decrease of the number of severe flares
ASA, topical therapy or oral steroids. Median time from discharge to re-referral (from 34.7% to 15% p50.05). 2/the age at onset of the disease didnt influence
was 31 months (range 11-60 months). 62/70 (88.6%) patients completed their the disease activity: 62%; 59.3%; 59.7% at diagnosis and 50%; 45.3%; 45.4% at
patient satisfaction surveys; 58 (93.5%) being satisfied with the programme and the end of follow- up in patients aged 520 years, 20-40 years, 440 years respec-
58 (93.5%) feeling involved in their treatment decisions. Over the 5 year period, tively (p 40.05).3/ the rate of activity tends to decrease over time when lesions
there was an estimated health-care cost saving of 147290. (Table 1) were located in both small intestine and colon (59.5% to 46.5% p50.05) whereas
it remained stable when lesions were located exclusively in the colon (from 48.8%
No. of patients in to 44.1%;p40.05). 4/decrease of activity was more often observed in inflamma-
self-management Local follow-up tory type lesions (from 50% to 41.3% p 5 0.05). 5/smoker (S), non smoker (NS)
programme at appointment and previous smoker (PS) statutes didnt influence activity outcome
start of year No. of tariff x estimated (from:S 60%;PS 60%; NS 57.6% to S 45.4%; PS 43.4%; NS 47%:
patients re-referred appointments Estimated p40.05).6/ however, the need for surgery increased progressively over the time
Year to service in each year per year Cost-savings (from 4% the first year to 7% the last year).
CONCLUSION: This prospective study showed that the overall Crohns Disease
Year 1 157- 2 155 103 x 2 31930 activity decreased and became less severe over time, which probably expresses a
slight tendency to a disease extinction. The course of disease hasnt been signifi-
Year 2 155- 6 149 103 x 2 30694 cantly influenced neitherby the age at onset of disease, nor by tobacco consump-
Year 3 149- 7 142 103 x 2 29252 tion. The outcome of initial inflammatory type lesions was more favourable than
Year 4 142- 6 136 103 x 2 28016 stricturing or penetrating lesions.
Year 5 136- 3 133 103 x 2 27398 Disclosure of Interest: None declared
Overall savings 147290

CONCLUSION: This study shows that self-management is an effective long

term strategy for selected stable patients with IBD and is acceptable to patients.
Few patients are re-referred and the substantial 5-year cost savings could be re-
invested in developing specialist IBD services.
United European Gastroenterology Journal 2(5S)
P0880 PREVALENCE OF ANAEMIA IN A COHORT OF PATIENTS
WITH IBD AND ITS RELATIONSHIP TO FAECAL AND SERUM
BIO-MARKERS OF INFLAMMATORY BURDEN, AND MARKERS OF
IRON STATUS
N.S. Taylor1,*, D.A. Lloyd1, S. Cotton1, L.-A. McCabe1, J.N. Gordon1
1
Gastroenterology, Hampshire Hospitals NHS Foundation Trust, Winchester,
United Kingdom
Contact E-mail Address: john.gordon@hhft.nhs.uk
INTRODUCTION: Anaemia is common in IBD and usually due to either iron-
deficiency or anaemia of chronic disease. Serum ferritin is a frequently used
marker of iron status in patients with IBD. It is influenced by inflammatory
status with CRP commonly used in clinical practice to aid in determining the
presence or absence of iron deficiency. However, the correlation of ferritin with
markers of mucosal disease activity such as faecal calprotectin (FC) is unknown
and may have important implications in determining the effect of inflammation
on the diagnosis of iron deficiency. The aim of this study was to investigate the
prevalence of anaemia and its relationship to markers of iron stores and faecal
and serum markers of inflammation in IBD.
AIMS & METHODS: We performed a computer database search of all IBD
clinic patients who had paired blood tests (including Hb, mean cell volume, CRP,
ferritin) and FC in the last 12 months. Blood and faecal samples were accepted as
paired if taken within 7 days of each other. Anaemia was defined using WHO
criteria, with a ferritin of 530ng/ml taken to indicate iron-deficiency. An FC of
550 ug/g was taken to indicate inactive disease, an FC of 50-200 ug/g a border-
line result and an FC 4200 ug/g as active disease. Results were analysed to assess
for prevalence of anaemia and iron deficiency and their correlation with faecal
and biochemical markers of disease activity.
RESULTS: 124 patients (79 Crohns disease, 45 Ulcerative Colitis) with a diag-
nosis of IBD and paired blood tests and faecal inflammatory markers were
identified and their data analysed. 30/124 (21%) of the whole cohort were anae-
mia, and 34% were iron-deficient. There was a clear negative correlation between
disease activity and both haemoglobin and ferritin levels. 20/30 (66%) of the
anaemic patients had a ferritin of 530 and could clearly be classified as iron-
deficient. The average CRP in this group was 11.4mg/l and calprotectin 686ug/g.
9/30 (30%) of patients had a ferritin of 430 with one patient having a ferritin of
4100. The average CRP in this group was 17.8 and calprotectin 832ug/g. 40% of
anaemic patients with a ferritin 430 had a CRP 55 and would not be classified
as iron deficient. All these patients had a raised calprotectin (av 1030). Use of a
raised Calprotectin of 4500ug/g as a marker of inflammatory burden rather
than CRP would have resulted in half these patients being classified as iron
deficient which was supported by other markers of iron stores.
CONCLUSION: Anaemia (21%) and iron deficiency (34%) were common in
this cohort of patients with IBD. There was a clear negative correlation between
markers of anaemia and iron deficiency and faecal calprotectin. There was a
closer correlation between calprotectin and anaemia than CRP and anaemia.
Calprotectin may be a more effective marker of inflammatory burden than
CRP in the assessment of IDA in patients with active IBD.
Disclosure of Interest: None declared
P0881 UTILITY OF FAECAL CALPROTECTIN IN PREDICTING
RELAPSE IN INFLAMMATORY BOWEL DISEASE: A META-
ANALYSIS
N. Mohammed1,*, E. Telakis2, V. Subramanian1
1
Gastroenterology, Leeds Institute of Biomedical and Clinical Sciences, St Jamess
University Hospital, University of Leeds, Leeds, United Kingdom,
2
Gastroenterology, Bioclinic of Piraeus, Piraeus, Greece
Contact E-mail Address: v.subramanian@leeds.ac.uk
INTRODUCTION: Faecal calprotectin (FCP) is a non-invasive marker of gas-
trointestinal inflammation. Its utility in the clinical management of inflammatory
bowel disease (IBD) is still under evaluation. We aimed to perform a meta-
analysis of prospective studies in assessing the ability of baseline FCP for pre-
dicting disease relapse with 12 months in patients with Crohns disease (CD) and
ulcerative colitis (UC) in clinical remission.
AIMS & METHODS: Multiple electronic databases were searched including
Pubmed, Embase and Ovid looking for studies providing data on relapse predic-
tion in IBD using FCP. Pooled sensitivity, specificity, negative (LR-) and positive
(LR) predictive value diagnostic odds ratio (DOR) and pooled area under the
receiver operating characteristic (AUROC) was calculated using MetaDiSc
ver1.4 software. A random effects model was used and publication bias was
assessed using Funnel plots and Eggers test and heterogeneity was assessed
using Cochrans Q and the I2 test.
RESULTS: 8 studies involving 507 patients with CD and 8 studies involving 587
patients with UC were included. The predictive value for a relapse within 12
months for baseline FCP in patients with CD was sensitivity 73%(64-80), speci-
ficity 78% (74-82), LR 2.9 (1.9-4.5), LR- 0.4 (0.2-0.6), DOR 10.1 (4.5-22.6) and
AUROC 0.83 (0.04). The cut off for baseline FCP used for the CD studies
ranged from 130-340 mg/g. The predictive value for a relapse within 12 months
for baseline FCP in patients with UC was sensitivity 72%(65-77), specificity 78%
(74-83), LR 3.0 (2.3-4.0), LR- 0.4 (0.2-0.6), DOR 9.2 (5.4-15.7) and AUROC
0.82 (0.03). The cut off for baseline FCP used for the UC studies ranged from
130-250 mg/g. There was significant heterogeneity (I2 4 50%) for all the analysis
likely because of the differences in relapse rates and FCP cut off values used.
CONCLUSION: FCP is a simple non-invasive marker with the potential to
predict relapse in CD and UC. With pooled sensitivity and specificity under
80% for both CD and UC but with a likelihood ratio of a negative test being
0.4, its value may be mainly to identify low risk patients. However wide varia-
tions in the cut off values for FCP used in these studies makes it difficult to apply
A373
this to routine clinical practice. Serial measurements of FCP to check for a rise
from baseline may be the way forward for future studies.
Disclosure of Interest: None declared
P0882 IS THERE ANY RELATION BETWEEN RED BLOOD CELL
DISTRIBUTION WIDTH AND MUCOSAL REMISSION IN
ULCERATIVE COLITIS?
O. Kocaman1,*, A. Danalioglu1, A.T. Ince1, K. Turkdogan1, H. Senturk1,
B. Baysal1, M. Tozlu1, Y. Kayar1
1
Department of Gastroenterology, Bezmialem Vakif University, Istanbul, Turkey
Contact E-mail Address: drokocaman@hotmail.com
INTRODUCTION: A higher red blood cell distribution width (RDW) has been
shown as an indicator of disease activity in ulcerative colitis (UC). However, the
relation of mucosal remission with RDW has not been investigated. We aimed to
determine if RDW level as a categorical variable (high or normal) could be used
as a parameter for predicting mucosal remission in UC.
AIMS & METHODS: This study was conducted prospectively at a university
hospital with high volume of inflammatory bowel disease patients. C-reactive
protein (CRP), RDW value and colonoscopic findings were analyzed in UC
patients. The endoscopic procedures were performed by a dedicated IBD endos-
copist. Mucosal remission was defined as a Mayo score of 0 for UC. The groups
were compared using chi-square test. SPSS version 16 was used for statistics.
RESULTS: A total of 178 patients (102 male, 76 female; age range: 19 to 82
years) were included in the study. The number of patients with mucosal-remission
was 57 (normal or inactive disease). No correlation between CRP levels and
mucosal remission was found. Of the patients in mucosal remission, 46 had
normal RDW level. Of the 121 patients with no mucosal remission, 75 had
normal RDW level. RDW was found as a significantly useful parameter for
identifying mucosally active UC patients (p50.005).
CONCLUSION: This study shows that categorical RDW value is a useful para-
meter for identifying mucosally active UC patients and could be used as a marker
for non-invasive monitoring of mucosal activity in UC patients.
Disclosure of Interest: None declared
P0883 PREVENTION OF OPPORTUNISTIC INFECTIONS IN PATIENTS
ON BIOLOGICAL AGENTS FOR MANAGEMENT OF
INFLAMMATORY BOWEL DISEASE
H. Gordon1,*, A. Steel1
1
Gastroenterology, Chelsea and Westminster Hospital, London, United Kingdom
Contact E-mail Address: hannah.gordon@chelwest.nhs.uk
INTRODUCTION: Patients with inflammatory bowel disease are at increased
risk of infection; this is especially true of the 20% on biological agents. ECCO
guidelines recommend the following vaccines: Influenza (annual), Pneumococcal,
Hepatitis B, Varicella, HPV (women under 26). The guidelines also highlight the
need to exclude latent TB; local policy is to perform an interferon gamma release
assay. Within the UK vaccination services are provided by primary care.
AIMS & METHODS: The measures taken to prevent opportunistic infection in
patients prescribed anti-TNFs for IBD at Chelsea and Westminster Hospital in
2013 were audited against the ECCO OI Guidelines. The following were retrieved
from electronic records: age, sex, anti TNF prescribed, pneumococcal antibodies,
hepatitis B core and surface antibodies, varicella IgG, Elispot. Attempts were
made to retrieve vaccination history from General Practice.
RESULTS: 60 patients were prescribed infliximab and 15 patients were pre-
scribed adalimumab. 46 GPs were able to provide vaccination history.
Influenza: 50% (23/46) patients received vaccination against influenza within the
past year.
Pneumococcus: 55% (47/85) patients demonstrated immunity. 6% (5/85) were
not immune and the remainder were not tested. The vaccination history of 26
patients who were not immune or not tested was retrieved. 27% (7/26) had since
been vaccinated.
Hepatitis B: No patients were core Ab positive. Surface Ab levels demonstrated
immunity in 7% (6/85). 53% (45/85) were not immune, and the remainder were
not tested. Vaccination history of 44 patients who were not immune or not tested
was retrieved. Of these, 25% (11/44) had since been vaccinated.
HPV: 4 patients were women under 26 years old. 25% (1/4) had confirmed HPV
vaccination.
Varicella: 21% (18/85) patients demonstrated immunity to varicella. 2% 2/85
were not immune.
Elispot: 65% (55/85) patients had a nonreactive assay. 1% (1/85) had a positive
result and the remainder were not tested.
CONCLUSION: The standards set out by ECCO to protect patients from
opportunistic infection are not being met.
Problems obtaining accurate vaccination history from GP records include incor-
rect surgery details, lack of availability of staff able to review records and incom-
plete records. HPV vaccination usually takes place at school and is not routinely
recorded by primary care.
Potential service improvements include provision of vaccines at clinic, improved
patient education regarding the importance of vaccination and a check list to
review bloods at first anti-TNF prescription.
REFERENCES
1. Rahier JF, Ben-Horin S, Chowers Y, et al. European evidence-based
Consensus on the prevention, diagnosis and management of opportunistic infec-
tions in inflammatory bowel disease. J Crohns Colitis 2009; 3: 4791.
Disclosure of Interest: None declared
A374
P0884 EFFICACY, SAFETY, AND DEMOGRAPHICS FACTOR OF ORAL
TACROLIMUS THERAPY IN 666 JAPANESE PATIENTS WITH
REFRACTORY ULCERATIVE COLITIS
H. Ogata1,*, T. Yamamoto2, R. Kunisaki3, K. Ishida4, T. Hibi5
1
School of Medicine, Keio University, Tokyo, 2Yokkaichi Hazu Medical Center,
Yokkaichi, 3Yokohama City University Medical Center, Yokohama, 4Astellas
Pharma Inc., 5Kitasato University Kitasato Institute Hospital, Tokyo, Japan
Contact E-mail Address: kota.ishida@astellas.com
INTRODUCTION: Ulcerative colitis (UC) is a form of chronic inflammatory
bowel disease and is characterized by periods of remission and episodes of
relapse. The pathogenesis of UC remains unclear. This study aims to evaluate
the efficacy and safety of tacrolimus (TAC).
AIMS & METHODS: Aims: To evaluate the safety and efficacy of oral TAC in
Japanese patients with refractory (corticosteroid-resistant or -dependent) active
UC in a real clinical setting.
Methods: The observation period of this study was 6 months. Six hundred and
sixty-six UC patients were enrolled between 2009 and 2011 in 145 medical insti-
tutions. Efficacy was evaluated using the Disease Activity Index (DAI) score (1),
clinical remission and endoscopic remission. DAI score improvement was defined
as either a reduction in DAI of more than 4 points with improvement of all
categories (Stool frequency, Rectal bleeding, Mucosal appearance, Physicians
global assessment) or complete resolution of all categories (2). Clinical remission
was defined as stool frequency  3 per day and no rectal bleeding. Endoscopic
remission was defined as mucosal appearance  1.
RESULTS: Mean DAI score was 8.9  1.97 at baseline. Adverse drug reactions
(ADRs) occurred in 39% of the patients. The most frequent ADRs were Nervous
system disorders (serious: 2 patients, non-serious: 71 patients) such as finger
tremor (50 patients), and the most frequent serious ADRs were infections and
infestations (20 patients) such as cytomegalovirus-related events (7 patients) and
pneumonia-related events (5 patients). In 18 out of 20 patients, serious infections
and infestations were resolved or became mild during the observation period.
When serious infections and infestations occurred, 6 patients discontinued the
TAC treatment and 11 patients continued after they occurred. One patient had
discontinued before the event. In another 2 patients, one patient (age 81) devel-
oped sepsis and died 2 days after it occurred. One patient (age 56) developed
herpes zoster and didnt improve during the observation period. TAC treatment
was continued after it occurred. Serious renal and urinary disorders were
reported in 8 patients. Seven out of 8 patients were resolved or became mild
during the observation period. One patient (age 62) developed renal impairment
and didnt improve during the observation period. All of the 8 patients discon-
tinued the TAC treatment when serious renal and urinary disorders occurred.
DAI score improvement was observed in 63% of the patients during the obser-
vation period. Sixty-seven percent of the patients had clinical remission during
the observation period. The endoscopic remission rate increased with time during
the observation period (17% after 3 months, 31% after 6 months).
CONCLUSION: Oral TAC therapy, with monitoring of blood trough concen-
tration was well tolerated and induced clinical and endoscopic remission with
time in Japanese patients with refractory active UC.
REFERENCES
1. Schroeder KW, Tremaine WJ and Ilstrup DM. Coated oral 5-aminosalicylic
acid therapy for mildly to moderately active ulcerative colitis, a randomized
study. N Engl J Med 1987; 317: 16251629.
2. Ogata H, Matsui T, Nakamura M, et al. A randomised dose finding study of
oral tacrolimus (FK506) therapy in refractory ulcerative colitis. Gut 2006; 55:
1255-1262.
Disclosure of Interest: H. Ogata Financial support for research from: Astellas
Pharma Inc., Zeria Pharmaceutical Co., Ltd., AstraZeneca, Boston Scientific
Corporation, Otsuka Pharma, Kyorin Pharmaceutical Co.,Ltd., Lecture fee(s)
from: Astellas Pharma Inc., Mitsubishi Tanabe Pharma Corporation, Dainippon
Sumitomo Pharma Co. Ltd., Given Imaging Ltd., Takeda Pharmaceutical
Company Ltd, Kyorin Pharmaceutical Co.,Ltd., Consultancy for: AbbVie Inc.
Mochida Pharmaceutical Plant Co., Ltd., Johnson & Johnson, T. Yamamoto:
None, R. Kunisaki Lecture fee(s) from: Astellas Pharma Inc., Shareholder of:
Astellas Pharma Inc., K. Ishida: Employee of: Astellas Pharma Inc., T. Hibi
Financial support for research from: JIMRO Co. Ltd., AbbVie Inc. Zeria
Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Lecture
fee(s) from: Astellas Pharma Inc., Yoshida Pharmaceutical, Zeria
Pharmaceutical Co., Ltd., Eisai Co. Ltd., JIMRO Co. Ltd., Kyorin
Pharmaceutical Co.,Ltd. AbbVie Inc. Mitsubishi Tanabe Pharma Corporation,
Nippon Kayaku Co. Ltd., Consultancy for: Astellas Pharma Inc., Nippon
Kayaku Co. Ltd. Eisai Co. Ltd., AbbVie Inc. Ajinomoto Pharmaceuticals Co.,
Ltd.
P0885 WITHDRAWAL OF AZATHIOPRINE IN PATIENTS WITH
CROHNS DISEASE IN STABLE CLINICAL REMISSION: A
DOUBLE-BLIND, PLACEBO-CONTROLLED 2 YEARS TRIAL
H.H. Wenzl1,*, C. Primas2, G. Novacek2, A. Teml2, A. Offerlbauer-Ernst2,
C. Hogenauer1, H. Vogelsang2, W. Petritsch1, W. Reinisch2
1
Internal Medicine, Medical University of Graz, Graz, 2Internal Medicine, Medical
University of Vienna, Vienna, Austria
INTRODUCTION: Many patients with quiescent Crohns disease are main-
tained on long-term treatment with azathioprine (AZA), but controlled data
are limited. The aim of the present study was to evaluate the efficacy of AZA
therapy for more than 4 years to maintain clinical remission.
AIMS & METHODS: We performed a randomized double-blind placebo-con-
trolled AZA withdrawal trial with a follow-up period of 24 months. Patients had
to have continuous AZA therapy for a minimum of 4 years without exacerbation
United European Gastroenterology Journal 2(5S)
of disease during the previous 12 months before enrollment, and a Crohns
disease activity index 5150 at baseline. Patients were randomized to continue
on AZA (n 26) or switch to placebo (n 26). The primary endpoint was time to
clinical relapse during follow-up.
RESULTS: During the 2-year follow-up clinical relapse occurred in 4 patients on
continued AZA and in 8 patients on placebo. Time to clinical relapse averaged
22.3 months (95% CI 20.6-24.0) in the AZA group, and 19.2 months (95% CI
16.4-22.1) in the placebo group (p 0.20). According to life-table analysis, the
proportion of patients in remission after 12 and 24 months was 964% and
867% in patients receiving AZA versus 768% and 689% in patients receiv-
ing placebo (month 12, p 0.035; month 24, p 0.30). A higher AZA dose at
enrollment was an independent predictive factor for relapse (p50.05).
CONCLUSION: In patients with clinically inactive Crohns disease on mainte-
nance therapy with AZA for 4 4 years discontinuation of AZA resulted in a
numerically higher relapse rate compared to further AZA treatment. Our results
are in line with previous observations.
Disclosure of Interest: H. Wenzl Lecture fee(s) from: Abbvie, MSD, and SHIRE,
C. Primas Lecture fee(s) from: MSD, G. Novacek Lecture fee(s) from: MSD,
AbbVie, and Ferring, Consultancy for: MSD, AbbVie, and Astro Pharma, A.
Teml: None declared, A. Offerlbauer-Ernst: None declared, C. Hogenauer
Lecture fee(s) from: MSD, AbbVie, Signatis Pharma and Astro Pharma, H.
Vogelsang Lecture fee(s) from: MSD, AbbVie, Astro Pharma, Johnson &
Johnson and Ferring, W. Petritsch Lecture fee(s) from: Abbott Laboratories,
AbbVie, Aesca, Ferring, Merck and MSD, Consultancy for: Abbvie and MSD,
W. Reinisch Financial support for research from: Abbott Laboratories, Abbvie,
AESCA, and MSD, Lecture fee(s) from: Abbott Laboratories, Abbvie, Aesca,
Aptalis Centocor, Ferring, Janssen Millenium, Mitsubishi Tanabe Pharma
Corporation, MSD, PDL, Pharmacosmos, Schering-Plough, Shire, Takeda,
and Therakos, Consultancy for: Abbott Laboratories, AbbVie, Aesca, Amgen,
AM Pharma, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb,
Cellerix, Chemocentryx, Celgene, Centocor, Danone Austria, Elan, Ferring,
Galapagos, Genentech, Grunenthal, Janssen, Johnson & Johnson, Kyowa
Hakko Kirin Pharma, Lipid Therapeutics, Millenium, Mitsubishi Tanabe
Pharma Corporation, MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos,
Pfizer, Procter & Gamble, Prometheus, Robarts Clinical Trial, Schering-
Plough, Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor,
Yakult, Zyngenia, and 4SC, Other: Lipid Therapeutics, Pharmacos and Pfizer
P0886 COST-EFFECTIVENESS OF ADALIMUMAB IN MODERATELY
TO SEVERELY ACTIVE ULCERATIVE COLITIS (SUB-ACUTE) IN
THE UK
H. Yang1, A. Curry2, S. Wang3,*, M. Yang1, M. Skup3, J. Chao3, Y. Bao3
1
Analysis Group, Inc., Boston, United States, 2AbbVie Ltd, Berkshire, United
Kingdom, 3AbbVie Inc., North Chicago, United States
Contact E-mail Address: song.wang2@abbvie.com
INTRODUCTION: The objective was to compare the cost-effectiveness of ada-
limumab (ADA) versus standard of care (SOC) for the treatment of patients with
moderately to severely active ulcerative colitis (UC) (sub-acute) who have an
inadequate response to SOC in the UK. The base case was conducted for a
UC patient population including patients who are na ve to the cytokine inhibi-
tors affecting tumour necrosis factor alpha (anti-TNF-) and patients who have
previously been exposed to anti-TNF- agents other than ADA.
AIMS & METHODS: A Markov model was constructed to simulate the treat-
ments and disease course of adults with moderately to severely active UC
(including both anti-TNF- na ve and experienced patients) who had an inade-
quate response to conventional therapies receiving ADA therapy, or receiving
SOC. SOC refers to conventional treatments including anti-inflammatory drugs
or immunosuppressants. The model estimated the direct health care costs and
quality-adjusted life years (QALYs) over a 10-year time horizon. The model was
conducted from the perspective of the U. K. National Health Service. Only direct
costs were considered. Eight health states were defined in the Markov model,
including three pre-surgery states (i.e. remission, mild, and moderate-to-severe),
surgery state, and four post-surgery states (i.e. post-surgery without complica-
tion, transient complication, chronic complication, and surgery-related death).
The transitional probabilities of the pre-surgery states were primarily derived
from the randomized, controlled clinical trials of ADA in the treatment of mod-
erately to severely active UC patients [the Ulcerative Colitis Long-term
Remission and Maintenance with Adalimumab M06-827 (ULTRA 2) trial and
M10-223 (the ULTRA 1/2 extension trial)]. The transitional probabilities for the
surgery and post-surgery states were derived based on published literature.
Utility values were specified for each disease state, and were based on published
literature. The model considered drug costs, disease states costs, hospitalization
costs, surgery costs, surgery-related complication costs, and costs associated with
surgery-related death. These costs inputs were derived from published literature.
Results were expressed in the incremental cost-effectiveness ratio (ICER) per
QALY gained. The impact of uncertainty of model parameters was examined
using deterministic sensitivity analyses (DSA) and probabilistic sensitivity ana-
lyses (PSA).
RESULTS: The ICER per QALY gained for ADA vs. SOC was 34,417 over a
10-year time horizon in the base case (in 2013 GBP pounds). DSA varying key
model inputs produced ICER per QALY gained in the range of 29,437 to
38,073. The probability for ADA to be cost-effective at the willingness-to-pay
threshold of 30.000 was 30%.
CONCLUSION: With no NICE recommended biologic options, there is cur-
rently a high unmet need for patients in England and Wales with moderately
to severely active UC (sub-acute) who have failed on standard of care. This
economic evaluation demonstrated that when compared to SOC, the ADA ther-
apy has a reasonable cost-effectiveness ratio. The cost-effectiveness result of the
ADA strategy was shown to be robust in a range of sensitivity analyses.
United European Gastroenterology Journal 2(5S)
Disclosure of Interest: H. Yang Other: Employee: Analysis Group, Inc, under
contract with AbbVie, A. Curry Shareholder of: AbbVie, Other: Employee:
AbbVie, S. Wang Shareholder of: AbbVie, Other: Employee: AbbVie, M.
Yang Other: Employee: Analysis Group, Inc, under contract with AbbVie, M.
Skup Shareholder of: AbbVie, Other: Employee: AbbVie, J. Chao Shareholder
of: AbbVie, Other: Employee: AbbVie, Y. Bao Shareholder of: AbbVie, Other:
Employee: AbbVie
P0887 MAINTENANCE OF REMISSION OF ULCERATIVE COLITIS:
PREBIOTICS AND DIETARY FIBER
I. Copaci1,*, G. Chiriac1
1
Center of Internal Medicine, FUNDENI CLINICAL INSTITUTE, Bucharest,
Romania
Contact E-mail Address: laurentiumicu2000@yahoo.com
INTRODUCTION: Butyrate enemas may be effective in the treatment of active
distal ulcerative colitis (UC). Colonic fermentation of Plantago Ovata seeds
(dietary fiber) yields butyrate. UC patients have an altered intestinal flora
which can be modified by administration of prebiotics such as fructo-oligosac-
charides, and probiotics like bifidobacterium longum w11, which promote selec-
tive growth of saccharolytic bacteria with low inflammatory potential.
AIMS & METHODS: We conducted an open-label, parallel group, randomized
clinical trial. A total of 36 patients with ulcerative colitis who were in remission
for over 3 months (45C. A. I. Rachimilewitz) were randomized into 3 groups to
receive oral treatment with mesalamine (group A), Plantago Ovata (Colon help)
mesalamine (group B) and fructo-oligosaccharides/bifidobacterium longum
w11 mesalamine (group C). All patients were 18-65 years old. At day 0 and
weeks 12 and 24 we determined the clinical activity index (C. A. I.) and the
endoscopic index. Clinical safety was monitored using the Gastrointestinal
Symptom Rating Scale (GSRS) questionnaire every 4 weeks.
RESULTS: After 6 months, treatment failure was 35% in group A, 28% in
group B (p 0.02) and 30% in group C (p 0.05). Probability of continued
remission was similar (Mantel Cox test, p 0.76; Breslow test, p 0.52). Mean
times to treatment failure were 4.340.44, 4.570.76 and 4.620.81 months,
respectively for groups A, B and C. It was shown that patients with total colitis
as compared to those with left-sided colitis had an increased probability of
relapse during the 1 year follow-up. Patients of group B experienced more asymp-
tomatic nights (90% vs 77% in group C vs 58% in group A, p 0.0011) during
the first 3 months. Fecal calprotectin was lower in group C vs A and B (p50.05).
CONCLUSION: Plantago Ovata seeds and the combination of fructo-oligosac-
charides/bifidobacterium longum w11 maintain UC remission and increase the
response to mesalamine.
Disclosure of Interest: None declared
P0888 DRUG SURVIVAL AND REASONS FOR DISCONTINUATION OF
ANTI-TNF THERAPY IN INFLAMMATORY BOWEL DISEASE (IBD)
IN CLINICAL PRACTICE
J.P. Gisbert1,2,*, M. Arredondo2,3, M. Chaparro1,2, I. Canamares2,4,
E. Dauden2,5, G. Fernandez-Jimenez2,3, V. Meca2,6, A. Morell2,4, J. Aspa2,7,
L. Carmona2,8, J.M. Alvaro-Gracia2,9
1
Gastroenterology Unit, Hospital de La Princesa, CIBERehd and IP, 2Biologic
Therapies Unit, 3Documentation Service, 4Pharmacy service, 5Dermatology
Service, 6Neurology Service, 7Medical Director, Hospital de La Princesa, 8Institute
for Musculoskeletal Health, 9Reumatology Service, Hospital de La Princesa,
Madrid, Spain
Contact E-mail Address: javier.p.gisbert@gmail.com
INTRODUCTION: Since its introduction, anti-TNF therapy has shown to be
effective for the treatment of IBD in several clinical trials. However, its long-term
effectiveness and reasons for discontinuation in clinical practice might be differ-
ent from those observed in clinical trials
AIMS & METHODS: Aims: To evaluate the drug survival and reasons for
discontinuation of the first anti-TNF therapy in IBD patients in clinical practice.
Methods: IBD patients under anti-TNF therapy from 2000 to 2012 in our center
were included. Data regarding the first anti-TNF treatment were extracted from
clinical records fulfilled prospectively. Kaplan-Meier method was used to esti-
mate the long-term drug survival of the treatment.
RESULTS: 160 IBD patients were included: 130 with Crohns disease (mean age
4214 years; 47% male) and 30 with ulcerative colitis (mean age 4517 years;
63% male). The distribution of first biologic in Crohns disease was 76 (58%)
adalimumab and 54 (42%) infliximab, while in ulcerative colitis it was 1 (3%)
adalimumab and 29 (97%) infliximab. Time to a probability of 50% discontinua-
tion was 3.94 years in Crohns disease compared with 0.97 years in ulcerative
colitis (p50.001). The reasons for discontinuation of the drug, respectively in
Crohns disease and ulcerative colitis, were: intolerance (20% and 19%), lack of
response (30% and 24%), loss of response (22% and 19%), remission achieve-
ment (17% and 29%), and others (11% and 10%). The probability of maintain-
ing (retention rate) the anti-TNF treatment in Crohns disease was 69% at 1 year,
59% at 2 years, 52% at 3 years, 50% at 4 years, 45% at 5 years, and 41% at 10
years. The corresponding figures for ulcerative colitis were 48% at 1 year, 41% at
2 years, 36% at 3 years, 31% at 4 years, and 15% at 5, 6 and 7 years
CONCLUSION: The probability of maintaining the first anti-TNF drug in
Crohns disease patients is around 50% after 5 years of treatment.
Discontinuation rate was even higher in ulcerative colitis, with only 15% of
patients maintaining anti-TNF therapy at 5 years. The most frequent reasons
for discontinuation of anti-TNF therapy were lack of response, loss of response,
remission achievement and intolerance
Disclosure of Interest: J. P. Gisbert Other: Dr. P. Gisbert has served as a speaker,
a consultant and advisory member for, and has received research funding from
A375
MSD and Abbvie., M. Arredondo: None declared, M. Chaparro Other: Dra. M
Chaparro has served as a speaker and has received research funding from MSD
and Abbvie, I. Canamares: None declared, E. Dauden: None declared, G.
Fernandez-Jimenez: None declared, V. Meca: None declared, A. Morell: None
declared, J. Aspa: None declared, L. Carmona: None declared, J. M. Alvaro-
Gracia: None declared
P0889 CLINICAL BENEFIT OF ADALIMUMAB DOSE ADJUSTMENT
FOR PATIENTS WITH MODERATELY TO SEVERELY ACTIVE
CROHNS DISEASE IN EXTEND
J.-F. Colombel1,*, P. Rutgeerts2, W.J. Sandborn3, D. Wolf4, W. Reinisch5,
G.Van Assche2, S. Eichner6, Q. Zhou6, J. Petersson6, A.M. Robinson6,
R.B. Thakkar6
1
Icahn School of Medicine at Mount Sinai, New York, United States, 2University
of Leuven, Leuven, Belgium, 3UCSD, La Jolla, 4Atlanta Gastroenterology
Associates, Atlanta, United States, 5McMaster University, Hamilton, Canada,
6
AbbVie Inc, North Chicago, United States
INTRODUCTION: Weekly dosing was shown to have a clinical benefit for
adalimumab (ADA)-treated patients with Crohns disease enrolled in the clinical
trial CHARM who had flares or lost response to every other week (EOW) ADA
dosing1. The clinical outcomes of dose escalation in patients enrolled in the
EXTEND2 trial are evaluated.
AIMS & METHODS: EXTEND was a 52-week double-blind (DB) trial in which
patients received open-label (OL) ADA 160/80 mg at weeks 0/2. At week 4,
patients were randomized to placebo or ADA 40 mg EOW. Patients with
flares/non-response could move to OL ADA 40 mg EOW beginning at week 8,
followed by escalation to 40 mg weekly (EW) for continued flare/non-response.
Week 52 clinical remission (CDAI5150), clinical response (decrease in CDAI 
70 from baseline), and mucosal healing (absence of mucosal ulceration) were
assessed in patients who moved to and remained on OL ADA EOW and in
those who moved to OL ADA EW. Endpoints are reported using non-responder
imputation (NRI) for patients with missing data and as observed for patients
remaining in the study at week 52. Logistic regression analysis was used to
determine predictors of moving to OL EW ADA.
RESULTS: In EXTEND, 42.2% (27/64) of patients randomized to DB ADA
moved to OL ADA, and 23.4% (15/64) escalated to EW dosing. The only sig-
nificant predictor of dose escalation was week 4 non-response (odds ratio 24.2,
95% CI 1.6, 365.2, p 0.021). Week 52 outcomes for patients who completed the
study on OL ADA (EOW or EW) are shown in the table. Increased adverse event
rates were not observed with OL EW dosing.
Table. Week 52 efficacy in patients randomized to ADA who completed the
study on OL EOW or EW ADA dosing
NRI Observed
OL EOW OL EW OL EOW OL EW
n/N (%) n/N (%) n/N (%) n/N (%)
Remission 3/12 (25.0) 3/15 (20.0) 3/6 (50.0) 3/9 (33.3)
Response 6/12 (50.0) 6/15 (40.0) 6/6 (100) 6/9 (66.7)
Mucosal healing 1/12 (8.3) 2/15 (13.3) 1/7 (14.3) 2/7 (28.6)
CONCLUSION: Escalation to weekly ADA dosing demonstrated clinical benefit
in patients who met protocol criteria for dose escalation. No new safety risks
were observed with EW ADA dosing.
REFERENCES
1. Sandborn WJ, et al. Inflamm Bowel Dis 2011; 17: 141-151.
2. Rutgeerts P, et al. Gastroenterology 2012; 142: 1102-1111.
Disclosure of Interest: J.-F. Colombel Consultancy for: AbbVie, Bristol Meyers
Squibb, Ferring, Genentech, Giuliani SPA, Given Imaging, Merck & Co.,
Millenium Pharmaceuticals Inc., Pfizer Inc. Prometheus Laboratories, Sanofi,
Schering Plough Corporation, Takeda, Teva Pharmaceuticals, UCB Pharma
(previously named Celltech Therapeutics, Ltd)., P. Rutgeerts Financial support
for research from: AbbVie, Centocor, Merck and UCB Pharma, Lecture fee(s)
from: AbbVie, Centocor, Merck and UCB Pharma, Consultancy for: AbbVie,
Bristol-Myers Squibb, Centocor, Merck, Millennium Pharmaceuticals Inc. (now
Takeda) and UCB Pharma, W. Sandborn Financial support for research from:
AbbVie, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Janssen,
Millennium, Novartis, Pfizer, Procter and Gamble Pharmaceuticals, Shire
Pharmaceuticals, and UCB Pharma., Lecture fee(s) from: AbbVie, Bristol-
Myers Squibb, and Janssen, Consultancy for: AbbVie, ActoGeniX NV, AGI
Therapeutics, Inc., Alba Therapeutics Corporation, Albireo, Alfa Wasserman,
Amgen, AM-Pharma BV, Anaphore, Astellas, Athersys, Inc., Atlantic
Healthcare Limited, Aptalis, BioBalance Corporation, Boehringer-Ingelheim
Inc, Bristol-Myers Squibb, Celgene, Celek Pharmaceuticals, Cellerix SL,
Cerimon Pharmaceuticals, ChemoCentryx, CoMentis, Cosmo Technologies,
Coronado Biosciences, Cytokine Pharmasciences, Eagle Pharmaceuticals, Eisai
Medical Research Inc, Elan Pharmaceuticals, EnGene, Inc., Eli Lilly,
Enteromedics, Exagen Diagnostics, Inc., Ferring Pharmaceuticals, Flexion
Therapeutics, Inc., Funxional Therapeutics Limited, Genzyme Corporation,
Genentech, Gilead Sciences, Given Imaging, GlaxoSmithKline, Human
Genome Sciences, Ironwood Pharmaceuticals, Janssen, KaloBios
Pharmaceuticals, Inc., Lexicon Pharmaceuticals, Lycera Corporation, Meda
Pharmaceuticals, Merck Research Laboratories, MerckSerono, Merck & Co.,
Millennium, Nisshin Kyorin Pharmaceuticals Co., Ltd., Novo Nordisk A/S,
NPS Pharmaceuticals, Optimer Pharmaceuticals, Orexigen Therapeutics, Inc.,
PDL Biopharma, Pfizer, Procter and Gamble, Prometheus Laboratories,
A376 United European Gastroenterology Journal 2(5S)
ProtAb Limited, Purgenesis Technologies, Inc., Receptos, Relypsa, Inc., Salient Table: Clinical outcomes based on continuous clinical response at Wk54 in the
Pharmaceuticals, Salix Pharmaceuticals, Inc., Santarus, Shire Pharmaceuticals, PURSUIT-SC maintenance study*
Sigmoid Pharma Limited, Sirtris Pharmaceuticals, Inc. (a GSK company), S. L. Table to abstract P0890
A. Pharma (UK) Limited, Targacept, Teva Pharmaceuticals, Therakos, Tillotts
Pharma AG, TxCell SA, UCB Pharma, Viamet Pharmaceuticals, Vascular Non-CCR: CCR:
Biogenics Limited (VBL), Warner Chilcott UK Limited, D. Wolf Financial sup- Non-CCR: Combined CCR: Combined
port for research from: AbbVie, Elan Pharmaceuticals, Given Imaging, Clinical endpoints PBO GLM PBO GLM
GlaxoSmithKline, Genentech, Janssen, Millennium Pharmaceutical, Pfizer,
Prometheus Laboratories, Receptos, Shire Pharmaceutical, Tsumura, and UCB Randomized pts receiving con- 60 87 27 73
Pharma., Consultancy for: AbbVie, Elan Pharmaceuticals, Genentech, Given comitant steroids at Wk 0
Imaging, Janssen, Prometheus Laboratories, Salix Pharmaceuticals, UCB (n)
Pharma, and Warner Chilcott. He has received lectures fees from AbbVie,
Janssen, Prometheus Laboratories, Santarus, Salix Pharmaceutical, Shire Pts not receiving corticosteroids 1.7 4.6 66.7 75.3
Pharmaceutical, and UCB Pharma., W. Reinisch Consultancy for: AbbVie, at Wk54(%)
Aesca, Amgen, Astellas, Astra Zeneca, Biogen IDEC, Bristol-Myers Squibb, Remission: Randomized pts(n) 106 156 48 146
Cellerix, Chemocentryx, Celgene, Janssen, Danone Austria, Elan, Ferring, Pts in clinical remission at 0.9 1.9 68.8 67.1
Genentech, Grunenthal, Johnson & Johnson, Kyowa Hakko Kirin Pharma, Wk54(%)
Lipid Therapeutics, Millenium, Mitsubishi Tanabe Pharma Corporation, Mucosal healing:Randomized 106 156 48 146
MSD, Novartis, Ocera, Otsuka, PDL, Pharmacosmos, Pfizer, Procter & pts(n)
Gamble, Prometheus, Robarts Clinical Trial, Schering-Plough,
Setpointmedical, Shire, Takeda, Therakos, Tigenix, UCB, Vifor, Yakult, Pts with mucosal healing at 1.9 2.6 87.5 90.4
Zyngenia, Austria and 4SC., G. Van Assche Financial support for research Wk54 (%)
from: AbbVie, Janssen Biologicals, MSD, Pfizer, Lecture fee(s) from: AbbVie, IBDQ score:Randomized pts 105 156 48 144
Ferring, MSD, Janssen, UCB Pharma, Shire, Consultancy for: AbbVie, Biogen, (n)
BMS, MSD, Janssen Biologicals, Novartis, S. Eichner Shareholder of: AbbVie, Change from Wk0 through -38.9(32.1) -36.9(37.6) 10.6(18.2) 11.3(28.1)
Other: Employee: AbbVie, Q. Zhou Shareholder of: AbbVie, Other: Employee: Wk54 [mean(SD)]
AbbVie, J. Petersson Shareholder of: AbbVie, Other: Employee: AbbVie, A. Pts with IBDQ score 4170 at 18.1 24.4 81.2 75.0
Robinson Shareholder of: AbbVie, Other: Employee: AbbVie, R. Thakkar Wk54 (%)
Shareholder of: AbbVie, Other: Employee: AbbVie

P0890 CLINICAL OUTCOMES IN CONTINUOUS CLINICAL
RESPONDERS WITH MODERATELY TO SEVERELY ACTIVE
ULCERATIVE COLITIS: SUB-ANALYSES FROM THE PURSUIT-SC
MAINTENANCE STUDY
J. Colombel1,*, W. Reinisch2, P. Gibson3, W.J. Sandborn4, B.G. Feagan5,
C. Marano6, R. Strauss6, J. Johanns6, H. Zhang6, H. Weng7, R. Yao7,
D. Tarabar8, Z. Hebzda9, P. Rutgeerts10
1
Hopital Claude Huriez, Lille Cedex, France, 2Universitatsklinik fur Innere
Medizin III/McMaster University, Vienna/Hamilton, Austria, 3Alfred Hospital,
Melbourne, Australia, 4University of California San Diego, La Jolla, United
States, 5Robarts Research Institute, University of Western Ontario, London,
Canada, 6Janssen Research & Development, LLC., Spring House, 7Merck Sharp &
Dohme, Kenilworth, United States, 8Military Medical Academy, Belgrade, Serbia,
9
Klinika Chorob Wewnetrznych, Krakow, Poland, 10University Hospital,
Gathuisburg, Belgium
AIMS & METHODS: The objective was to evaluate long-term clinical outcomes
in patients with moderately to severely active UC who achieved complete con-
tinuous response (CCR) compared with patients who did not achieve CCR (non-
CCR) through Wk54 of SC golimumab (GLM) maintenance therapy. During
PURSUIT-Maintenance, GLM induction responders (464 patients) were rando-
mized to receive PBO, SC GLM 50mg, or SC GLM 100mg at baseline (Wk0) and
q4wks through Wk52. The primary endpoint was clinical response through Wk54
(CCR). Clinical remission, mucosal healing, corticosteroid use, and IBDQ out-
comes and fecal markers at Wk54 among CCR versus non-CCR were assessed.
All sub-analyses are based on patients randomized at Wk0 of maintenance
(n 456).
RESULTS: On all of the selected endpoints evaluated, CCR patients had better
results when compared with non-CCR patients (Table). Among patients receiv-
ing corticosteroids at baseline, a greater proportion of CCR patients were not
receiving corticosteroids at Wk54 versus non-CCR patients. Greater proportions
of CCR patients were also in clinical remission versus non-CCR patients.
Additionally, mean decreases in fecal lactoferrin and fecal calprotectin at
Wk54 from Wk0 of maintenance were greater for CCR patients compared
with non-CCR patients. Data between the GLM groups were similar and thus
were pooled in the table.
CONCLUSION: These data continue to support that patients induced into clin-
ical response who maintain a clinical response through Wk54 are more likely to
have better clinical outcomes.
Disclosure of Interest: J. Colombel Financial support for research from: Janssen
Research & Development, LLC, W. Reinisch Financial support for research
from: Janssen Research & Development, LLC, P. Gibson Financial support
for research from: Janssen Research & Development, LLC, W. Sandborn
Financial support for research from: Janssen Research & Development, LLC,
B. Feagan Financial support for research from: Janssen Research &
Development, LLC, C. Marano Other: Employee of Janssen Research &
Development, LLC, R. Strauss Other: Employee of Janssen Research &
Development, LLC, J. Johanns Other: Employee of Janssen Research &
Development, LLC, H. Zhang Other: Employee of Janssen Research &
Development, LLC, H. Weng Other: Employee of Merck Sharp & Dohme, R.
Yao Other: Employee of Merck Sharp & Dohme, D. Tarabar Financial support
for research from: Janssen Research & Development, LLC, Z. Hebzda Financial
support for research from: Janssen Research & Development, LLC, P. Rutgeerts
Financial support for research from: Janssen Research & Development, LLC
P0892 INTRA-ABDOMINAL ABSCESSES IN CROHNS DISEASE:
OUTCOMES FOLLOWING INFLIXIMAB THERAPY
J. Ruel1,*, J.-F. Colombel2, B. Cohen2
1
Gastroenterology, Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke,
Canada, 2Gastroenterology, Icahn School of Medicine at Mount Sinai, New York,
United States
Contact E-mail Address: benjamin.cohen@mssm.edu
INTRODUCTION: Crohns disease (CD) may be complicated by a sealed-off
perforation that results in the development of an abscess typically located next to
adjacent loops of bowel. Traditional treatment has been antibiotics, surgical or
CT-guided drainage of drainable collections, bowel rest, and, ultimately, in some
patients, resection of the affected bowel segment. Most gastroenterologists avoid
immune suppression in this setting because of the potential for disseminated and
systemic infection. Data regarding use of anti-tumor necrosis factor (TNF) in this
situation are scarce. The aim of this study was to examine outcomes for patients
with CD who developed an abdominal abscess that was subsequently treated
with infliximab without initial drainage in order to evaluate its safety and efficacy
in a larger number of patients than previously reported.
AIMS & METHODS: We retrospectively reviewed the records of all CD patients
attending the Mount Sinai Medical Center in New York City, between 2000 and
2013, with an intra-abdominal abscess who were treated with infliximab in order
to evaluate its safety and efficacy.
RESULTS: There were 18 patients with CD complicated by an intra-abdominal
collection treated with antibiotics and infliximab at our center between 2000 and
2013. The median age was 25.5 (18-46) years and eleven patients were males.
Seventeen patients had ileal disease. Fourteen patients developed an intra-
abdominal abscess (size ranging from 1.1 cm to 7.9 cm) and four had a phlegmon
only. In addition to anti-TNF therapy, all patients were treated with broad-
spectrum antibiotics. No complications following infliximab therapy were
reported including sustained fever or sepsis. None required a surgical drainage
but four patients required abscess drainage by interventional radiology. Eight
patients underwent surgery within 6 months after initiating anti-TNF therapy.
CONCLUSION: Penetrating CD complicated by intra-abdominal abscess for-
mation may be safely and effectively managed with a combination of antibiotics
and infliximab therapy without drainage. Prospective trials are required to con-
firm these findings.
Disclosure of Interest: J. Ruel: None declared, J.-F. Colombel Consultancy for:
Janssen and Abbvie, B. Cohen Lecture fee(s) from: Abbvie
United European Gastroenterology Journal 2(5S)
P0893 HIGH SERUM CRP PREDICTS FASTER CLEARANCE OF
INFLIXIMAB AND POOR OUTCOME IN MODERATE-SEVERE
ULCERATIVE COLITIS
J.F. Brandse1,*, G.R. van den Brink1, D.van der Kleij2, T. Rispens3, K. Bloem3,
Y. Ashruf1, J.M. Jansen4, M. Lowenberg1, C. Ponsioen1, R.A. Mathot5,
G.R. DHaens1
1
Department of Gastroenterology & Hepatology, Academic Medical Center,
2
Sanquin Diagnostic Services, 3Sanquin Research, Sanquin Laboratories,
4
Department of Gastroenterology & Hepatology, Onze Lieve Vrouwe Gasthuis,
5
Pharmacy, Academic Medical Center, Amsterdam, Netherlands
Contact E-mail Address: j.f.brandse@amc.uva.nl
INTRODUCTION: Insufficient serum concentrations have been suggested as a
cause of lack of response to infliximab (IFX) in Ulcerative Colitis (UC) and may
be associated with a high inflammatory load. Early pharmacokinetics (PK) of
IFX related to inflammatory markers and response to induction therapy have
been poorly studied.
AIMS & METHODS: We studied the PK of IFX induction therapy and mar-
kers/predictors for response in patients with moderate-to-severe UC (endoscopy
Mayo 2 or 3) in a multicenter prospective study. Serum IFX concentrations and
antibodies to IFX (Radioimmunoassay, Sanquin Laboratories, Amsterdam),
serum CRP and albumin and fecal samples (for calprotectin and IFX concentra-
tions) were collected at 10 serial time points during the first 6 weeks of therapy.
Endoscopic response was defined as improvement by at least 1 Mayo point at
week 6-8.
RESULTS: Twenty patients were included, all but one receiving IFX according
to standard induction regime (5mg/kg at week 0.2,6). 11/19 patients showed
endoscopic improvement. The median IFX serum concentration at week 6 was
2.9 (0.01-5.8) ug/ml for endoscopic non-responders versus 8.1 (3.0-13.7) ug/ml for
responders (p 0.03). Serum IFX7ug/ml at week 6 was defined as a predictive
cut-off (OR:18.67, 95%CI 1.56-223.1, p 0.02) for endoscopic non-response.
The presence of antibodies to IFX at week 6 (n 4) was associated with a 2.93
fold increased clearance of the drug. Fecal IFX concentrations at day 1 were 4.1
(1.3-20.1) ug/ml in non-responders compared to 1.3 (0-5.8) ug/ml for responders
(P[GD1] 0.10). Median area under the curve (AUC), IFX concentration versus
time, was 1229 mg/L/day in the endoscopic non-responders compared to 1352
mg/L/day for the responders (p 0.65). Patients with a baseline CRP450mg/l
had a significantly smaller AUC than those below 50mg/l (578 vs. 1361 mg/L/
day, p 0.001), with IFX clearance 1.63 fold increased (P50.001, multivariate
analysis).
CONCLUSION: Ulcerative Colitis patients with a high baseline serum CRP
have increased clearance and lower serum IFX concentrations during IFX induc-
tion therapy, predicting poor outcome as early as week 6. These patients can be
selected for more intensive induction regimens.
Disclosure of Interest: J. Brandse Lecture fee(s) from: MSD, Abbvie, Takeda, G.
van den Brink Financial support for research from: Abbott laboratories, Crucell
and Ferring Pharmaceuticals, Lecture fee(s) from: Abbott laboratories, Merck
Sharp & Dohme and Ferring Pharmaceuticals, Consultancy for: Abbott labora-
tories, D. van der Kleij: None declared, T. Rispens: None declared, K. Bloem:
None declared, Y. Ashruf: None declared, J. Jansen Lecture fee(s) from: MSD en
Abbott, Consultancy for: Ferring Pharmaceuticals, Schering Plough, Abbvie,
and Pfizer, M. Lowenberg Lecture fee(s) from: Abbott, Dr. Falk, Ferring,
MSD and Tramedico, C. Ponsioen Financial support for research from:
Schering Plough, Falk Pharma, Tramedico, Abbott Inc., and Glaxo Smith
Klin, Lecture fee(s) from: Schering Plough, Falk Pharma, Tramedico, Abbott
Inc., and Glaxo Smith Kline, Consultancy for: Schering Plough, Falk Pharma,
Tramedico, Abbott Inc., and Glaxo Smith Kline, R. Mathot: None declared, G.
DHaens Financial support for research from: Abbott Inc, Jansen Biologics,
Given Imaging, MSD, DrFalk Pharma, Photopill, Lecture fee(s) from: Abbott
Inc, Tillotts, Tramedico, Ferring, MSD, UCB, Norgine, Shire, Consultancy for:
Abbott Laboratories, Actogenix, Centocor, Cosmo, Engene, Ferring
Pharmaceuticals, GlaxoSmithKline, Jansen Biologics, Millenium
Pharmaceuticals, MSD, Novonordisk, PDL Biopharma, Pfizer, SetPoint,
Shire, Takeda, Teva, UCB
P0894 PULMONARY INVOLVEMENT AND THE EFFECT OF TNF-
ALPHA-INHIBITORS ON PULMONARY FUNCTION IN IBD-
PATIENTS
J. Bethge1,*, M. Ellrichmann1, C. Conrad1, S. Nikolaus1, R. Noth2, D. Schuldt1,
S. Zeissig1, S. Schreiber1,2
1
Medical Department I, Gastroenterology, 2Medical Department I, Pulmonology,
University Medical Center, Schleswig Holstein, Campus Kiel, Kiel, Germany
Contact E-mail Address: jbethge@1med.uni-kiel.de
INTRODUCTION: Extraintestinal manifestations are a frequent complication
in patients with Inflammatory-Bowel-Disease (IBD). Pulmonary involvement is
commonly recognized but describe as a rare manifestation. Of note, increased
mortality from respiratory diseases was observed in patients with ulcerative coli-
tis. This may be due to an overlap between genetic causes in IBD and various
chronic inflammatory lung diseases. Therefore, pulmonary involvement may be
overlooked in IBD patients.
AIMS & METHODS: The aim of this prospective study was to assess pulmon-
ary-function-abnormalities in IBD patients in comparison to healthy controls
and investigate the effect of TNF-a-inhibitors on pulmonary-function-test
(PFT). 90 consecutive patients with IBD (51 Crohns disease (CD), 39 UC)
were included. 47 patients were in remission and 43 had active disease. Out of
these, 25 patients were seen for initiating anti-TNF therapy. 40 matched healthy
controls were included. Pulmonary function was evaluated using the Medical
Research Council (MRC) dyspnea index and a standardized spirometry. IBD
A377
activity was assessed using Harvey-Bradshaw index for CD and partial-Mayo-
score for UC. In patients treated with anti-TNF all parameters were reevaluated
6 weeks later. Data are presented as Median/25thpercentile/75thpercentile.
RESULTS: Patients with active IBD showed significantly reduced parameters in
their PFT. Tiffeneau index-values (FEV1%) were significantly reduced in IBD
patients with active disease (78,9/73,7/85,1) compared to controls (86/81,8/88,3;
p 0.001) and IBD patients in remission (84,5/81,2/89,4; p 0.0002). No differ-
ence was found between IBD patients in remission and controls (p40.05).
Parameters of peripheral airway obstruction (MEF 75-25%) showed comparable
changes (MEF75: IBDactive vs. controls p 0.01; IBDactive vs. IBDremission
p 0.002). Clinically significant peripheral airway obstruction was seen in
19.1%, obstructive dysfunction in 12.8% and restrictive dysfunction in 2.1%
of IBD patients with an active disease (IBDremission: 4.6%/2.3%/6.9%;
Control: 5%/0%/0%). Patients treated with anti-TNF showed a significant
improvement of obstructive parameters (p 0.003 FEV1%) compared to base-
line levels.
CONCLUSION: IBD patients with active disease showed significant abnormal-
ities in their obstructive PFT-parameters in comparison to healthy controls and
IBD patients in remission. Anti-inflammatory therapy with anti-TNF improves
obstructive abnormalities. Pulmonary obstruction and chronic broncho-pulmon-
ary inflammation might be the cause of reduced exercise levels during active
disease and may be overlooked in the majority of patients. Further studies are
necessary to determine whether chronic obstruction should be treated and
whether it contributes to the observed mortality from lung problems in IBD.
Disclosure of Interest: None declared
P0895 THE EFFECT OF ANTI-TNF TREATMENT ON FISTULAS IN
CROHNS DISEASE: A SYSTEMATIC REVIEW AND META-
ANALYSIS
J. De Groof1,*, S. Sahami2, C. Lucas3, C. Ponsioen4, W. Bemelman2, C. Buskens2
1
Department of Surgery and Gastroenterology & Hepatology, 2Department of
Surgery, 3Department of Epidemiology, Biostatistics & Bioinformatics,
4
Department of Gastroenterology & Hepatology, Academic Medical Centre,
Amsterdam, Netherlands
Contact E-mail Address: e.j.degroof@amc.uva.nl
INTRODUCTION: Peri-anal fistulas are an incapacitating complication of
Crohns disease affecting approximately 25% of patients in population-based
estimates. Since the introduction of anti-TNF agents (infliximab and adalimu-
mab), the treatment for Crohns fistulas has changed from almost exclusively
surgical to placing a much larger emphasis on medical therapy.
AIMS & METHODS: The purpose of this systematic review is to provide an
overview of the literature evaluating the success rate of perianal fistula treatment
with anti-TNF. PubMed, Embase and Biosis were searched. Randomized con-
trolled trials on the effect of anti-TNF treatment on Crohns perianal fistulas
were included. Studies assessing perianal fistulas in children, rectovaginal fistulas
and costs were excluded. The primary outcome of interest was complete fistula
closure with partial closure as a secondary outcome parameter. A subgroup
analysis for complete fistula closure was performed based on studies with a
follow-up longer than 4 weeks.
RESULTS: Four studies comparing placebo with anti-TNF therapy regimens
were included in the meta-analysis: one study on infliximab (ACCENT study)
and three studies analysing adalimumab (CLASSIC, CHARM and GAIN trial).
All patients with fistulising disease were included in the trials (peri-anal, entero-
cutaneous and entero-enteral fistulas). In total, 179 patients were treated with
anti-TNF medication whereas 109 patients received placebo. All studies assessed
complete closures rates and three studies reported partial closure rates. The mean
follow-up time was 13 weeks (range 4-26). In the anti-TNF group, 54 of 179
(30%) patients responded to treatment with complete fistula closure, whereas
complete healing was seen in 13 of 109 (12%) patients in the placebo group.
Partial fistula closure was seen in 48 of 109 (44%) patients in the anti-TNF
treatment group and in 15 of 62 (24%) patients in the placebo group. There
was no significant difference in complete or partial closure rates between the
two groups (RD 0.12, -0.06-0.30, I2 74% and 0.09, 95% CI -0.23-0.41, I2 78%,
respectively). The subgroup analysis showed a significant advantage for complete
fistula closure with anti-TNF in the two trials with follow-up longer than 4 weeks
(ACCENT: 46% versus 13%, p 0.003 and CHARM: 30% versus 13%,
p 0.03) when compared to the placebo group.
CONCLUSION: Meta-analysis of 4 randomized controlled trials did not show a
significant advantage for (partial) fistula closure with anti-TNF treatment as
compared to placebo. However, subgroup analysis showed an advantage of
anti-TNF treatment on complete fistula closure rates in the two trials with a
follow-up longer than 4 weeks.
Disclosure of Interest: None declared
P0896 SAFETY AND EFFICACY OF BUDESONIDE MMX IN
REMISSION OF ULCERATIVE COLITIS: A META ANALYSIS
n
1,*
J.A. D. M. Jalandoon , I.H. Y. cua 2
w
1
Gastroenterology, Institute of digestive and liver disease, St. lukes medical centre,
2
i t h ra
gastroenterology, st lukes medical center, quezon city, Philippines
d
Contact E-mail Address: doyangelie@yahoo.com
W
INTRODUCTION: Significance.
Budesonide MMX, a novel drug developed for the treatment of ulcerative colitis
using multi-matrix system. The effects on remission of disease would help to form
recommendations for efficacy and safety profile. Most of these trials conducted
have relatively small size, limited data and a meta-analysis for this drug could
have stronger conclusion.
A378
AIMS & METHODS: Manual search through MEDLINE & PUBMED using
ulcerative colitis and Budesonide MMX were merged yielding 9 studies. Six such as psoriasis or eczema could be a reason for discontinuation of anti-TNF
studies were shown which was limited to human. Excluded were two reviews and
a comment. Three multicenter, randomized, placebo-controlled trials were
included & Cochrane Review Manager Software Version 5 was used.
RESULTS: There was a significant remission of symptoms in patients using the
combined Budesonide MMX 9 & 6 mg with a p-value of 0.02. Sensitivity analysis
using Budesonide MMX 9 mg is effective in the remission compared to
Budesonide 6 mg alone and placebo with p-value 0.0005 at 95% confidence
ra w n
interval. Adverse effects showed no significant difference between Budesonide
MMX group and the placebo group with a p value of 0.71.
CONCLUSION: Budesonide MMX, on clinical improvement, is beneficial in
t h d
assessing the response to treatment in remission of symptoms. The adverse effects
Wi
have no significant difference with placebo thus further study is needed to assess
the safety profile of the drug.
REFERENCES
DHaens GR, et al. Clinical trial: preliminary efficacy and safety study of a new
budesonide-MMX 9 mg extended-release tablets in patients with active left-sided
ulcerative colitis. J Crohns Colitis 2010; 4: 153-160.
Sandborn WJ, et al. Once-daily budesonide MMX extended-release tablets
induce remission in patients with mild to moderate ulcerative colitis: results
from the CORE I study. Gastroenterology 2012; 143: 1218-1226.
Travis SPL, et al. Once-daily budesonide MMX in active, mild-to-moderate
ulcerative colitis: results from the randomised CORE II study. Gut Br J Med
2013; 0: 1-9.
Sandborn WJ, et al. MMX multi matrix system mesalazine for the induction of
remission in patients with mild-to-moderate ulcerative colitis: a combined ana-
lysis of two randomized, double-blind, placebo-controlled trials. Aliment
Pharmacol Ther 2007; 26: 205215.
Disclosure of Interest: None declared
P0897 PHLEGMONOUS CROHNS DISEASE: A REVIEW OF
OUTCOMES AT A TERTIARY CENTRE
K. V. Patel1,*, N. Griffin2, R. Goel1, E. Westcott3, A.B. Williams3,
A. Darakhshan3, S.H. Anderson1, P.M. Irving1, J.D. Sanderson1
1
Gastroenterology, 2Radiology, 3Colorectal Surgery, Guys and St Thomas NHS
Foundation Trust, London, United Kingdom
Contact E-mail Address: kamal0079@hotmail.com
INTRODUCTION: Penetrating Crohns disease (CD) can be complicated by
sealed-off perforation resulting in the development of an inFammatory mass or
phlegmon. This typically involves the mesentery and adjacent bowel loops, and
can be further complicated by an abscess or a Estula. The optimal management
strategy and long-term outcomes of phlegmons in CD remains unknown.
AIMS & METHODS: Patients with CD and confirmed phlegmons on MRI/CT
between January 2009 and December 2012 were identified retrospectively.
Radiographic evidence of co-existing strictures, abscess, fistula and/or perfora-
tion was recorded. Medical records were reviewed and demographic data, CD
phenotype, CD therapy prior to and following presentation, requirement for
abscess drainage or surgical resection, and clinical status at most recent follow-
up were recorded. Clinical remission was defined as a Harvey -Bradshaw index of
55. Repeat imaging was evaluated to assess phlegmon resolution.
RESULTS: 13 patients (7 male) were identified with median follow up of 40
months (range 33-61 months). 3 had ileal and 10 had ileocolonic CD. 11 had
co-existing strictures, 5 had co-existing abscess, and 4 had co-existing enteroen-
teric fistula. 4 patients were receiving a thiopurine at presentation with phlegmon.
12 patients reported significant abdominal pain with 8 requiring admission. In 4
of these, imaging studies confirmed perforation. 2 patients required short-term
parenteral nutrition and 6 were managed with exclusive liquid diet.
7 patients were treated primarily with medical management (2 with prolonged
courses of antibiotics, 5 with thiopurine and corticosteroids, and subsequently 2
escalated to an anti-TNF agent) and this led to phlegmon resolution in 4 patients,
and clinical remission in 3 patients. 2 patients have subsequently required sur-
gery, and 2 persist with low grade obstructive symptoms treated conservatively.
6 patients were managed with primary surgery. All received a thiopurine as post-
operative prophylaxis, of whom 3 escalated to an anti-TNF agent for significant
post-operative recurrence. Repeat surgical resection or abscess drainage was not
required subsequently.
2 of 4 patients presenting with perforation and phlegmon at presentation were
treated surgically, 2 of 4 patients with enteroenteric fistula and phlegmon at
presentation were treated surgically, and 3 of 5 patients with abscess and phleg-
mon at presentation were treated surgically. All 4 patients on thiopurine at
presentation required surgery.
CONCLUSION: Phlegmonous disease remains challenging to treat. Medical and
surgical management are both viable options, however phlegmon resolution was
more likely in the surgically treated group. Medically treated patients remain at
risk of need for future surgery. Surgically treated patients require aggressive
medical treatment post-operatively, to limit recurrence of CD.
Disclosure of Interest: None declared
P0898 COMBINED USE OF AZATHIOPRINE/6-MERCAPTOPURINE
ARE ASSOCIATED WITH DECREASED RISK OF ANTI-TNF
INDUCED SKIN LESIONS
K.-J. Kim1,*, J.S. Soe1, S. Hyun1
1
Gastroenterology, Asan Medical Center, Seoul, Korea, Republic Of
Contact E-mail Address: capsulendos@gmail.com
INTRODUCTION: Anti-tumor necrosis factors (anti-TNF) agents are given for
treating patients with moderate to severe active inflammatory bowel disease
United European Gastroenterology Journal 2(5S)
(IBD). Among various adverse events during anti-TNF therapy, skin lesions
therapy.
AIMS & METHODS: We aimed to identify the risk factors for skin lesion
occurrence and compared the cumulative incidence of skin lesions in relation
to concomitant use of azathioprine/6-mercaptopurine during being treated with
anti-TNF agents in IBD patients. Methods: Between June 2002 and July 2013,
500 patients (404 Crohns disease and 96 ulcerative colitis) were treated with anti-
TNF at Asan Medical Center. Among them, new skin lesions occurred in 47 IBD
patients at the department of dermatology. We retrospectively reviewed the
medical records. To identify risk factors for skin lesions, we compared 47 patients
with skin lesions to 443 patients without any skin disease or history.
RESULTS: The incidence of skin lesions during anti TNF therapy was 9.4%.
The skin lesions were listed in Table 1. Face was the most common involved site
(n 21, 45%), followed by trunk (n 18, 38%) and upper extremities (n 18,
38%). Thirty three (70%) patients were treated with topical steroids with or
without antihistamine and showed good response. Four subjects (9%) discon-
tinued anti-TNF because of eczematiform (n 2), psoriasiform (n 1), linear
IgA dermatosis (n 1). On univariate analysis, skin lesion occurred more in
female (HR: 1.794, 95% CI: 1.011-3.181, p 0.046) than in male. Also, combined
use of azathioprine/6-mecaptopurine was associated with decreased risk of the
occurrence of skin lesions (HR: 0.452, 95% CI: 0.251-0.814, p 0.008). However,
only combined use of azathioprine/6-mercaptopurine (HR: 0.437, 95% CI: 0.242-
0.790, p 0.006) decreased the risk of occurrence for skin lesions on multivariate
analysis. Thus, we compared the cumulative incidence of skin lesions according
to the use of azathioprine/6-mercaptopurine. Combined use of azathioprine/6-
mercaptopurine at the time of starting anti-TNF agents tended to be lower
cumulative incidence of skin lesions (p 0.009 by log rank test) during follow-
up period.
Multivariate analysis of factors associated with skin lesion occurred during treat-
ment of anti-TNF agents in patients with inflammatory bowel disease
Variables HR 95% CI p-value
Sex Male 1
Female 1.741 0.978-3.105 0.059
Age 0.129
Concomitant use with IMM No concomitant use 1 0.941-1.008
(azathioprine / 6-
mecaptopurine)
Continue to concomitant 0.441 0.215-0.905 0.025
use during follow-up
period
Stop IMM during follow- 0.433 0.214-0.879 0.020
up period
IBD group CD 1
UC 0.672 0.230-1.961 0.467
HR, hazard ratio; CI, confidence interval; IMM, immunomodulator; IBD,
inflammatory bowel disease
CONCLUSION: Combined use of azathioprine/6-mercaptopurine may reduce
the occurrence of skin lesions on anti-TNF therapy at the time of starting anti-
TNF agents.
Disclosure of Interest: None declared
P0899 COSTS DRUG SAVINGS USING A TEST-BASED STRATEGY
VERSUS AN EMPIRIC DOSE ESCALATION IN PATIENTS WITH
CROHNS DISEASE LOOSING RESPONSE TO ANTI-TNF THERAPY
X. Roblin1, M. Lamure2, A. Attar3, B. Savarieau4, P. brunel1, G. Duru5,
L. Peyrin Biroulet6,*
1
university hospital, saint etienne, 2university hospital, Lyon, 3hopital beaujon,
4
Nukleus, Paris, 5universite claude bernard, Lyon, 6university hospital, Nancy,
France
Contact E-mail Address: xavier.roblin@chu-st-etienne.fr
INTRODUCTION: Pharmacokinetics of anti-TNF therapy is increasingly used
to treat inflammatory bowel disease (IBD). Whether this approach is associated
with significant cost savings beyond one year in a large cohort of patients with
IBD has yet to be determined (1,2).
AIMS & METHODS: We compared two cohorts of patients with Crohns disease
treated with anti-TNF therapy (infliximab and then adalimumab in case of inflix-
imab failure) and presenting loss of response. The first cohort followed a process
management based on current practice, with drug optimization (increasing dose
and/or shortening the interval) not taking into account pharmacokinetics of anti-
TNF. In the second cohort, results of trough levels and antibodies against anti
TNF were integrated when patient was not responding for the first time to an anti
TNF agent. We used a selected mathematical model to describe the trajectories of
Crohns disease patients in the management of their disease based on a discrete
event system. This allows tracking over a given period (1, 3 or 5 years) a double
cohort of patients (10.000 patients) who move randomly and asynchronously from
one state to another while keeping the whole information on their entire trajectory.
Both cohorts were modeled by a state diagram parameters where transition prob-
abilities from one state to another are derived from literature data. A stochastic
sensitivity analysis on the transition probabilities was conducted in order to assess
the stability of results. In the second analysis, we used the cost of an Elisa test from
Theradiag (France, 100 euros) and no other indirect costs were included in this test
based strategy. The costs of anti TNF therapy integrated in this model were
reported by the French healthcare system.
United European Gastroenterology Journal 2(5S)
RESULTS: There was a dramatic decrease in overall costs within the cohort of
Crohns disease patients benefiting from a test-based strategy (table 1)
Percentage of
Decrease in total decrease in Decrease in
costs (n 10.000) direct costs costs per patient
One year 23 847 619 E 14.1% 2 385 E
Three years 88 588 892 E 22.4% 8 859 E
Five years 131 300 293 E 24.6% 13 130 E
For this simulation, the mean decrease in costs was similar when testing a popu-
lation of 3 000 or 10 000 patients. At 5 years the mean decreased costs were 12
899 (95% CI:11820 - 13977) for 3 000 patients and 13 130 euros (95% CI:12535 -
13725) for 10 000 patients. After a stochastic sensitivity analysis (30 simulations
with random choice of transition probabilities and a bootstrap analysis), these
results were comparable with a decreased costs at 5 years for each patient using
tests with a 95CI [13 251,74 E - 13 565,05 E]. The impact of the direct cost of test
is not significant and our results were similar using cost of test of 2.000 euros.
CONCLUSION: A test-based strategy is associated with major cost savings
among Crohns disease patients treated with anti-TNF strategy. These findings
should be taken into account to guide decision making in clinical practice and
also by French healthcare system.
REFERENCES
Velayos T, et al. Clinical Gastroenterol Hepatol 2013; 11: 654-666.
Steenholdt C, et al. Gut in press.
Disclosure of Interest: X. Roblin Lecture fee(s) from: Theradiag, MSD, Abbvie,
M. Lamure: None declared, A. Attar: None declared, B. Savarieau: None
declared, P. brunel: None declared, G. Duru: None declared, L. Peyrin
Biroulet Financial support for research from: MSD, Lecture fee(s) from: Abbvie
P0900 LONG-TERM OUTCOME IN PATIENTS WITH CHRONIC
ACTIVE ULCERATIVE COLITIS STARTED ON INFLIXIMAB: A
RETROSPECTIVE SWEDISH MULTICENTER STUDY
L. Angelison1,*, S. Almer2, A. Bajor3, J. Bjork2, M. Eberhardsson2, A. Eriksson3,
O. Grip4, P. Hammarlund5, U. Hindorf4, P. Karling6, M. Thorn7, J. Torp8,
E. Hertervig4
1
Department of Medicine, Helsingborg Hospital, Helsingborg, 2Department of
Gastroenterology, Stockholm University Hospital, Stockholm, 3Department of
Gastroenterology, Sahlgrenska University Hospital, Gothenburg, 4Department of
Gastroenterology, Skane university Hospital, Lund/Malmo, 5Department of
Medicine, Angelholm Hospital, Angelholm, 6Department of Gastroenterology,
Umea University Hospital, Umea, 7Department of Gastroenterology, Uppsala
University Hospital, Uppsala, 8Department of Medicine, Kristianstad Hospital,
Kristianstad, Sweden
Contact E-mail Address: leif.angelison@skane.se
INTRODUCTION: Infliximab has been shown to be effective in acute severe
ulcerative colitis (UC) reducing the risk of colectomy. The ACT studies proved
efficacy for IFX in patients with a more chronic type of UC, However, long-term
data on clinical outcome of anti-TNF therapy are scarce. We assessed long-term
outcome in patients with chronic UC started on IFX.
AIMS & METHODS: METHODS: Retrospective data capture from local regis-
tries at 9 Swedish IBD centers from November 2004 to December 2011. Inclusion
criteria were: a) IFX treatment on an ambulatory basis. b) age 18 years, c) 8
weeks or more on continuous steroid use or more than 12 weeks during the last 6
months, d) steroid intolerance, e) insufficient response to, or intolerance to thio-
purine therapy. Patients were eligible if followed at least 12 months or until
colectomy.
RESULTS: 243 patients (145 males, 98 females) were included; median age 26.3
years (8-71.7) at diagnosis and a median disease duration of 5.0 years (0.2-39.5
years). 114/243 patients (47%) were on steroids and 116/243 (48%) were on
concomitant thiopurines, 25/243 (10%) started a thiopurine together with IFX
at inclusion and 90/243 (37%) patients had a previous thiopurine exposure.
Median follow-up was 3.3 years (0.1 8.9 years) during which a median of 6
(1-41) infusions were given. At 12 months 114/243 (46.9%) patients were in
steroid-free remission and 46/243 (18.9%) had a steroid-free response. Lack of
response was noted in 39/243 (16%) and 32/243 (13.2%) underwent colectomy.
The corresponding figures at a median follow-up of 3.3 years were steroid-free
remission: 114/243 (46.9%), steroid-free response 31/243 (12.8%), no response
14/243 (5.8%) while 75/243 (30.9%) had undergone colectomy. Of non-respon-
ders at 1 year, 21/39 (53.8%) had a colectomy during follow-up compared to 22/
172 (13%) patients with response or remission at 12 months. At last follow-up, 44
patients were on IFX maintenance treatment with a median of 24 (11-54) infu-
sions. The remaining 199 patients had a first course of IFX treatment with a
median of 4 (1-41) infusions, 41 patients had a second course with a median of 5
(1-29) infusions, 9 patients a third course with a median of 5 (1-14) infusions and
one patient a fourth course with 4 infusions. The main reasons for stopping IFX
at the first course was remission in 32%, loss of response 28%, non-response
18% and adverse events 10%. Overall 62 (25,5%) patients were switched to
adalimumab.
CONCLUSION: Anti-TNF is an efficacious long-term treatment in chronic
active UC with 47% of patients in steroid-free remission at 12 months and
sustained at 3.3 years. 66% had at least a clinically significant steroid-free
response at 12 months with a slight decrease to 60% at 3.3 years. In contrast,
non-response at 12 months was associated with a high risk of subsequent
colectomy.
Disclosure of Interest: None declared
A379
P0901 INFLIXIMAB POPULATION PHARMACOKINETIC MODELLING
IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE:
ESTIMATION OF INDIVIDUAL PHARMACOKINETIC
PARAMETERS AND TROUGH LEVELS PREDICTION
L. Rodr guez-Alonso1,*, E. Santacana2, N. Padulles2, H. Colom3, A. Padulles2,
C. Arajol1, S. Cobo2, A. Ruiz1, F. Rodr guez1, J. Bas4, J. Climent4,
F. Morandeira4, J. Guardiola1
1
Gastroenterology, 2Pharmacy, Hospital Universitari Bellvitge. Idibell,
3
Pharmacokinetics, School of Pharmacy (Universitat de Barcelona),
4
Immunology, Hospital Universitari Bellvitge. Idibell, Barcelona, Spain
Contact E-mail Address: eugenia.santacana@bellvitgehospital.cat
INTRODUCTION: Infliximab (IFX) trough levels (TLI) vary greatly between
inflammatory bowel disease (IBD) patients. This variability is relevant because
there is a relationship between IFX concentration and clinical response.
AIMS & METHODS: Main objective: estimate individual pharmacokinetic
parameters and predict trough IFX levels. Secondary objective: evaluate the
association between IFX exposure and covariates that could modify trough
levels.
(a) Observational and prospective study of patients on IFX treatment from July
2013 to March 2014. TLI and antibodies toward infliximab (ATI) were measured
by ELISA at steady-state. Variables recorded: demographic, disease location C-
reactive protein levels (CRP), serum albumin concentrations (SAC), immunomo-
dulatory treatment (IMM) and smoking. Individual pharmacokinetic parameters
were estimated and TLI were predicted using population PK modelling
(Nonmem 7.2).
RESULTS: 55 patients (49% women) were included. 93 TLI and ATI were
measured. Mean age: 43 yr (18-75); weight: 74 kg (IC95%: 71-77.5). Diagnose:
58.5% CD and 41.5% UC. 70 % received IMM. 27% patients were under
intensified IFX doses. Mean CRP: 6.45 mg/L (IC95%: 4.56-8.35), mean SAC:
4.70 g/dL (IC95% 2.55-6.84).
Mean TLI: 3.34 mg/L (CD: 3.62. UC: 2.49) (IC95%:2.66-4.02). TLI: 53: 56 %
and 3-7: 31.2%. ATI status: 4.3% of patients tested positive. All patients who
developed ATI had undetectable trough levels. 68.5% of patients with trough
levels53 were in remission. Mean estimated peak levels: 114.35 mg/L (IC95%:
107.37-121.305); mean estimated AUC: 27105.77 mg/h/L (IC95%: 24835-
29376.54).
Fasanmade et al (2011) population PK model for CD was used in both CD and
UC patients. Mean predicted TLI: 3.1 mg/L (IC 95%: 2.49-3.69). Bias 5.55%
(IC95 %: -7.98-(-3.129)) and precision 10.4% (IC95 %: 8.85-11.95). Fasanmade
et al (2009) population PK model for UC was not precise enough.
Individual estimated PK parameters (mean): central clearance (Cl) 5.65 ml/kg/
day (IC95%: 5.13-6.16), volume of distribution (central) (Vd) 50.59 ml/kg
(IC95%: 49.97-51.21), half-life (t1/2): 11.7 days (IC95%: 10.7 -12.7). Population
PK parameters: Cl 5.42 ml/kg/day, Vd 52.4 ml/kg. Difference between individual
and population PK parameters: 4% in Cl and 3.4% in Vd. Comparison of
exposures achieved showed that patients with positive ATI, SAC5 3.9 g/dL,
non receiving IMM and smokers had significant lower trough IFX levels,
higher Cl and lower t1/2. Patients with PCR46 mg/L and ileo-colonic CD had
lower IFX levels.
CONCLUSION: High interindividual variability in IFX PK and trough levels
exists in IBD patients. The influence of IMM, SAC, smoking and inflammation
on infliximab clearance suggests that individual adjustment of infliximab doses
according to disease activity may be useful in IBD.
REFERENCES
Fasanmade AA, Adedokun OJ, Blank M, et al. Pharmacokinetic properties of
infliximab in children and adults with Crohns disesase: a retrospective analysis
of data from 2 phase III clinical trials. Clin Ther 2011; 33: 946-964.
Disclosure of Interest: None declared
P0902 MESENCHYMAL STEM CELL TREATMENT DOES NOT
INCREASE COLITIS-ASSOCIATED COLON CANCER RISK
L.R. Lopetuso1,*, F. Scaldaferri1, V. Petito1, A. Puglisi1, S. Vetrano2,
M.E. Caristo3, V. Arena4, V. Cufino4, A. Sgambato4, A. Gasbarrini1
1
INTERNAL MEDICINE, GASTROENTEROLOGY DIVISION, CATHOLIC
UNIVERSITY OF ROME, Rome, 2Division of Gastroenterology, Humanitas
Clinical and Research Center, Rozzano, Milan, 3Experimental Center,
CATHOLIC UNIVERSITY OF ROME, 4Pathology, CATHOLIC
UNIVERSITY OF ROME, Rome, Italy, Rome, Italy
Contact E-mail Address: lopetusoloris@libero.it
INTRODUCTION: Mesenchymal stem cells (MSCs) are potent immune regula-
tors, proposed for local and systemic use in human IBD. Recent studies reported
that MSCs can promote tumorigenesis, warning their use in clinical condition
associated to increased cancer risk, such as IBD.
AIMS & METHODS: To evaluate the cancer risk associated to the therapeutic
effect of MSCs in murine model of colon cancer associated to chronic colitis.
MSCs were isolated from adipose tissue of C57BL/6 mice, and analyzed for
MSCs markers and for adipocyte and osteogenic differentiation. An MTT
assay was used to explore the direct effects of MSCs on tumor intestinal epithelial
cells proliferation and vitality. CT26 cells were incubated with TNF-a for 48 h
and then exposed to the surnatant of TNF-alfa pre- treated AMSC. C57BL/6
mice were injected intraperitoneally with azoxymethane (AOM) and exposed to 3
weekly cycles of 2.5% DSS.1 million of MSCs were injected intra-peritoneally at
day 3 of each DSS cycle, control (CT) mice received saline. Body weight, occult
blood test and stool consistency were used to calculate the Disease Activity Index
(DAI). Mice were sacrificed at week 10 and colon was analyzed macroscopically
and microscopically for number of cancer and degree of inflammation. Nude
mice were subcutaneously engrafted respectively with murine (CT26) or human
A380
(HCT116) tumor cells lines alone or in combination with MSCs to evaluate their
role in tumor cell growth. CT nude mice received MSCs alone.
RESULTS: MSCs differentiated into adipocytes and osteocytes, and expressed
low levels of CD31, CD34, LIN and cKIT markers, and highlevels of SCA-1,
CD44 and CD106. MSCs proliferation was increased when stimulated with TNF.
Their surnatant leaded to a not significant reduction of CT26 growth. MSCs
injection significantly reduced DAI in treated mice vs. CT. MSCs treated mice
showed lower body weight loss and better survival rate. Treated mice had a not
significant reduced rate of colon cancer development vs. CT. In nude mice, there
was no significant difference in tumor size between groups. No lesions were
found in CT mice.
CONCLUSION: MSCs did not increase cancer risk in this colitis model and did
not affect the progression of pre-existing tumor lesions. MSCs exerted an
immune-modulatory effect in vivo, by decreasing the severity of colitis in
mouse, suggesting that their anti-inflammatory effects may contra-balance
their pro-carcinogenetic potential, even in pre-cancer condition such as chronic
colitis. Further analyses are required to define mechanisms of action underlying
these findings.
Disclosure of Interest: None declared
P0903 INCREASED FREQUENCY OF ENDOSCOPIC MUCOSAL
HEALING AND REDUCED INTESTINAL RESECTION IN
PATIENTS WITH SEVERE IBD BY LONGTERM AZATHIOPRINE
THERAPY, BUT NEGATIVELY AFFECTED BY MALE GENDER
M. Basaranoglu1, M. Yuksel1,*, M. Kaplan1, N. Suna1, A.E. Demirbag1,
O. Coskun1, Y. Akpinar1, M. Yalinkilic1, Y. Ozin1, F. Saygili1, E. Kayacetin1
1
Turkiye Yuksek Ihtisas Hospital, Ankara, Turkey
Contact E-mail Address: metin_basaranoglu@yahoo.com
INTRODUCTION: Currently, safety and economic issues have increasingly
raised concerns about the long term use of biologics as maintenance therapies.
AIMS & METHODS: To evaluate the role of azathioprine (AZA) on mucosal
healing in patients with inflammatory bowel disease (IBD). Two thousand seven
hundred patients with IBD were evaluated from January 1995 to April 2014. The
searching criteria were as follows: (1) endoscopic records before the AZA and
during the AZA therapy; (2) AZA na ve patients with severe IBD. The data
included patients and disease demographics and the efEcacy of AZA. Patients
with a minimum duration of 4 months of AZA were included in this study.
RESULTS: A total of 120 patients treated with AZA for IBD were enrolled.
AZA therapy reduced the number of the surgical interventions in patients with
IBD* (*: p50.05). Male gender had a negative impact on the efficacy of AZA
therapy*. IBD patients with responce were older than the nonresponder*. There
was no difference between the operated CD patients and nonoperated for the
AZA responce rates (32% vs 34%, p4 0.05 respectively). Then, 33 AZA non-
responder patients with CD were put on biologics. Responce rate was 30%. Of
the nonresponders, intestinal resection performed in 35% .
mucosal
healing
number by AZA Nonresponce %
Patients with IBD 120 37 % 63%
UC 38%(45p) 42% 58%
CD 62%(75p) 33% 67%
Male 60% 25% 67%*
Operated after AZA 13% 4.5% 18.4*
AZA used (months) 31.524.7 (4-113) 31.225.7 (4-90) 31.624.3 (4-113)
Age at IBD 36.812.3 (11-72) 38.112.3 (17-58) 36.112.3 (11-72) *
diagnose (years)
Period (AZA 39.852.5 (0-264) 5669 (0-264) 3037 (0-204)
started-IBD
diagnosed (months)
CONCLUSION: In this study, we showed that AZA therapy increased endo-
scopic mucosal healing rates and decreased the frequency of the surgical inter-
ventions in AZA na ve patients with severe IBD. We believe that there is still
United European Gastroenterology Journal 2(5S)
AIMS & METHODS: Our aim was to evaluate the clinical efficacy of ADA in
steroid-dependent UC patients.
We designed an open-label, retrospective, consecutive, and multicentre study.
Inclusion criteria were patients over 18 years old with UC and ECCO criteria
of steroid-dependency: Patients who are either unable to reduce corticosteroids
below the equivalent of prednisolone 10 mg/day within three months of starting
corticosteroids, without recurrent active disease or who have a relapse within
three months of stopping corticosteroids. All patients received ADA treatment
for induction (160/80 mg) at weeks 0 and 2 and 40 mg every 2 weeks thereafter. In
the event of loss of response patients received higher doses of ADA. The main
endpoint evaluated was clinical remission without steroids during all the treat-
ment. Clinical response, mucosal healing and varying levels of C-reactive protein
(CRP) and calprotectine were also evaluated. Results are shown in percentages;
associations were analyzed by Cox regression whenever appropriate.
RESULTS: 37 steroid-dependent UC patients were treated with ADA: 67%
female, mean years since UC diagnosis being 11 years, 40% presenting extrain-
testinal manifestations and 65% with extensive colitis (E3). 12 patients (32%)
were na ve to anti-TNF and 25 (68%) had previously received infliximab. Mean
follow-up was 25.9 months. 83% received concomitant treatment with immuno-
suppressive drugs. 43% needed higher doses of ADA treatment due to loss of
response. After induction 35% of patients were in remission and after 12 months.
40% of patients were in remission without steroids. The mean partial mayo score
was 6.89 basal, 3.13 at month 6 and 2.33 at month 12 (p50.001). Mucosal
healing was achieved in 48% of patients. Mean calprotectine decreased from
563 basal to 218 at month 6 (p50.05) and to 61 at month 12. CRP decreased
from 19.13 to 6.13 at month 12 (p50.001). Only 3 patients (8%) needed a
colectomy during the first year. We did not observe any association between
concomitant treatment with immunosuppressive drugs and response to ADA,
but after Cox regression patients with need of intensification with ADA
(HR 48.1 95%IC:1.46-1589.1; p 0.03) and with previous IFX (HR 12.8;
95%CI: 2.24-73.54, p 0.004) had a lower remission rates.
CONCLUSION: Adalimumab can be effective for clinical remission without
steroids and mucosal healing in steroid-dependent UC. Previous IFX or need
of intensification are predictive factors of poorer efficacy.
Disclosure of Interest: None declared
P0905 ONE HOUR INFLIXIMAB INFUSIONS DO NOT AFFECT
ANTIBODIES ANTI-INFLIXIMAB AND TROUGH LEVELS IN IBD
PATIENTS
M. Marzo1,*, A. Armuzzi1, B. Tolusso2, D. Pugliese1, C. Felice1, G. Andrisani1,
O. Nardone1, F. Pizzolante1, G. Mocci1, S. Canestri2, E. Gremese2,
G. Ferraccioli2, A. Papa1, G. Rapaccini1, L. Guidi1
1
IBD Unit, 2Reumatology Unit, Complesso Integrato Columbus, Catholic
University, Rome, Italy
Contact E-mail Address: manuelamarzo@gmail.com
INTRODUCTION: Infliximab therapy in patients with inflammatory bowel dis-
ease (IBD) requires intravenous administration in over 2 hours, with a further 1
hour of post-infusion observation. Recent studies demonstrated the safety and
the tolerance of a shortened 1-hour infusion in IBD patients under scheduled
maintenance infliximab treatment. We report our experience in order to evaluate
if repeated 1-hour infliximab infusions could affect the antibodies to infliximab
(ATI) and the infliximab trough levels (TL).
AIMS & METHODS: This was a prospective cohort study on patients with IBD
receiving infliximab with shortened 1-hour infusions. All patients were treated
with scheduled maintenance infliximab therapy, after at least 5 well tolerated 2-
hours infusions before enrolment. For each patient we recorded diagnosis, vital
signs. All patients were routinely premedicated with 20 mg i.v. methylpredniso-
lone and oral antihistaminics. We analyzed serum samples collected before start-
ing the first shortened infusion and after one year of maintenance scheduled
infliximab treatment for ATI and TL by a commercial ELISA kit according to
the manufacturer instructions (DRG Diagnostics GmbH, Marburg, Germany).
All samples were analyzed simultaneously at the end of the collection period.
Statistical analysis was performed by Wilcoxon test for paired samples and
Fishers exact test.
RESULTS: Fifty-seven IBD patients (28 Crohns Disease, 29 Ulcerative Colitis)
were treated at our IBD Outpatient clinic with 1-hour infliximab infusion pro-
tocol: out of them 24 (42%) at the dose of 10 mg/kg and 18 (31.6%) with a
shortened interval of 6 weeks. Eleven patients (19.3%) were on concomitant
immunosuppressants. In total, 396 maintenance 1-hour infli