Professional Documents
Culture Documents
32. Universal Precautions and needle stick injuries Dr. V. J Anand (New Delhi)
33. Adrenocortical tumours Dr. S Chumber (AIIMS, New Delhi)
34. Adrenal and thyroid Incidentalomas Dr. A Agarwal, Dr. V. Agarwal (SGPGI, Lucknow)
35. Status of transplant surgery in the present era Dr. S Guleria (AIIMS, New Delhi)
36. Hodgkin's disease Dr. S. K. Jain (MAMC, New Delhi)
37. Gastrointestinal lymphomas Dr. N. S. Hadke (MAMC, New Delhi)
38. Chronic lower limb ischemia Dr. Pawanindra Lal (MAMC, New Delhi)
39. Diabetic foot Dr. Vinod K. Ramteke, Dr. A.K. Sarda, Dr. Sushanto Neogi (MAMC, New Delhi)
40. Medullary Carcinoma thyroid Dr. T. K. Thusoo (New Delhi)
41. Laparoscopy - Present and Future Dr. Jagdish Chander, Dr. Tarun Mittal (MAMC, New Delhi)
CME on Biliary Calculus Disease
Biliary calculus disease- is the scenario changing? Dr. P. N Agarwal (MAMC, New Delhi)
Recent advances in management of biliary calculi Dr. P. K Mishra (GBPH, New Delhi)
Open cholecystectomy in the era of laparoscopic surgery Dr. V Arora (SGRH, New Delhi)
Minimal Invasive surgery for biliary calculi Dr. Arun Prasad (I.P Apollo Hospital, New Delhi)
Scientific basis of clinical features of obstructive jaundice Dr. Gulshanjeet Singh (DDU, New
Delhi)
Introduction
There is similar global incidence of cancers with lung leading the list, followed by
breast and colorectal cancer with some regional variation.
cancer in Asia and Africa is far less than in North America and Europe
Mohandas and Desai from Tata Memoral Hospital in Mumbai reported in 1999 the
incidence rates of colon and rectal cancers in eight population registers and estimated that
the predicted incidence in 2001 of large bowel cancer was 18,247 in men and 13,092 in
women; a modest incidence for the size of the population.
Publications by Dr Deo and his colleagues from the All India Institute of Medical
Sciences in New Delhi suggest that like other developing countries, rectal cancer affects a
younger age group, is more common than colon cancer, and is mostly in the lower rectum,
with appreciable inoperability, abdomino-perineal resection being the more frequently
performed procedure, with low mortality and morbidity. The disease is usually at an
advanced stage. There seems to be no preference between preoperative and postoperative
radiotherapy. In two-thirds of patients adjuvant chemotherapy is not completed because of
poor patients compliance. The local recurrence rate is impressively low and corresponds
with that reported with optimal surgery by Total Mesorectal Excision. The 5 year disease
free and overall survival is more than 50% which compares well with other reports.
This introduction sets the scene around issues related to improving operability, the
feasibility and oncologic efficacy of sphincter saving resections and the role of adjuvant
therapy.
Preoperative assessment and Staging
Operability is determined by several parameters which include the age of the patient
and associated co-morbid medical conditions while resectability for cure is dependent on the
local extent of the disease and presence of distant metastases.
Local excision is restricted to small cancer limited to the submucosa (i.e. T1N0M0)
but once the muscularis propria (T2) or the serosa (T3) is involved, radical rectal resection is
required, and with lymph node disease without adjuvant therapy has to be considered.
Meticulous preoperative staging and assessment are therefore crucial:
1. Digital rectal examination is the simplest method of staging and is highly surgeon
dependent. The information obtained is the location of the tumour in relation to the anal
verge, and in males to the prostate, its surface features, its extent within and through the
rectal wall, its mobility and the experienced finger might also detect palpable para-rectal
lymph nodes. Assessment of the sphincter tone is part of the examination as incompetent
sphincters could preclude a sphincter saving resection. In females vaginal examination
should also be included to rule out infiltration in anterior rectal tumours.
2. Rigid sigmoidoscopy is performed in conjunction with digital rectal examination. It
provides a more precise measurement of the tumour location and the distance of the lesion
from the anal verge.
3. Colonoscopy should be performed to exclude synchronous neoplasms. Barium enema
is used for those patients unable to undergo complete colonoscopy, or if colonoscopy is not
available, as colonoscopy is regarded as the more accurate tool for screening the colon and
rectum for neoplasms and it allows endoscopic removal of synchronous polyps.
4. CT scanning of the abdomen and pelvis is performed in preference to ultrasonography to
rule out liver secondaries, because of its better accuracy.
5. Chest radiographs or chest CT scanning should be performed especially as rectal
cancer is more likely to be associated with lung metastases without liver metastases.
Abnormal findings on plain radiographs usually warrant chest CT scanning.
6. Endo rectal ultrasound (ERU) is the most useful preoperative method to stage the
depth of invasion and nodal involvement because of its high accuracy but is operator
dependent and has its limitations in near-obstructing lesions and in down staged tumours
after chemoradiation. It is the investigation of choice when planning local excision MRI is
less accurate than ERU, and is limited by its relatively small field of view, expense and
patients intolerance and like ERUS restaging patients after preoperative chemoradiotherapy
does not appear to be as accurate. MRI reliably determines extent of tumour mesorectal
involvement in up to 100% of cases and is employed exclusively to determine extra rectal
spread into the lymph nodes and the mesorectum; it also identifies the plane between the
mesorectal fascia and the pelvic wall fascia. It is the investigation of choice for determining
resectability.
Objectives of Cancer Treatment
These include complete clearance of the tumour, with minimal risk of local
recurrence, and whenever feasible restoration of bowel continuity to avoid a stoma, provided
satisfactory bowel function can be maintained with respect to stool consistency, frequency
and continence. Since the early introduction of abdomino-perineal resection by Miles in
1908, several innovative developments have been introduced towards achieving these
objectives. In 1970s the stapling instruments became available which promoted sphincter
saving resection. In 1982 Total Mesorectal Excision (TME) was advocated as a prerequisite for optimal oncologic clearance. In 1985 Buess introduced Transanal endoscopic
microsurgery which by improving accessibility widened the scope for sphincter
preservation. In order to improve bowel function, in 1986 the colonic pouch and later in
1997 coloplasty were suggested as means of increasing rectal capacity lost with sphincter
saving resections.
Surgical resection has been inadequate treatment for rectal cancer without adjuvant
chemo and radiotherapy and their role has been under constant evaluation.
The evolution of surgical techniques and developments in chemo and radiotherapy
were not without challenge and debate; most important of which will be discussed.
Sphincter saving resection vs excision of rectum
As sphincter saving resection was made easier with the availability of stapling
techniques, surgical adventure extended to restorative resection for cancers at levels that
previously could only be treated by excision of the rectum to ensure distal margin clearance;
this was at the expense of limiting the level of distal resection in order to retain a rectal
stump to allow an anastomosis. Thus the 5cm distal resection margin rule was gradually
being overlooked and hence there was anxiety about cancer clearance and risk of local
recurrence.
The Rationale for sphincter saving resection and excision of the rectum and
comparative results
The anal canal measures 2 to 3 cm and is shorter in females than males. The full
length of the rectum from the anal verge is 15cm. Traditional teaching dictated a 5cm distal
clearance margin, which restricted restorative resections to lesions at least 7cm from the
anal verge in order not to encroach into the anal sphincters and the anal canal. Hence only
lesions in the upper half of the rectum were treated by anterior resection while lesions in the
mid and lower rectum were treated by rectal excision. However with stapling devices midand low rectal cancers were increasingly being treated by restorative resection.
Several series compared restorative resection with excisional surgery, for mid-rectal
cancers (7-13cm from the anal verge) the local recurrence rates were similar and varied
from 4 to 18%. The 5 year survival was also the same.
However anterior resection for low rectal cancer showed alarmingly high local
recurrence rates that reached 20-30% within a short follow up of less than 5 years, while in
some series with follow up that extended to up to 14 years the recurrence rate was less than
10%, noticeably was a recurrence rate of only 2.6% reported by Bill Heald in 1986 which he
explained by adopting a mesorectal excision and which has become a milestone in rectal
cancer surgery.
The safe distal resection margin
The principal objective of surgical treatment is to obtain clear surgical margins. The
proximal resection margin is determined by blood supply considerations.
Multiple studies have demonstrated that 81 to 95% of rectal cancers have intramural
spread <1cm from the primary lesion. Spread beyond 1cm tend to be in high grade, node
positive cancers and those with distant metastases, whose prognosis is unfavourable
irrespective of local cancer clearance by excision.
Therefore in the majority of cases with favourable prognosis a distal surgical margin
of 2cm would remove all microscopic disease. For cancers of the low rectum (<5cm from
the anal verge), a cm is the minimum acceptable length of distal margin, but with larger
tumours
especially those
demonstrating
adverse
histological features
i.e.
poorly
differentiated cancers, more than a cm is required and probably the 5cm rule should still be
applied.
These criteria are currently employed when considering sphincter saving resection.
margin of the mesorectum removing it en bloc with the rectum. The mesorectum is the fatty
tissue that encompasses the rectum and contains lymphovascular and neural elements.
Surgical excision of the mesorectum is accomplished by sharp dissection in the plane
between the fascia propria of the rectum and the presacral fascia-referred to as the Holy
Plain. Radical clearance of mesorectal tissue enables en bloc removal of the primary rectal
cancer with associated lymphatic, vascular or perineural tumour deposits. The significance
of en bloc resection of an intact mesorectum is supported by pathologic studies that
demonstrated tumour deposits in the mesorectum up to 4cm distal to the tumour. Soon
Pathologists also recognised cancers spread laterally into the mesorectum and the
importance of lateral or circumferential margins in cancer clearance.
The priority of operations for middle and distal third rectal cancers is total mesorectal
excision and as long as the mesorectum is completely excised, it is safe to limit the distal
resection margin to keep a longer length of rectal stump for anastomosis.
The dissection along the
holy plane also allows clear identification and preservation
of the autonomic nerves.
Quality control of TME
With a successful and complete TME, the rectum is removed with the mesorectum
within an intact endovisceral fascia ie. Mesorectal fascia, as a cylinder. The current
pathological protocol after quantifying the quality of the mesorectum includes fixation, inking
of the mesorectal fascia and slicing the specimen transversely.
TME is regarded as complete when the mesorectum is intact, with no visible defect in
the fascia and the CRM is smooth otherwise TME is considered as nearly complete or
incomplete when the bulk of the mesorectum is moderate or is little with defects in the
mesorectum or the muscularis propria.
Definition of a positive or negative CRM and its prognostic significance
When microscopic tumour deposits are noted in the mesorectum outside the main
tumour, the circumferential margin is regarded as positive if a deposit is less than 1mm from
the circumferential margin, and is negative if is more than a mm away from the
circumferential margin or no deposit is present.
The significance of involvement of the CRM with respect to local recurrence and
distant metastases has been demonstrated in several studies; patients with a negative CRM
the local recurrence and distant metastases were significantly less than in patients with
positive CRM. Furthermore both the Leeds Group in UK and the Dutch group reported
survival benefit in patients with negative CRM compared with patients with positive CRM.
Having established the prognostic significance of CRM, it has becomes evident that surgical
technique is crucial in achieving a complete and clear margin.
Relationship of TME and CRM
The Dutch Colorectal Cancer Group has investigated the relation of completeness of
mesorectal excision with recurrence. They found no difference in the recurrence rates
between the patients who had complete or nearly complete mesorectal excision and as a
combined group, the overall recurrence rate was significantly less than in the group who had
incomplete mesorectal excision at 2 year follow up. With complete TME the overall
recurrence rates were significantly less in patients with incomplete TME, mainly attributable
to lower local recurrence rates, although the difference was not significant. In this Dutch
study there no survival difference between the groups probably because the period of follow
up was short.
The completeness of TME is not of prognostic value when CRM is positive. However
this is not the case in patients with clear CRM. The overall recurrence, local and distant
recurrence rates were significantly higher and survival was significantly lower when TME
was incomplete than when it was complete. Therefore, a patient with a ve CRM is
disadvantaged if TME is incomplete.
Factors influencing Completeness of TME
In abdomino perineal excision the mesorectum was complete in a third compared
with three-quarters in the group who underwent low anterior resection; tumours <5cm from
the anal verge showed complete mesorectum in only 39% of cases compared with 67% in
patients with tumours more than 10cm from the anal verge. There was no relation between
the tumour stage and the quality of the resection specimen.
Therefore, TME is of oncologic benefit and has allowed limiting the distal resection
margin for lower anastomosis; the resected specimen should be examined for completeness
of TME and for involvement of the CRM; CRM influences local recurrence and survival and
incomplete TME compromises the result of a negative CRM.
Extended Restorative Resection and Restorative Options
The oncologic disadvantage of abdomino perineal excision has furthered interest in
restorative resection. Abdomino perineal intersphincteric excision combines transanal
intersphincteric resection with partial or total excision of the internal sphincter. Schiessel
introduced this procedure for tumours that extended into the anal canal, for the purpose of
preserving the anal sphincters and avoiding anorectal excision in view of the superior
oncologic results observed with sphincter preservation combined with TME, and has also
been employed after tumour down-staging with chemoradiotherapy. In the reported series
while anal manometry show reduced resting pressure and squeeze pressures this did not
seem to compromise function.
There have been only few large series, which all have shown a low mortality, and
except for a German series by Hohenberger, the local recurrence rates were low, and in all
series the 5 year survival was more than 80%. All patients had received adjuvant
chemoradiotherapy either pre or post operatively. During the period study Hohenberger was
able to reduce rectal excision by 20%.
Restorative options
Patients with low and ultra-low anterior resection with straight colo-rectal or coloanal
anstomosis (CAA) suffer symptoms compounded by radiotherapy referred to as the anterior
resection syndrome that include increased bowel frequency, tenesmus and incontinence
which have been attributed to reduced rectal capacity, disruption of the anorectal reflex, and
sphincter dysfunction.
Therefore colonic J pouch provides optimal postoperative bowel function with lower
morbidity than transverse coloplasty and in most cases should be the primary method of
bowel reconstruction.
Oncologic Efficacy of Anorectal Excision
Uncertainty about incompleteness of TME after abdomino perineal resection has
raised concern about the oncologic adequacy of the procedure.
Three series have demonstrated that the rates of positive resection margins after
abdominoperineal resection were at least double the rates after anterior resection.
Indeed except for Chuwa and his colleagues who reported comparable low
recurrence and survival rates, others have reported significantly higher local recurrence and
poorer survival rates after abdomino-perineal excision than after anterior resection. Chuwa
and his colleagues argue that with appreciation of the anatomic relations in TME and
standardised surgical technique, the oncologic outcomes of patients treated by abdominoperineal resections are not worse than those treated by sphincter-saving anterior resections.
Several reasons have been reported that explain the unfavourable outcome of
abdomino-perineal resection: higher extramural invasion and positive CRM, lateral pelvic
lymph node (LN) spread related to depth of invasion and the level of the tumour from the
anal verge, a 30% LN involvement in advanced low tumours, incomplete TME in more than
60% of patients with low tumours, considerable risk of perforation in low tumours which is
associated with local recurrence.
Therefore the evidence does not favour anorectal excision and this is related to
lymph node involvement in low lying rectal tumours and inadequate surgical excision, which
could be addressed chemoradiotherapy for down grading and down-staging tumours to allow
anterior resection and for improvement in operative technique.
Pelvic Lymphadencectomy and Sentinel Lymph Node Biopsy
Pelvic Lymphadenectomy commonly adopted in Japan but criticised for its morbidity
could be justified on the above evidence and may play a role in improving the outcome.
Hence selective sentinel lymph node may allow a selective approach.
In large Japanese series reporting on extended lymphadenectomy, less than 20% of
lymph nodes were involved commonly in cancers in the low rectum. Thus lymphadenectomy
was unnecessary in the majority. The local recurrence rates were higher and the 5 year
10
survival was lower when the lymph nodes were involved. The 5 year survival after
lymphadenectomy, in patients with positive lymph nodes was less than 50%.
Sentinel Lymph Node Scintigraphy
While TME is accepted as a standard surgical procedure for rectal cancer, there is
risk of aberrant distribution of nodes beyond the extent of TME particularly in low rectal
cancer. Since less than 20% of lymph nodes are involved, a selective extended
lymphadnectomy would save the majority, the morbidity of this procedure. Sentinel lymph
node biopsy could have a useful role in selecting those patients who could benefit from
lymphadenectomy. A dye guided method is not applicable for rectal cancer because of the
anatomical configuration of the rectum, it is impossible to trace the flow of blue dye without
destroying the lymphatic network. Sentinel lymph node mapping with scintigraphy for
accurate staging without extensive lymph node dissection, is a logical approach that may
prove useful in the future.
However Professor Muto has recognised the role of chemoradiotherapy that could
spare many patients an extensive procedure.
LOCAL EXCISION
Besides anterior resection local excision has been another mode of treating rectal
cancer while preserving sphincter function but its oncologic efficacy has been scrutinised.
Local excision is performed tranasanally for lesions less than 10cm from the anal
verge, while transanal endoscopic microsurgery or TEM using specially designed equipment
allows access to lesions at higher levels that are otherwise inaccessible by standard
transanal excision. The tumour is excised intact by full-thickness excision with clear
margins, it is orientated and pinned out for complete pathologic examination.
Rationale for Local Excision
In rectal cancer the main prognostic factor is dependent on the extent of invasion of
the tumour through the wall and into the nodes. The risk of LN involvement increases with
the depth of wall invasion. There is a wide range but consistent relationship in the incidence
of LN involvement and depth of invasion. Other features associated with increased risk of
lymph node metastases include poor differentiation, lymphovascualar invasion and tumour
size greater than 3cm. Since the node bearing areas are not removed by local excision
these procedures are inadequate for node-positive tumours.
11
Furthermore in tumours with extension beyond the muscularis mucosa (i.e. T3 or T4)
even when node-negative the 5 year survival probability is reduced by approximately 2030%, making the T stage of critical importance in local excision.
Management Strategy
Local excision is reserved for carefully selected T1 tumours, less than 3cm in size
and mobile, not occupying more than 40% of the circumference of the rectum, with depth of
invasion determined by ultrasonography and the lesion is histologically well differentiated.
Not infrequently the preoperative assessment is inaccurate when the postoperative
histological examination of the excised lesion identifies unfavourable features,and either
chemoradiotherapy or salvage resection is required.
Reported Results of Local Excision
Sengupta and Tjandra in a review of 41 publications reported a range of recurrence
rates, with an average of less than 10% for T1 cancers which is increased two fold for T2
and 4 folds for T3. Post operative chemoradiotherapy did not influence the recurrence rate
in T1 tumours but reduced the recurrence rates in T2 and T3. tumours. In 15 papers the
survival rates after salvage surgery for failed local excision in 84 of 115 patients ranged from
40 to 100% over a follow up period that extended from less than a year to 13.5 years.
The differences in the published data must be related to patient selection, surgical
technique, duration and frequency of follow up in all these studies.
Individual large series show local recurrence rates that varied from 7 to 40% and
much higher recurrence rates for T2, with overall survival of 65 to 89%. However in most
studies follow up was less than 5 years although Paty and his colleagues from Memorial
Sloan Kettering Centre reported a 74% 10 year disease survival.
Although local excision of early rectal cancer offers minimal morbidity and minimal
long term functional problems, local recurrence is higher that radical resection.
In this
controlled study the local recurrence rates were higher after local excision compared to
radical surgery; for both T1 and T2 cancers. There was also a higher rate of overall
recurrence including distant metastases which was statistically significant for T2 cancers; the
5 year cancer specific mortality was similar between the two groups but the 5 year survival
rate after local excision for T2 lesions was significantly less.
12
13
In the largest series published to date, 49 patients who underwent salvage surgery
for local recurrence after local excision for T1, 55% required an extended pelvic dissection
with en bloc resection of adjacent organs, and although 47 of 49 patients had complete
clearance, 58% had recurrence or died of disease within 33 months and the 5 year disease
free survival was 53%.
Conclusion
Local excision is strictly recommended for T1 lesions, although this is still associated
with a 20% local recurrence rate at 10 years. Therefore it should be restricted to unfit
patients and those unwilling to have a stoma. A long follow up is required in these patients
as local occurrence can occur after 5 years.
Post surgical T2 lesions are treated by radical resection while, T3 or 4 are treated by
preoperative chemoradiotherapy followed by resection. Salvage surgery for recurrence or
unfavourable post surgical lesions can be extensive with less than 50% cure rate. Local
excision can be considered for palliation in T2-4 or advanced rectal cancer after
chemoradiotherapy in unfit patients or those who do not wish to undertake radical surgery
unsuitable for radical resection.
LAPAROSCOPIC SURGERY
It has been evaluated in colonic cancer in randomised trials, but not in rectal cancer.
Metanalysis of so far published reports suggest that laparoscopic assisted TME is feasible
with a conversion rate in nearly a third of cases, although the operative time is increased
which should improve as surgeons get more familiar with the procedure, the morbidity is
much reduced, and the oncologic outcome is not compromised.
However pending
prospective randomised trials its safety and its oncologic efficacy remain unclear.
ADJUVANT THERAPY
The 5 year survival of patients with rectal cancer undergoing curative resection has
been about 50% because of the high risk of local recurrence or of distal metastases.
Therefore improved survival has been a major issue in the long term management of
resectable rectal cancer.
The evidence for the benefit of adjuvant therapy is based on several early
randomised controlled trials that compared, surgery alone with postoperative chemotherapy
only, with post operative radiotherapy and with combined chemo and radiotherapy.
Compared to surgery alone chemotherapy improved disease free survival but not loco-
14
regional recurrence while radiotherapy reduced local recurrence but did not improve survival,
and in combination local recurrence and disease free survival were significantly improved.
Adjuvant Treatment Policy
Two main adjuvant treatment policies have evolved preoperative and postoperative.
The Sweedish approach is non selective and employs preoperative short course
radiation (SCRRT) of 25Gy in five fractions and the North American which restricts
postoperative radiotherapy combined with 5 Fluoro-uracil only for stage II or III disease,
based on randomised controlled trials that showed improvement in overall survival and was
endorsed by the NIH consensus statement in 1990..
The Sweedish approach is not selective, hence patients with early cancer are
unnecessarily over-treated while the North American approach is restricted to high risk
patients but is associated with greater acute toxicity, as higher dose of radiation is required..
The compliance is lower if surgical recovery is prolonged and due to acute toxicity curtailing
treatment before the planned total dose has been reached.
Postoperative chemoradiotherapy vs chemotherapy
The National Surgical Adjuvant Bowel and Breast Project (NSABP) compared post
operative chemotherapy with chemoradiotherapy in stage II and III in a randomised trial to
explore the feasibility of avoiding postoperative radiotherapy.
15
16
when compared to the group who had preoperative radiotherapy with an incidence not
different from those who had surgery alone.
radiotherapy and surgery lost slightly more blood during the operation than those assigned
to surgery alone, and patients who had abdomino-perineal resection had more perineal
complication with radiotherapy. No other significant differences with respect to postoperative
morbidity and mortality were found between the groups.
Among 1748 patients who underwent a macroscopically complete TME in this study,
the overall rate of local recurrence at 2 years was 5.3%. The local recurrence rate was 2.4%
in those who had radiotherapy and TME, significantly less compared to 8.2% after TME
alone.
Unlike the Swedish experience this study did not show a survival advantage with
preoperative radiotherapy, but the follow up was shorter. However even if no survival benefit
was achievable with radiotherapy, improvement in the quality of life with better control of
local failure with radiotherapy justifies its use.
17
chemoradiotherapy over radiotherapy alone. The rate of complete pathologic response was
significantly increased and the local recurrence was significantly reduced, but the rate of
sphincter preservation and the overall survival was the same in both groups. Grade 3-4
toxicity was increased in the chemotherapy arm.
18
19
unwillingness to reappraise their indication for APR based on the clinical tumour response
after neoadjuvant chemoradiotherapy or the clinical tumour response with concurrent
chemotherapy was small to influence the surgical decision. However this study shows short
course radiotherapy is ineffective in downstaging.
Preoperative Short Course Radiotherapy or Postoperative Chemoradiotherapy
The MRC trial in the UK which has just been completed compared non-selective
short course pre-operative radiotherapy consisting of 25Gy given a 5 daily fractions of 5 Gy
with radiotherapy and chemotherapy (45Gy in 25 fractions over 5 weeks plus 5 FU) for
patients deemed to be at high risk mainly Stage III and those with unfavourable pathological
features.
radiotherapy results in significant reduction in local recurrence and improved disease free
survival at 3 years.
Timing of Surgery after Radiotherapy
The Lyon R90-01 trial compared a short delay with a long delay after preoperative
radiotherapy to determine the optimum interval between radiotherapy and surgery. The
main end point was sphincter preservation; 201 patients with T2-3 tumours in the lower
rectum were allocated to have surgery either 2 weeks or 6-8 weeks after completion of
radiotherapy (39 Gy in 13 fractions over 17 days). The long interval was associated with
significantly better clinical response and pathologic downstaging, with a trend towards
increased sphincter preservation. The complications were the same in both groups. The
local recurrence rates were similar and were related to the distance of the resection margin
from the tumour in the operative tumour; when less or more than 15mm the rate of local
recurrence was 16% and 8% respectively. The 5 year overall survival was the same in both
arms. Thus there is a potential benefit in delayed surgery in increasing the chance of
sphincter preservation.
Other Combination Chemotherapy
Preoperative radiation is intensified either by escalating the dose of radiation or
exploiting the interaction between chemotherapy and radiation by adding more
chemotherapy during the period of irradiation. Current interest has focused on the latter
approach and Phase I and II trials have been designed examining these different
combination protocols.
20
21
22
In the last three decades great advancement has taken place in the field of plastic
surgery. The most remarkable achievement has been in the development of new techniques
of providing skin cover. From the skin graft to free microvascular flaps and cultrured skin
graft, there has been a revolution in the innovative techniques of providing skin cover. The
use of flaps with intact blood supply has completely changed the field of plastic surgery yet
the split skin graft has been the most important achievement in the field of plastic surgery.
Baronio performed the first successful skin graft in 1804 on lamb. However, Jacques
Reverding, a Swedish medical student was first to do epidermal auto skin graft on to a
granulating wound in 1869.
Today, the reconstructive plastic surgeon faced with a soft tissue defect has a
plethora of options. With the knowledge of the muscle flap, the musculocutaneous flap, the
fasciocutaneous flap and the technique of microvascular composite tissue transplantation,
plastic surgeon has the ability to restore form and function in the congenital and acquired
defects in most topographic regions.
To provide cover to a wound, a typical reconstructive ladder has been described and
was in use in last two or three decades.
complicated or complex technique of providing skin cover. At the bottom of the ladder was
split skin graft and at the top of it was free vascularised (microvascular) tissue transfer. With
the advancement in microvascular technique, the dictum has now changed
why use ladder
when lift is available, provided one can ensure the safety of lift.
23
Wounds with poor vascularity post radiation ulcer, long standing ischaemia of
granulation tissue.
24
Haematoma
Infection
Technical error
Poor vascularity.
Full Thickness Graft: It includes entire thickness of skin i.e. both epidermis and dermis.
Donor site of FTG has to be closed either primarily or is to be covered by SSG if the area is
big and cannot be closed. Full Thickness graft is harvested by Scalpal. Sites from where
FTG can be taken are:
Supraclavicular
Groin
Prepuce
Labia majora
Nipple, areola
2.
3.
Preservation by freeze drying: Freeze dried graft sealed in vacuum can be stored for
many years at room temperature.
FLAPS
.. Flap is a tongue of tissue with intact blood supply. Flaps can be classified
according to:
Composition
Method of Movement
25
A major blood vessel lying deep to the muscle gives off perforator-musculo
cutaneous branches which reach the dermal-sub dermal plexus of skin. Based on
these plexus, a flap consisting of skin and subcutaneous tissue can be raised.
The maximum surviving length of such a flap-random pattern flap (consisting of
skin and subcutaneous tissue) is dependent on the vascular perfusion pressure.
A rough guide to safe flap dimensions is to have 1:1 ratio of length to breadth. It
was a logical evolution to exploit the random pattern skin areas by raising it with
the underlying muscle- musculocutaneous flap. This not only makes the flap safe
but skin can be made to reach longer distances in a single stage.
2.
The other pattern has a large blood vessel giving off a direct cutaneous artery
which lies superficial to the muscle and has branches which reach the dermal-sub
dermal plexus. Skin flaps based on this system are axial pattern flaps and they
must include the full thickness of subcutaneous tissue. The vascular territory of
the axial vessel dermines the length of the flap a longer surviving length.
Anatomical studies further revealed a plexus of blood vessels lying under and
over the deep fasica, and some perforating vessels were found to reach the
overlying dermal-sub demal plexus by passing through the intermuscular septa
(septo cutaneous vessels). This showed that in random pattern areas loner flaps
could be raised if the deep fascia were included in the flap design. Such flaps
were designated fasciocutaneous flaps.
26
Local Flaps
Local flaps can be classified on the basis of movement:
Advancement Flaps : These are flaps of choice for small defects. Simple
advancement flap requires excision of skin triangles (Burrows triangles) at the
base of the flap. A V-Y advancement of skin is also carried out in some situations
These flaps pivot around a point to move into a defect. The defect is generally triangulated.
The donor defect can be closed primarily or split skin grafted.
Distant Flaps
Direct : A pedicled flap is placed directly on the defect in the first stage and detached
after 3-4 weeks, eg. Cross finger flap, groin flap, delto-pectoral flap.
Indirect: This is multi staged procedure, eg. Tube flap, jump flap.
rarely, if ever,
employed these days. If skin from abdomen had to reach the leg, it would be first tubed
on the abdomen, then placed on wrist and finally made to reach the defect with base on
the wrist. Reconstruction would take several months.
Free Flaps: Axial flaps, myocutaneous flaps, fasciocutaneous flaps, perforator flaps,
omentum, jejunum, bone etc. can be transferred to recipient site by microvascular
techniques after completely detaching from the donor area.
Reconstruction can be
27
Type IV; Segmental vascular pedicles: There are several pedicles entering the muscle at
various level
and dividing two or three during flap elevation can result in distal
expanders are made in various sizes and shapes for different needs. Expansion is begun a
few weeks after insertion by injecting saline. As the expander enlarges it stretches the
overlying skin. Depending on the size of the expander the expansion can be completed in a
few weeks after which the lesion is removed and the resurfacing carried out.
Tissue expansion is employed for breast augmentation and post-mastectomy breast
reconstruction. It is very useful for reconstructing large scalp defects, and for nose, cheek,
forehead and ear reconstruction. Scars, tattoos and benign lesions on the trunk and
extremities can be removed easily by using tissue expanders. Larger lesions may require
insertion of multiple expanders.
Tissue expansion is also fraught with many complications like seroma, haematoma,
infection,, extrusion, exposure, spontaneous deflation and failure to achieve the desired
result due to poor planning.
Skin substitute
Skin performs a wide variety of protective (barrier, UV Light, absorption , immune
seervellance ,mechanical) perceptive (touch, temperature, pain) and regulatory (thermal,
hydration, excretory) functions. That maintains the homeostasis of the human body with the
28
terrestrial environment.
complicated functions of the skin which are very difficult to replicate. It is not surprising that
till today no skin substitute has been developed that closely matches human skin. The
followings properties are desirable in a skin substitute.
1.
2.
3.
4.
5.
6.
Skin substitute can provide temporary cover to opened wound for example in the patients
with extensive burns where the donor site is limited. Biological substitute like homograft,
heterograft and amnion has been in use over a century and several synthetic skin
substitutes are now available in the market.
Advantages of Skin Substitute
1. It convert an open wound to close one thereby preventing bacterial proliferation
2. It protects tendons, nerves and vessels from desiccation.
3. It prevents loss of protein and RBC from the wound
4. It provides physical cover to the wound and thereby prevents above evaporative
water loss , thus conserving heat.
5. It covers expose nerve endings thus decreasing pain during joint movement.
6. It temporarily obviates the need to harvest autograft in a patient who may not be fit to
undergo surgery.
7. It prepares wound for autologous grafting .
29
Epidermal component
Human Keratinocytes
(Allograft Cells)
Integra
Synthetic polysiloxane
Polymer
Synthetic
None
None
Transcyte
Alloderm
Dermagraft
Skin Temp
Medifil
Kollagen
Epicel
Dermal component
Human fibroblast (allograft cells) in
bovine type 1 collagen other ECM
proteins, cytokines
Bovine type 1 collagen and
Chondroitin-6-sulphate
Human dermal tissue
Processed Allograft Skin
Human fibroblast seeded 3 D
bioresorbable scaffold
Reconstituted bovine collagen
Reconstituted bovine collagen
Reconstituted bovine collagen
None
Cultured epidermal
autograft
Suggested Reading
1.
2.
3.
4.
5.
6.
7.
8.
9.
10.
11.
12.
13.
14.
15.
th
Mcgregor IA, MCgregor AD, Fundamental Techniques of Plastic Surgery (9 ed). Edinburgh, Churchill
Livingstone, 1955: o 35.
Pruitt BA, Goodwin CW, Pruitt SK, Burns; Including cold, chemical and electrical injures. In: Sabiston DC
th
(ed) Text Book of Surgery. The Biologic Basis of Modern Surgical Practice (14 ed.) Philadelphia. W.B.
Saunders Co. 1991: p 178.
Rudolph R. Ballantyne DL. Skin grafts, In; Mccarthy JG (ed) Plastic Surgery, Vol I, Philadelphia, W.B.
Saundera Co., 1990; p221
Mathes SJ, Issa E. The principles of muscle & musculocutaenous flaps. In: McCarthy JW (ed), Plastic
Surgery, Vol. I. Philadelphia, W.B. Saunders Co., 1990; p379.
Mathers SJ, Nahal F. Classification of the vascular anatomy of muscles : Experimental & Clinical correlation.
Plast reconstr Surg 1981:67:17.
Mcgregor IA, Mcgregor AD. Foundamental Techniques of Plastic Surgery (th ed). Edinburgh, Churchill
Livingstone, 195; p61.
MCgraw JB, Arnold PG. Basic principles of muscle flap surgery. In: Mcgraw JB, Arnold PG (eds), Atlas of
Muscle & Musculocutaneous Flaps, Virginia, Hampton Press Publishing Co., 1980; P 1.
Vasconez LO, Mcgraw JB, Camargos AG, Muscle, musculocutaneous & fasclocutaneous flaps. In: Smith
th
JW, Aston SJ (eds), Grabb & Smiths Plastic Surgery (4 ed). Boston, Little, Brown& Co., 190; p 1113.
Cormack GC, Lamberty BGH. A classification of fascioutaneous flaps according to their pattern of
vascularization, Br J plast Surg 1984; 37:80.
nd
Cormack GC, Lamberty BGH. Arteral Anatomy of Skin Flaps (2 ed). Edinburgh, Churchill Livingstone. 194;
p 105.
Daniel R.K; Kerrigan CL. Principles & Physiology of Skin flap surgery. In: Mccarthy JG (ed), Platic surgery,
Vol.1 Philadelphai, W.B. Saundes Co., 1990; 9 275.
OBrien BM, Morrison WA, Gumley GJ. Principles and Techniques of microvascular surgery; In: Mccarthy
JW (ed) Platic Surgery, Vol1. Philadelphia, W.B. Saunders Co., 190 p 412.
Argenta LC, Marks MW, Pasyka KA. Advances in tissue expansion. Clin Plast Surg 1985 12:159.
Boyce S.T. Design Princip;es for composition and performance of cultured skin substitute & Burns 2001:
27:523
Balasubalomani. M., Kumar. T.R. & Baby M. Skin substitute : A review. Burns, 2001:27:534.
30
Cleft lip and cleft palate are the fourth most frequent birth defects in the world. The
incidence in India is about 1 in 800 and it is estimated that about 35000 new children are
born with these defects. Accordingly it is presumed that about 2.5 million children suffer from
this defect in India.
Role of Team Work
The cleft deformity is much more than a mere physical defect: there is a cosmetic
deformity and a functional
31
palate are more frequent in males, whereas clefts of the palate alone are more frequent in
females. In general, clefts occur more often in males.
If parents with no cleft history give birth to one child with a cleft lip or palate the
chances would be about one in 25 of having another child with a cleft lip or palate. A mother
with a cleft lip and palate gave birth to a child with the same deformity, and then her chances
of having another child with a cleft lip and palate are approximately about one in ten.
Development of Face
The face of the infant begins to develop at approximately seven to nine weeks after
conception. The lip develops, about the seventh week and the roof of the mouth, which is the
hard and soft palate, at approximately nine weeks of life. The lip and palate develop
independently; it is therefore possible to have either a cleft of the lip or a cleft of the palate
separately or together.
The cleft lip and palate may be associated with some other abnormalities like
craniosynostosis, craniofacial clefts, syndactyly, retruded mandible etc; these are then
known as syndromic clefts. However majority of the cleft lip and palate patients are nonsyndromic.
PRENATAL DIAGNOSIS
It is now possible to find out the presence of cleft deformity early in the pregnancy
with the help of safe and non invasive investigations like ultrasound and the availability of 3D
imaging with this technique has allowed easier identification of the deformity. The parents
can be better prepared to face the situation when the child is born.
INTRAUTERINE SURGERY
Antenatal correction of the deformity has the advantage of scar-less wound healing
which is characteristic of the fetal surgery. However the maternal and child safety can not be
ascertained; this modality of treatment has, therefore, practically remained experimental
only.
GROSS DEFORMITY
The deformity can involve lip and palate in continuity, lip alone or palate alone or lip
and palate both with intervening normal alveolus. The defect may be unilateral or bilateral
and may vary from a small notch to full fledged defect in the lip and palate.
32
Lip: The degree of the cleft can vary from a slight notching of the red portion of the lip to a
complete separation of the lip. The portion of the bone where the teeth grow
through the gum may also be involved. The lip can be cleft to any degree on one or
both sides.
Palate: Clefts of the hard and soft palate may also vary in degree from a slight notching of
the end of the soft palate to a complete separation through the roof of the mouth.
Sub mucous Cleft : This is a cleft of the palate, which is not visible at birth. In the submucous cleft the muscles of the soft palate are not joined together even though the
lining of the roof of the mouth is intact. Though the palate may appear structurally
normal on appearance there can be serious speech disturbances if not investigated
and treated correctly
Facial Changes due to Growth
The infant's face has the potential for growing and developing normally. Although a
wide cleft of the lip and palate may be present at birth, the two separate portions of the
palate can still grow and develop normally. However as a result of cleft surgery the growth of
the midface is adversely affected, probably due to scarring induced after the surgery. These
children need to be followed up closely after surgery for facial growth and necessary
measures are taken to ensure that the growth of midface and lower jaw is as normal as
possible. The orthodontists play an important role in achieving this objective. Sometimes the
balance of growth of the upper and lower jaw is not appropriate and orthognathic procedures
have to be undertaken later in life when the patient is about 18 years old.
Cleft Lip Counseling
A plastic surgeon should be consulted to examine the newborn infant. Usually the
cleft lip is repaired shortly after birth. Lip closure aids in feeding and improves facial
appearance. The intact lip also helps mould the underlying bone. The physical condition of
the child will determine the timing of the first operation. The number of operations necessary
to accomplish a good final result depends on the type and degree of the cleft and associated
problems.
If there is a bilateral cleft of the lip, the plastic surgeon may repair the lip either in one
or two stages. He may operate on both sides or he may do one side as in the unilateral cleft;
then three to four weeks later, close the other side. Much depends on the nature of the
clefts. The tip of the nose is usually pulled down following bilateral lip closure. This may
33
require a later operation before school age. The initial results in the bilateral cleft lip are
rarely as satisfactory as in the single cleft and later additional surgery is often the rule.
Cleft Palate Counseling
The cleft of the hard or soft palate is usually not repaired until the child is over one
year of age. There are three aims of cleft palate surgery. The most important is to help the
patient speak well and this requires an adequate length of the palate that is mobile. The
second aim is to help re-establish palatal-eustachian tube- muscle function related to normal
hearing. The third is to establish normal dental function and appearance. Before closure of
the cleft palate, the orthodontist may take dental impressions. This will allow him to watch
changes that come from growth and surgery. X-ray films of the head (cephalometric studies)
may be taken for the same purpose. The cleft of the hard and soft palate is repaired
simultaneously although some centers repair only the soft palate at the time of lip repair and
close the hard palate cleft later.
Dental Care
Routine dental care is important in all children. The condition of the baby teeth or
their absence can affect the success of the child's total cleft lip and palate treatment. A full
set of baby teeth is normally present by age three.. When there is a cleft in the bone, which
supports the teeth, changes generally occur in the structures of the teeth next to the cleft. In
some instances, extra teeth are present. Any of these teeth may be malformed or grow outside of their normal position. They may interfere with feeding to the extent that removal may
be required. It is usually important that all baby teeth be kept until the growing second teeth
normally replace them.
The dentist often takes x-ray pictures as early as possible to help detect cavities,
extra, malformed or missing teeth. General inspection alone will not suffice to establish the
presence of cavities or other problems. Parents must be fully aware of how to establish good
mouth care and proper Brushing habits in their children.
Orthodontics
The orthodontist straightens the teeth and jaws. Most children with clefts of both the
lip and the palate require two stages of orthodontic treatment:
The first stage of treatment may begin as early if age two. The after-effects of surgery
on the cleft lip/palate creates a "dental cross bite," a condition where the upper teeth
are inside of the lowers when the teeth are together. The overlap can be corrected
34
The second stage of treatment adjusts the final positioning of the permanent teeth
and jaws to establish proper contact between teeth (occlusion), satisfactory dental
appearance and acceptable speech production. This stage is more complicated and
may require several years of treatment. The procedures may entail the movement of
bone as well as teeth. The widening of the upper jaw does not damage the palate nor
affect previous surgery performed. In either of the two stages of orthodontic
treatment, as the edges of the cleft palate are spread apart, a space in the roof of the
mouth, a portion of the original cleft, may become apparent. This space can be
closed surgically after the adjacent parts are fully developed.
35
Since these changes occur early in life, the child may not show obvious symptoms
but may learn to live with the disease. Moderate hearing loss may not be noted until the
baby is older when it is obvious that he/she does not hear properly. Occasionally, the
infection will be severe enough to cause a perforation of the eardrum with a discharging ear.
Speech and Cleft Palate Child
There is general agreement that the major potential handicap for a child with cleft
palate is a "speech defect." Defective speech was a common accompaniment in cleft palate
children in the past.
There are three major physical problems, which may lead to defective speech for
children with cleft palate. These are:
(1) Inadequate Palatal Function
(2) Dental Problems
(3) Hearing Loss.
Inadequate Palatal Function: A definite relationship exists between speech and the function
of the soft palate. Muscles of the soft palate and the throat must work together to close the
velopharangeal port the child to be able to make most speech sounds in the mouth.
Dental Problems: Both improper alignment of the teeth and missing teeth may be a
mechanical hazard to the development of clear speech.
Hearing Loss: Hearing loss from severe or frequent infection in the middle ear appears to be
a third, significant problem which can cause speech disorders.
Medical and dental specialists working together have developed procedures for early
treatment of these physical problems related to speech. They will try to correct them early so
that normal speech can develop.
Infants normally learn speech in the first three years of life. Children without cleft
palate or other physical problems sometimes learn to speak abnormally. Poor learning or
psychological problems can also cause defective speech in a young child. The chance of
such problems occurring is greater for any child born with any physical handicap.
Parental anxiety for an infant with a congenital malformation may lead to
overprotection. This can cause a lack of normal speech development. A speech pathologist
may help attain normal speech early in life mainly by evaluating and understanding his
special problems in learning speech.
36
37
38
Aesthetic plastic surgery/ cosmetic surgery can best be described as one of the
many subspecialties within the superspeciality of plastic surgery and which consists of a
series of surgical procedures, considered by many as operations performed only for the
improvement in appearance from an acceptable normal to a more coveted normal.
Aesthetic plastic surgery should not be confused with reconstructive plastic surgery which
aims at reconstructing the missing tissue, with an attempt to restore the lost function to as
near normal as possible. In simple words, reconstructive procedures have a dominant
functional goal, while cosmetic surgery procedures have a dominant aesthetic goal. Truly
speaking, all plastic surgical procedures have both cosmetic & reconstructive aspects and
should aim at a achieving maximum functional and aesthetic outcome.
Commonly performed cosmetic procedures in plastic surgery include aesthetic
rhinoplasty, breast augmentation, breast reduction, liposuction and body contouring, face lift,
brow lift, blepharoplasty, dermabrasion, chemical peel, hair transplantation, laser
resurfacing, soft tissue augmentation of face, botox injections etc. Many chapters have been
published on each one of these operations & it is beyond the scope of this article to
elaborate these procedures in detail. An overview of each shall be briefly described with the
idea of making the general surgery post-graduates aware of the scope of cosmetic surgery.
Aesthetic Rhinoplasty
Aesthetic rhinoplasty is the most frequently performed cosmetic surgery procedure
and is the most challenging of all aesthetic operations. Besides correcting both form and
function, the final, highly visible result must meet the patients high expectations. The
operative technique needs to be individualized for every case.
Indications
The external appearance of the nose may be altered in patients with congenital,
developmental or traumatically acquired abnormalities. The common indications for aesthetic
rhinoplasty are the dorsal hump, depressed dorsum, broad dorsum, asymmetric dorsum,
broad tip, bifid tip, asymmetry of tip, drooping tip, hanging columella, septal deviations,
crooked nose, nasal airway obstruction etc. Aesthetic rhinoplasty is usually performed after
the nasal skeleton has matured in adolescence.
39
Preoperative considerations
It is advisable to have the written record of patients complaints, his/her expectations,
previous nose jobs (if any), findings of external & internal nasal examination and nasal
aesthetics. Preoperative counseling with the patient in presence of his/her relative along with
patients photographs is recommended.
Technique
Rhinoplasty may be performed under general anaesthesia or local anaesthesia with
i.v. sedation by either open (external) or closed (internal) approach. The goal is to alter the
underlying bone and cartilage and to allow the overlying skin to contract over the modified
framework. An open rhinoplasty involves an incision in the skin at the base of the columella
that is then carried inside the nose along the alar rim. The closed technique employs
incisions inside the nose either in between the upper and lower lateral cartilages
(intercartilaginous incision) or through the lower lateral cartilages (intracartilaginous
incision).The skin is dissected off the osseocartilaginous framework. Dorsal nasal hump is
removed (rasped or excised) and the upper and lower lateral cartilages are modified as
required. Osteotomy of frontal process of maxilla and also at frontonasal suture line is done
and the nasal pyramid is narrowed by infracture of nasal bones. Minor irregularities are then
corrected, if necessary with pieces of cartilage as onlay grafts; by removing excess
subcutaneous fat in the region of nasal tip; by excising a small wedge of tissue from alar
base to correct alar flare etc.
Septo-rhinoplasty
Post-traumatic nasal deformity is often associated with septal deviation that may
interfere with nasal breathing and alter the quality of voice. The septal deformity should be
corrected simultaneously with rhinoplasty. Through an incision in the membranous septum,
the deviated portion of the quadrilateral/septal cartilage is resected or sculpted to its correct
curvature. Deformities in the posterior bony portion of the nasal septum (perpendicular plate
of ethmoid & vomer bone) are also corrected to remove any obstruction. Excision of the
hypertrophied inferior turbinate also improves the nasal airway. The incisions are then
closed, nose packed lightly with Vaseline ribbon guaze, skin taped with steristrips and the
reshaped nasal framework and tip immobilized in POP nasal splint for 8-10 days.
Augmentation Mammoplasty
The operation of surgically increasing the size of breast by placement of an implant
is referred to as augmentation mammoplasty
40
Indications
The indications for the procedure are cosmetic interests of the patient, clinically
significant breast asymmetry due to unilateral hypoplasia/aplasia, bilateral hypoplastic
breasts and in cases of subcutaneous mastectomy.
The implant
The implants have an outer solid shell of silicone surrounding a hollow interior that
can be filled with silicone gel (gel filled implant) or saline (saline filled implant) or both
(double lumen implant). Specific concerns of carcinogenicity, autoimmune diseases (both
suspected due to silicon bleed phenomenon), product failure, and impaired mammographic
evaluation led to moratorium on the use of silicone gel implants in 1992. However, saline
implants have been available without restriction. The breast implants are available in many
sizes (range: 80cc to 400cc) and shapes (e.g. round, teardrop etc.). The implants can also
be custom made on request for a particular requirement.
The outer shell of the implant can have either smooth surface or rough surface. As
smooth surface implants were associated with unacceptably high rate of capsular
contracture, polyurethane foam was incorporated in the silicone shell to make the outer
surface rough. However, due to reports of carcinogenic breakdown products of polyurethane
in animals, FDA banned all polyurethane-coated implants in 1991. Thereafter, alterations in
surface physical characteristics have been done to create textured surface implants in an
attempt to imitate polyurethare coating. Implants do not interfere with lactation and silicone
has not been identified in the milk of lactating women.
Technique
The operation can be performed under general anaesthesia or local anaesthesia with
i.v. sedation. The prosthesis may be placed behind the mammary tissue (subglandular) or
behind the subjacent pectoral muscle (subpectoral). Four separate incision sites viz.
periareolar, inframammary, transaxillary and transumbilical have been used for placement of
a implant. Each location has its advantages and disadvantages. In general, periareolar
approach provides excellent access to all portions of the breast for either subglandular or
subpectoral placement. The transaxillary approach has gained in popularity with the
introduction of endoscopically guided placement.
41
Complications
The possible complications include haematoma, seroma, infection, hypertrophic
scarring, implant malposition, unfavourable shape etc.
Reduction Mammoplasty
A woman who has breasts significantly larger than the aesthetic standards of her time is
seen as grotesque rather than sensuous. An attribute then becomes a deformity.
The operation of surgically decreasing the size of breast by excising a part of breast
tissue is referred to as reduction mammoplasty. The procedure of reduction mammoplasty
is one of the examples of interface between reconstructive and aesthetic plastic surgery.
Although the goals of this surgery are weight and volume reduction of the breast, aesthetic
enhancement, bilateral symmetry, with preservation of both sensation and physiologic
function is equally important.
Indications
Overly large breasts are not only aesthetically unacceptable, they often put strain on
spine and shoulder, cause bad posture, neck and back pain, abrasions & grooving of
shoulders from brassiere straps and intertrigo/skin maceration in the inframammary region.
Moreover, such patients with huge, heavy and pendulous breasts often develop
psychological problems as they find it socially embarrassing and thus remain aloof.
Unilateral hypertrophy with asymmetry heightens embarrassment. A breast reduction is
performed either to alleviate the physical symptoms or to improve the appearance of the
breasts.
The operation is best performed when breast growth is complete. However, surgery
may be indicated in young females with virginial breast hypertrophy before the completion of
growth, where the prospect of reoperation is outweighed by the benefits of more normal
psychological development.
Technique
Various techniques and their modifications have been described in literature for
reduction mammoplasty. Many of them are obsolete. The methods which are currently being
practiced are:1.
2.
3.
4.
42
Most commonly used procedure is the bipedicle technique. Markings are done
preoperatively with patient in standing position, using Wise template. The operation is done
under geneal anaesthesia. The nipple-areola complex with a reduced diameter, is left as an
island on the de-epithelialized central pedicle, which is later buried in the subcutaneous
position. Medial and lateral segments of breast tissue & fat are excised. Suction lipectomy
may be performed on the outer aspects and to reduce the axillary fat. The incisions are
closed over suction drains with nipple-areola complex sutured on to the center of the
keyhole.
Complications
Possible complications include haematoma, marginal flap necrosis, reduces nipple
sensation, hypertrophied scars, breast asymmetry and nipple loss due to ischaemia.
Liposuction and Body Contouring
Liposuction (suction assisted lipectomy) and body contouring are surgical techniques
designed to improve the appearance of any area of the body by combinations of fat
aspiration, skin excision and musculo-aponeurotic tightening.
Indications
The most frequent indication of liposuction is undoubtedly a cosmetic one, in the
removal of unwanted subcutaneous fat, but it also has a role in routine plastic surgical
practice in removing large lipomas, grade I gynaecomastia, as an adjunct in reduction
mammoplasty, face lift, abdominoplasty etc. and in defatting unduly bulky skin flaps. With
refinements in instrumentation and technique, any region of the body can be sculptured
(face, submental region, breasts, arms, abdomen, buttock, back, trochanteric region, thighs,
knees, calves, ankles etc.). However, it is prudent to note that patients with reduced skin
tone and sagging skin are poor candidates for the procedure. Moreover, liposuction should
neither be viewed as a treatment modality for obesity nor is it meant to reduce weight by
removing excess fat.
Technique
Excess fat deposits are marked preoperatively with patient in standing position. The
areas to be treated are preinjected with large volumes of tumescent solution (25cc, 2%
xylocaine + 1cc, 1:1000 epinephrine + 1000cc Ringers lactate solution) to reduce bleeding
and pain. Blunt tip, multiple-hole, small diameter cannula is inserted through diminutive skin
incisions. The cannula is attached to a high vacuum suction machine which causes the fat to
43
adhere to the openings at the distal end of the cannula. The adherent fat is avulsed from its
bed by to and fro motion of the cannula and is aspirated by suction device. The fibrous
stroma surrounding the neurovascular bundles is relatively resistant to suction thus
preserving blood supply and innervation to the overlying skin. With suction completed, a
pressure dressing is applied to the site. Local bruising, although temporary can be
considerable. With healing, the overlying skin shrinks to the reduced fat volume.
For patients with loose excess skin and excess subcutaneous fat, liposuction alone is
inadequate. These patients are benefited by direct excision of fat and skin. The most
commonly performed procedure involving direct excision of fat and skin is abdominoplasty.
Excess lower abdominal fat and skin, particularly common in postpartum females, can be
removed from the level of umbilicus down to pubis and skin can be closed primarily.
Umbilicus is relocated to its original level in the superior skin flap as the flap is advanced
over the lower abdomen. Any accompanying diastesis recti or ventral hernia needs plication.
The final scar is at the level of pubis that can be easily concealed with the under clothings.
Other areas that can be also be contoured by similar excision of excess skin and fat
are arms (brachioplasty), thighs (thighplasty), flanks (flankplasty), buttocks, lower back etc.
These are less popular as they do produce significant unaesthetic scars.
Face Lift
The facelift or rhytidectomy is designed to excise excess skin and reposition the
sagging soft tissue of the face. The process of facial aging represents a combination of
gravitational effects and aging of the skin itself. Gravity affects all tissue layers resulting in
brow ptosis, hollow infraorbital regions, nasolabial folds, jowls and submental skin excess.
Aging of the skin itself is manifested by fine wrinkles and irregular pigmentation. Facelift
addresses only the effects the gravity. It is not a treatment for fine wrinkles which need to be
tackled with chemical peel or laser resurfacing after the patient has recovered from the
facelift operation.
Technique
The procedure may be performed under general or local anaesthesia with
i.v.sedation. The face and neck are infiltrated with 0.5% lidocaine with 1:200,000
epinephrine. The standard incision begins in the temporal scalp 5cm above the ear and 5cm
behind the hairline, curves down parallel to hairline towards the root of the helix, along the
preauricular skin crease, curves posteriorly under the earlobe and along the posterior sulcus
of the ear terminating in the hair bearing scalp over mastoid. This incision allows the
44
elevation of cheek and neck flap which is advanced postero- superiorly to resect an effective
ellipse of facial and scalp skin.
The cheek flaps can be elevated in the subcutaneous plane (subcutaneous face lift)
down the neck to the level of hyoid. Quite often, the superficial muscular aponeurotic system
(SMAS) which is continuous with platysma muscle below is elevated as a separate layer,
transposed postero-superiorly (SMAS-platysma face lift). The SMAS layer may be dissected
alongwith the skin flap (composite face lift). After excess SMAS and skin is excised, the
SMAS is sutured to the fascia anterior to the ear and over the mastoid process. Ancillary
techniques often used with the face lift procedure include suction assisted lipectomy of the
face & submental fat, direct submental lipectomy through an incision beneath the chin,
excision of redundant medial platysma borders & or suturing them in the midline.
Complications
Possible complications include haematoma, skin slough in pre & postauricular region
& injury to facial nerve branches.
Forehead Lift / Brow Lift
The primary indications for forehead/brow lift are forehead/brow ptosis & lateral
upper lid ptosis. However, the procedure also helps to improve transverse forehead lines,
deep vertical glabellar creases and transverse lines at the root of the nose. It should be
noted that these lines/creases can never be eliminated.
The procedure is usually performed under local anaesthesia, either through a coronal
incision or through two separate elliptical incisions just above the brow. Recently,
endoscopic approach to forehead & brow has become popular. Through three small ports
made in the temporal & frontal scalp regions, the brow musculature is altered by resection of
corrugator & procerus muscles in the nasofrontal region & then the forehead/brow is
elevated. The potential complications are haematoma and injury to supraorbital &
supraorbital nerves. Injury to frontal branch of facial nerve leads to inability to elevate the
forehead & eyebrow on ipsilateral side.
Blepharoplasty
Facial aging can result in laxity of the soft tissues of the eyelids leading to formation
of the bags under the eyes. Excessive upper eyelid skin may reduce the visual field on
superior gaze. Excision of this excess fat & skin from the upper & lower eyelids is
accomplished in blepharoplasty to give the eyes a more youthful appearance. The incision
45
Chemical peeling or chemexfoliation is indicated for correction of fine facial wrinkles &
hyperpigmented areas. Although various chemical agents in suitable concentrations are
being used, the goal remains the same i.e., to produce a predicable & uniform injury
followed by uncomplicated normal wound healing and rejuvenation. The most common
chemicals used are trichloroacetic acid (TCA), phenol and glycolic acid. By gradually
increasing the concentration of TCA from 10% to 50%, the depth of destruction
increases correspondingly (10%-25% TCA : superficial peel, 25%-40% TCA : medium
depth peel, >40% TCA : deep peel). Higher concentrations have exceedingly high risk of
scarring. The facial skin feels tight and drawn over the days following the peel. Because
of the mobility of the skin around the mouth, the skin first starts to peel at the oral
46
commissures. The old, dead, recently peeled skin serves as a biologic dressing to the
underlying regenerating skin. It should not be mechanically disrupted. To accelerate the
healing process by maintaining the moist environment, emollients e.g. Vaseline ointment
can be gently applied.
Depending on the depth of the peel, complete healing may require 6-14 days. Following
a chemical peel, sun exposure is to be avoided for several months. The erythema can
persist for several months before the normal skin colour returns.
Hair Transplantation
Hair transplantation / autografting of hair is based on the concept that if a graft is
taken from an area destined to be permanently hair bearing, and is transplanted into an area
of male pattern baldness, it will, after an initial short period, continue to grow hair in its new
site for as long as it would have in its original one.
Three types of hair graft have been described:
a) Standard round grafts: approx. 4-5mm in diameter, contain 10-30 hairs and are
placed into holes punched out with round trephines.
b) Minigrafts: contain 3-4 hairs (small minigrafts) or 5-6 hairs (large minigrafts), obtained
by sectioning strips of donor tissue or large round grafts. If placed into slits made
with scalpel blade, they are referred to as slit grafts. If placed into holes made with
round trpehines, they are referred to as round minigrafts.
c) Micrografts: are 1-2 hairgrafts obtained by sectioning strips of donor tissue or large
round grafts. They are place into holes prepared with 16G needle.
The procedure is usually done under i.v. sedation & field block. Approximately 2mm
subcutaneous tissue is left below the deepest hair bulb to prevent injury to the hair matrices.
The transplanted grafts shed their hairs in 2-6 weeks. New hair growth usually begins
18-20 weeks after surgery. It is approximately 9 months after surgery before the ultimate
cosmetic effect can be actually perceived.
Recent developments
Endoscopic plastic surgery
The increased awareness of benefits of minimally invasive techniques in other surgical
specialities has led to the application of endoscopes in plastic surgery. Endoscopic
47
techniques have been applied to a wide variety of both aesthetic and reconstructive
plastic surgical procedures such as face lift, forehead/brow lift, cyst removals, tissue
expander placements, breast augmentation, capsulotomy, miniabdominoplasty, carpal
tunnel release, nerve graft harvest, fascia lata harvest, gracilis muscle/latissimus dorsi
muscle harvest etc. The need to remove excess skin is the most common
contraindication to endoscopic aesthetic surgery procedures.
Laser resurfacing
Conventional treatment of fine wrinkles and sun damaged skin includes dermabrasion
and chemical peeling. Recent advances in CO2 laser technology provide a laser
alternative to these modalities. Precise surface tissue ablation allows resurfacing
wrinkles and removal of surface pigmentary lesions. Treatment may be limited to
individual cosmetic units or extended to the entire face. CO2 lasers have also been
effectively used for correction of irregular skin contour after surgical or acne scarring.
The pulsed dye laser (PDL) can be used alone or in combination with intralesional
steroids and silicone sheets to improve hypertrophic scars and keloids. Multiple
treatments are usually required.
Botulinum injection
Botox or botulinum toxin is the neurotoxin derived from the bacteria Clostridia
botulinum. It is the most poisonous substance known and is a potentially potent
bioweapon. A single gram of purified toxin, widely dispersed and inhaled, could kill a
million people. Injected locally in highly dilute therapeutic concentrations, it paralyses a
small area of skeletal muscle. The effect is temporary lasting for 4-5 months only. It is
being used extensively in the West to get rid of wrinkles and creases over the forehead,
periocular and perioral region. Unlike a face lift, where essentially the skin is stretched
taut, botox paralyses the underlying facial muscles responsible for causing creases /
lines & various facial movements. There has been growing concern regarding the
diminished ability of facial expression in an extensively botoxed patient.
Injectable Fillers
As we age, the cumulative effect of aging, sun exposure, gravity and years of facial
muscle movements inevitably lead to the development of wrinkles and creases over
various parts of the face. The underlying tissues that keep our facial skin smooth and
plumped-up, giving youthful appearance gradually breakdown, leaving fine wrinkles
especially over the upper lip, forehead, lower eyelid and perioral region. Facial creases
48
gradually form over the various parts viz. around the oral commissures (laugh/smile
lines), around lateral orbital commissure (crow's feet), transverse creases over forehead
and vertical creases in between the eyebrows (frown lives), at the junction of cheeks and
lips (nasolabial folds) etc. These give the face an aged, tired and sunken appearance.
Several injectable materials have been used for the purpose of soft tissue augmentation
over past few years. These 'soft tissue fillers' help in temporarily smoothing these lines
and creases, restoring youthful, fuller and fresh look to the face. Fillers can also be used
to add fullness to the lips and cheeks. Most commonly used substances while are being
used as injectable fillers are collagen (Zyderm, Zyplast, Surederm etc.) and hyaluronic
acid gels (Restylane, Sheba, Perlane etc). Other substances which have also been tried
as fillers are silicone, fat, 'Goretex' implants etc. Injectable fillers may be used alone or in
conjunction with a resurfacing procedure (laser treatment) or a recontouring surgery
(facelift, browlift etc.) However, injectables alone can not alter the facial contours the way
surgery can.
The most important fact to remember about fillers is that the results are not permanent.
The longevity ranges from 3-12 months. The injected material gets eventually
metabolized by the body making repeat injections mandatory to maintain the rejuvenated
appearance.
Contour threads
Contour threads are specifically designed barbed sutures, made of clear polypropylene
and are used for the elevation & fixation of mid-face, brow & neck areas. The procedure
can be performed under local anaesthesia with i.v.sedation. By gently shifting the
sagging tissues in the upward direction, this minimally invasive technique restores a
youthful appearance while preserving & enhancing the natural contours of the face. It
should be noted that this technique is not a replacement of the conventional face lift
procedure.
Suggested Reading
Aesthetic Rhinoplasty
Daniel, R.K. (ed.) Aesthetic Plastic Surgery-Rhinoplasty, Boston: Little, Brown and Co., 1993.
nd
Sheen, J.H., Sheen, A.P. Aesthetic Rhinoplasty, 2 ed. St. Louis, Mosby, 1981
49
Augmentation Mammoplasty
Slavin, S.A., and Golywyn, R.M. Silicone gel implant explanation: Reasons, results and
admonition, Plast Reconstr. Surg. 95:63,1995.
Young, V.L., Nemecek J.R., and Nemecel, D.A. The efficacy of breast augmentation: breast size
increase, patient satisfaction and psychological effects. Plast. Reconstr. Surg. 94:959, 1994.
Reduction Mammoplasty
Georgide, N.G., et al. Reduction mammoplasty utilizing an inferior pedicle nipple areola flap. Ann.
Plast. Surg. 3:211, 1979
Pitman, G.H. Liposuction & Aesthetic Surgery. St. Louis: Quality Medical Publishing, Inc., 1993.
Pitman, G.H., Aker, J.S., Tripp, Z.D. Tumuscent liposuction: a surgeons perspective.
Clin.Plast.Surg. 23:633, 1996.
Greenbaum, S.S., and Lask, G.P. Aesthetic Dermatology. New York: McGraw-Hill, 1991
Hair Transplantation
rd
Unger, M. Scalp Reduction. In Unger, W. (ed.), Hair Transplantation.(3 ed.), New York: Marcel
Dekker, 1995,pp509-569
50
Burn injuries are a major health hazard throughout the world. On a rough estimate,
they are approximately six million burn injuries annually in our country. Out of this, half to
one million patients require hospitalization.
First aid
As for any trauma, first aid measures at the scene of accident may prove life saving
or at least restrict the morbidity.
Damage due to heat is directly proportional to the temperature of the burning agent
and also to the duration of contact. The objective is to bring down the skin temperature to
normal in as short a time as possible. Damage due to thermal trauma can be minimized by
removing the victim from the scene of fire, by pouring large amounts of tap water and by
removing smoldering clothes and rolling on the ground can also help in extinguishing fire, but
covering with a blanket is not advisable as it tends to retain heat. When inhalation injury is
suspected, the patient must be brought out in the open and airway patency must be assured
and oxygen is administered on the way to the hospital. When old people get burnt in their
house most of the time there is no body at home to remove them from the burning process
and they are not swift enough to rush out in the open. This often leads to extensive burns
and inhalation injury in these cases.
Injury due to chemicals can be limited by prolonged washing under running tap
water. No time is wasted in looking for an antidote. In electrical burns the current source is
switched off. In case of cardiac arrest the victim is given cardio-pulmonary resuscitation.
No household remedy or topical agent is applied at the burned site lest evaluation of
depth become difficult. The patient is covered with a clean sheet, reassured and taken to
the hospital.
Initial assessment
In the hospital, burn wound has to be evaluated for depth, and the extent in relation to
the total body surface area (TBSA). An assessment is also made of the associated injuries
of the chest, abdomen, bone and central nervous system. This is important:
(i)
51
(ii)
(iii)
(iv)
to spell out prognosis with regard to survival, expected time of healing, need for
surgical interventions etc.
In addition, many burn patients requiring admission are medico-legal cases, and in them,
recording the history accurately the local police station has to be informed.
Estimating burn size
Burns in adults are commonly estimated by
Wallaces Rules of Nine. According to this, the
head and neck constitute 9%, each upper
extremity is 9%, each lower extremity is 18%, the
anterior and posterior trunk are 18% each, and
the genitalia is 1%. As a general rule, for
measuring irregular and scattered areas in all age
groups, patients own palm represents 1% TBSA.
(Fig No. 1)
partial thickness
(ii)
full thickness.
In partial thickness burns only a part of dermal thickness is burned and these wounds heal
by spontaneous epithelialization. On the contrary, the entire thickness of dermis is burned in
a full thickness injury and this invariably requires skin grafting. According to another
52
classification, (table 1) the burn wound can be graded into degrees depending on the
depth of dermis involved.
Table 1: Classification of Depth of Burns
Burns
Histology
Features
Depth
First degree
Epidermis
Erythema only.
Partial
thickness
Grade I
Second degree
Epidermis &
Partial
-superficial dermal
papillary dermis
formation.
thickness
Grade II
-deep dermal
Epidermis,
Grade IIIa
appearance.
Partial
part of reticular
thickness
dermis
Third degree
Entire thickness
Full
Grade IIIb
of skin
thickness
53
Admission criteria
It is convenient to categorize patients as minor, moderate or critical for the purpose of
establishing admission criteria.
Critical burns
(1) Partial thickness burns > 25% TBSA (total body surface area)
(2) Full thickness burns >10%
(3) Burns of special sites like hands, face and perineum.
(4) Burns with associated injury or any pre-existing illness and old age.
(5) Electrical burns.
(6) Burns complicated by respiratory tract involvement.
Moderate burns
(1) Partial thickness burns 15-25% TBSA
(2) Full thickness burns 1-3% TBSA
Minor burns
(1) Partial thickness burns <10-15% TBSA.
Patients with minor burns are managed as outpatients. All other patients are admitted; the
critically burned are preferably admitted to a specialized burn facility.
Management
On admission patients are given tetanus prophylaxis.
Analgesia
Superficial burns with exposed nerve endings are painful whereas full thickness burns
are insensitive because all nerve endings get destroyed.
restlessness seen in a majority of patients with extensive burns is not due to pain but is a
result of hypoxemia which develops due to hypovolemia or inhalation injury. Only after
this has been corrected the patient is given analgesics and sedatives. Injection
morphine, pethidine or pentazocine in small titrated doses may be given by intravenous
route as intramuscular absorption may be unpredictable in a shock patient.
54
Respiratory support
There can be a direct thermal damage to the upper respiratory tract, a parenchyma damage
following inhalation of smoke or intoxication by toxic agents like CO, CO2, and HCN etc. It is
suspected in patients with burns in enclosed area involving head and neck and who develop
hoarseness, cough, and wheezing and produce carbonaceous sputum. The diagnosis is
established by arterial blood gas analysis, by measuring carboxy-haemoglobin levels and by
fiber-optic bronchoscope.
Role of steroids in inhalation injury is controversial.
inflammatory response they also decrease the immunity and delay wound healing which are
already compromised because of old age.
Management of Upper Airway Involvement:
Thermal damage
Head & neck burn and stridor:
Resp. Rate:
Adult:
Mode:
initially on SIMV
FIO2:
Initially at 100%
PEEP:
7.5 cm H2O
Inspiratory: Expiratory:
6-20
Child:
12-35
1:2
55
Fluid therapy
Following burn injury there occurs an increased capillary permeability, which leads to
leakage of protein rich plasma like fluid into the extracellular space. In extensive burns
(involving > 30% TBSA) this phenomenon is not limited to the burnt area alone but also
occurs throughout the body. Capillary integrity gets restored within 24 hours of injury. In
the cases of geriatric burns it is mandatory to start fluid resuscitation in all injuries > 5%
TBSA as they have reduced blood volume and oral intake is generally inadequate.
Restoration of the blood volume is the single most important factor essential to the
survival of a burned patient in the initial period. Effective fluid therapy aims at restoring
blood volume, maintaining acid-base and electrolyte balance, and preventing organ
dysfunction.
Several fluid regimens have been advocated but they all need to be
A venesection may be
necessary in the critically ill and it should preferably be done through an unburnt
area.
(3) Fluid requirements are calculated from the time of burns and not from the time of
starting therapy.
(4) The initial resuscitation should be with a sodium containing solution e.g. Ringers
lactate for normal saline.
(5) Fluid requirements may be calculated by any one of the many available formulae.
The most popular formula today is Parklands. According to this, in the first 24
hours following burns, Ringers lactate solution is infused in a volume 4
ml/kg/percent of burn surface area.
transfused in first eight hours and each quarter volume in subsequent eight-hour
period respectively.
56
(6) In the second 24 hours, the fluid requirements are approximately half of the first
day. If Parklands formula has been used initially the resuscitation is continued
with 5% dextrose solution. Plasma, albumin or any other colloid (e.g. dextran etc.)
may be given during this period in doses of 0.3-0.5 ml/kg/percent of burn surface
area.
(7) Blood transfusions are not required in the first 48 hours unless the patient was
severely anaemic before getting burned. After this period, blood may be given to
maintain hematocrit between 30-35% and a hemoglobin level more than 10 g/dl.
(8) Additional potassium is never required in first 24048 hours because injured and
burnt cells release potassium.
Hematocrit
should be maintained around 35% with hemoglobin labels more than 10-11 gm%. Acidbase balance is monitored by arterial blood gas analysis. This is necessary in patients
with more than 50% TBSA burns, and in cases of inhalation injury and septicemia.
57
As a
58
penicillin should be given prophylactically for first few days following burns but with
changing wound flora and with emergence of new strains even this has been
discontinued at a majority of centres.
Rountine bacteriological monitoring of the burn wound is carried out with surface swab
cultures and burn wound biopsies. Local signs of burn wound sepsis include
development of black or purple necrotic areas in the wound and hemorrhage in subeschar area.
Pseudomonas, Kledsiella, sSaph, aureus, Strep.fecalis, Proteus and E coli. Fungi and
viruses are also being increasingly isolated. Septicemia in burns can also result by
invasion of bacteria from the respiratory tract, indwelling cannulae, urinary tract and
sometimes by transmigration of bacteria from the gastro-intestinal tract. Whereas no
clinical sign is diagnostic of septicemia, it is clinically suspected with a change in
condition of the wound, presence of hyper or hypothermia, deterioration in the level of
consciousness, tachypnea, tachycardia, abdominal distension, diarrhoea and oliguria.
Although, infection is accompanied by fever and leukocytosis, burn wound sepsis may
manifest as hypothermia with leukopenia. Blood is also sent for culture and sensitivity
tests if the patient is suspected to be in septicemia.
Systemic antibiotics are the mainstay of treatment of sepsis. If culture-sensitivity reports
are available then treatment is directed towards the identified bacteria.
Otherwise,
59
Enteral route is generally available for nutritional support. Oral feeding is instituted by
third post-burn day and fifth day it is increased to meet the predicted calorie
requirements. In old age the oral intake is limited and a nasogastric tube may be placed,
through which freshly prepared feeds at body temperature can be given as a drip. The
feeds should have 1 Kcal/ml and a low osmolarity (300-700 mOsm/L) or else they will
lead to osmotic diarrhea as the intestinal function is compromised in old age. Parenteral
alimentation or supplements are necessary if the patient is having vomiting, diarrhea,
mal-absorption or prolonged septicemia.
combination of 10-20% dextrose solution, emulsified fats and aminoacid solutions. With
parenteral nutrition patients can develop hyperglycemia and it may be necessary to
provide insulin.
The daily caloric requirement in burn patients can be estimated by Curreris formula:- 60
Kcal/Kg body weight + 35 Kcal/percent burn. Alongwith calories, an adequate amount of
protein has to be given. A calorie : nitrogen ratio of 100-150:1 should be maintained.
Diets calculated in the above manner can lead to positive nitrogen balance and prevent
weight loss. Dietary supplements of vitamins, iron, and trace elements including zinc,
copper, chromium and molybdenum are also important for wound healing and should be
given in therapeutic doses.
Metabolic Modulation
Modulating postburn hypermetabolism for the burned patient is of overwhelming
importance in both the immediate care stage and the rehabilitative stage. Postburn
hypermetabolism cannot be completely reversed but may be modulated by
nonpharmacologic and pharmacologic means. Early burn wound excision and complete
wound closure, prevention of sepsis, the maintenance of thermal neutrality for the patient
by elevation of the ambient temperature, and graded resistance exercises during
convalescence are simple, highly effective modalities. Several anabolic and anticatabolic
agents are available for use during immediate care and rehabilitation. Exogenous,
continuous low-dose insulin infusion, beta-blockade with propranolol, and the use of the
synthetic testosterone analogue oxandrolone are the most cost-effective and least toxic
therapies to date. These greatly assist therapeutic minimization of the loss of lean body
mass and linear growth delay and are effective in burned patients with and without
sepsis. Adverse effects, cost benefits, and the ease of administration and monitoring
must be examined when considering the possibility of their use.
60
antibacterial agents, it is essential that the topical agent used should also effectively
penetrate the eschar for better control of infection at subeschar level, which is actually
responsible for systemic infection. Systemically administered antibiotics cannot reach
sub-eschar level in sufficient concentration to control infection because of impaired
microcirculation in the burn wound. Topical agents used currently are silver
sulphadiazine cream, a combination of neomycin, polymyxin and bacitracin, povidoneiodine or framycetin.
Dressing technique
The wounds are gently cleaned with dilute Savlon and saline. After applying the topical
chemotherapeutic agent the wound is covered with a layer of vaseline gauze. Next,
Gamgee pads (cotton pads sandwiched between layers of gauze) are applied and held
in place with a gentle compressive dressing. The dressings are changed daily. Only in
minor burns the dressings are changed less frequently. Soakage of dressing, foul smell
and fever are indications for an earlier inspection of the wound. Areas like face, peineum
and bottocks are difficult to dress and, are therefore, kept exposed. After cleaning, the
wound is left to dry. The exudate alongwith the superficial layer of burned skin forms a
protective cover under which a partial thickness wound can heal.
Burn wound excision
By conventional dressing techniques, a deep dermal wound heals by hypertrophic
scarring and a full thickness burn is ready for getting after only 4-5 weeks time, leaving
the patient with the attendant risk of septicemia and a prolonged period of negative
nitrogen balance. Improvement in intensive care management has allowed surgeons to
be positively aggressive towards the burn wound. This involves excising the dead skin,
layer by layer, till a healthy tissue is reached which can then be immediately split grafted.
61
Skin grafts can be applied as small stamps, strips and as methods or unmeshed sheets
depending on the availability of the graft. If enough autograft skin is not available the
excised wound is covered temporarily with a skin substitute to prevent plasma loss by
exudation. Burn wound excision is done after the patient has been fully resuscitated but
before significant bacterial proliferation has occurred. This is usually between third and
seventh day following the burn.
experienced team, sufficient operating time, and adequate blood, autograft skin and skin
substitute. While exercising this surgical approach of burn wound management one must
consider the compromised physiological state in old age and most of the time it is
worthwhile to manage the wound conservatively.
Suggested Reading
1. Principles and Practice of Burns Management. Ed. John A. D. Settle, Churchill Livingstone
New York, 1996.
2. Burns A Team Approach, Eds. Artz C. A., Moncrief J. A., Pruitt B. A., W. B. Saunders
Company, Philadelphia, 1979.
3. An analysis of 11,196 burn admissions and evaluation of conservative management
techniques R. B. Ahuja, S. Bhattacharya, Burns : 28 (2002), 555-561.
4. Burns in India: epidemiology and problems in management. Sawhney C. P., Ahuja R.B., Goel
A. Indian J Burns, 1(1993), 1-4.
62
There have been so many advances taking place in the management of breast
cancer in the last decade. However it is not possible to incorporate all the advances in this
small write up. I have tried to incorporate few of the current trends in diagnosis and
treatment of this dreaded disease which will be important to know by practicing surgeons
and post graduate students alike.
Diagnosis
MRI magnetic resonance imaging is not routinely used in the breast diagnosis but it may
be indicated in the following scenarios: (a) evaluation of the integrity of the breast prosthesis
(b) determining the presence of any breast disease in the women with proven malignant
axillary nodes and normal mammography and ultrasound (c) evaluating extent of disease
(multifocality) where this cannot be reliably excluded on conventional imaging: (d) It has
been found useful in screening women with inherited mutations of breast cancer genes
(BRCA1 or BRCA2). Mammography has very poor sensitivity for breast cancer detection in
women with gene mutations. The most recent data from a United Kingdom trial showed MRI
to have a much higher sensitivity than mammography (77% v 40%; P ==0.001).
Digital mammography- Recent evidence indicates that digital mammography is more
sensitive than film mammography in screening women who have dense breasts and women
who are younger than 50 years or are premenopausal or perimenopausal. Potential
advantages of DM include the use of computer-aided detection (algorithm-based computer
programs that alert the radiologist to possible abnormalities on the mammogram), and
allowing centralized film reading.
PET scanning positron emission tomography is currently accepted to be the most
accurate way to stage and monitor cancer. Cancer cells have alterations in the normal
metabolism of the sugar, glucose and have increased glucose uptake and decreased
glucose clearance. Glucose is bound to the positron 18-F to make a compound 18 Ffluorodeoxyglucose, FDG. When injected into a patients blood stream, it is taken up by the
cancer cells at a more rapid rate than normal cells and allows cancers to be seen as hot
spots on the PET scan. It is necessary to curtail any vigorous exercise, just as jogging or
weight lifting, for at least 48 hours prior to a PET scan as the recovering muscles will
continue to take up glucose for about 24 hours. Although positron imaging is very useful in
identifying recurrent metastatic disease, its use for diagnosis of primary breast tumor is not
63
recommended. The tumor size and cell type are factors that affect PET scan accuracy.
Accuracy in detecting tumors larger than 2 cm is high, PET may miss approximately one
third of the invasive cancers smaller than 1 cm. PET and combined PET/CT scanners are
also being used to direct radiation therapy in patients who have localized metastatic disease
in areas such as the chest wall or in bone.
Surgery
Stage I and Stage II breast cancers are early cancers that are not fixed to the skin or
muscle. Modified radical mastectomy continues to be appropriate for some patients but
breast conservation surgery is now regarded as the treatment of choice. The prospective
randomized studies have shown no change in survival when MRM is compared with
conservative surgery plus radiation for stage I and stage II breast cancer.
Trial
Milan cancer institute trial (n = 701)
Institute Gustave Roussay (n = 179)
NSABP B-06 (n=1,843)
National cancer institute (n=237)
EORTC (n- 903)
Danish Breast cancer Group (n=905)
End point
(years)
18
15
12
10
8
6
P value
65
73
63
77
54
79
NS
.19
.12
.89
NS
NS
65
65
59
75
61
82
64
nodes can be found during surgery with a gamma handheld device that identifies the hot
spot representing the node. When dye technique is used the sentinel node is colored blue
for visual identification. The sentinel node can be removed and analyzed for tumor cells. The
positive predictability of the sentinel lymph node biopsy is 96%, with a sensitivity of 89 %.
Thus the sentinel lymph node biopsy can predict whether axillary node metastasis is present
and the need for extensive axillary dissection. Contraindications to sentinel node biopsy
include a clinically positive axillary nodes, prior axillary surgery, pregnancy or lactation,
women who have received preoperative chemotherapy, who have multicenteric and
extensive multifocal carcinoma and who have tumors larger than 5 cm should not have
sentinel lymph node biopsy but directly axillary dissection should be done. Sentinel lymph
node biopsy is an appropriate initial alternative for routine staging to axillary lymph node
dissection for patients with early stage breast cancer with clinically negative axillary nodes.
Completion axillary lymph node dissection remains standard treatment for patients with
axillary metastases identified on sentinel lymph node biopsy. Appropriately identified patients
with negative results of sentinel lymph node biopsy, when done under the direction of an
experienced surgeon, need not have completion axillary lymph node dissection. Isolated
cancer cells detected by pathologic examination of the sentinel lymph node with use of
specialized techniques are currently of unknown clinical significance. Although such
specialized techniques are often used, they are not a required part of sentinel lymph node
evaluation for breast cancer at this time. Data suggest that sentinel lymph node biopsy is
associated with less morbidity than axillary lymph node dissection.
Locally advanced breast cancer
Neo-adjuvant endocrine therapy Neo-adjuvant chemotherapy has been widely
used with patients with locally advanced breast cancer, but there have been relatively few
studies on neo-adjuvant endocrine therapy. The new aromatase inhibitors have significant
advantages over tamoxifen in the neo-adjuvant setting. In one randomized study letrozole
produced a higher response rate than tamoxifen (55% Vs 36%) and higher breast
conservation rates (45% Vs 35%). A higher rate of conversion from mastectomy to breast
conservation surgery with aromatase inhibitors compared with tamoxifen has also been
shown in the trails of anastrazole and exemestane. Patients whose tumors expressed only
low levels of estrogen receptor and those that over expressed the growth factor receptors
HER1 and / or HER2, which are usually associated with a worse prognosis, had a significant
greater chance of responding to letrozole than to tamoxifen. Neo-adjuvant endocrine therapy
can be used in post-menopausal women with larger tumors to avoid mastectomy and to
render operable those tumors that are locally advanced at diagnosis and not suitable for
65
surgery. The optimal duration of therapy remains unclear, but current evidence suggests that
tumor shrinkage with agents such as letrozole continues beyond 3 4 months and treatment
can be continued until cancer has shrunk sufficiently either to become operable or to allow
breast conserving surgery.
Neoadjuvant Chemotherapy -Numerous studies have demonstrated high rates of downstaging with the use of neoadjuvant chemotherapy. Most studies have used doxorubicin- or
epirubicin-containing regimens. Trials using CAF have shown a complete response in 17%
and a pathologically complete response rate of about 7%. However newer trials using
Gemcitabine, epirubicin and paclitaxel (GET) and Gemcitabine, adriamycin and paclitaxel
(GAT) have reported a higher complete response (20%) and pathologically complete
response rates (17% and 15% respectively).
Metastatic breast cancer
Essentially incurable with a median survival time of approximate 2 years from the
documentation of the metastasis. The median survival of the patients with bone and soft
tissue metastasis is more than those compared with visceral metastasis.
Surgery Surgery has no evidence of additional benefit in prolonging the survival of the
patient in metastatic breast cancer. But early assessment of the metastasis to the lung, liver,
brain or sternum may be appropriate for surgical excision. More aggressive treatment
approach may be appropriate for those patients in whom metastatic disease is limited to a
solitary lesion or to multiple lesions at a single organ site. When these patients can be
rendered clinically disease free by local treatment (surgery or radiation), there is a potential
of achieving a complete remission from chemotherapy and patients can remain disease free
for prolonged period. Thus surgery combined with adjuvant therapy, compared with radiation
or systemic therapy alone can result in significantly better survival in breast cancer patients
with metastatic disease in the lung, liver, brain, or sternum.
Local management in bone metastasis External beam radiotherapy in dosage
ranging from 800 1000 cGY (single fraction) to 3000 cGY (10 fractions) in the relief of pain
due to bony metastasis. Patients with disseminated bony disease can also receive hemibody
irradiation 600 cGY for upper hemibody and 800 cGY for the lower half. Patients with
widespread bone metastasis can be treated with phosphorus P32 which has an expected
response rate of 80% or strontium Sr89 which has a response rate of 83%. Strontium is
selectively taken up by the involved bone in the ration of 10:1. At present these two agents
are only approved for treatment of metastatic bone disease.
66
Hormonal
Tamoxifen is the gold standard for receptor positive breast cancer for over 2
decades. Though the agonistic activity of tamoxifen reduces osteoporotic bone fractures, this
property increase the risk of endometrial cancer, including uterine sarcomas, and venous
thromboembolisim.
Aromatase inhibitors - The third generation aromatase inhibitors has changed the algorithm
for the treatment of postmenopausal metastatic breast cancer. Superiority of anastrozole
and letrozole over tamoxifen for post menopausal hormone sensitive metastatic breast
cancer has led to their approval as the first line therapy and made tamoxifen as the second
line therapy of choice.
Fulvestrant,
newer
anti-estrogen
has
been
approved
in
tamoxifen
resistant
postmenopausal metastatic breast cancer. Fulvestrant is well tolerated and the estrogen
receptor down regulation with its use did not preclude response to subsequent hormonal
therapy.
Hormone sensitive premenopausal women with metastatic breast cancer should be
treated with tamoxifen with or without ovarian ablation i.e. oophorectomy or leutinizing
hormone receptor agonists (LHRH-a) like goserelin. The recent mode of treatment is
combination of tamoxifen and LHRH-a. Premenopausal women with metastatic breast
cancer, resistant to tamoxifen and LHRH-a should be treated with megestrol acetate. Nonsteroidal benzothiphene selective estrogen receptor modulator, aroxifene has been tried in a
phase II randomized study in two different dosages (20 mg and 50 mg) with response rate
varying from 10 25 % as per the patient profile.
Chemotherapy Doxorubicin is considered the most active cytotoxic agent in the treatment
of breast cancer, but the popular use in adjuvant setting has increased the likelihood of
anthracycline resistant metastatic breast cancer. In the above setting taxane have become
the current choice of therapy.
Taxanes have been used as a single agent or in combination in metastatic breast
cancer. The two taxanes popularly used are docitaxel and paclitaxel. Pacitaxel in the dosage
80 mg/ m2/wk has shown to be well tolerated, feasible and effective treatment for metastatic
breast cancer. The advantage of weekly regimen is the low incidence of myelosuppression.
Docetaxel is used either as a single agent or in combination with capecitabine; the
combination is shown to be superior to the use of docetaxel alone.
67
68
Bibliography
1. Bapsy.P.P, Sahoo.T.P. Recent advances in the management of metastatic breast cancer.
Indian journal of Medical and pediatric oncology: 19-27: 25(2); 2004.
2. Apantuku L.M. Breast conserving surgery for breast cancer. American Family physician. 1-9:
Dec 15:2002.
3. Gonzaga AG, Robertson C, Bonanni B et al. Preliminary results on safety and activity of
randomized double blind, 2 x 2 trial of low dose tamoxifen and Fenretinide for breast cancer
prevention in premenopausal women. J Clin. Onco. 129-135: 24(1):2006
4. Lyman GH, Giuliano AE, Somerfield MR et al. American society of clinical oncology guideline
recommendations for sentinel lymph node biopsy in early stage breast cancer. J Clin Onco.
7703-7719: 23(30): Oct. 2005.
5. Wu D, G SS. Positron Emission tomography in Diagnosis and Management of Invasive breast
cancer: Current status and future perspectives. Clinical breast cancer. 55-63:4(1):2003
6. Levine EA, Freimanis RI et al. Positron Emission mammography: initial clinical results. Ann.
Surg Oncol. 86-91: 10(1): 2003
7. Clavarezza M, Del Mastro L et al: Taxane containing chemotherapy in the treatment of early
breast cancer patients. Annals of oncology: 22-26:17(7):2006.
8. Mano M, Bordet IJ. Vinorelbine in the management of the breast cancer: New perspectives,
revived in the era of targeted therapy. Cancer treatment reviews. 106-118: 32:2006.
69
Historical Background
Before the mid 19th century, surgical patients commonly developed postoperative
Irritative Fever followed by purulent drainage from their incisions, overwhelming sepsis,
and often death. In 1846 Ignaz Senumelweis (Vienna) reduced the mortality in puerperal
fever from over 10% to under 2% by advocating the practice of rinsing of hands thoroughly in
chlorine water before examining the next patient.
It was in 1860`s Joseph Lister introduced the principles of antisepsis. His work
radically changed surgery from an activity associated with infection and death to a discipline
that could eliminate suffering and prolong life. Louis Pasteur in the latter part of nineteenth
century gave the Germ theory and was able to elucidate the principle that contagious
diseases are caused by specific microbes and these microbes are foreign to the infected
organism. He developed techniques of sterilization and identified several bacteria
responsible for human illness, including staphylococcus, streptococcus and pneumococcus.
During the twentieth century the discovery of effective antimicrobials added another
tool to the armamentarium of Surgeons. Sir Alexander Flemings discovery of Penicillin, the
first effective antibacterial agent subsequently led to the development of hundreds of potent
antimicrobial and these became a critical component to treat aggressive, lethal surgical
infections. In-spite of advances in infection control practice including improved operating
room ventilation, sterilization methods, barriers, surgical technique and availability of
antimicrobial prophylaxis, SSI remains a substantial cause of morbidity and mortality among
hospitalized patients. Emergence of antimicrobial resistant pathogens and the increased
numbers of surgical patients, who are elderly and/or have a wide variety of chronic,
debilitating or immunocompromised conditions, may be a contributory factor. Increased
number of prosthetic implant and organ transplant also add to the risk.
Incidence
Among surgical patients, SSI were the most common nosocomial infection
accounting for 38%. Of all such infections of these SSIs, two thirds were confined to the
incision and one third involved organ or spaces accessed during the operation. Available SSI
surveillance data indicate that laparoscopic operations generally have a lower SSI risk when
contrasted to open operations.
70
Definition
Surgical site infections are infections of the tissues, organs or spaces exposed by
surgeon during performance of an invasive procedure. SSIs are classified as being either
Incisional or organ/space. Incisional SSIs are further divided into those involving only skin
and subcutaneous tissue (superficial Incisional SSI) and those involving deeper soft tissues
of the incision (deep Incisional SSI). Organ/Space SSIs involve any part of the anatomy (e.g.
organ or space) other than incised body wall layers that was opened or manipulated during
an operation. For example, in a patient who had an appendectomy and subsequently
developed an intra abdominal abscess not draining through the incision, the infection would
be reported as an organ/space SSI at the intra abdominal site.
71
Stitch abscess with minimal inflammation and discharge confined to the points of suture
penetration and newborn circumcision site and infected burn wound should not be
included in SSI.
Deep incisional SSI
Infection occurs within 30 days after the operation if no implant is left in place or within 1
year if implant is in place and the infection appears to be related to the operation.
Infection involves deep soft tissues (e.g., fascial and muscle layers) of the incision. The
patient has at least one of the following signs or symptoms: fever (>38 deg. C), localized
pain, tenderness. Deep incision spontaneously dehisces or is deliberately opened by a
surgeon with a purulent drainage or evidence of an abscess or infection involving the
deep incision on radiological examination.
Organ / space SSI
Infection involves any part of the anatomy (e.g., organs or spaces), other than the
incision, which was opened or manipulated during an operation with either purulent
drainage from a drain that is placed through a stab wound into the organ/space or
evidence of abscess or infection involving the organ/space that is found on direct
examination during re-operation or by radiological examination.
Microbiology
The distribution of pathogens isolated from SSIs has not changed markedly during
the last decade. Staphylococcus aureus coagulase-negative staphylococci, Enterococcus
slop, and Escherichia coli remain the most frequently isolated pathogens. An increasing
proportion of SSIs are caused by antimicrobial resistant pathogens, such as methicillinresistant S.aurens (MRSA) or by Candida albicans.
Outbreaks or clusters of SSIs have also been caused by unusual pathogens, such as
Rhizopus oryzae, Clostridium perfringens, Rhodococcus bronchialis, Nocardia Farcinica,
Legionella Pneumophilia and Legionella dumoffii and Pseudomonas multivorans. These rare
outbreaks have been traced to contaminated adhesive dressings, colonized surgical
personnel, tap water or contaminated disinfectant solutions.
72
Percentage of Isolates
1986-89
(N=16727)
Staphylococcus aureus
Coagulase-negative staphylococci
Enterococcus spp.
Escherichia coli
Pseudomonas aeruginosa
Enterobacter spp.
Proteus mirabilis
Klebsiella pneumoniae
Other Streptococcus spp.
Candoda albicans
Group D streptococci (non-enterococci)
Other gram-positive aerobes
Bacteroides fragilis
17
12
13
10
8
8
4
3
3
2
-
1990-96
(N=17671)
20
14
12
8
8
7
3
3
3
3
2
2
2
Pathogenesis
Microbial contamination of the surgical site is a necessary precursor of SSI. The risk
of SSI can be conceptualized according to the following relationship.
Dose of bacterial contamination X virulence / Resistance of the host patient= Risk of surgical
site infection
Quantitatively, it has been shown that if a surgical site is contaminated with > 105
microorganisms per gram of tissue, the risk of SSI is markedly increased. However, the dose
of contaminating microorganisms required to produce infection may be much lower when
foreign material is present at the site (i.e., 100 staphylococci per gram of tissue introduced
on silk sutures).
Surgical wounds are also classified on the presumed magnitude of bacterial load at the
time of surgery.
Clean wounds (class I) include those in which no infection is present; only skin microflora
potentially contaminate the wound and no hollow viscus that contains microbes is
entered. Class I D wounds are similar except that a prosthetic device (e.g., mesh or
valve) is inserted.
73
Clean / contaminated wounds (class II) include those in which hollow viscus such as the
respiratory, alimentary, or genito urinary tracts with indigenous bacterial flora is opened
under controlled circumstances without significant spillage of contents.
Contaminated wounds (class III) include open accident wounds encountered early after
injury, those with extensive introduction of bacteria info a normally sterile area of the
body due to major breaks in sterile technique ( e.g., gross spillage of viscus contents
such as from the intestine.
Dirty wounds (class IV) include traumatic wounds in which a significant delay in treatment
has occurred and in which necrotic issue is present.
TABLE 3: Wound class. Representative procedures, and expected infection rates
Expected Infection
rates
Wound Class
Example of cases
Clean (class I)
1.0 5.4 %
Clean/contaminated
(Class II)
Cholecystectomy, elective GI
surgery
2.1 9.5 %
Contaminated
(Class III)
3.4 13.2 %
3.1 12.8%
74
The risk of SSIs for class I wounds varies from approximately 1 to 2% for patients with
low NNIS scores to approximately 15% for patients with high NNIS score (e.g., long
operations and /or high ASA scores).
Patient Characteristics
Patient characteristics possibly associated with an increased risk of SSI include
coincident remote site infections or colonization, diabetes, cigarette smoking. Systemic
steroid use, obesity (>20% ideal body weight), extremes of age, poor nutritional status and
preoperative transfusion of certain blood products.
Contribution of diabetes to SSI, the recent studies show a significant relationship
between increasing levels of Hg Ac and SSI rates, also increased glucose levels
(>200mg/dl) in the immediate postoperative period was associated with increased SSI risk.
Nicotine use delays primary wound healing and may increase risk of SSI. Patients who are
receiving steroids or other immuno suppressive drugs pre operatively may be predisposed to
SSI. In a study of long term steroid use in patients with Crohn`s disease, SSI developed
significantly more often in patients receiving preoperative steroids than in patients without
steroid use.
Severe protein calorie malnutrition is crudely associated with postoperative
nosocomial infections, impaired wound healing dynamics or death. Theoretical arguments
can be made for a belief that severe pre operative malnutrition should increase the risk of
both incisional and organ/space SSI. However an epidemiologic association between
incisional
SSI
and
malnutrition
is
difficult
to
demonstrate
consistently.
Total
parenteralnutrition (TPN) and total enteral alimentation (TEA) have enthusiastic acceptance
by surgeons and critical care specialists. When a major elective operation is necessary in a
severely malnourished patient, experienced surgeons often use both pre and post operative
nutritional support in consideration of the major morbidity associated with numerous potential
complications one of which is organ/space SSI.
Prolonged pre operative hospital stay is frequently suggested as a patient
characteristic associated with increased SSI risk. Pre operative nares colonization with
staphylococcus aureus has been found to be the most powerful independent risk factor for
SSI following cardiothoracic operations as per a recent multivariate analysis. It has been
reported that perioperative transfusion of leukocyte containing allogeneic blood components
is an apparent risk factor for the development of post operative bacterial infections, including
SSI.
75
76
Relative humidity
30 60%
Air movement
From
clean to less clean areas
Air changes
Antimicrobial Prophylaxis
Surgical anti-microbial prophylaxis (AMP) refers to a very brief course of an antimicrobial agent initiated just before an operation begins. The initial dose of antimicrobial
agent should be timed in such a way that the bactericidal concentration of the drug is
established in the serum and tissues by the time the skin is incised and the therapeutic
levels of the antimicrobial agent is maintained in both scrum and tissues throughout the
operation. Antimicrobial agent is selected on the basis of its efficacy against the most
common pathogens causing SSI for a specific operation. AMP is indicated for all operations
that entail entry into a hollow viscus under controlled conditions. Certain clean-contaminated
operations, such as elective colon resection, low anterior resection of the rectum, also
require an additional preoperative protective maneuver called
preparation of the colon, to
empty the bowel of its content and to reduce the levels of live micro organisms. This
maneuver includes the administration of non-absorbable antimicrobial agents in divided does
the day before the operation.
Operative Technique
Rigorous adherence to the principles of asepsis by all scrubbed personnel is the
foundation of surgical site infection prevention. Excellent surgical technique is widely
believed to reduce the risk of SSI. Such techniques include maintaining effective hemostasis
while preserving adequate blood supply, preventing hypothermia, gently handling tissues,
avoiding inadvertent entries into a hollow viscus, removing devitalized (e.g., necrotic or
charred) tissues using drains and suture material appropriately, Eradicating dead space.
Drains placed through an operative incision increase Incisional SSI risk. It appears that SSI
risk also decreases when closed suction drains are used rather than open drains. Closed
77
suction drains can effectively evacuate postoperative hematomas or seromas, but timing of
drain removal is important. Bacterial colonization of initially sterile drain tracts increases with
the duration of time the drain is left in place.
Hypothermia in surgical patients is defined as a core body temperature below 36
degree C, may result from general anesthesia, exposure to cold, or intentional cooling such
as is done to protect the myocardium and central nervous system during cardiac operations.
In one study of patients undergoing colorectal operations, hypothermia appears to increase
SSI risk by causing vasoconstriction, decreased delivery of oxygen to the wound tissue and
subsequent impairment of function of phagocytic leucocytes (i.e., neutrophils).
Appropriate post operative management of incision includes covering of the incision
site with sterile dressing for 24 to 48 hours, Beyond 48 hours it is unclear whether an incision
must be covered by a dressing or whether showering or bathing is detrimental to healing.
Delayed primary skin closure or incision is left open to heal by second intention if it is
considered that the surgical site is heavily contaminated e.g., class III and class IV wounds.
Conclusion
SSI continues to be responsible for considerable postoperative morbidity and
occasional death. Three categories of variables have proven to be reliable predictors of SSI
risk: (1) intrinsic degree of microbial contamination of the surgical site. (2) The duration of an
operation and (3) Host susceptibility. Proper asepsis and good surgical technique can
reduce SSI considerably and as far as possible every surgeon should handle tissue gently,
maintain hemostatis, minimize devitalized tissue and foreign bodies (i.e., sutures, charred
tissues, necrotic debris), and eradicate dead space at the surgical site, avoid hypothermia
and perform the surgical procedure in a reasonable time frame and administer appropriate
ant microbial prophylaxis where ever indicated.
References
1. Nuland SB: The Doctors plague: Germs, childbed fever and the strange story of Ignaz
semmelweis, New York: ww Norton & co., 2003, P 1.
2. Wangensteen OH, Wangensteen SD: Germ theory of infection ad disease; The rise of surgery
from empiric craft to scientific discipline. Minneapolis: University of Minnesota Press, 1978, P-387.
3. Altemeier W A: Manual of control of infection in surgical patients. Chicago: Americal college of
surgeons press, 1976, P-1
4. Horan TC, Gaynes RP, Martone WJ, Jarvis WR, Emori TG, CDC definitions of nosocomial
surgical site infections, 1992 : a modification of CDC definitions of surgical wound infections.
Infect control Hosp Epidemiol 1992; 13 (10) : 606-8.
78
13. Weiss CA 3 , starts CL, Danms RA, et al : Six years of surgical wound infection surveillance at a
fertiary care center. Review of the microbiologic and epidemiological aspects of 20,007 wounds
Arch Surg 134 : 1041, 1999.
14. Roy MC, Herwaldt LA, Embrey R, et al : Does the centers for Disease controls NNIS risk index
stratify patients undergoing cardiothoracic operations by their risk of surgical site infection. Infect
control hosp Epidemiol 21:186, 2000.
15. Valentine RJ, Weigett TA, Dryer D, Rodgers C, Effect of remote infections on clean wound
infection rates.
16. Gordon SM Serley TM, Barr C, Cosgrove D, Potts W, The relationship between glycosylated
haemoglobin (hg 1c) levels and postoperative infections in patients undergoing primary coronary
artery bypass surgery (CABG)- Infect control Hosp Epidemiol 1997: 18 (No. 5, part 2) : 29 (58).
17. Terranova A; The effect of diabetes methtuson wound healing. Plast. Surg. Nurs 1991; 11(1):205.
18. Ziv Y Church JM, Fazio VW, King TM, Laveryl C. Effect of systemic steroids on ileal pouch-aval
anastomosis in patients with ulcerative lolitis. Dis colon rectum 1996; 39 (5); 504-8.
19. Shukla HS, Rao RR, Banu V, Gupta RM,Yadav RC, Enteral hyperalimentation in malnounished
surgical patients. Indian J Med Res 1984; 80: 339-46
20. Moore EE, Tones TN, Benefits of immediate fesunotomy feeding after major abdominal trauma- a
prospective, randomized study. J Trauma 1986; 26: 874-81.
21. Mishriki SF, Law DJ, Jeffery PJ, Factors affecting the incidence of post operative wound infection.
J Hosp. Infect 1990, 16:223-30.
22. Kluytnans TA, Izerman EP, Vandenbroucke- Grauls CH, Maat AW, Wayenvoort JH, et al. Nasal
carriage of staphylococcus aureus as a major risk factor for wound infections after cardiac
surgery. J Infect Dis 1995; 171:216-9.
23. Vamvakas EC, Carven JH, Hibberd PL, Blood transfusion and infection after colorectal cancer
surgery, Transfusion 1996; 36:1000-8.
24. Seropain R, Reynolds BM, Wound infections after preoperative depilatory versus razor
preparation, An J surg, 1971; 121:251-4.
25. Hardin WD, Nichols RL, Hand washing and patient skin preparation. In : Malangoni MA, ed.
Critical issues in operating Room Management, Philadelphia :Lippincott-Raven; 1997. P 133-49.
26. Babb JR, Davies JG, Ayliffe GA. A test procedure for evaluating surgical hand disinfections. J
Hosp Infect 1991:18(suppl B) :41-9.
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27. Materson BJ. Cleansing the surgeons hands. Scientific American surgeon.1996; 2:3-9.
28. Association of operating Room Nurses. Standards, Recommended practices, Guidelines
Denver: Association of operating room nurses; 1999.
29. American Institute of Architects. Guidelines for design and construction of hospital and health care
facilities. Washington (DC) : American Institute of Architects press; 1996.
30. Nichols RL. Surgical antibiotic prophylaxis, Med clin North AM 1995; 79 (3): 509-22.
31. Clarke JS, Condon RE, Bartlett JG, Gorbach SL, Nichols RL,Ochi S, Preoperative oral antibiotics
reduce septic complications of colon operations:results of prospective, randomized, double blind
clinical study. Ann Surg. 1977;186:251-9.
32. Concon RE, Bartlett JG, Greenlee H. Schutte WJ, Ochis, Abbe R, et al. Efficacy of oral and
systemic antibiotic prophylaxis in colorectal operations. Arch Surg 1983; 118:496-502.
33. Hunt TK, Hopf HW, Wound healing and wound infection. What surgeons and anaesthesiologists
can do. Surg clin North AM 1997; 77:587-606.
34. Buknall TE. Factors influencing wound complications : a clinical and experimental study. Ann r
coll. Surg Engl 1983; 65: 71-7.
35. Drink water CJ, Neil MJ. Optimal timing of wound drain removal following total joint arthroplasty. J
Arthroplasty 1995; 10(2) :185-9.
36. Kurtz A, Sessler DI, Lenhardt R. Perioperative normothermia to reduce the incidence of surgical
wound infection and shorten hospitalization. Study of wound infection and temprature group. N
Engl J Med 1997; 334(19) :1209-15.
37. Wenisch C, Narzt E, Sessler DI, Parschalk B, Lenhardt R, Kurtz A, et al. Mild intraoperative
hypothermia reduces production of reactive oxygen intermediates by polymorphonuclear
leukocytes. Anaesth Analg 1996;82:810-6.
38. Morain WD, Colen LB. Wound healing in diabetyes methitus. Clin plast surg 1990;17:493-501.
80
Surgical site infections (SSI) are the most common nosocomial infections in surgical
patients and remain a major source of postoperative morbidity. Surgical site infections are
common surgical complication occurring in about 3% of all surgical procedures and up to
20% of patients undergoing emergency intra-abdominal procedures. While many
environmental measures can be taken to reduce the risk of postoperative infections (Table
1.), there is no debate on the role of antimicrobial agents in surgical patients to prevent and
treat postoperative infections.
Table 1: Measures used to prevent surgical site infections
a) Preoperative showers with disinfectant soap
b) Skin disinfection
c) Theatre environment
d) Gloving and hand wash techniques
e) Elimination of nasal carriers
f)
An increased rate of surgical site infection above the hospital or national averages suggests
a need of investigations of ones preoperative preparation, operative technique,
postoperative wound care and operative room protocols and sterile processing.
Perioperative antibiotic administration has been defined on the basis of the relation
between the time of first dose of prophylactic antibiotics and the time of initial surgical
incision1.
Postoperative if it occurred more than 3 hours after incision but less than 24
hours after surgery
81
For this discussion, it is presumed that antimicrobial agents can be administered in surgical
patients at three levels
b) Preoperative antibiotics : Prophylactic antibiotics
c) Intraoperative antibiotics: Continued prophylaxis during prolonged procedures and
major blood loss
d) Postoperative antibiotics: Prolonged prophylaxis or treatment of wound infections
Optimal use of prophylactic antibiotics is the subject of majority of studies and
discussions on the subject of use of antibiotics in surgical patients. Valid reasons for
administration of prophylactic antibiotics include a significant decrease of SSI or reducing a
risk of SSI in procedures where the consequences of infections are serious or disastrous.
It is important to know classification of surgical site infections and stratification protocols
in order to understand prophylaxis.
Classification of surgical site infections
Superficial incisional:
Deep incisional
Involves fascial/muscles
Organ/Space
urinary tracts are not entered); Are primarily closed; and if necessary, drained with
closed drainage.
2. Clean contaminated (respiratory, alimentary, genital and uninfected urinary tracts are
entered under controlled conditions and without unusual contamination.
3. Contaminated wounds include open, fresh and accidental wounds
82
4. Dirty or infected wounds include old traumatic wounds with retained devitalized
tissue. Involve existing clinical infection or perforated viscera.
It was suggested that, without prophylactic antibiotics, clean wounds had an infection rate of
less than 5% and dirty wounds had a much higher chances of infections.
But later studies suggested that results using this classification were variable and few
intrinsic variables were identified. Based on this, CDC National Nosocomial Infection
Surveillance (NNIS) derived index 3(Table 5) was proposed to stratify surgical wound
infection data. NNIS uses American society of Anesthetist (ASA) classification (Table 3),
surgical wound class (Table 2) and duration of procedure (Table 4).
Table 3:. ASA Score
I.
II.
III.
IV.
V.
Moribund patient who is not expected to live for more than 24 hours with or
without operation
NNIS (Table 5) did not recommend specific guidelines for use of prophylactic
antibiotics. Currently CDC recommends prophylactic antibiotics for operations associated
with high risk of infection or in those where occurrence of an infection is associated with
severe consequences. These are nonspecific and leave the determination of who needs
prophylactic antibiotics to the surgeons.
Depending upon the results of these studies and recommendations of various societies,
procedures for which antibiotic prophylaxis is generally recommended have been identified:
a) Clean-contaminated and contaminated operations (risk of infections > 5-30%)Colorectal; Appendectomy; Oesophageal; Gastroduodenal high risk; Small intestinal;
Biliary high risk; Gynecological- hysterectomy, high risk caesarian section, second
trimester and high risk first trimester abortion; and Head and neck procedures
involving incisions through oropharynx.
b) Clean operations (risk of infections is low but consequences are serious)- Cardiac
procedures with median sternotomy; Noncardiac thoracic- pulmonary; Craniotomy;
83
Description
COLO
CHOL
HPRO
Arthroplasty of Hip
LAM
CBGB
CBGC
CSEC
Cesarean section
Points
Clean or clean contaminated
Contaminated or dirty/infected
1 or 2
3, 4 or 5
84
0
1
Current guidelines also suggest procedures where prophylactic antibiotics are not
indicated: Peripheral vascular carotid artery and vein surgery; surgery of spine without
prosthesis; most plastic surgery and urological procedures with sterile urine.
No statistically significant decrease in infection rate was demonstrated by us using
prophylactic antibiotics, regardless of the NNIS classification in clean general surgery
cases4.
Low risk endoscopic procedures like cholecystectomy and arthroscopic surgery do
not require prophylaxis but in contaminated laparoscopic procedures such high risk
cholecystectomy and bowel surgery it is better to administer prophylactic antibiotics as per
guidelines for similar open procedures.
Microbiology
The pathogens isolated from infections differ, primarily depending on the type of
surgical procedure. In clean surgical procedures, in which the gastrointestinal, gynecologic,
and respiratory tracts have not been entered, Staphylococcus aureus from the exogenous
environment or the patient's skin flora is the usual cause of infection. In other categories of
surgical
procedures,
including
clean-contaminated,
contaminated,
and
dirty,
the
polymicrobial aerobic and anaerobic flora closely resembling the normal endogenous
microflora of the surgically resected organ are the most frequently isolated pathogens.
Choice of antimicrobial agent
Characteristics of ideal prophylactic antibiotic5 are:
a) Has the necessary spectrum of activity and is active against the pathogens
causing postoperative surgical site infections in patients
b) Reaches adequate concentrations in the tissues of the operative field
c) Has half-life that permits single dose injections
d) Can be given by bolus injection at induction of anaesthesia
e) Has no adverse effects associated with short term administration
f)
Is not allergenic
j)
Is not expensive
85
Ideally, data on the sensitivities of the bacteria from human commensal flora in the
same geographical area should be used. If possible data from hospital infection surveillance
programme should be used to monitor resistant patterns of pathogens causing SSI. As most
incisional surgical infections are caused by Staphyloccocus aureus, activity against S.
aureus is needed for all procedures which require at least one incision through skin.
Cefazolin, a first generation cephalosporin has been considered the drug of choice in most
situations6. A recent Indian study has shown that E coli was the most common
microorganism followed by Ps aureuginosa and coagulase positive S aureus7.
Although cefazolin has limited activity against anaerobes, addition of single dose of
metronidazole provides the same results as higher antibiotics (cefotetan). Since teicoplanin
and vancomycin are the last resource in the treatment of methicillin resistant infections it is
prudent to limit their use prophylaxis in patients who are MRSA or MRSE carriers.
If the oropharyngeal flora is susceptible to penicillin and cefazolin, it is not necessary
for -lactamase inhibitors or drugs with specific activity against anaerobes.
For all procedures whre activity against anaerobes is required, metronidazole can be
combined with cephalosporin. Metronidazole requires slow infusion but no resistance has
developed to it. Second generation cephalosporins like cefotetan or cefoxitin have been
used as a substitute for the combination. Cefotetan has a longer serum half-life than
cefazolin and does not require repeat dose in longer procedures. Amoxycillin-clavulanic acid
inhibits -lactamase producing methicillin sensitive S aureus and S epidemidis. Methicilin
resistant strains are resistant to this combination. Alternative drugs against Staphylococci
are clindamycin and vancomycin. These can be used for patients sensitive to -lactams but
cost factor should be considered.8
Timing and duration of antimicrobial prophylaxis
Protection against infection is maximum when the antibiotic is present in the tissues
before microbial inoculation of the wound occurs. The half life of the drug should be long
enough such that a single dose of antimicrobial drug would ensure adequate concentrations
till the end of the procedure or an additional dose of antibiotic will be required; same would
apply if there is blood loss of more than 2 liters.
Administration of intravenous antimicrobial for prophylaxis has been considered to be
optimal when given about 30 minutes before incision i.e. at time of induction of anaesthesia.
A single dose of antibiotic is considered adequate for most procedures. Administration of
antimicrobial more than one hour preoperatively results in higher infection rate. In addition,
86
infection would be more if the drug was given more than 2 hours preoperatively or at any
time postoperatively.
Many surgeons continue antibiotics for 2-3 days after surgery with the rationale that
surgical wound drains and intravenous catheters might lead to surgical site infections but
there is evidence that this practice does not further decrease the risk of infection9.
Adverse effects of antimicrobial prophylaxis
1. Drug reactions: Any drug used for prophylaxis should not produce adverse events
and should not interact with anaesthetic agents. A carefully history of allergies should
be obtained from the patients. Due to low risk of allergy, cephalosporins are preferred
to penicillins.
2. Development of resistance: Because the development of resistance is associated
with antimicrobial use, prophylactic antibiotics should be used as little as possible,
with drugs with as narrow a spectrum as possible. Preference should be given to
drugs that will not be used in therapy. Third generation cephalosporins eg cefotaxime
and ceftriaxone, ceftazidime and ceftizoxime do not offer any advantage over the first
generation cephalosporins because they are less active against staphylococci.
3. Superinfection: It is defined as a new infection that develops during antibiotic
treatment for original infection. There is an estimated incidence of 2-10% of
superinfections that commonly include fungal infections, antibiotic-associated colitis
die to C. difficile etc.
4. Cost
Antibiotic Prophylaxis before Elective Colon Resection
The human colon and distal small intestine contain an enormous reservoir of
facultative and anaerobic bacteria, separated from the rest of the body by the mucous
membrane. A reliable method of sterilizing the colonic contents has been a goal of surgeons
throughout this century. To substantially reduce septic complications after elective colon
surgery, antibiotics must have activity against both colonic aerobes (e.g., Escherichia coli)
and anaerobes (e.g., Bacteroides fragilis). Today, approaches to mechanical cleansing differ
widely. Modern approaches include standard outpatient mechanical cleansing with dietary
restriction, cathartics, and enemas for a 2-day period, or whole-gut lavage with an electrolyte
solution of 10% mannitol, Fleet's phospho-soda, or polyethylene glycol, done the day before
the operation.
87
Most surgeons use both antibiotics and mechanical cleansing for preoperative
preparation before elective colon resection. Three regimens of oral agents combine
neomycin with erythromycin base, metronidazole, or tetracycline. The most popular regimen
in the United States has been the neomycin-erythromycin base preparation, given only on
the day before surgery, 19,18 and 9 hours before the scheduled start of surgery. Many
recent reports show a decreased rate of infections with a combination of oral nonabsorbable
and intravenous antibiotics which is followed by most surgeons now a days.
Antibiotic Prophylaxis for Appendectomy
The pathologic state of the appendix is the most important determinant of
postoperative infection. Wound infection after appendectomy for perforative or gangrenous
appendicitis is four to five times higher than for early disease. Because the pathologic state
of the appendix often cannot be determined before or during operation, a parenteral
antibiotic agent is recommended as prophylaxis in all patients. Antibiotic prophylaxis is
effective in the prevention of postoperative complications in appendectomised patients,
whether the administration is given pre-, peri- or post-operatively, and could be considered
for routine in emergency appendectomies10. Regimens with activity against both facultative
gram-negative bacilli and anaerobes are more effective than those active only against
aerobes. The use of antimicrobial agents in perforated appendicitis with evidence of local or
general peritonitis or intraabdominal abscess, or both, should be considered therapeutic
rather than prophylactic.
Preventive Antibiotics in Penetrating Abdominal Trauma
Proven role of prophylactic antibiotics in penetrating abdominal trauma is to reduce
incidence of wound infection. Prophylactic antibiotics should be administered prior to the
incision, the duration should be short (less than 24 hours) as no benefit has been shown with
prolonged therapy.
Hollow-lumen
visceral
damage
with
associated
escape
of
endogenous
microorganisms is the main risk factor for postoperative infections after exploratory
laparotomy for penetrating abdominal trauma. A single dose of parenterally administered
antibiotic, given just before abdominal exploration for penetrating abdominal trauma, is
associated with low postoperative infection rate in patients with no observed gastrointestinal
leakage. If gastrointestinal leakage is identified at the time of the operation, continuing the
antibiotic agents for 1 to 3 days is usually recommended. It is important to use antibiotic
88
agents with both facultative and anaerobic activity. Leaving the operative wound open,
packed with saline-soaked gauze, decreases the incidence of postoperative wound infection
in patients at high risk.
Blunt abdominal trauma
Blunt abdominal trauma is associated with a low risk of injury to the microorganismcontaining hollow viscera. Therefore, routine pre-operative administration of antibiotics is not
necessary. Antibiotics are given intraoperatively, if laparotomy discloses transmural injury of
a hollow organ and peritoneal contamination. If intervention is early (< 12 hours) and there is
no evidence of purulent exudate in the abdominal cavity, the antibiotic should be considered
prophylactic and not exceed one dose. Neglected injuries should be treated with antibiotics
for a maximum of 5 days11.
Preventive Antibiotic Use in Traumatic Chest Injuries
Recently published studies have shown the value of parenteral antibiotic prophylaxis
in the prevention of pneumonia or empyema after the placement of a chest tube to correct
the hemopneumothorax associated with chest trauma. In one study, 500 mg of cefazolin was
given intravenously every 8 hours for 24 hours. In the other study, 1 g of cefonicid was
administered every 24 hours until the chest tube was removed, usually before 5 days. In
both studies patients receiving antibiotics had substantially lower infection rates than those
receiving placebos.
Innovations:
New innovations have been combined with established surgical protocols for prevention
of surgical site infections. These include
a) Use of implantable tissue expander shells impregnated with antimicrobials.
b) Use of Octylcyanoacrylate tissue adhesive for wound closure. It has been shown to
be an effective barrier to gram positive and gram-negative motile and immotile
bacteria.
c) An antibacterial suture, wherein polyglactin suture is coated with triclosan an
antibacterial agent, has been shown to inhibit S aureus, S epidemidis and methicillinresistant strains of Staphylococcus.
d) Antimicrobial dressings containing polyhexaguanidine biguanide are also being used
that resists bacterial colonization and reduces bacterial penetration.
89
Use of early enteral feeding combined with viable probiotic bacteria and
polygalactosaccharides has been shown to reduce postoperative surgical infections.
These act by correction of intestinal microbial imbalance cause by surgical stress12.
Postoperative antibiotics
In the present day management protocols, most surgical procedures shall not
require postoperative antibiotics. Whenever postoperative antibiotics are used, the aim of
therapy is to achieve adequate levels at the site of infection. It is again stressed, that
antibiotics do not replace surgical interventions like drainage and debridement of infected
wound. Open drainage may be adequate for most superficial SSIs. Antibiotics are required if
there is evidence of systemic infection (fever and leukocytosis) or cellulitis that extends
beyond two centimetres from incision. Antibiotics are also indicated as an adjunct for various
surgical and medical complications.
For most mild infections, control can be achieved on outpatient basis with the help of
oral antibiotics. But in severe infections, it is necessary to use parenteral antibiotics. Each
patient requiring therapeutic antibiotics should be assessed daily for response to treatment.
If no improvement is seen, one has to reevaluate choice of antibiotics. As the patient
improves, clinician must decide when to stop antibiotic therapy. Although no specific duration
of antibiotic therapy is advised, for most procedures, a general guide is to continue
antibiotics until the patient has shown an obvious clinical improvement based on clinical
examination and has had a normal temperature for 48 hours or more. Signs of clinical
improvement include improved mental status, return of bowel function reduction of
tachycardia and spontaneous diuresis.
Use of antibiotics during "contaminated" or "dirty" procedures is considered therapy rather
than prophylaxis. Treatment rather than prophylaxis is indicated for procedures with obvious
preexisting infection (abscess, pus, necrotic tissue). Depending upon the severity of
infection, antibiotics may be administered for variable duration.
a) Contamination (gastroduodenal peptic perforations operated within 12 hours,
traumatic enteric perforations operated with 12 hours, peritoneal contamination with
bowel contents during elective or emergency procedures, early or phlegmonous
appendicitis or phlegmonous cholecystitis): single dose prophylaxis.
90
91
8. Barie PS, Eachempati SR. Surgical site infections. Surg Clin N Am 2005;85:1115-1135.
9. Coskun H, Erisen L, Basut O. Factors affecting wound infection rates in head and neck
surgery. Otolaryngol Head Neck surg 2000;123:328-333.
10. Andersen BR, Kallehave FL, Andersen HK. Antibiotics versus placebo for prevention of
postoperative infection after appendicectomy. Cochrane Database Syst Rev. 2005 Jul
20;(3):CD001439.
11. Melcher GA, Ruedi TP. Duration of antibiotic treatment in surgical infections of the abdomen.
Blunt abdominal trauma. Eur J Surg Suppl. 1996; (576):59-60.
12. Kanazawa H, Nagino M, Kamiya S, Komatsu S, Mayumi T, Takagi K et al. Synbiotics reduce
postoperative infectious complications: a randomized controlled trail in biliary cancer patients
undergoing hepatectomy. Langenbecks Arch Surg 2005; 390: 104-113.
13. Schein M, Wittmann DH, Lorenz W. Duration of antibiotic treatment in surgical infections of
the abdomen. Forum statement: a plea for selective and controlled postoperative antibiotic
administration. Eur J Surg Suppl. 1996;(576):66-9.
92
Overview
Superior vena cava syndrome (SVCS) is an array of symptoms caused by the
impairment of blood flow through the superior vena cava (SVC) to the right atrium.
Symptoms that prompt suspicion of this syndrome include dyspnea, coughing, and swelling
of the face, neck, upper trunk and extremities. In rare instances, patients may complain of
hoarseness, chest pain, dysphagia, and hemoptysis. Physical signs that may be noted on
presentation are neck vein distention, thoracic vein distention, edema of the face or upper
extremities, plethora, and tachypnea. Rarely, cyanosis, Horner's syndrome, and a paralyzed
vocal cord may also be present.[1]
SVCS is usually a sign of locally advanced bronchogenic carcinoma. Survival
depends on the status of the patient's disease. When small cell bronchogenic carcinoma is
treated with chemotherapy, the median survival times with or without SVCS are almost
identical (42 weeks or 40 weeks). The 24-month survival is 9% in patients without SVCS and
3% in those with the syndrome. When the malignancy is treated with radiation therapy, 46%
of patients who have non-small cell lung cancer experience relief of symptoms compared
with 62% of patients who have small cell bronchogenic carcinoma. The 2-year survival of 5%
is almost the same for both groups.[2]
Most
non-Hodgkin's
lymphoma
patients
with
SVCS
respond
to
appropriate
93
75% of patients have symptoms and signs for longer than 1 week before seeking
medical attention.
Cancer patients diagnosed with SVCS do not die of the syndrome itself but from the
extent of their underlying disease.
94
95
slow enough to allow sufficient collateral circulation, the symptoms and signs may
stabilize and the patient may be comfortable enough to forego further therapy. Shortterm palliation of a symptomatic patient who does not want aggressive treatment may
be achieved by elevating the head and using corticosteroids and diuresis. Although
potentially useful to treat respiratory compromise, there are no definitive studies that
prove the effectiveness of steroids. Diuretics may give symptomatic relief of edema
but can ultimately cause systemic complications, such as dehydration.[18][19]
Radiation therapy
If the obstruction of the SVC is caused by a tumor that is not sensitive to
chemotherapy, radiation therapy should be given. Treatment with larger fractions of
radiation is thought to be beneficial in developing a rapid response. One study
shows, however, that there is no obvious need for large radiation fraction sizes for
the first few radiation treatments as was previously believed.[20] Many fractionation
schemes have been used, with doses ranging from 30 Gy in 10 fractions to 50 Gy in
25 fractions. Relief of symptoms in small cell lung cancer is reported to be 62 to 80%,
while in non-small cell lung cancer, approximately 46% of the patients experienced
symptomatic relief.[21][22] In one study, more than 90% of the patients achieved a
partial or complete response with a 3-week regimen of 8 Gy given once a week for a
total dose of 24 Gy.[23]
Chemotherapy
Chemotherapy is the treatment of choice for sensitive tumors such as lymphoma or
small cell lung cancer. SVCS does not appear to be an independent prognostic
factor, and its presence should not be used to change the treatment approach. Rapid
initiation of chemotherapy can result in complete and partial response rates of the
SVCS of more than 80% in small cell lung cancer patients.[21][22]
Thrombolysis
It has been suggested that SVCS arises when a thrombus forms in a partially
occluded vein. In patients with a documented thrombus in the SVC, treatment may
include thrombectomy, with or without tissue plasminogen activator (TPA) or other
thrombolytic agents such as streptokinase or urokinase.[13]
96
Stent placement
There have been numerous small studies using an intravascular expandable stent to
reopen the occluded SVC, however, no prospectively designed comparative studies
have been published.[24] The reported response rates have been about 90% or
greater.[25] There is no agreement on the need for anticoagulant therapy after stent
placement. In one series that used anticoagulant therapy for patients as part of the
treatment protocol, there were reports of reocclusion after this therapy was
stopped.[26] However, in another study, 17 cancer patients who were treated with
stents and who did not have anticoagulant therapy had no occlusions.[27]
Surgery
Surgical bypass of an obstructed SVC is more appropriate for patients with a benign
obstruction than with a malignant obstruction,[28] although surgical bypass has also
been used for patients with malignant obstructions.
Psychosocial Considerations
Patients and family members are often frightened and anxious because of the
symptoms produced by superior vena cava syndrome (SVCS), particularly swelling,
dysphagia, coughing, and hoarseness. It is important to provide information to patients and
family members on the cause of the symptoms and on short-term measures for palliation,
especially during the diagnostic period. When aggressive treatment is declined because of
the terminal nature of the underlying disease, it may be necessary to teach symptom
management approaches to patients and family members.
Because most adult patients who develop SVCS have lung cancer, the treatment and
psychologic support approaches that are developed for SVCS should take into account the
patient's prognosis and psychologic condition and other symptoms caused by the
malignancy.[29]
Pediatric Population
As described in other sections of this summary, superior vena cava syndrome
(SVCS) refers to the symptoms associated with the compression or obstruction of the
superior vena cava (SVC); the compression of the trachea is termed superior mediastinal
syndrome (SMS). Because SMS and the resulting respiratory compromise frequently occur
in children with SVCS, the 2 syndromes have become almost synonymous in pediatric
practice.[30][31] In adults, the trachea and the right mainstem bronchus are relatively rigid
97
structures compared with the vena cava, but in children these structures are more
susceptible to compression. In addition, the relatively smaller intraluminal diameters of a
child's trachea and bronchus can tolerate little edema before respiratory symptoms occur.
Because of this accompanying respiratory component, SVCS in children differs from the
adult syndrome and constitutes a serious medical emergency.
The most common symptoms of SVCS in children are similar to those in adults and
include coughing, hoarseness, dyspnea, orthopnea, and chest pain. Symptoms that are less
common but more serious are anxiety, confusion, lethargy, headache, distorted vision, a
sense of fullness in the ears, and, especially, syncope.[30]
SVCS is rare in children and appears at presentation in 12% of pediatric patients with
malignant mediastinal tumors.[32][33] The etiology, diagnosis, and treatment of SVCS in
children differs from that in adults. While the most frequent cause of SVCS in adults is
bronchogenic carcinoma,[34] in children the most frequent malignant cause of the syndrome
is non-Hodgkin's lymphoma. As in adults, a frequent nonmalignant cause is thrombosis from
catheterization for venous access.[30]
A physical examination, chest radiograph, and the medical history of the patient are
usually sufficient to establish a diagnosis of SVCS. If lymphoma or other malignant disease
is suspected, it is desirable to obtain a tissue sample for diagnosis. However, the procedure
to obtain the specimen may involve significant risk and may not be clinically feasible.
Children with SVCS have a poor tolerance for the necessary general anesthesia because
the accompanying cardiovascular and pulmonary changes aggravate the SVCS, often
making intubation impossible. Also, extubation may be difficult or impossible, thus requiring
prolonged airway provision (intubation). A computed tomography scan of the chest to
determine tracheal size, upright and supine echocardiography, and a flow volume loop may
help evaluate anesthetic risk. Because anesthesia use is a serious risk, the diagnosis should
be made with the least invasive means possible.[35] Published reports suggest a stepwise
approach to diagnosis.[30]
When a malignant mass is the cause of the SVCS, the situation may be a medical
emergency with no opportunity to establish a tissue diagnosis. In these cases, the most
appropriate course may be to initiate empiric therapy prior to biopsy. The traditional empiric
therapy is irradiation, with the daily dose governed by the presumed radiosensitivity of the
tumor. After irradiation, respiratory deterioration from the apparent tracheal swelling may
occur because of the inability of narrow lumens in children to accommodate edema and
because of the greater degree of edema at onset, which is due to the rapid speed at which
98
99
16. Schraufnagel DE, Hill R, Leech JA, et al. Superior vena caval obstruction. Is it a medical
emergency? Am J Med 70 (6): 1169-74, 1981.
17. Shimm DS, Logue GL, Rigsby LC Evaluating the superior vena cava syndrome. JAMA 245
(9): 951-3, 1981.
18. Abner A Approach to the patient who presents with superior vena cava obstruction. Chest 103
(4 Suppl): 394S-397S, 1993.
19. Baker GL, Barnes HJ Superior vena cava syndrome: etiology, diagnosis, and treatment. Am J
Crit Care 1 (1): 54-64, 1992.
20. Chan RH, Dar AR, Yu E, et al. Superior vena cava obstruction in small-cell lung cancer. Int J
Radiat Oncol Biol Phys 38 (3): 513-20, 1997.
21. Urban T, Lebeau B, Chastang C, et al. Superior vena cava syndrome in small-cell lung
cancer. Arch Intern Med 153 (3): 384-7, 1993.
22. Wrschmidt F, Bnemann H, Heilmann HP Small cell lung cancer with and without superior
vena cava syndrome: a multivariate analysis of prognostic factors in 408 cases. Int J Radiat
Oncol Biol Phys 33 (1): 77-82, 1995.
23. Rodrigues CI, Njo KH, Karim AB Hypofractionated radiation therapy in the treatment of
superior vena cava syndrome. Lung Cancer 10 (3-4): 221-8, 1993.
24. Tanigawa N, Sawada S, Mishima K, et al. Clinical outcome of stenting in superior vena cava
syndrome associated with malignant tumors. Comparison with conventional treatment. Acta
Radiol 39 (6): 669-74, 1998.
25. Nicholson AA, Ettles DF, Arnold A, et al. Treatment of malignant superior vena cava
obstruction: metal stents or radiation therapy. J Vasc Interv Radiol 8 (5): 781-8, 1997 SepOct.
26. Dyet JF, Nicholson AA, Cook AM The use of the Wallstent endovascular prosthesis in the
treatment of malignant obstruction of the superior vena cava. Clin Radiol 48 (6): 381-5, 1993.
27. Irving JD, Dondelinger RF, Reidy JF, et al. Gianturco self-expanding stents: clinical
experience in the vena cava and large veins. Cardiovasc Intervent Radiol 15 (5): 328-33,
1992 Sep-Oct.
28. Doty DB Bypass of superior vena cava: Six years' experience with spiral vein graft for
obstruction of superior vena cava due to benign and malignant disease. J Thorac Cardiovasc
Surg 83 (3): 326-38, 1982.
29. Holland JC Lung Cancer. In: Holland JC, Rowland JH, eds.: Handbook of Psychooncology:
Psychological Care of the Patient With Cancer. New York, NY: Oxford University Press, 1989,
pp 180-187.
30. Lange B, O'Neill JA, D'Angio G, et al. Oncologic emergencies. In: Pizzo PA, Poplack DG:
Principles and Practice of Pediatric Oncology. 2nd ed. Philadelphia, Pa: JB Lippincott, 1993,
pp 951-972.
31. Ingram L, Rivera GK, Shapiro DN Superior vena cava syndrome associated with childhood
malignancy: analysis of 24 cases. Med Pediatr Oncol 18 (6): 476-81, 1990.
32. Pokorny WJ, Sherman JO Mediastinal masses in infants and children. J Thorac Cardiovasc
Surg 68 (6): 869-75, 1974.
33. King RM, Telander RL, Smithson WA, et al. Primary mediastinal tumors in children. J Pediatr
Surg 17 (5): 512-20, 1982.
34. Yellin A, Rosen A, Reichert N, et al. Superior vena cava syndrome. The myth--the facts. Am
Rev Respir Dis 141 (5 Pt 1): 1114-8, 1990.
35. Neuman GG, Weingarten AE, Abramowitz RM, et al. The anesthetic management of the
patient with an anterior mediastinal mass. Anesthesiology 60 (2): 144-7, 1984.
100
Bone is the 3rd most common metastatic site, after lung and liver.
Most common primary sites are breast and prostate.
Other primaries - kidney, thyroid cancer and multiple myeloma.
Increasing age and size of population with longer patient survival, increases the incidence
of metastatic lesion to bone.
Incidence
BREAST -
30%
80%
70%-80%
Depends upon areas of increased blood flow venous or arterial - involves axial skeleton
+ribs/ vertebrae/ proximal long bones. Batsons venous plexus- vertebral Cytokinal factors
induced- angiogenesis/ adhesion mol/ invasion/ proliferation/ osteolysis. Tumor also
releases osteolytic factors stim osteoclasts
Clinical Presentation
Asymptomatic.
Patient with metastatic disease to the skeleton most often present with pain as the
principal symptom. Pain has two components :
Biological pain-intermittent,sharp,severe and nocturnal.
Mechanical pain (Mostly in osteolytic lesion)- more constant-appears later
101
Patient with metastatic disease can present with pathological fracture. (Most often occur
with osteolytic lesion). Hypercalcemia, soft tissue mass, deformity or spinal cord
compression.
Medulla most
Also tells about the amount of bone destruction. if 30% of the cortex has been destroyed,
the risk of fracture is high
Radio-Path Types
Osteoblastic or Osteosclerotic- is reaction to the metastasis pattern not to the tumor cell.
- Proportional to rate of growth of metastasis
- Reactionary bone -fragile (normal Harvesian structure absent)
Ca prostate - CAB - GIT Ca- Ca bladder
Osteolytic
Margin -
102
Periosteal reaction
So???
is the Plain x-ray insensitive? - limitations ? Yes but
Plain radiographs are the foundation for evaluating and for surgical planning. Sequential
films correlate best with clinical features. For monitoring response to treatment, local
recurrence and disease progression.
Essential for cancer staging. Early diagnosis as compared to x-ray imaging for symptomatic and asymptomatic lesion
Locates potential sources of referred pain. Can show multiple foci on 85% of SBM. Do
Measures solely the metabolic activity of the bone and not its structural integrity.
CaB 15% have an initial inc uptake
flare phenomenon
-indicates healing response of new bone formation around a quiescent lesion.
- later activity decreases
Has to be combined with plain x-ray/ CT scan
Alternatives
103
very effective in evaluating 3-D integrity of bone and the characteristics of lesion identified
on bone scan.helps in confirming the presence of metastatic disease.Particularly useful
for girdles - shoulder or pelvic- NOT optimal for
Excellent bone marrow evaluation which is the FIRST metastasis bone site.Very useful
for marrow infiltrating lesion lymphoma leukaemias - multiple myl. esp for spine
spinal canal details dural impingement- spinal cord compression .Excellent adjacent soft
tissue involvement.esp D/D- fracture because of osteoprosis metastasis.Imperfect
discriminator so close correlation regd.
Diagnoses
Basic screening
Systemic evaluation
S. electrolytes ,LFT,ESR
Specific tests
Chest radiography and CT scans of chest, abdomen and pelvis identifies 85% primary
site and additional secondary site
PCR or reverse transcriptase PCR (RT PCR)- for specific tumour cell DNA may be used
as a tool for diagnosing marrow or circulating malig cells and thus identifies pts at risk of
metastatic disease and following the response to systemic therapy
can diagnose 1
Addl
sp
tests-PTH
level-
metabolic
bone
disease-serum
beta2 microglobulin-
Fibrous Dysplasia
Osteoblastoma
104
NEMONIC- FOGMACHINES
Most primary tumors- in areas of rapid bone growth - distal femur ,proximal tibia , and
proximal humerus .
- Exceptions to this rule exist - chordoma and osteoblastoma ,enchondroma ,
chondrosarcoma , adamantinoma and simple cysts .
a tumor of a given cell type usually arises
Johnson s metabolic field theory states that
in that metabolic field where the homologous normally cells are most active Thus most
primary tumors develop in metaphysis .Exceptions are chondroblastoma and round cell
tumors .A giant cell tumor arises in the metaphysis but extends into the epiphysis by the
time that it is discovered
Metastases and hemotogenously spread infection often begin in metaphyses where distal
vessels are looped and blood flow is more sluggish , allowing for easier deposit of tumor
or infectious cells
Bx is essential why? Most confirmatory
105
Therapeutic modalities
Systemic Radiation -Surgery
Depends on- -whether solitary or multiple or -symptomatic/asymptomatic
solitary- prefer local form-rad/surg -
Chemotherapy
-Tumour specific anticancer agents
-Bisphosphonates prevent bone reabsorption
in metastasis by osteoclastic inhibition or
apoptosis esp in Ca breast/ multiple myeloma
BM transplantation
Hormone therapy
Immuno therapy
Medications
Bisphosphonates-
inhibit bone resorption, particularly that occurring in certain metastatic lesions of bone.
The goal of chemotherapy and hormone therapy with metastatic disease involving bone
are pain control, disease stabilization and reduction of the risk of morbid skeletal events
18% and 65%
Radiation therapy
106
80% of patients with a limited number of well localized bony metastases can be
treated effectively by external beam irradiation.
antineoplastic effect both relieves pain and allows for healing of the underlying bone
lesion.
Metastatic tumor deposit should be excised under fracture circumstances and in related
instances of bone biopsy, and as part of the treatment of impending fracture and solitary
bone metastasis.
Excision may be intra lesional excision, wide excision or excision plus surgical adjuvant.
Amputation .
Fracture Treatment
Amputation is quite suitable for a distal extremity lesion particularly in the foot. Depending
on the primary diagnosis, amputation may provide an opportunity for extended disease
control of early or solitary metastases.
107
108
The practice of oesophageal surgery has seen a sea change in the last one hundred
years and is particularly so for the management of cancer. In this presentation attempts are
made to put these changes in the right perspective and to focus the phenomenal
developments that are taking place in molecular biology, which may change our strategy to
treat this disease.
The past
When one considers the present practice of anything one should see what our
predecessors have done in this field. It is through this outlook one can better see the future.
The famous statement of Sir Winston Churchill who once said
Farther backward you can
look, farther forward you are likely to see aptly reflects this.
The story of oesophageal surgery is older than the present civilisation as
documented in the Smith Surgical Papyrus (3000-2000 BC) discovered by the American
Egyptologist, Edwin Smithi. The Chinese knew that cancer of the oesophagus could present
with dysphagia more than 2000 years ago. It is amazing that subsequent 2000 years was
quite silent on the art of oesophageal surgery until Czerny; a pupil of Billroth performed the
first oesophageal resection for cancer of the cervical oesophagus in 18771.His patient lived
for a year before succumbing to recurrence. Resection of the thoracic oesophagus had to
wait for nearly 50 more years until the introduction of endotracheal intubation and positive
pressure ventilation. Frank Torek1,ii in 1913 performed the first thoracic esophagectomy for
cancer. His patient lived for 13 long years a feat that can be envied by surgeons even to
day. His patient lived with a cervical esophagostomy and a gastrostomy; the two connected
by a rubber tube. Ohsava and Pfeimister did first intrathoracic anastomosis independently in
1933. In 1943 Richard Sweet introduced the left thoraco-abdominal approach for the first
timeiii. Till then the diaphragm remained a stumbling block to access the chest from the
abdomen because division of the diaphragm was considered unphysiological. A couple of
years later Ivor Lewis introduced the right thoracotomy and laparotomy approach, a practice
followed extensively all over the worldiv. The intrathoracic oesophago-gastric anastomosis
was the ban of oesophageal surgeons for the first half of the 20th century. A leaking
anastomosis was almost always associated with mortality. Sweet provided the earliest
description of a consistent oesophago-gastric anastomosisv. The technique involved
109
removing a small button from the gastric fundus near the greater curvature. The
anastomosis was done in two layers with interrupted fine silk avoiding tension or twist. His
technique achieved a leak rate of less than 5% that is an astounding result in oesophageal
surgery. Even today this forms the gold standard against which other techniques are
compared. McKeown described an alternative solution to the problem of intrathoracic
anastomotic leakagevi. In a Hunterian lecture (1972) he described the three-staged
oesophageal resection and a cervical oesophago-gastric anastomosis. The cervical
anastomotic leakage was considered less problematic. Another advance in the field of
surgery
for
oesophageal
cancer
came
with
the
re-popularisation
of
transhiatal
oesophagectomy by Marc B Orringer (1978). Though Ong had used it earlier in pharyngooesophagectomy for hypopharyngeal cancer but the resurrection of transhiatal approach is
credited to Orringer. Initially described as a reckless blind operation by a person no less than
Ronald Belsey, the procedure has been validated by the results of over 1000
oesophagectomies performed by Orringer with mortality as low as 4% vii. To this list of
pioneers we can add the names of Denk, Nakayama, Akiyama, Belsey, and Skinner for their
contributions during 60s through 80s in the field of surgery for oesophageal cancer.
Despite advances in various fields of medicine the results of treatment of cancer of
the oesophagus remained pretty dismal as is evidenced by the two large reviews in 1980
and 1990.
1980viii
1990ix
2000x
Resectability
39
56
54-69
Mortality
13
4-10
1-year survival
18
27
NA
2-year survival
NA
12
35-42
5-year survival
10
15-24
110
Transhiatal
Axi
Bxii
Cxiii
Dxiv
Mortality
3.3%
6%
8.7%
4.5%
3%
Resectability
90%
89%
98%
68%
5 yr survival
24.7 %
20 %
10%
23%
23%
21%
Local Recurrence
30%
31%
33%
50%
Series
Exv
Fxvi
2%
-
------------------------------------------------------------------------------------------------------------------------It is amply clear there is nothing much to chose between the two. One can employ
any one of these procedures based on his/her personal philosophy, expertise and local
working environment. Our preference is for transhiatal but threshold for conversion to
transthoracic resection is quite low. With this attitude we have the following resultsxvii:
Transthoracic
1. Mortality
2. Resectability
3. 5 year survival
Transhiatal
7.6%
7.9%
81%
28%
32%
111
3-year survival
Bossetxxv
Surgery alone
CT+RT+Surgery
19 months
37%
19 months
39%
18 months
16%
17 months
30%
Urbaxxvi
Surgery alone
CT+RT+Surgery
112
Burmeisterxxvii
Surgery alone
22 months
--
CT+RT+Surgery
19 months
--
Median survival
RTOGxxviii
EORTCxxix
12 months
10 months
2 year survival
42%
20%
5 year survival
25%
10%
Toxicity
64%
--
Thus these results of primary chemo-radiotherapy do not seem very encouraging either.
In the light of all these developments a concept of stage directed surgery emerged.
This is based on the observation that depth of tumour infiltration determines the nodal
spread. Altorki et al (2000) has shown that lymph node involvement occurs in only 4% of
cases in T0 and Tis tumours.xxx The same rises to 30% when the tumour invades the
muscularis mucosae (lamina propria) and 50% if the tumour penetrates the submucosa. In
T2 and T3 lesions the lymph nodal metastasis occurs in 60% and 80% of cases. What
emerges from this is that early stage disease (To, Tis) can be managed with an
esophagectomy or even an endoscopic mucosal resection. It also emerges that not all T1
and T2 lesions have nodal spread. The advent of endoscopic ultra sound with FNA facility
can confirm which patients have no nodal spread. This group of patients
(with tumour
localised to the oesophageal wall; stage1 and stage 2A) can also be adequately treated with
simple esophagectomy. Those with lymph node involvement (stage 2B and 3) are treated
with neoadjuvant treatment. Lightdale has published the results of stage directed surgery as
given belowxxxi:
Treatment
5- year survival
Stage 0
EMR
100%
Stage 1 &2A
Esophagectomy
80%
Stage 2B &3
10%
We at the Institute have in the last 25 years managed surgically more than 1025
cases of oesophageal diseases. Of these 763 were oesophageal cancers (615: squamous
113
cell cancer and 148: adenocarcinoma). With an over all mortality of 10% we have achieved
25% survival at 5 years (unpublished data).
Future
It is quite obvious from the above discussion that despite advances made in the last
century we are nowhere near conquering this disease. It is possible that the attempt so far,
is made only at improving the treatment options without understanding the biologic
characteristics of the disease. Fortunately rapid strides have been made in the field of
molecular biology in the last decade or so. This has helped understanding molecular and
genetic basis of oesophageal cancer better. The immediate fall out of these is to develop
strategies to prevent and detect oesophageal cancer early. Since cure is unlikely attempts
must be made to bring down the incidence or to detect the disease by surveillance of
identified high-risk population.
Molecular biology: several genetic mutations have been identified in cancer of the
oesophagus. Over expression of epidermal growth factor (EGF) has been shown in up to
80% of cases. Nearly half of oesophageal cancer has been found to have transforming
growth factor gene (TGF) expression. Fragile Histidine Triad (FHIT) gene mutation occurs
early in the course of carcinogenesis particularly in Barretts oesophagus in nearly 60-100%
of cases.xxxii Similarly vascular endothelial growth factor (VEGF) expression has been noted
which has been associated with lymph node metastasis and patient survival. We, at the
AIIMS, also have evaluated other genetic markers in oesophageal cancer. These are: over
expression of p53 mutants has been associated with cancer of the oesophagus. Protooncogene Bcl2 with apoptosis inhibition has been detected in these cancers. C-myc gene,
also a proto-oncogene, however, is not associated with anti apoptotic activity. Ets-1 gene, a
proto-oncogene has been shown to have greater penetrating potential with resultant invasive
behaviour.
We have also studied the role of Telomerase activity in multigenetic tumorigenesis.
Matrix metalloprotienase over expression has been shown to be associated in the early
stages of cancer development.
Proto-oncogene: Bcl-2, Cyclin D, Est-1, ERB2, C-myc, VEGF, Rb, EGF, TGF etc.
Tumour suppressor gene/protein: p53, p16, Telomerase, Matrix metalloprotienase, FHIT etc.
Over expression of proto-oncogene has been shown to be associated with high incidence of
metastasis and poor survival. Mutations of tumour suppressor genes are associated with
tumour progression. With gene therapy, scientists have been able to arrest cell cycles of
114
cancer cells by increasing apoptosis. Such approach has been shown improved response to
both chemo and radiotherapy.
It is thus clear now that with the help of molecular biology one can detect malignancy
in the most primitive stage of cancer development: For this, one has to introduce a
surveillance programme to detect high risk group through data driven epidemiological
studies (with the help of the above biomarkers) so that a tumour can be detected even
before overt tumour manifests. These patients can then be managed at a stage early
enough to be cured with surgery. It can even be successfully treated with gene therapy.
Chemoprevention of oesophageal cancer is another area of active research. There is
now evidence that COX2 inhibitor can prevent cancer in Barretts oesophagus.xxxiii Similarly
EGF antagonist can arrest cell proliferation in oesophageal cancer.10
Conclusions
Oesophageal cancer is a lethal disease and surgery continues to be the mainstay of
treatment. Aim of treatment is to achieve symptomatic relief and prolong life. Combined
modality may improve survival? Stage directed treatment?
Future direction: Cure is unlikely; so attempt to bring down the incidence, identify high-risk
group through epidemiological study, subject them to genetic study and endoscopic
surveillance to detect early lesion. Consider targeted therapy like EGF antagonist or COX-2
inhibitor
I will end here with a quotation:
We only see so far because
We stand on the shoulders of giants
Isaac Newton
References
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Deslauriers J, Ginsberg RJ, Hiebert CA, Patterason GA, Urschel HC, eds. Oesophageal
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3. Sweet RH. Surgical management of the carcinoma of the mid thoracic oesophagus. Preliminary
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4. Lewis I. The surgical treatment of carcinoma of the oesophagus with special reference to a new
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5. Sweet RH. Thoracic Surgery. 2
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6. Keown KC. Total three-stage oesophagectomy for cancer of the oesophagus. Br J Surg
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7. Orringer MB, Marshal B, Iannettoni MD. Transhiatal Oesophagectomy: clinical experience and
refinements. Ann Surg 1999; 230:392-400.
8. Earlam R, Cunha-Mello JR. Oesophageal squamous cell carcinoma: A critical review of
surgery. Br J Surg 1980;67:381-90.
9. Muller JM, Erasmi H, Stelzner M, Zieren U, Pichlmaier H. Surgical therapy of oesophageal
carcinoma.Br J Surg 1990;77:845-57.
10. Enzinger PC and Mayer RJ. Oesophageal cancer. NEJM 2003;349:2241-52.
11. Ellis FH Jr. Standard resection for cancer of the oesophagus and cardia. Surg Oncol Clin N Am
1999;8:279-94.
12. Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with
surgery alone for localized oesophageal cancer. N Engl J Med 1998;339:1979-84.
13. Law S, Fok M, Chow S, Chu KM, Wong J. Preoperative chemotherapy versus surgery alone for
squamous cell carcinoma of the oesophagus: a prospective randomised trial. J Thorac
Cardiovasc Surg 1997;114:210-17.
14. Orringer MB,Marshall B, Iannettoni MD. Transhiatal esophagectomy: Clinical experience and
refinements. Ann Surg 1999;230:392-400.
15. Gertsch P,Vanthey JN, Lustenberger AA, Friedlander KH.Long term results of transhiatal
esophagectomy for esophageal carcinoma;a multivariate analysis of prognostic factors. Cancer
1993;72:2312-19.
16. Vigneshwara WT, Trastek VF, Pairolero PC, Deschamps C, Daly RC, Allen MS. Transhiatal
oesophagectomy for carcinoma of the oesophagus. Ann Thorac Surg 1993;56:838-44.
17. Rao YG, Pal S, Pande GK, Sahni, Chattopadhyaya TH. Transhiatal oesophagectomy for benign
and malignant conditions. Am J Surg 2002;184:136-42.
18. Skinner DB, Little AG, Fergusion MK, Soriano A, Staszak VM. Selection of operation for
oesophageal cancer based on staging. Ann Surg 1986;204:391-401.
19. DeVitta, cancer, principles and practice of oncology, 2001.
20. Fok M, Sham JS, Choy D, Cheng SW, Wong J. Postoperative radiotherapy for carcinoma of the
oesophagus: a prospective, randomised controlled srudy.Surgery 1993;113:138-47.
21. Teniere P, Hay JM, Fingerhut A, Fagniez PL. Postoperative radiation therapy does not increase
survival after curative resection for carcinoma of the middle and lower oesophagus as shown by
a multicenter controlled trial. Surg Gynecol Obstet 1991; 173:123-30.
22. Arnott SJ, Duncan W, Gignoux M et al. Prreopereative radiotherapy in oesophageal carcinoma:
a metaanalysis using individual patient data (Oesophageal Cancer Collaborative Group). Int J
Radiat Oncol Biol Phys 1998;41:579-83.
23. Kelsen DP, Ginsberg R, Pajak TF, et al. Chemotherapy followed by surgery compared with
surgery alone for localized oesophageal cancer. N Engl J Med 1998;339:1979-84.
24. Medical Reasearch Council Oesophageal Cancer Working Group. Surgical resection with or
without postoperative chemotherapy in oesophageal cancer: a randomised controlled trial.
Lancet 2002;359:1727-33.
25. Bosset JF, Gignoux M, Triboulet JP et al: Chemoradiotherapy followed by surgery compared to
surgery alone in squamous cell carcinoma of the esophagus. N Engl J Med 1997; 337:161-167.
26. Urba SG, Orringer MB, Turrisi A, et al.: A randomized trial of preoperative chemoradiation
versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol 2001;
19:305-313.
116
27. Burmeister BH, Smithers BM, Fitzgerald L et al.: A randomized phase III trial of preoperative
chemoradiation followed by surgery (CR-S) versus surgery alone (S) for localized resectable
cancer of the esophagus. Proc Am Soc Clin Oncol 2002; 518 (abstract).
28. Al-Sarraf M, Martz K, Herskovic A, et al. Progress report of combined chemotherapy versus
radiotherapy alone in patients with oesophageal cancer: an intergroup study. J Clin Oncol
1997;15:277-84.
29. Proc Am Soc Clin Ocolo 1994.
30. Altorki et al Three field lymphadenectomy for esophageal cancer. Chest surg Clin of N America
2000;10:553-60
31. Lightdale CJ. Oesophageal cancer. American college of gastroenterology. AM J Gastroenterol
1999;94:20-9
32. Schrump DS and Casson AG. Biology of oesophageal cancer. In : Pearson FG, Cooper JD,
Deslauries J, Ginsberg RJ, Hiebert CA, Patterson GA, Urschel HC, eds. Oesophageal surgery.
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2 ed. New York: Churchill Livingstone, 2002,655-67.
33. Kuo KT, Chow KC, Wu YC, Lin CS, Wang HW, Li WY, Wang LS. Clinicopathologic significance
of cyclooxygenase-2 over expression in oesophageal squamous cell carcinoma. Ann Thorac
Surg 2003;76:909-14.
117
The use of thin section helical computerized tomographic scans (CT) has increased
the sensitivity of CT for detection and diagnosis of pancreatic cancer. But its utility in the
118
diagnosis and assessment of ampullary lesions has not been systematically evaluated to
date.
10,11
Most often CT demonstrates a dilated common bile duct down to the level of
duodenum, absence of pancreatic mass and occasionally a mass at the ampulla. These
features often helpful in differentiating ampullary or periampullary neoplasm from a
pancreatic tumor. Endoscopy is proved to be most accurate diagnostic test, because it
allows the direct visualization of ampulla of Vater and access for biopsy. Four distinct types
of appearance of ampulla may be seen on endoscopy namely a polypoidal tumor mass, an
ulcerating mass, an infiltrating mass and a normal ampulla. Polypoidal mass is most
common finding and has a better prognosis than ulcerating tumor.
in 30-40% cases ampulla may appear norma.l
13,14
12
before the tumor can be visualized. Recognition of tumor may be obscured endoscopically
immediately after sphincterotomy, but is usually evident at subsequent examinations, 10
days to 4 weeks later.12 Accuracy of biopsy for diagnosis of malignancy has been shown to
be related to the gross morphological characterstics of the tumor, 14 88% for ulcerating type,
64% for protruding type and 50% for intrampullary type. Clinical decision making based on
incomplete endoscopic removal of tissue must be done with care, fully recognizing that
carcinoma may be missed.
However, a consensus is lacking with regard to optimal imaging modalities in the
evaluation of patients with suspected periampullary tumors. Recently several studies have
attempted to define a role for endoscopic ultrasonography (EUS) for suspected
periampullary tumors by comparing results of endoscopic ultrasound and computed
tomography with operative and pathologic findings. EUS has been consistently shown to be
superior than spiral CT for detection of small tumors.15-17 In approximately 20% patients
EUS can detect small periampullary lesions not detected by computed tomography.
Therefore, patients with smaller tumors undiagnosed by CT scanning would be a candidate
for improved detection by EUS.
Treatment and Results
At time of initial diagnosis of ampullary cancer Stage I disease is observed in about
10%, stage II disease in 35%, Stage III disease in 45%, Stage IV disease in 10% of cases.
Surgical treatment of ampullary cancer has ranged from ampullectomy as described by
William Halsted in 1899 to pancreaticoduodenectomy. However, because of its remarkably
less aggressive behaviour and a better prognosis than the more common pancreatic
carcinoma, indications for attempts at curative resection should be more liberal and much
broader than pancreatic ductal carcinoma. Ampulla of Vater has distinct pattern of lymphatic
drainage and in contrast to pancreatic tumors with a more diffuse wide spread lymphatic
119
spread, ampullary carcinoma tend to involve a single group of lymph node near to the
ampulla even in advanced cases. This tumor biology makes the ampullary carcinoma a
distinct clinical entity and probably in part explains the substantially superior prognosis of
these lesion if they do not infiltrate the pancreatic tissue
Ampullectomy for Periampullary Cancer
In patient with pT1 cancer, local resection by ampullectomy has been advocated by
some investigators as being equal to or better than pancreaticoduodenectomy. Ampulla of
Vater has distinct pattern of lymphatic drainage and in contrast to pancreatic tumors with a
more diffuse wide spread lymphatic spread, ampullary carcinoma tend to involve a single
group of lymph node near to the ampulla even in advance cases. This tumor biology makes
the ampullary carcinoma a distinct clinical entity and probably in part explains the
substantially superior prognosis of these lesion if they do not infiltrate the pancreatic tissue.
Some groups believe that local resection may be indicated in T1NoMo cancer (except
high grade) or adenoma containing focus of carcinoma in situ. If intraoperative findings show
cancer more than T1 lesion, high grade tumor on frozen section evaluation after review of
ampullectomy specimen and lymphatic metastasis, these preclude resection and necessitate
immediate pancreaticoduodenectomy. A more difficult problem is when the pathologist
defines a more advanced lesion than was suspected preoperatively or intraoperatively by
review of permanent section in the early postoperative period after completion of
transduodenal ampullectomy. Most surgeons would advocate pancreaticoduodenectomy to
provide best chance for cure. Because of these uncertanities most surgeons would
recommend a pancreaticoduodenectomy for all resectable lesions.
Review of out come after ampullectomy has revealed, tumor size was not a
significant prognostic factor for survival in few studies. The prognosis of patient even with
invasion into the muscle of sphinctor of Oddi seems to be good provided there is no invasion
into pancreatic parenchyma, or any associated nodal metastasis.18-20
Based on their histopathological and clinical correlations, Hanyu et al, 21 have defined
D0N0Pa0 as early carcinoma which is quite favourable for ampullectomy. Ultimately the most
Important factor for long term outcome are absence of invasion outside the sphinctor of Oddi
(D0) and absence of nodal and lymphatic vessel invasion. After ampullectomy median
survival is around 24 months, with 5 years survival between 15 to 35%. Local recurrence
and distant metastasis is a major cause of treatment failure after ampullectomy
120
Pancreaticoduodenectomy
Today most surgeons consider pancreatico-duodenectomy as the procedure of
choice in patients with cancer of ampulla. As with local transduodenal resection, survival
after pancreaticoduodenectomy is determined by absence of lymph node metastases, the
absence of invasion into pancreatic parenchyma and ability to perform R0 resection. In most
large series the chance for cure after pancreaticoduodenectomy approaches to 50%.22
Median survival after R0 resection following pancreaticoduodenectomy is about 45 months.
In contrast median survival for periampullary pancreatic ducal cancer following
pancreaticoduodenectomy is about 16 to 18 months. This difference in tumor biology justifies
aggressive treatment and importance of differentiating ampullary from pancreatic duct lesion
preoperatively. Though most recent studies suggest 5 year survival more than 50%.,
22
it is
23
known that nearly 24% of 5 year survivors can subsequently died of recurrence. Willet et
al
24
described high incidence of both local (28%) and distant recurrence (44%) after
resection. Robertson et al
25
26
neoampullary carcinoma arising at site of hepaticojeiunostomy five and fifteen years after
pancreaticoduodenectomy for cancer of ampulla of Vater. Therefore five year disease free
survival is not a guarantee of cure and life long follow up is advisable after resection for
periampullary carcinoma.
.Post Operative Adjuvant Therapy
Data supporting use of adjuvant therapy in perimpullary carcinoma is limited.
Inclusion of patients with ampullary cancer when analyzing result of pancreatic cancer is
inappropriate because two conditions do not have a similar prognosis. Splinter et al
27
in a
trial of adjuvant combination chemotherapy for ampullary carcinoma showed poor patient
tolerance of treatment and no survival benefit compared with historical controls. Willet et al
24
described a trend towards better local control ( 83% Vs 50%) in 12 of 29 patients with high
risk pathological features (tumor invading the pancreas, poorly differenciated histology,
positive lymph nodes, positive resection margins) who received post operative irradiation
after pancreatico-duodenectomy, but there was no improvement in survival.
Major criticism of these clinical studies is the lack of randomization and small number
of patients. A Norwegian multicentre randomized trial,28 involving 14 patients with ampullary
carcinoma demonstrated that adjuvant chemotherapy reduces the incidence
of recurrence
at least in the first 2 years after resection but an increased cure rate was not observed. So
121
122
after
25. Robertson JFR, Boyle P, Imrie CW. Patients with ampullary carcinoma are prone to other
malignant tumours. Br J Cancer 1988;58:216-218.
26. Nordback IH. Hruban RH. Cameron JL. Second primary lesions in the biliary tree after successful
resection of ampullary carcinoma. Surgery 1992;112:111-115.
27. Splinter TAW, Obertop H, Kok TC. Jeckel J. Adjuvant chemotherapy after resection of
adenocarcinoma of the periampullary region and head of the pancreas. J Cancer Res Clin Oncol.
1989;115-200-202.
28. Bakkevold KE, Arnesjo B, Dahl O, Kambestad B. Adjuvant combination chemotherapy (AMP)
following radical resection of carcinoma of the pancreas and papilla of Vater. Results of a
controlled, prospective, randomised multicentre study. Eur J Cancer 1993; 29A: 698-703.
123
Multiple Cancers
Ravi Kannan
Oncosurgeon, Chennai
Definition
Cancer registries use different rules for defining multiple primaries when registering
cancer cases. The IARC, WHO and the IACR have framed international rules for multiple
cancers as part of the ICD-O (third edition) for reporting data on cancer incidence and
survival, so that cancer risk and outcome are comparable between different populations.
Rules for reporting incidence and survival
1. The recognition of the existence of two or more primary cancers does not depend on
time.
2. A primary cancer is one that originates in a primary site or tissue and is not an extension,
nor a recurrence, nor a metastasis.
3. Only one tumour shall be recognised as arising in an organ or pair of organs or tissue.
Multifocal tumours that is, discrete masses apparently not in continuity with other primary
cancers originating in the same primary site or tissue, for example bladder are counted as
a single cancer.
4. Rule 3 does not apply in two circumstances:
4.1 Systemic (or multicentric) cancers potentially involving many different organs
are only counted once in any individual. These are Kaposi's sarcoma and tumours of the
haematopoietic system.
4.2 Neoplasms of different morphology should be regarded as multiple cancers
(even if they are diagnosed simultaneously in the same site).
When reporting on multiple cancers, it is important to mention whether multiple
tumours of the same site or of paired organs have been included. When cancers of the
same histology occur at multiple sites, one needs to distinguish multiple cancers from
multiple metastases.
occurring cancers in the same/paired organ have to be differentiated from recurrence of the
original cancer. Criteria of location, time interval between two cancers and presence or
absence of premalignancy surrounding the second cancer have been used for this purpose.
The frequency risk, with which second cancers occur may be expressed as an actuarial risk
within a given cohort, as a relative risk when compared with a standard population, or as an
attributable risk with the latter reflecting the additional cases associated with a specific
124
exposure or other etiology. Each of these methods has inherent limitations when attempting
to ascribe causation, especially when several factors are implicated.
In many registries multiple cancers account for one of the top ten common cancer
groups. An individual with an index cancer has twice the risk of a second malignancy when
compared to an individual without any cancer. Increased survival after cancer treatment,
fewer competing causes of mortality resulting in an aging population, common underlying
aetiology and possibly field cancerisation, carcinogenic effects of radiation therapy and
chemotherapy and genetic inheritance account for many of these.
Cancer is the seventh leading cause of death in India with a cumulative incidence of
1 in 9.
This
demonstrates that the probability of surviving the first cancer is a critical factor determining
the increased risk of developing second neoplasms. Another potential factor is detection
bias. During the work-up of the index cancer and its subsequent follow up surveillance after
treatment, otherwise clinically unrecognized malignancies may be detected introducing an
element of detection bias. The Hospital Registry of the Cancer Institute (WIA), Chennai
reports a 1.1 % incidence of second cancers while the Population Registry shows an
incidence of 0.8 per 100.000 population.
True pair associations could be unidirectional or bi-directional.
Unidirectional
association would indicate treatment of the index cancer to be a cause of the second cancer.
Examples would include endometrial cancers following treatment of breast cancer with
tamoxifen and leukemia following Hodgkins disease. Bi-directional associations indicate a
shared aetiology.
cancers or multiple cancers in the same organ like the colon and cancers at multiple sites of
the upper aero digestive tract. Non- associated second cancers reflect an over diagnosis
bias caused by enhanced surveillance resulting in detection of clinically occult cancers that
would not have otherwise been picked up. An example would be older men with colorectal
or gastric cancers or any other cancer being detected with prostate cancer on follow up.
These could also be due to chance or a sporadic incidence of the second cancer. Some of
the two way associations seen in India are listed in table I.
125
Table I
Index primary cancer
Head and neck squamous cell cancer
Breast cancer
Subsequent primaries
Other Head and Neck site primaries
Lung
Oesophagus
Contralateral breast
Ovary
Colon
Endometrium
TCC of the ureters, contralateral pelvis and ureter,
urinary bladder
Other sites in the colo-rectum
Ovary, endometrium, breast
Vagina, vulva
account for this problem with the index cancer representing the winner amongst the
cells in the carcinogenic race. More recently Sidransky and others have suggested that
there is a greater degree of monoclonality in these tumours representing migration of a
malignant clone through the epithelium.
126
127
Polymorphisms of metabolizing
enzymes, also inherited, could also contribute to the process. The penetrance of these
mutations will determine the occurrence of malignancies in the individual.
This is
because a single mutation is not adequate for the development of cancer. Other genetic
changes and environmental factors may act as promoters.
The first of these to be reported in 1986 was the retinoblastoma gene (RB) a tumour
suppressor gene located on chromosome 13. Knudson proposed the two-hit hypothesis
in 1971. Cancer develops when both alleles are mutated. In 40 % of individuals one of
these mutations occurs through the germline and is present in all the cells. The other
mutation usually occurs after birth.
retinoblastoma and also bone and soft tissue sarcomas, melanoma, brain tumours and
histiocytosis X. Radiaton increases the risk of second malignancies. Retinoblastoma
usually unilateral could also occur due to mutations of both genes after birth. Other
tissues are not at risk in this situation. Table II gives some examples of inherited cancer
syndromes.
Table II
Name of
the gene
RB
Location
Cancers seen
Comments
13q14
Autosomal recessive
inheritance
P53
17p13
APC
5q21
BRCA1
17q21
BRCA2
13q14
VHL
3p25
NF1
17q11.2
128
Autosomal dominant
inheritance. Li Fraumeni
syndrome and Li
Fraumeni like syndromes
(CHK gene on
chromosome 21)
FAP, Turcots syndrome
(with brain tumours),
Gardners syndrome (with
desmoids, fibrosarcomas)
von Recklinghausens
disease
PTC
9q22.3
msh2/
mlh1,2
2p21/
3p21-3
MEN1
11q13
STK11/
LKB1
19p13
RET
10q11.2
PTEN
ATM
10q23
11q22
Multiple endocrine
neoplasia 2a and 2b
Cowden syndrome
Ataxia telangiectasia
telangiectasia,
Blooms
syndrome,
Fanconis
anaemia
and
Xeroderma
HIV associated
malignancies include cervical and anal canal cancers, lymphomas and Kaposis
sarcomas. Some of these especially non Hodgkins lymphoma of the central nervous
system and Kaposis sarcoma occur in the same individual. On the other hand EBV
associated cancers rarely occur in the same individual.
129
Similarly while the entire alimentary tract shares common risk factors, large bowel cancer
following small bowel cancer is commoner than the other way round.
Treatment related second cancers
Radiation Therapy
Ionizing radiation has long been known to cause mutations and cancer. Bone and soft
tissue sarcomas, skin, breast, brain and thyroid cancers are the most common post
radiation malignancies.
following pelvic radiation for cervical cancer. Leukemias following radiation develop after
a latent period of 4 to 8 years while solid tumours usually occur after 10 to 40 years.
Radiation therapy for an index primary imparts a risk for development of a second
cancer, usually in the field of radiation or at its margins. The risk of a second cancer is
higher when exposure occurs in childhood and adolescence during periods of rapid
growth of tissues. Mature non-proliferating cells appear less susceptible. Adolescent
girls receiving mediastinal radiation for Hodgkins disease are at greater risk for breast
cancer when compared to adults. Tissues receiving lower doses of radiation are at
greater risk.
Treatment
Radiation therapy to the
mediastinum
Chemotherapy with alkylating
agents/ topoisomerase inhibitors
130
Second cancer/s
Breast cancer
Lung cancer
Thyroid cancer
Leukemias- AML
Risk
8.8 (AER)
9.7
1.4
8.8 (AER)
Cervical cancer
Radiation therapy
Breast cancer
Tamoxifen
Radiotherapy
Testicular cancer
Wilms tumour
Chemotherapy
Radiation therapy,
chemotherapy with doxorubicin
Childhood
cancers
Radiation therapy
Rectal and
urinary bladder
malignancy
Endometrial
cancer
Lung cancer,
angiosarcoma
Leukemia - AML
Leukemias,
lymphomas,
osteosarcoma,
soft tissue
sarcoma
Bone cancers
Alkylating agents
7.5 at 5
yrs. (RR)
2-3, 8.3 at
10 yrs. RR
36 RR
12.4-64.7
(10-50 Gy)
RR
1.3-3.3
RR
Treatment
Diagnosis of the first cancer may be a good teachable point for initiating a tobacco
cessation programme. Continued use of tobacco after treatment of the first cancer has been
shown to increase the incidence of second malignancies and cancer mortality.
Chemopreventive measures could also be considered. Vaccines used in the treatment of
cervical cancer have shown to reduce the incidence of subsequent HPV associated vaginal
and vulval cancers. Counseling of survivors should include instructions for primary and
secondary prevention of new malignancies.
While planning management for a second cancer, it is important to attempt to find an
aetiologic factor since it may have an impact on the patient (for prevention of additional
malignancies) and the family (for a possible genetic syndrome).
outcome of second or third cancers is not different from that of the first cancer. They may
have a better outcome due to increased surveillance and better overall medical care of the
cancer survivor. Sometimes, physicians while focusing on the primary cancer neglect
screening for second cancers. Some second malignancies appear to be less amenable to
treatment than primary tumors of the same histologic type. The best example of this is
therapy-related acute myelocytic leukemia (t- AML) where the prognosis is much worse than
for de novo AML. Presumably this reflects enhanced mutations and other molecular genetic
abnormalities stemming from exposure to chemotherapy or radiation. Treatment for a
second cancer must also take into account the toxicity from the initial therapy. This would
131
include dose limitations for certain chemotherapeutic agents and inability to use or at least
modification of dose and fields for radiation therapy.
Treatment of metachronous cancers is along the same lines as primary tumours of
the same site and stage with the limitations mentioned above. Treatment of synchronous
cancers however poses significant challenges in terms of choice/s, timing and sequencing of
treatment modalities. Treatment of synchronously detected well differentiated thyroid cancer
and locally advanced breast cancer may not pose much of a challenge. Differentiated thyroid
cancers are relatively indolent cancers. The breast cancer may be treated with appropriate
neoadjuvant chemotherapy and/ or radiation therapy and both the thyroid and breast
cancers operated upon subsequently. Treatment of synchronously occurring breast cancer
and any haematological malignancy may require tailoring of the chemotherapeutic agents
and radiation. Surgery may have to take into consideration the haematological parameters.
Conclusions
Screening for possible synchronous and metachronous cancers must be part of
management of the index primary cancer depending on the likely aetiology. Women treated
for a cancer must be screened periodically for breast and cervical cancer using
recommendations prevalent in that country. While planning treatment for the initial cancer,
the potential for second cancers as a result of treatment must be borne in mind and
treatment appropriately tailored.
th
132
9. Demark-Wahnefried W, Aziz NM, Rowland JH, et al: Riding the crest of the teachable moment:
Promoting long-term health after the diagnosis of cancer. J Clin Oncol 2005;23:5814-5830
10. Hudson, M. M., Merten, A. C., Yasui, Y, Hobbie, W., Chen, H. Gurney, et al . "Health status of
adult long-term survivors of childhood cancer: A report from the childhood cancer survivor study."
JAMA 2003;290 (12): 1583-1592.
133
Soft-tissue Sarcomas
Ravi Kant
Maulana Azad Medical College, New Delhi
The soft-tissue sarcomas are a group of rare but anatomically and histologically diverse
neoplasms. They are tumors of tissues of mesenchymal origin including muscles,
endothelium, cartilage and supporting elements, excluding the reticulo-endothelial system
and blood elements. They constitute 1% of adult and 15% of paediatric malignancies.
Epidemiology
Unlike the more common malignancies, such as colon cancer, little is known about the
epidemiology of soft-tissue sarcomas. This, again, reflects the uncommon nature of these
lesions.
Gender There is a slight male predominance, with a male to female ratio of 1.1:1.0.
Age The age distribution in adult soft-tissue sarcoma studies is: < 40 years, 20.7% of
patients; 40-60 years, 27.6% of patients; > 60 years, 51.7% of patients.
Race Studies in large cohorts of patients demonstrate that the race distribution of softtissue sarcomas mirrors that of the US population (86% Caucasian, 10% AfricanAmerican, 1% Asian-American, 3% other)
Etiology and risk factors
In the majority of cases of soft-tissue sarcoma, no specific etiologic agent is identifiable.
However, a number of predisposing factors have been recognized:
Genetic factors STS is commonly associated with a number of genetic syndromes like Li
Fraumeni syndrome, Gardners syndrome, hereditary retinoblastoma syndrome, Von
Recklinghausens disease etc. Also mutations in certain oncogenes and tumor
suppressor genes ( e.g. RB1, p53, NK-1, c-myc ) have been associated with sporadic
STS.
Radiation therapy Soft-tissue sarcomas have been reported to originate in radiation fields
following therapeutic radiation for a variety of solid tumors. By definition, radiationinduced sarcomas arise no sooner than 3 years after radiation therapy and often develop
decades later. The majority of these sarcomas are high-grade lesions (90%), and
osteosarcoma is a predominant histology. Malignant fibrous histiocytoma (MFH),
angiosarcoma, and other histologic subtypes have also been reported.
134
135
the anterior intra-abdominal organs, these tumors often grow to substantial size before the
patients nonspecific complaints are evaluated or an abdominal mass is noted on physical
examination.
Viscera Visceral soft-tissue sarcomas, which comprise 15% of all soft-tissue sarcomas,
present with signs and symptoms unique to their viscus of origin. For example, GI
leiomyosarcomas present with GI symptoms that are usually indistinguishable from the more
common adenocarcinomas. Similarly, uterine leiomyosarcomas frequently present with
painless vaginal bleeding like that often noted in patients with more common uterine
malignancies.
Head and neck Head and neck sarcomas comprise 10% of all soft-tissue sarcomas.
Although generally smaller than sarcomas in other sites, they may present with important
mechanical problems related to compression or invasion of adjacent anatomy (eg, orbital
contents, airway, or pharynx). In addition, their close proximity to critical anatomy can pose
management difficulties due to compromise in the delivery of both surgery and radiotherapy.
Pathology
Histopathologic classification As a consequence of the wide spectrum of soft tissues, a
variety of histologically distinct neoplasms have been characterized. The current
histopathologic classification is based on the putative cell of origin of each lesion. Such
classification based on histogenesis is reproducible for the more differentiated tumors.
However, as the degree of histologic differentiation declines, it becomes increasingly difficult
to determine cellular origin.
In addition, many of these tumors dedifferentiate. This results in a variety of overlapping
patterns, making uniform classification difficult. Experienced soft-tissue pathologists
frequently disagree on the cell of origin of an individual tumor. Comparative studies have
demonstrated concordance in histopathologic diagnosis in only two-thirds of cases.
Assignment of a specific histologic subtype is of secondary importance. This is because,
with the possible exceptions of certain small-cell sarcomas, rhabdomyosarcoma,
fibrosarcoma, and some forms of angiosarcoma, histogenesis is not directly related to
biological behavior. The propensity for distant metastases and disease-related mortality are
best predicted on the basis of histologic grade and tumor size.
Cellular classification of soft tissue sarcoma
Angiosarcoma
Dermatofibrosarcoma Protuberans
136
Epithelioid Sarcoma
Extraskeletal Chondrosarcoma
Extraskeletal Osteosarcoma
Fibrosarcoma
Gastrointestinal Stromal Tumor (Gist)
Leiomyosarcoma
Liposarcoma
Malignant Fibrous Histiocytoma
Malignant Hemangiopericytoma
Malignant Mesenchymoma
Malignant Schwannoma
Malignant Peripheral Nerve Sheath Tumor
Peripheral Neuroectodermal Tumors
Rhabdomyosarcoma
Synovial Sarcoma
Sarcoma, NOS
137
B. Musculoskeletal tumor society This system utilizes three grades along with the anatomic
position
of
the
lesion
(intracompartmental
138
vs.
intercompartmental
vs
extra
Favourable
Unfavourable
Size
< 5 cm
> 5 cm
Site
Superficial
Deep
Grade
Low
High
Staging
II
III
IV
Metastasis
A major limitation of the current staging system is that it does not take into account the
anatomic site of soft-tissue sarcomas. Anatomic site, however, is an important determinant
of outcome. Patients with retroperitoneal, head and neck, and visceral sarcomas have a
worse overall prognosis than do patients with extremity tumors. Although site is not
incorporated as a specific component of any current staging system, outcome data should
be reported on a site-specific basis.
Screening and diagnosis
Currently, there are no screening tests for soft-tissue sarcomas. Since the majority of
patients with soft-tissue sarcoma have lesions arising in the extremities or superficial trunk,
most of the comments here apply to soft-tissue lesions in those sites. A separate algorithm is
usually employed for the evaluation of a primary retroperitoneal mass or visceral sarcoma.
Physical examination should include an assessment of the size of the mass and its mobility
relative to the underlying soft tissues. The relationship of the mass to the investing fascia
of the extremity (superficial vs deep) and nearby neurovascular and bony structures
should be noted. Site-specific neurovascular examination and assessment of regional
lymph nodes should also be performed.
Percutaneous approaches Percutaneous tissue diagnosis can usually be obtained with fineneedle aspiration (FNA) for cytology or by percutaneous core biopsy for histology. The
needle track should be placed in an area to be excised. In most instances, when an
experienced cytopathologist and/or histopathologist examines the specimen, a diagnosis
139
Incisional
Frozen
No.
60
45
36
93
100
94
95
100
88
Correct grade(%)
88
96
62
75
84
47
140
141
(vi) to evaluate benign post operative complications like hematoma and seroma.
MRI Vs CT Scan
MRI: This is especially suited for extremity and pelvic lesions. STS appears as intermediate
to low signal intensity on spin-echo T1 weighted images and bright on T2 weighted images.
Recurrences are seen as high signal mass on T2 weighted images. Malignancy on MRI is
suspected when
(a) Lesion > 5 cm
(b) Heterogenous lesion
(c) Location below deep fascia
Advantages:
(i) Multiplanar assessment of lesion
(ii) Superior soft tissue enhancement
Disadvantages:
(i) Lack of specifity to differentiate between malignant and benign lesions.
(ii) Contraindications like
(a) Absolute -cardiac pacemaker, cerebral aneurysm clips
(b) Relative-patient size, claustrophobic patient, metallic artifact from orthopaedic hardware
CT Scan:
Advantages:
(i) Useful in areas such as ribs where motion artifacts make MRI examination difficult
(ii) Calcifications as in synovial sarcoma are better seen
142
X-ray chest: This is generally sufficient for small low grade lesions of the extremity
Liver should be evaluated along with visceral and retroperitoneal lesions as a single
modality imaging .
scan sensitivity and specificity (86.7% and 100%) compares favourably with CT
scan (100% and 96.4% respectively ). The intensity of uptake can also be correlated
with the grade of malignancy; higher grade lesions show more intense uptake.
More invasive studies, such as angiography and cavography, are almost never required for
the evaluation of soft-tissue sarcomas.
Treatment
Surgical resection is the cornerstone of therapy for patients with localized disease. Over
the past 20 years, there has been a gradual shift in the surgical management of extremity
soft-tissue sarcoma away from radical ablative surgery, such as amputation or compartment
resection, and toward limb-sparing approaches combining wide local resection with
preoperative or postoperative radiotherapy. The development of advanced surgical
techniques (eg, microvascular tissue transfer, bone and joint replacement, and vascular
reconstruction) and the application of multimodality approaches have allowed most patients
143
to retain a functional extremity without any compromise in survival. The surgical approach to
soft-tissue sarcomas depends on careful preoperative staging with MRI or CT for extremity
lesions and a percutaneous histologic diagnosis and assessment of grade. In most
instances, preoperative imaging studies allow for accurate prediction of resectability.
Extremity soft tissue sarcoma (6)
Categorisation of excision
Radical excision( Amputation )- excision of entire anatomical structure containing the tumor
Limb saving procedures
1.
Compartmental excision
2.
3.
Compartmental excision
This is most commonly carried out in thigh and involves resection of tumor along with
surrounding muscles within a well defined compartment. This is based on the premise that
fascial boundary would prevent direct tumor extension, hence only tumors which do not
violate compartmental boundaries are amenable to such resections. The muscles are
detached from bony and ligamentous insertion using well defined fascial planes to direct
dissection.
Anterior compartment excision: This involves resection of quadriceps femoris, rectus
femoris and sartorius muscle along with femoral nerve. The functional consequences of this
operation are weakness of leg extension and loss of sensation in the anterior thigh and
medial lower leg. Use of brace improves gait and stability. This procedure can further be
modified by preserving the portion of quadriceps muscle located away from tumor to improve
functional result.
Posterior
compartment
excision:
This
involves
removal
of
hamstring
muscles
144
knee adduction in upright position is gravity aided and knee and ankle stability is not
dependent on these muscles.
Buttockectomy: involves removal of gluteus maximus and if necessary portions of gluteus
minimus, while sparing sciatic nerve. This results in significant gait impairment.
Distal lower extremity: This is an uncommon site for STS (8-12%); here compartmental
excisions are generally not performed. Only in the anterior compartment of leg it may be
possible. Even here, one or two of three muscles (tibialis anterior, extensor hallucis longus,
extension digitorum longus) should be preserved with intact personal innervation.
Marginal excision
This was an earlier practice when tumors were shelled out of its pseudocapsule with
resultant high recurrence rate (33-63%). Presently this is practised for retroperitoneum and
head and neck regions with adjuvant radiotherapy. In the extremity this is practised for
lesions which involve nerves and vessels or other vital structures where negative or close
margin or microscopically positive margin is acceptable. It has to be followed by adjuvant
RT. Such situation arises only for deep, high grade tumors which have an increased
incidence of systemic metastasis and decreased survival, irrespective of local recurrence
and also morbidity associated with wider resection or amputation may be unacceptably high.
Wide excision
This, when used along with adjuvant radiotherapy, is regarded as the most appropriate
treatment, presently for adult STS: recurrence rate of 30% is seen for surgery alone without
radiotherapy. The point of doing a wide surgical excision is to obtain a negative surgical
margin. For small T1 sarcomas, carefully performed wide excision alone may be adequate
with a reported recurrence rate of 10%. Low grade lesions are ideally resected with
(histologically negative) margins of 1 cm or more while high grade lesions are resected with
a 3 cm negative margin. But as is usually seen, the margin at its most narrow point is < 1
cm. Hence adjuvant RT is needed.
While performing wide excision, the skin incision should incorporate the biopsy incision
which is removed en bloc with tumor. Since STS rarely invade skin and bone, excessive
resection of these structures should be avoided. Care is taken to preserve nerve and
vessels. Metal clips should be placed at the margins of resection in order to facilitate
radiation field planning, when and if external radiation is indicated. Drain sites should be
positioned close to the wound to allow inclusion in RT fields.The avoidance of transverse
145
incisions greatly facilitates the ability to include the tissues at risk in radiation target vo lume
without unduly large fields.
Given the low, 2%-3% prevalence of lymph node metastasis in adult sarcomas, there is
no role for routine regional lymphadenectomy. Patients with angiosarcoma, embryonal
rhabdomyosarcoma, synovial sarcoma, and epithelioid histologies have an increased
incidence of lymph node metastasis and should be carefully examined and radiographically
imaged for lymphadenopathy. Clinically apparent lymphadenopathy should be treated with
therapeutic lymphadenectomy
Surgery for retro-peritoneal sarcoma
Primary surgical resection is the dominant therapeutic modality and complete surgical
excision is the primary factor in the outcome of visceral and retroperitoneal sarcomas.
Adequate surgical exposure must be obtained using appropriate incisions. Preoperative
bowel preparation is desirable. Complete surgical excision for retroperitoneal tumours may
involve resecting contiguous structures, where as for visceral lesions, wide excision is
recommended. Complete surgical excision is usually possible in 60-70% cases. Local
recurrence occurs in 40-50% cases. Re-resection to completion is possible in most cases
and should be performed. This has been shown to improve the survival especially in low
grade lesions.
Role of Radiation Therapy
Contrary to earlier belief, soft tissue sarcomas are now regarded as radiosensitive
tumors and further it has been seen that at moderate doses, RT is shown to inactivate
microscopic tumor extensions. RT can be given as adjuvant therapy or as primary therapy
(for patients who refuse surgery or are medically unfit to undergo surgery). (7)
Radiation therapy is always combined with surgical resection in the management of
extremity soft-tissue sarcomas. The decision of whether to use preoperative (neoadjuvant)
or postoperative (adjuvant) irradiation remains controversial (see box).
Preoperative irradiation has a number of theoretical and practical advantages:
Smaller radiation portals can be utilized, as the scar, hematomas, and ecchymoses
do not need to be covered.
It is easier to spare a strip of skin and thereby reduce the risk of lymphedema.
146
The size of the tumor may be reduced, thus decreasing the extent of surgical
resection.
Lower radiation doses can be utilized, as there are less relatively radioresistant
hypoxic cells.
147
Five-year local control rates of 70%-90%, survival rates of 70%, and limb preservation rates
of 85% can be expected.
Equivocal or positive histologic margins are associated with higher local recurrence
rates, and, thus, adjuvant external-beam radiation should be considered in all patients with
extremity sarcoma with positive or close microscopic margins, in whom reexcision is
impractical. Postoperative doses of 60-65 Gy should be used.
Interstitial/Intra-operative therapy with iridium-192 is used at some institutions as a
radiation boost to the tumor bed following adjuvant external-beam irradiation. At Memorial
Sloan-Kettering, 89% of patients randomized to adjuvant brachytherapy achieved local
control, as compared with only 66% of those who had surgery alone. If an implant alone is
used, the dose is 40-45 Gy to a volume that includes all margins; when a boost is combined
with additional external-beam radiation, a dose of 20-25 Gy is utilized. Some data suggest a
higher rate of wound complications and a delay in healing when implants are afterloaded
prior to the third postoperative day. Although some centers load implants sooner, this must
be done with caution and with strict attention to the incision site.
Comparison of radiation techniques
Comparable local control results (90%) are obtained with preoperative, postoperative,
and interstitial techniques, although rates of wound complications are higher with
preoperative techniques (see box on page 495). Brachytherapy can offer a number of
advantages for the patient. When brachytherapy is employed as the sole adjuvant, the
patients entire treatment (surgery and radiation) is completed in a 10- to 12-day period,
compared with the 10-12 weeks required for typical external-beam radiation (6-7 weeks) and
surgery (4- to 6-week break before or after radiation). Generally, smaller volumes can be
irradiated with brachytherapy, which could improve functional results. However, smaller
volumes may not be appropriate, depending on the tumor size, grade, and margin status.
Regardless of the technique employed, local control is a highly achievable and a
worthwhile end point, as demonstrated in a study of 911 patients treated by various
techniques at Memorial Sloan-Kettering. Of the 116 patients who developed a local
recurrence, 38 subsequently developed metastases and 34 died. Metastases after local
recurrence were predicted in patients with high-grade or large (> 5 cm) tumors.
148
149
used in many studies, and the lack of consistent policies in determining the indications for
radiation therapy.
Postoperative radiation Given in all high grade tumors. Radio-therapy is given in early postoperative period ; as soon as surgical wound is healed.
Two-year local control rates of 70% have been reported with the addition of
postoperative irradiation. However, radiation of the retroperitoneum/abdomen in doses that
have effected local control in extremity soft-tissue sarcoma (50-65 Gy) is usually associated
with significant GI toxicity. Obviously, the incidence of GI toxicity depends on the exact fields
and technique used. However, as most retroperitoneal sarcomas are > 10-15 cm, the
radiation fields employed are generally also quite large, and bowel is often located and/or
tethered in the high-risk area. Three-dimensional treatment planning and conformal
techniques can now be utilized to maximize the radiation dose to the tumor bed while
minimizing the dose to the surrounding normal tissues.
Preoperative radiation The advantages of preoperative radiotherapy have already been
discussed for extremity soft-tissue sarcomas. In the retroperitoneum, an additional
advantage is that bowel is frequently displaced significantly by the tumor. In contrast to the
postoperative setting, the bowel being treated is also very unlikely to be tethered by
adhesions from prior surgery. These features significantly offset acute toxicity of large-field
intra-abdominal radiotherapy (eg, nausea and vomiting, and diarrhea) as well as the
potential for late-onset bowel toxicity. Conformal techniques capable of sparing normal
tissues are also more easily applied in the preoperative setting when the tumor can be
visualized and the target area more readily defined.
Intraoperative radiation In a prospective trial from the NCI, 35 patients with completely
resected retroperitoneal sarcomas were randomized to receive either intraoperative electronbeam radiation (IORT) followed by low-dose (30-40 Gy) postoperative external-beam
radiation or high-dose postoperative external-beam radiation (35-40 Gy plus a 20-Gy boost).
Absolute local recurrence rates were significantly lower in the IORT group (P < .05), but
disease-specific and overall survival rates did not differ between the two groups.
A similar suggestion of improved local control was reported in a smaller nonrandomized
series from Massachusetts General Hospital. Although these local control results are
encouraging, IORT remains investigational and cannot be advocated on a routine basis at
this time.
150
151
. Trimetrexate
. Edatrexate
The Canadian group also have studied the antifols, trimetrexate, and edatrexate.
In the first study, 25 evaluable patients with soft tissue sarcomas were treated on the
daily x 5 schedule repeated every 3 weeks, and four partial responses were noted for a
response rate of 16% (95% CI, 4.5 to 36%).
. Navelbine ( Vinca alkaloid )
. Raletrexed
Newer chemo-response modifiers/ sensitisers
. Pegylated liposomal Doxorubicin
. Alpha interferon
. Idoxuridine
. Razoxane
Isolated limb perfusion
Recent studies have evaluated the role of isolated limb perfusion (ILP) in the
management of extremity sarcoma. These studies have generally been extrapolations from
protocols initially designed to treat locally advanced melanoma.
The agents most commonly employed for ILP have been melphalan and tumor necrosis
factor-alpha (TNF-a), with or without interferon-gamma (IFN-g [Actimmune]). The results of
the largest series of ILP in patients with locally advanced extremity soft-tissue sarcoma were
recently reported by Eggermont and colleagues (see box). TNF has now been approved in
Europe for ILP in patients with locally advanced, grade 2/3 soft-tissue sarcomas of the
extremities.
Alternative treatments in trial
Angio-genesis inhibitors (used in Angio-sarcoma ,haemangio-endothelioma )
152
Alpha interferon
Cis-retinoic acid
Differentiation Therapy
1. PPAR i.e. Peroxisome proliferator-activated receptor alpha ( for incurable Liposarcoma)
2. RXR i.e.Retinoid X receptor
The idea of programming the rapidly proliferating malignant cell to differentiate towards
normalcy and stabilize or even convert it to normal tissue sounds both appealing and
fascinating. There is laboratory evidence that the heterodimeric complex of proliferatorsactivated receptor-gamma) PPAR) and the retinoid X receptor (RXR) alpha functions as a
centeral regulator of adipocyte differentiation. It has also been shown that human
liposarcoma cells can be induced to undergo terminal differentiation by treatment with PPAR
ligand pioglitazone (the differentiation block is overcome by maximal activation of this
pathway (14)
Gene therapy
Onco-gene suppression
In PNET, inhibition of expression of EWS-FL11 oncoproteins using antisense oligonuleotides
Tumor suppressor gene
Re-introduction of wild type p53 gene into leiomyosarcoma cells using recombinant
adenovirus vector
Thirteen published trials have compared postoperative chemotherapy to observation
alone in adult patients who had undergone resection of a primary or recurrent soft-tissue
sarcoma. Most of these trials included fewer than 100 patients, and even the largest trial had
inadequate statistical power to detect a 15% difference in survival. Other flaws confound the
interpretation of many of the studies. Some trials included low-risk patients with small and/or
low-grade sarcoma. In some trials, patient ineligibility rates were as high as 20%, and in
none of these trials was ifosfamide part of the combination evaluated.
In five of the six trials in which doxorubicin monotherapy was studied, including one
study limited to patients with uterine sarcoma, a significant improvement in survival could not
be demonstrated. Among the trials of combination chemotherapy, most used the
combination of cyclophosphamide, vincristine, Adriamycin, and DTIC (CyVADIC). A
significant survival advantage was seen only in one combination chemotherapy trial.
153
Nonetheless, some of the trials showed a trend toward improved disease-free survival or
a statistically significant improvement in this end point in patients given adjuvant
chemotherapy, especially among those with high-grade extremity sarcoma. Analyses of the
pooled results of the published literature are consistent with this observation.
SMAC meta-analysis A formal meta-analysis of individual data from 1,568 patients who
participated in the 13 published trials (plus one additional unpublished trial) has been
performed by the Sarcoma Meta-Analysis Collaboration (SMAC). Although not all data were
available for all patients, the analysis demonstrated a significant reduction in the risk of local
or distant recurrence in patients who received adjuvant chemotherapy.
The overall hazard ratio for distant relapsefree survival was 0.70; ie, the risk of distant
relapse (metastasis) was reduced by 30% in treated patients. The absolute benefit at 10
years was 10%, so that the recurrence-free survival rate at 10 years was improved from 60%
to 70%. Also, the hazard ratio for local recurrencefree survival was 0.73 (27% reduction in
the risk of local recurrence), and the absolute benefit was 6%.
The hazard ratio for overall survival, however, was 0.89, which did not meet the criteria
for statistical significance. The observed survival at 10 years was 54% for patients who
received chemotherapy, and 50% for those who did not. Subset analysis failed to show that
the effects of chemotherapy differed by primary site, although the best evidence for an effect
of adjuvant chemotherapy was seen in patients with extremity sarcoma.
Ifosfamide-containing trials Only one trial included in the meta-analysis used an
ifosfamide-containing regimen; that trial involved only 29 patients. An attempt to conduct a
large prospective trial of postoperative chemotherapy with the MAID regimen in the United
States failed because of insufficient patient accrual.
The Italian Sarcoma Group conducted a trial in which patients 18-65 years old with highgrade extremity sarcoma > 5 cm were randomized to either postoperative chemotherapy
with 5 cycles of epirubicin (60 mg/m2 on days 1 and 2) plus ifosfamide (1.8 g/m2 on days 1-5)
given with granulocyte colony stimulating factor (G-CSF, filgrastim [Neupogen]) every 3
weeks, or observation alone. The trial had been planned for 200 patients, but was
interrupted after accrual of 104 patients when an interim analysis showed a significant
survival advantage for the chemotherapy-treated group. With a minimum follow-up of 36
months, a statistically significant advantage was still evident in chemotherapy-treated
patients with respect to overall survival (P = .01), disease-free survival, freedom from local
recurrence, and freedom from distant metastasis.
154
Preoperative chemotherapy
Preoperative chemotherapy has been adopted at many centers for patients with large
high-grade sarcoma, especially those of the extremity like Ewings sarcoma and
osteosarcoma. Other centers favor alternating chemotherapy and radiation.
Aside from theoretical considerations, there are several pragmatic reasons to favor
preoperative over postoperative treatment. First, a reduction in the size of a large lesion may
permit surgical resection with less morbidity. Second, compliance may be better with
preoperative therapy. Finally, it has been suggested that response to preoperative therapy
may provide important prognostic information, although this remains controversial.
Thus, the superiority of preoperative chemotherapy remains speculative. In fact, the
European Organization for Research and Treatment of Cancer (EORTC) is conducting a
prospective, randomized trial in which patients are randomized to receive or not to receive
preoperative therapy.
Treatment recommendations
Ideally, patients should be offered participation in clinical trials. Unfortunately, there are
no active trials in the United States that will definitively answer the most important
questions. Thus, a decision to treat must be made on an individual basis.
For patients who opt for preoperative or postoperative, chemotherapy, a regimen that
includes doxorubicin (60-75 mg/m2) and ifosfamide (9-10 g/m2) or the MAID regimen
155
Outside of the context of a clinical trial, concurrent chemotherapy and radiation should
be avoided.
156
with the limited efficacy of systemic therapy, is the basis for the recommendation that
patients with limited pulmonary metastases and no extrapulmonary disease should undergo
thoracotomy and metastasectomy.
Appropriate patient selection for this aggressive therapeutic approach to metastatic
disease is essential. The following are generally agreed upon criteria: (1) the primary tumor
is controlled or controllable; (2) there is no extrathoracic metastatic disease; (3) the patient is
a medical candidate for a thoracotomy; and (4) complete resection of all disease appears to
be possible.
Preresection chemotherapy Chemotherapy is often recommended before resection of lung
metastases. However, there are no convincing data to support this approach.
Chemotherapy for Unresectable Locally Advanced or Metastatic Disease
Single agents
Doxorubicin Early trials of doxorubicin reported major responses in approximately 30% of
patients with advanced soft-tissue sarcoma. In more recent randomized series, however, the
rate of response has been closer to 17%.
Subset analysis of patients with soft-tissue sarcoma from a broad phase II trial in which
patients were randomized to receive various doses of doxorubicin demonstrated a steep
dose-response relationship; patients treated with doses < 60 mg/m2 rarely responded.
Whether dose-intensification of doxorubicin is associated with improved survival remains an
open question (see "Intensifying chemotherapy").
Several phase II trials have explored the activity of liposomal doxorubicin (Doxil) in
previously treated patients. Although responses have been observed in some patients, the
overall response rate is low.
Ifosfamide In a randomized phase II trial conducted by the EORTC, 18% of patients treated
with ifosfamide (Ifex) (5 g/m2) experienced major responses, in contrast to 12% of patients
treated with cyclophosphamide (1.5 g/m2), despite the greater myelosuppression with the
latter agent. In a large American phase II trial, 17 of 99 patients with soft-tissue sarcoma
responded to ifosfamide (8 g/m2). All of the patients had been treated previously with
doxorubicin-based therapy, suggesting a degree of non-cross-resistance.
Increasing ifosfamide dose Recent trials have focused on increasing the dose of ifosfamide.
12 g/mResponses to ifosfamide (2) have been observed in patients who progressed while
receiving lower doses, supporting the concept of a dose-response relationship.
157
In a randomized trial, the response to 9 g/m2 of ifosfamide (17.5%) was superior to the
3% response observed among patients treated with 5 g/m2 . The reason for the low response
to the lower dose was unclear. In a subsequent trial by the same investigators, the response
to 12 g/m2 was only 14%, however.
Among 45 "assessable" patients enrolled in a Spanish phase II trial of ifosfamide (14
g/m2 given by continuous infusion over 6 days), the response rate was 37.7%, but 47% of
patients developed febrile neutropenia and 32%, grade 3 neurotoxicity.
At M. D. Anderson, ifosfamide (14 g/m2 given by continuous infusion over 3 days) yielded
responses in 29% of 37 patients with soft-tissue sarcoma, and 40% of patients with bone
sarcoma. Also within that report was a small cohort of patients in whom the response to the
same total dose of ifosfamide was higher when the drug was given by an intermittent bolus
rather than a continuous infusion; this led the authors to suggest that bolus therapy is more
efficacious than continuous infusion. Pharmacokinetic studies, however, have shown no
difference between a 1-hour infusion or bolus injection of ifosfamide with respect to the area
under the curve for serum ifosfamide or its metabolites, or the levels of ifosfamide
metabolites in urine.
In a European Organization for Research and Treatment of Cancer ( EORTC) phase II
trial, ifosfamide 12g/m2 given as a 3-day continuous infusion every 4 weeks yielded a
response rate of 17% among 89 chemotherapy-nave patients, and 16% among 25
previously treated patients.
Ifosfamide doses as high as 14-20 g/m2 have been given with hematopoietic growth
factor support; reported response rates are high, but neurologic and renal toxicity often are
dose-limiting. The available data suggest that synovial sarcoma is particularly sensitive to
ifosfamide.
DTIC The activity of dacarbazine (DTIC) in soft-tissue sarcoma has been recognized since
the 1970s, and was confirmed in a formal phase II trial. This marginally active agent has
been used mostly in doxorubicin-based combinations.
Other agents, including the taxanes, vinca alkaloids, and platinum compounds, have
demonstrated only marginal activity in phase II trials. Gemcitabine (Gemzar) has
demonstrated modest activity in several recent phase II studies including previously treated
patients. A novel marine compound, ET-743, has been reported to have activity in sarcoma
during phase I and early phase II evaluation. CT-2584, an inhibitor of cholinephosphate
cytidyltransferase, is another new compound that has shown activity in phase II testing.
158
Targeted therapy
Gastrointestinal
stromal
tumors
(GIST)
are
notoriously
resistant
to
conventional
chemotherapy. The recognition that GIST expresses the c-kit oncogene (CD117), a tyrosine
kinase, has lead to a novel targeted therapeutic approach. STI-571, synthesized as an
inhibitor of the bcr-abl tyrosine kinase that characterized CML, also inhibits c-kit. Preliminary
observations indicate that dramatic response have been seen in patients with advanced
GIST who have been treated with that compound. Trials are ongoing.
Combination chemotherapy
Combination chemotherapy regimens have been used widely in the management of
patients with soft-tissue sarcoma. High response rates have been reported in a number of
single-arm phase II trials. Most combination regimens include an anthracycline (either
doxorubicin or epirubicin) plus an alkylating agent, DTIC, or both agents. Overall, response
rates are higher in these single-arm trials than rates observed when the same regimens are
tested in larger, randomized studies.
AD and CyVADIC regimens The combination of Adriamycin plus DTIC (AD regimen) has
been studied extensively. Also, for over a decade, the CyVADIC regimen was widely
accepted as the standard of care. In a prospective, randomized trial, however, CyVADIC did
not prove to be superior to doxorubicin alone.
Doxorubicin (or epirubicin) plus ifosfamide Combinations of doxorubicin (or epirubicin)
plus ifosfamide consistently have yielded responses in over 25% of patients in single-arm
trials. In sequential trials conducted by the EORTC, doxorubicin (75 mg/m2) plus ifosfamide
(5 g/m2) was superior to doxorubicin (50 mg/m2) plus ifosfamide (5 g/m2). However, a
prospective, randomized trial comparing the two regimens found no difference in response
rate or survival.
MAID regimen The MAID regimen (mesna, Adriamycin [60 mg/m2], ifosfamide [7.5 g/m2],
and DTIC [900 mg/m2], all given over 3 days) yielded an overall response rate in 47% of
patients in a large phase II trial. In a randomized comparison of AD vs MAID, the response
to MAID was 32%, compared to a 17% response with the two-drug regimen (P < .002).
However, the price paid for the higher response was toxicity; of eight toxic deaths reported in
this trial, seven occurred among the 170 patients treated with MAID. All treatment-related
deaths occurred in patients > 50 years old. During the study, the doses of MAID were
reduced to lessen toxicity. Median survival did not differ significantly between the two
regimens, although a trend favoring the AD regimen was noted.
159
160
Prognostic factors for response to therapy Over the past 20 years, the EORTC has
collected data on more than 2,000 patients with metastatic disease who participated in firstline anthracycline-based chemotherapy trials. Multivariate analysis of this data set indicated
that the patients most likely to respond to chemotherapy are patients without liver
metastases (P < .0001), younger patients, individuals with high histologic grade, and those
with liposarcoma. In this Cox model, the factors associated with superior survival were good
performance status, absence of liver metastases, low histologic grade, a long time to
metastasis after treatment of the primary, and young age.
More recently, these same investigators have reported that the observed response rate
is superior in patients who have lung metastases only, as compared with those who have
metastases to the lung and other sites, or to other sites only. These findings highlight the
danger of reaching broad conclusions based on extrapolations from small trials that include
highly selected patients. The EORTC data are also consistent with the observation that
patients with metastatic GI sarcoma rarely respond to standard chemotherapy regimens.
This increasingly recognized observation has been used to explain the low response rates
seen in some trials.
Treatment recommendations
All patients should be considered for clinical trials of novel agents or combinations,
especially those with metastatic sarcoma of the GI tract.
Periods of watchful waiting may be appropriate for many patients with metastatic
sarcoma who have no or only minimal symptoms.
Suggested Reading
1.
2. Fleming ID, Cooper JS, Hansen DE, et al: Soft tissue sarcoma. AJCC Cancer staging handbook.
th
5 edn. Philadelphia: Lippincot-Raven: 139, 1998
3. HeslinMJ , Lewis JJ , woodruff JM,Brennan MF: Core needle Biopsy for diagnosis of soft tissue
sarcomas. Ann Surg Oncol , 4 :425, 1997
4. Akoury DA, seo jj, james CD, Zaki SR: RT-PCR detection of mRNA recovered from archival glass
slide smears, mod pathol 1993;6:195-200.
5. Singer S, Sivarage M, Souza K, et al: H-NMR detectable fatty acyl chain unsaturation in excised
leiomysarcoma correlate with grade and mitotic activity. J Clin Invest 1996;98;244-250
6. Davis AM: Functional outcome in extremity soft-tissue sarcoma. Semin Radiat Oncol 9(4):360
368, 1999.
161
7.
OSullivan B, Wylie J, Catton C, et al: The local management of soft-tissue sarcoma. Semin
Radiat Oncol 9(4):328348, 1999.
18. Merimsky O, Meller I, Flusser G, et al: Gemcitabine in soft-tissue or bone sarcoma resistant to
standard chemotherapy: A phase II study. Cancer Chemother Pharmacol 45(2):177181, 2000.
162
Correa believed that thyroid nodules begin as focal hyperplasia of the thyroid lobule
and thus thyroid neoplasms are a clinical presentation of a single focus of replicating cells
representing an early stage in the development of thyroid cancer1. Consequently, till the
advent of fine needle aspiration cytology (FNAC), more thyroidectomies were done for
solitary thyroid nodules to exclude malignancy than for any other thyroid disorder. Even
today, the advent of a thyroid nodule excites considerable anxiety in the physicians mind
despite the modest probability of malignancy in such a nodule.
Iodine deficiency has been reported officially as a National Health problem and is
tackled as a National Programme in India2. People in these goitrous areas normally do not
bother about the neck swelling which is so common amongst neighbours and relatives.
Clinicians dealing with thyroid diseases in these areas, on the other hand, face the dilemma
of having to deal every thyroid nodule as a neoplastic disorder requiring investigations in an
effort to exclude malignancy.
Today it is recognised that optimal management must take into account several
factors such as clinical and laboratory indicators of malignancy, patients preference and a
current understanding of the benefits and potential harm in conservative management.
Further, in the evaluation of thyroid nodules various diagnostic tools are available; however,
none of these is specific in identifying cancers requiring surgical intervention.
Prevalence of Thyroid Nodules
Thyroid nodules may be solitary, i.e. confined to one lobe when the contralateral lobe
is impalpable, or may be multinodular, involving one, or more commonly both lobes of the
thyroid gland. Approximately 1.5% of adolescents may have palpable nodules with reports in
3% to 7% of adults with a male to female ratio of 1:5.3,4 Patients suspected clinically to have
solitary thyroid nodules were found to have one or more additional nodules in 16% to 48% of
cases as assessed by preoperative ultrasound and in 29% to 48% of cases based on careful
histologic examination5,6. One recent study of patients undergoing surgery for apparent
solitary thyroid nodules showed that palpation alone missed 58% and 78% of additional
nodules in partial and total thyroidectomy specimens respectively, and that even
preoperative ultrasound missed between 41% and 58% of nodules ultimately detected on
histologic evaluation.7,8 The significance of correctly identifying solitary thyroid nodules lies in
163
10
The prevalence of malignancy in solitary thyroid nodule (STN) varies from 1.7% to
28.7%, and in cold STN, the prevalence of malignancy is even higher, varying from 8% to
31%.8,11 Amongst 546 patients with STN from an endemic area, the prevalence of
malignancy was 17.8% (31/174) in males and 7.5% (28/372) in females.12
Differential Diagnosis of Apparent Solitary Thyroid Nodules
Benign thyroid neoplasms
Follicular adenoma
* Colloid
* Simple
* Foetal
* Embryonal
* Hurthle cell
Papillary adenoma
Teratoma
Lipoma
Dermoid cyst
Malignant thyroid neoplasms
Papillary carcinoma
Follicular Carcinoma
Medullary carcinoma
Anaplastic carcinoma
Metastatic cancer
Sarcoma
Lymphoma
Other thyroid abnormalities
Thyroiditis
Thyroid cyst
Infections
Granulomatous disease (e.g., sarcoidosis)
Nonthyroid lesions
Lymphadenopathy
Thyroglossal duct cyst
Parathyroid adenoma
Laryngocele
164
positive
family
history
of
thyroid
cancer,
hyperparathyroidism
or
phaeochromocytoma should raise the suspicion of medullary thyroid cancer. It may occur
sporadically as well as in conjunction with multiple endocrine neoplasia MEN 2A and MEN
2B, and also with the familial medullary thyroid cancer (FMTC) syndrome.4
STN: Suspicious clinical features4,8,12,19
Age: less than 20 years or more than 60 years
Male sex
Prior head and neck irradiation
165
Rapid growth
Pain
Hoarseness of voice
Hard consistency
Fixation to adjacent structures
Regional lymphadenopathy
Nodule in Graves disease
However, clinical symptoms and signs lack specificity for detecting thyroid cancer.4,8,12,19
Many clinical features suspicious of malignancy may be seen in benign thyroid nodules.12
Suspicious clinical features
Histologically benign
29%
Hard consistency
50%
Nodule fixity
29%
Voice change
(true vocal cord paralysis)
17%
Laboratory Tests
Thyroid function tests may be required to establish the functional state of the thyroid;
however, they have no role in identifying goitres harbouring malignancy. 19 (Algorithm 1)
Serum TSH estimation is sufficient and decides the further course of management of
clinically euthyroid nodules. Approximately 10 percent of patients with a solitary nodule have
a suppressed level of serum thyrotropin, which suggests a benign hyperfunctioning nodule.4
Goitres with either subclinical or overt hyperthyroidism rarely have a concomitant thyroid
malignancy;
conversely,
thyroid
cancers
only
rarely
cause
hyperthyroidism.4,21
Hyperthyroidism, either overt or subclinical, in the setting of a thyroid nodule may suggest an
autonomously functioning thyroid nodule (AFTN), a toxic multinodular goiter, or the MarineLenhart syndrome (multinodular form of Graves disease).
If a patient has a family history of medullary thyroid cancer or multiple endocrine
neoplasia type 2, a basal serum calcitonin level should be obtained; an elevated level
suggests medullary thyroid cancer.4
166
Algorithm 119
Radionuclide Scanning
Scintillation scanning with
123
I or
93m
euthyroid patients with solitary thyroid nodules. In a review of 546 patients with thyroid
nodules undergoing preoperative scanning, 84% of nodules were hypo-functional or cold,
10% were isofunctional or warm, and 6% were hyperfunctional or hot; thyroidectomies of
these patients with thyroid nodules revealed malignancy in 16% of the patients with cold
nodules, 9% of patients with warm nodules, and 4% of those with hot nodules.21 Since the
overwhelming majority of both benign and malignant solitary thyroid nodules appear cold on
scanning, and because even some warm and hot nodules may actually be malignant, the
finding of a cold nodule on radionuclide scanning is neither sensitive nor specific nor costeffective in detecting malignancy.4,9,22 Thus, radionuclide scanning for nodular goitres is not
routinely indicated.
However, there are two clinical situations in thyroid nodular disease where
radionuclide scanning serves a useful purpose. Firstly, scanning for thyroid nodules in
patients with overt or subclinical hyperthyroidism would separate the hyperfunctioning (`hot)
nodules and diffusely hyperfunctioning gotre; the treatment would, therefore, be accordingly
modified. On the other hand, a cold nodule in the setting of Graves disease would raise the
probability of malignancy in such a nodule.8 Secondly, scintillation scanning may be
performed for clinically euthyroid nodules yielding suspicious cytology on FNAC. 23 The
finding of a hyperfunctioning nodule in this circumstance would theoretically exclude
167
malignancy while a non-functioning area in a cold nodule would help in identifying the area
for FNAC.
Ultrasonography
Ultrasonography has a great value in differentiating a cystic from solid thyroid
nodules. Pure cysts are rarely malignant and can be treated by aspiration. 24 Complex cysts,
on the other hand, have equal propensity for harbouring malignancy as the solid nodules. In
such a situation, ultrasound can guide FNAC from solid areas of complex cyst.9,24
High resolution ultrasonography discloses multinodularity in up to 40% of clinically
apparent solitary thyroid nodules; however, such incidentally seen nodules are of unknown
clinical significance.4 In endemic goitrous areas possibly such an investigation, especially
when identifying nodules in both lobes, may help the physician into deciding to initiate
thyroxine suppression even when the FNAC report is `suspicious signifying a follicular
neoplasm. It is also important to emphasise that such ultrasonographically seen multiple
nodules may actually be multicentric foci of a malignant follicular neoplasm. Blum reports the
ultrasonic findings that are
statistical probabilities and not dependable criteria.25
Thyroid malignancies tend to be hypoechoic when compared with the rest of the
thyroid.. Since most benign thyroid nodules, which are far more common than
malignancies, are also hypoechoic, this finding is not particularly useful except that it
is reasonably safe to conclude that hyperdense nodules are probably not cancerous.
The presence of calcification is also not a straight forward diagnostic aid. Micro
calcifications are relatively more common in malignant lesions than benign and may
represent psammoma bodies. Micro calcifications have been reported as
demonstrating a 95.2% specificity for thyroid cancer, but a low sensitivity of 59.3 %
and a diagnostic accuracy of 83.8%. However, large coarse calcifications and
calcifications along the rim of nodule are common in all types of nodules and reflect
previous hemorrhage and degenerative changes. Thus, thyroid calcifications as
detected by sonography provide little practical help in identifying cancer in the
individual case. In one study, the highest incidence of calcification was found in
thyroid cancer (54%), followed by multinodular goiter (40%), solitary nodular goiter
(14%), and follicular adenomas (12%). The authors reported that calcifications in a
"solitary" nodule in a person younger than 40 years person should raise a strong
suspicion of malignancy because of a relative cancer risk of 3.8 versus 2.5 in patients
older than 40 years with calcified nodules. It is useful to note that large calcifications
are seen with increased frequency in medullary thyroid carcinoma.
168
A halo around the nodule may be seen with benign or malignant conditions. It
suggests that there is an acoustic interface that does not reflect the ultrasound
across two different types of histology in the region, the nodule and the surrounding
thyroid. Some observers have suggested that cancer should be suspected when the
periphery of a halo has a blurred appearance.
Thus, ultrasonography has little discriminatory value in the distinction of benign from
malignant disease. Sonography also demonstrates micronodules (incidentalomas) of the
thyroid that are less than one centimeter in diameter, non-palpable, common, and of
questionable clinical significance, which increase with age to involve approximately 50% of
older adults especially women and the risk of malignancy appears to be considerably much
less than palpable nodules.25
Fine Needle Aspiration Cytology (FNAC)
FNAC has now become the first-line investigative modality for solitary thyroid
nodules. It has resulted in 35% to 75% reduction in the number of patients requiring surgery
for this condition, a two to three fold increase in the yield of malignancy in operated cases,
and a reduction in thyroid nodule management cost by as much as 25%,12,26-28 FNAC also
helps to differentiate cystic from solid nodules, and may be therapeutic for a purely cystic
nodule.24
Adequacy rate for diagnosis is in the range of 80%90 %.; the rate of false-negative
diagnoses is in the range of 6.6%25.5%; the false-positive diagnoses is in range of 2%20
%; sensitivity is in the range 84%97 %; specificity ranges from 6087 %; and the diagnostic
accuracy is in the range of 69 %87%.10 Sampling errors occur in very large (more than 4
cm) and very small (less than 1 cm) nodules, and can be minimized by using ultrasoundguided biopsy.19
Suspicious results on FNAC are a special problem with a majority of them being
follicular and Hurthle cell neoplasms, since FNAC benign from malignant follicular
neoplasms. Repeat FNAC is unlikely to improve the chance of a definite diagnosis. Further,
about 20% (range 10-50%) of solitary thyroid nodules with suspicious FNAC turn out to be
malignant on histopathology.26 Although some centers have developed complex cytologic
criteria (such as ploidy studies, cell morphology, mitotic figures, etc.) in an effort to isolate
follicular cancers29, these have not been universally accepted, nor they have been uniformly
successful in isolating malignant follicular lesions.
169
170
Cystic STN
- recurs after complete aspiration (one or more times depending on the centre)
- residual swelling after aspiration
- malignant or suspicious cytology of aspirated fluid
Hemithyroidectomy (a lobectomy and isthmusectomy with removal of a sleeve of the
contralateral lobe laying the trachea bare) is the ideal surgery for a benign nodule requiring
surgery and also for nodules with suspicious cytology. Patients with suspicious cytology
should be managed with hemithyroidectomy with, if necessary, completion thyroidectomy if
the histology of the excised specimen reveals malignancy32; alternatively, the extent of
surgery may be decided on the basis of the frozen-section report33. Patients with malignant
aspirates should undergo total or near-total thyroidectomy.34 Near total thyroidectomy
protects the recurrent nerve at the site of its entry into the larynx, as well as spares the
superior parathyroid gland and is considered an oncologically equivalent procedure to total
thyroidectomy for well-differentiated thyroid cancers.34
With increasing surgical experience, total thyroidectomy has become an effective
treatment for benign thyroid disorders, especially in benign multinodular goiter35-40 on the
premise that a less than total resection leaves behind some nodules which may cause
persistence of symptoms because of their strategic location (behind the esophagus or in the
tracheo-esophageal groove) or may cause recurrence of goiter in approximately 19% of
patients, if they have a long term follow up.35 Total thyroidectomy is advocated for Graves
disease41 and is reported to be extremely beneficial in limiting the deterioration of eye
disease in patients with Grave's disease38. Another reason sited in favour of total rather than
subtotal thyroidectomy is a reduction in risk of recurrent hyperthyroidism. 42 Although good
results with minimal complications related to recurrent laryngeal nerve injury and permanent
hypoparathyroidism are reported, the necessity of lifelong thyroxine replacement in all
patients with a benign thyroid disease cannot be overlooked. However, it seems difficult to
assert total thyroidectomy as the best surgical option for thyroid nodules.
THYROID HORMONE SUPPRESSIVE THERAPY
Use of TSH suppressive therapy with thyroxine to manage benign, solitary thyroid
nodules remains controversial.19,43 Treatment with levothyroxine at a dose sufficient to keep
the serum thyrotropin at a level below 0.3 mU per liter has been suggested as a way to
prevent growth of an apparently benign nodule.4 The use of thyroid hormone suppressive
therapy in the treatment of patients with benign thyroid nodules is based on the premise that
the nodule is TSH dependent. The suppression needs to be continued from 6 months to one
year with regular follow up for evaluation by ultrasonography. More prolonged therapy
171
172
Larger
Smaller
Surgery
Benign
LT4 therapy
(target TSH
0.5-3.0 mU/L)
Unchanged
Malignant
Nodule growth
LT4 therapy
Restart LT4
(target TSH
(target TSH
*low risk: 0.05-0.1 mU/L) 0.1 -0.5 mU/L)
No change
Follow up
LT4
The task of the clinician is to distinguish the few potential responders from the majority who
would either fail to respond or would experience spontaneous nodule regression. Further,
the patient and the physician must weigh the benefits of long-term therapy and the potential
risks.
Sclerotherapy
A number of studies have reported the benefits of sclerotherapy after up to three
aspirations of purely cystic thyroid nodules.4,9,24,47,49 In addition, reluctance to use radioactive
tracers has been the incentive for numerous Italian centers to introduce percutaneous
ethanol injection therapy (PEIT) during the last 15 years as a proposed alternative to
radioiodine therapy and surgery for patients with autonomously functioning thyroid nodules.45
The procedure involves the instillation of ethanol directly into the nodule under ultrasound
guidance. Absolute ethanol (70100%) can cause permanent tissue ablation due to
coagulative necrosis and local small vessel thrombosis. The procedure requires prior
173
documentation of benign cytology, skill, and experience.4 In patients who refuse surgery or
are medically unfit to undergo surgery PEIT has also been advocated.46 A single small dose
of ethanol injected into benign cold solitary solid thyroid nodules results in relief of clinical
symptoms in 50% of patients, based on a nodule volume reduction of approximately 50%.47
Repeat (i.e., seven or more) injections result in a reduction in nodule volume of 80%.47 A
limitation is the need of repeat ethanol injections to prevent renewed growth in solid cold
nodules. The drawbacks cited by Hegedus include limited experience with treatment,
decreasing efficacy with increasing nodule size, success dependent on operators skill,
painful (reducing compliance), risk of thyrotoxicosis and vocal-cord paralysis (approximately
12%), seepage of ethanol, interpretation of cytologic and histologic findings impeded in
treated nodules.4 An autoimmune response with development of thyroid autoantibodies can
be seen in up to 11% of treated patients.47 The procedure should still be considered
experimental and reserved for those who cannot or will not undergo standard therapy. The
experimental status is illustrated by only 1% of the European clinicians and none of the
American clinicians advocating this therapy.47
Recently, data from a preliminary study suggested that the use of laser
photocoagulation may be as effective as ethanol injection, with fewer adverse effects.48
Radioiodine Therapy
Due to this effect on gland volume,
131
the treatment of compressive nontoxic nodular goiters.47,50 It has recently been shown that
patients with a substernal goiter may also benefit from
131
131
therapy on the whole gland is hampered by the irregular 131I uptake in the multinodular goiter.
The number of suppressed nodules and extent of degenerated tissue probably set an upper
limit for the obtainable reduction with this treatment. Most nodules do not disappear after
radioiodine therapy but may become harder on palpation and may reveal unusual cytologic
features as a result of irradiation.4 Only in very few European countries, like Denmark and to
some extent The Netherlands, is
nontoxic multinodular goiter.
47
131
131
include low thyroid iodine uptake (especially if the dietary iodine intake is high), lack of
experience, decreasing effect with increasing size, small risk of acute goiter enlargement,
risk of thyroiditis (3%),
hypothyroidism (1520%), and long-term cancer risk are unknown.47 The fact that
131
174
131
occasionally persistent cases, therapy of the hyperthyroidism and the ophthalmopathy can
be troublesome.
However, radioiodine is an option for treatment of a functioning nodule, with or
without biochemical hyperthyroidism. Normalization of the results of thyroid radionuclide
scanning and the serum thyrotropin level (often referred to as a
cure) is achieved in 75
percent of patients, and thyroid volume is reduced an average of 40 percent, after a single
dose of iodine-131 aiming at a level of 100 Gy, independent of pretreatment thyroid
function.4,47 Radioiodine therapy is as effective as surgery for the treatment of patients with
autonomously functioning thyroid nodules and those with toxic multinodular goiters. The
reversal of hyperthyroidism after radioiodine therapy is, however, more gradual than that
after surgery. On the whole,
131
Hypothyroidism after radioiodine treatment is considerably less common in patients with toxic
nodular goiter than in those with Graves' hyperthyroidism. Among patients with
autonomously functioning thyroid nodules, the cumulative incidence of subclinical and clinical
hypothyroidism is 10 percent, on average, after mean follow-up ranging from 1 to 10 years.51
Among patients with toxic multinodular goiter, hypothyroidism occurred in less than 20
percent in most studies, even after long-term follow-up. The frequency of hypothyroidism is
highest among patients who also have thyroid autoimmunity.52 In a large follow-up study, the
risk of thyroid carcinoma was not increased and the risk of carcinoma elsewhere was not
increased or only marginally increased.51
Conclusions
There are no data from studies comparing the outcome and cost-effectiveness of
various strategies of evaluating a nodule (e.g., using radionuclide imaging and
ultrasonographic guidance for fine-needle aspiration). There is agreement on the central role
of FNAB in addition to serum TSH determination in the initial evaluation of such individuals.
Evidence suggests that US guidance increases adequacy of sampling. There are also
insufficient data comparing the outcome (including quality of life) of various management
approaches in the absence of cancer. The available evidence suggests that suppressive
therapy should be abandoned in the euthyroid individual. Surgery should be recommended
for younger patients, for those with a large goiter (especially if intrathoracic), and in case of
clinical or cytological suspicion of malignancy. An algorithm for the management of solitary
thyroid nodules is presented.
175
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Wheeler MH. Total thyroidectomy for benign thyroid disease. Lancet 1998; 351: 1526-1527.
Total thyroidectomy for bilateral benign multinodular goiter. Effect of changing practice. Arch Surg
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Acun Z, Comert M, Cihan A, Ulukent SC, Ucan B, Cakmak GK. Near total thyroidectomy could be
better treatment for thyroid diseases in endemic regions. Arch Surg 2004; 34:444-447.
Friguglietti CU, Lin Cs, Kulcsar MA. Total thyroidectomy for benign thyroid disease. Laryngoscope
2003; 113:1820-1826.
Bron LP, OBrien CJ. Total thyroidectomy for clinically benign diseases of the thyroid gland. Br J
Surg 2004; 91:569-574.
Colak T, Akca T, Karik A, Yapia D, Aydin S. Total versus subtotal thyroidectomy for the
management of benign multinodular goitre in an endemic area. ANZ J Surg 2004; 74:974-978.
Barakate MS, Agarwal G, Reeve TS, Barraclough B, Robinson B, Delbridge LW. Total
thyroidectomy is now the preferred option for the surgical management of Graves' disease. ANZ J
Surg 2002; 72:321-324
Winsa B, Rastad J, Akerstrom G. Retropective evaluation of subtotal and total thyroidectomy in
Graves' disease with and without endocrine ophthalmopathy. Er J Endocrinol 1995; 132: 406-412.
Wmeau JL, Caron P, Schvartz C, Schlienger JL, Orgiazzi J, Cousty C, Vlaeminck-Guillem V.
Effects of Thyroid-Stimulating Hormone Suppression with Levothyroxine in Reducing the Volume
of Solitary Thyroid Nodules and Improving Extranodular Nonpalpable Changes: A Randomized,
Double-Blind, Placebo-Controlled Trial by the French Thyroid Research Group. J Clin Endocrinol
Metab 2002; 87:4928-4934 .
Burch HB. Evaluation and management of the solid thyroid nodule. Endocrinol Metab Clin N Am
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Zingrillo M, Collura D, Ghiggi MR, Nirchio V, Trischitta V. Treatment of Large Cold Benign Thyroid
Nodules Not Eligible for Surgery with Percutaneous Ethanol Injection. J Clin Endocrinol Metab
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178
Operation Room (OR) techniques implies the knowledge of basic OR design and the
development of OR protocols with the following principles in mind (a) infection control (b)
safety (c) efficient use of personnel, time and space. Often the surgeon is called to
commission a new set up after the design has been conceived and put in place by an expert
who is not going to be the actual user. The surgeon is then forced to adopt policies which
are different from those originally thought of during planning resulting in an inefficient use of
facilities. The subject is complex as new ideas are being constantly developed and even
when the surgeon is involved from the beginning he is often not aware of the principles
involved in OR design or development of protocols.
1. Number and location of the OR Complex. The workload and the number of
specialties would determine the number of OR to be made. It is generally seen that
OR are underutilized. Efficient use of the OR by sharing the operating rooms and
having planned and staggered sessions could reduce the number of OR required to
be built. The OR complex should be easily accessible from the wards and should be
at the same level as the Intensive Care Unit (ICU).
2. Spacing. The movement in the OR is generally segregated into the following access
zones
General Access zone. This includes the entrance and reception; patient
transfer area, staff changing rooms and disposal hold area. A single main
entrance will simplify the security. Transfer of the patients will be guided by
the patient transport policy adopted. If the patient is brought to the OR on
ward trolley he can be transferred to the OR- trolley in this area. In case the
patient is transferred to the OR on his bed, a policy adopted by many centers,
space has to be designed for parking the beds. In the staff changing rooms
there has to be provision for personal lockers. OR clothing can be stored in
open shelves.
In this zone, an area has to be planned for temporary holding of soiled linen
and dressings. The bags containing these should be labeled indicating the
OR number and released after all counts have been verified.
179
Limited Access Zone. Entry into this zone is allowed only after change to OR
suites and protective caps. Space has to be provided for the staff control
base, rest rooms, teaching rooms and storage rooms. The staff control base
is the point where coordination of OR activities take place. The area is also
used for receiving and temporary storage of blood for transfusion and
pathology samples and specimen for onwards transmission. Opinions can
vary whether we have a common rest room for all staff or have different
rooms for each category of staff. A practical solution could be to have the
changing rooms with two partitions. The inner partition can be used for rest
room purposes. It is always good to have a room for teaching purposes in the
OR. There has to be a room for the administrator-usually the sister in-charge.
Adequate planning must be done to have ample storage space in this zone. A store
is required for disposable items, dressings, intravenous fluids and drugs. A store is
also required for equipments not used very frequently and the operation table
accessories. Another store is required for storing gas cylinders. A store is also
required for keeping the cleaning items used exclusively for the OR.
An exclusive area has to be planned for the post-anesthesia recovery of the patients.
This area must have central supply of gases like the OR, monitoring equipments and
anesthesia machine.
Restricted Access Zone. This area has the operating rooms, the anesthesia
rooms, the scrub-up and gowning area the sterile store and the utility. There
must be a sterile store in this zone for storage of sterile instrument trays,
sterile linen and gowns bundles and sutures. A utility area adjacent to the OR
is required for the preliminary decontamination and washing of used
instruments and non-disposable linen
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brightness of 50 000 to 100 000 Lux at the center of the operating field. To reduce
shadows even when light is obscured by heads of the operating team OR lights are
designed to give light from various angles. This is achieved by a single light bulb
source with multiple reflectors or more commonly the use of multiple light bulbs fitted
into a single housing or many bulbs mounted individually in pods. The later has the
advantage of allowing free flow of air without causing turbulence. Heat emitted from
the light source is reduced by use of heat absorbing reflectors, which reflect the
visible portion of light but transmit the infrared backwards for heat dissipation.
The pressures in the operation rooms are kept at 25 Pascal (Pa) above atmospheric
pressure, in the scrub area at 14 Pa, in the corridors and changing rooms at 3 Pa
and in the disposal area at 0 to 5 Pa so that flow of air is always outwards
minimizing air-borne contamination. Air is installed in the OR using high efficiency
particulate air (HEPA) filters. They remove particles of size0.3 microns or greater in
diameter. The air- flow supply to an average OR is about 0.75 to 1.0 cubic
meters/sec.
To minimize the harmful effects of anesthesia gases on personnel it is advisable to
have a scavenging system to remove the gases. The temperature of OR is
maintained at 22 degrees C with a relative humidity of 40-60%.
4. OR protocols. Entry to the limited and restricted access areas is always done after
changing into clean OR scrub suits and footwear with the head covered by a
headgear. The aim is to prevent the entry of pathogenic organisms into the OR.
Taking of pre-operative shower in the OR complex is not recommended nowadays as
this causes shedding of skin cells for several hours afterwards. The scrub suits
should have leggings and sleeves with elastic stockinet cuffs so that any skin
particles shed remain contained. The colour used is usually blue or grey to
differentiate from the green colour of sterile OR gowns and towels. The benefit of
wearing masks has been questioned. Best protection is offered by synthetic or
fibreglass masks moulded to fit the facial contour.
OR linen is usually coloured green, which is most comfortable to the eyes. Use of
standard cotton and cotton-polyester mixed textiles has the disadvantage of allowing
liquids, particles and microorganisms to penetrate. Use of barrier surgical drapes and
gowns using liquid repellent micro-filament materials is desired (1). The usual towels
for covering the operative area are 4 feet square. For covering the lower limbs drape
towel are of the size 6feet by 5 feet. The cut-sheets are usually sized 7 feet by 6 feet
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having a reinforced slit of 12in by 4in. Gowns should have stockinet cuffs with an
overlap piece at the back which when tied over would cover the back. Sponges used
during surgery are usually 9in square with 24 layers of gauze.The ready made ones
contain a radio-opaque marker line. Swabs or gauze should be arranged in bundles
of 5s. To avoid confusion in counts it is a good idea to have anaesthesia swabs
coloured green.
In a modern OR complex there is no place for the Cheatles forceps or the drum
system. Standard set of instruments should be packed in trays and wrapped in
double sheets-an outer blue wrapping which is opened by the circulating nurse and
an inner green wrap handled by the scrub nurse. Other sets containing gowns and
hand towel, drapes, towels and cut-sheets and gowns are opened for each case. Any
item unused is discarded or packed for re-sterilization. Fresh packs are opened for
the next procedure. Some of the instruments, linen and dressings are packed
individually in single packs to add to the supplies if needed.
5. Sterilization & Storage. The most efficient and convenient method of sterilization for
reusable items is by autoclaving. Most centers now have the high- vacuum highpressure sterilizers. The air in the load is first extracted by a series of vacuum and
steam pulsations. Sterilization is then achieved by steam at 134 degrees C for 3.5
minutes-the holding time of the cycle. The load is then dried by adequate vacuum.
The entire cycle is recorded as a tracing for each lot.
Periodic checks are required for to ensure proper functioning. A simple test is called
the Bowie- Dick test. A test pack is made by folding OT towels to form a stack 10in
high. In the middle of this test pack is placed a paper 12in square on which sterilizing
tapes have been pasted in the form of an X. This pack is then placed in the sterilizer
and the standard sterilizing cycle run. The pack is then removed and examined. The
sterilizing tape should show uniform color change at all points. If the color change is
irregular and incomplete the sterilizer need to be attended to. The standard protocol
requires that everyday the first cycle of the autoclave should be an empty chamber
cycle. The second cycle should use the Bowie- Dick test kit. If the autoclave fails the
Bowie Dick test the machine should not be used till it is repaired. Ready-made cubes
of paper packs are now commercially available as an alternative to the Bowie Dick
towel pack.
It is essential that before sending for sterilization the instruments must be cleaned
thoroughly to remove all organic debris. In a recent study (2) it was demonstrated
182
that 17% of instruments from autoclaved sets had organic matter above an accepted
threshold of 200 micrograms which could pose risk of cross contamination.
6. Disinfection. Disinfection is a process by which most but not all pathogenic
organisms on inanimate surfaces are destroyed. Patient care equipment is classified
into categories based on the degree of risk of infection associated with use of each
item.
a. Category I-Critical items are those that must be sterile. Example of these are
the surgical instruments, catheters and implants.
b. Category II-Semi-critical items are those that come in contact with mucosa.
The items in this category must be free of microorganisms except for spores.
They require high and intermediate level disinfection. Examples of this
category are anaesthesia equipment, endoscopes, thermometers.
c. Category III-Non-critical items come in contact with skin. They require
intermediate and low level disinfection.
The chemical disinfection recommended for patient care items and instruments
include glutaraldehyde, hydrogen peroxide, paracetic acid, sodium hypochlorite,
alcohol, iodophors, phenolics and quaternary ammonium compounds (3)
Protocols. All furniture, lights and fixed equipment in the OR must be damp dusted
every day before the start of the list using chemical disinfectant. The floors should be
mopped in between cases with a disinfectant. At the end of the day pads of the
operating tables should be removed to expose the table tops which should be
cleaned. The table must be moved so that one can clean under the table. Doors and
wall should be cleaned and cabinet doors and latches must be cleaned.
Effect on surfaces of ceiling and wall mounted Ultraviolet Lights has been compared with
standard cleaning and disinfection protocols and found to be as effective (4)
7. Antisepsis. Antisepsis is a process that destroys most pathogenic micro-organisms
from animate surfaces. During hand wash for surgery the organic debris is removed
and the transient and resident microbial flora reduced. It is also desired to inhibit
growth of bacteria over time. Chlorhexidine in detergent base, povidone-iodine with
detergent and chlorhexidine with alcohol containing emollients to prevent dryness of
skin are all effective (5,6,7). For patient preparation hair should be removed as close
183
to the time of surgery as possible and is best removed with electric clippers. No
benefit of pre-operative bathing with antiseptics have been found (8)
References
st
1. Patel SR, Urech D, Werner HP. Surgical gowns and drapes into the 21 .century. Br J
Theatre Nurs 1998;27:30-37
2. Murdoch H, Taylor D, Dickinson J, Nalker JT, Perrett D, Raven ND, Sutton JM. Surface
decontamination of surgical instruments: an ongoing dilemma. J Hosp Inf 2006;63:432-438.
3. Rutala WA, Weber DJ. Infection control: the role of disinfection. J Hosp Infec 1999;43:S 4355
4. Andersen BM, Banrud H, Boe E, Bjordal O, Drangsholt F. Comparison of UVC light and
chemicals for disinfection of surfaces in hospital isolation units. Infec Control Hosp Epidemiol
2006;27:729-734.
5. Hsieh HF, Chiu HH, Lee FP. Surgical hand scrub in relation to microbial counts: systemic
literature review. J Adv Nurs 2006;55:68-78
6. Nishimura C. Comparison of antimicrobial efficacy of povidone-iodine, povidone-iodineethanol and chlorhexidine gluconate-ethanol surgical scrubs. Dermatology 2006;212:21-25.
7. Grabsch EA, Mitchell DJ, Hooper J, Turnidge JJ. In-use efficacy of a chlorhexidine in alcohol
surgical rub; a comparitive study. ANZ J Surg 2004;74:769-772
184
Introduction
The objective of this chapter is to re-introduce the surgical residents to the airway
and the indicators that point towards problem with the airway, and various maneuvers,
devices and techniques that they may use to manage the airway. These then will form the
basis to highlight the decision making and handling of the airway related problems that they
may face in their surgical practice. The chapter does not intend to deal with ventilatory
management.
Case 1: A fifty year male underwent excision of Ca. buccal mucosa with reconstruction in a
seven-hour surgery. He was shifted to the postoperative ward after an uneventful
extubation. After about an hour, the nurse informs you that the patient is drowsy and
the SpO2 is falling progressively. One of your resident colleagues says that he can
see clear signs of airway obstruction. How will you know whether he is right or
wrong? What are the common causes of airway obstruction in such patients? How
can you relieve them till expert help arrives?
Case 2: A forty five year lady is wheeled into the surgery postoperative ward after
laparoscopic cholecystectomy at around 4 pm. The surgery resident visits her at 4.30
pm and, finding her complaining of pain, gives tramadol 100mg IM but does not enter
on the treatment sheet. The nurse in the postoperative ward comes to the patient for
BP check at 4.40 pm. The patient complains of pain and she gives her another shot
of IM tramadol 100 mg and makes an entry. The anesthesiology resident comes to
see her before leaving the OT for the day at 4.50 pm and instructs the staff to give IM
diclofenac 75 mg to the patient to supplement the tramadol as she is still in some
pain. You (the surgery resident on night duty) are summoned by the nurse on duty at
around 6 pm saying that the patient is not OK. You find her extremely sleepy,
arousable only on painful stimuli. Her respiration is noisy and strenuous, the SpO2 is
82% and pulse and BP are 124bpm and 140/96mmHg respectively. How will you
proceed?
Case 3: A 30 year lady underwent total thyroidectomy over almost 5 hours for huge Ca.
thyroid. On your evening round you find her very restless, making sharp noises with
each effort to breathe. Her chest and abdomen are moving up and down deeply but
in a rather unnatural manner. The monitor shows a pulse rate of 146 bpm with
185
The Dual Pathway consisting of nasal cavity and nasopharynx on one side and oral
cavity on the other;
Airway obstruction (AO) may occur due to many reasons. Some of these are depicted in
Figure1. The obstruction may be Acute (one that needs to be treated immediately) or
Chronic (such as obstructive sleep apnea, COPD, asthma etc.); and it may be Partial or
Complete. It is simple to deduce that acute and/or complete airway obstruction is more likely
to occur in the areas that have no alternative routes
the single path.
186
Nasal Cavity
DNS, Polyp, FB,
Trauma, Tumor
Nasopharynx
Adenoids,
Retropharyngeal abscess,
Trauma, Tumor
Oral cavity
Tongue, Facial Trauma,
Tumor
Hypopharynx
FB, hemorrhage,
secretions
Oropharynx
Base of tongue, epiglottis,
tonsils, hemorrhage,
secretions
The recognition of AO depends upon the recognition of symptoms and signs. These
symptoms and signs are caused due to turbulent breathing, breathing against obstruction
leading to lower intra-thoracic pressures that sucks the soft tissues in place of air, lack of
oxygen, and increased CO2. Classically, recognition of airflow, and thus airway obstruction
has been described under the heading of Look, Listen, and Feel. Here is how we can apply
this:
187
And finally, one feels for air flow (on back of hand or cheek), which is reduced when
there is partial obstruction and is absent during complete obstruction.
The location of AO may also be guessed. While snoring sound or gurgling indicates foreign
matter, secretions or soft tissue causing obstruction in and around oropharynx, hoarseness
indicates problem around the larynx, stridor (most often inspiratory) typically originates from
the larynx, upper trachea, or hypopharynx due to obstruction in the larger airways, and
wheeze is an expiratory sound produced by the turbulent flow of air through constricted
small airways (bronchioles).2
A working knowledge of airway anatomy and the symptoms and signs of AO helps in
quickly identifying AO, its severity and its probable location. This then forms the basis of
deciding the level of emergency and the time available for intervention to bypass/ameliorate
the precipitating cause. The intended intervention should aim at changing a complete/partial
airway obstruction to an open airway, and saving precious lives.
Oxygen Enrichment during Airway Management
The means to manage an obstructed airway can vary from the simple manual
maneuvers to the more sophisticated ones like tracheostomy or the use of fiber-optic
bronchoscope. But it must be clearly understood that right from the time airway management
is started and then throughout the airway management efforts, the end result one is aiming
for is to ensure adequate tissue oxygenation. Although oxygenation will be stabilized and
optimized only once an open airway is ensured, but while the effort to open the airway is on
and the airway is only partially open, better tissue oxygenation and thus better outcome, can
be achieved if the importance of oxygen enrichment during airway control is understood. For
this, all one needs besides oxygen source is the knowledge that oxygen should be and can
be given throughout the airway management attempts (e.g., rescuer wearing nasal cannula
to enrich his expired air while giving mouth-to-mouth respiration!), and a bit of skill.
In the airway related emergency/semi-emergency situations most often faced by the
surgical colleagues, it can be said with reasonable confidence that one should use
whichever oxygen delivery system that is easily available and then deliver as much oxygen
that one can deliver. The only other things worth remembering are: (i) the O 2 flow rate
should be kept at less than 6 liters per minute (lpm) when using cannula/catheter and it
188
should be kept 10-15 lpm when using any kind of mask; and (ii) if you dont have a flowmeter
and are dependent on counting bubbles through water to guess the O2 flow, remember that
when the bubbles are just uncountable, the flow rate is only around 1-1 lpm!
Call for Help
Whenever handling an emergency or potentially life threatening situation for your
patient, it is advisable to ask for help (expert help is ideal but some help is better than no
help). Airway related problems have the notorious habit of worsening as fast as a free fall
and even in expert hands the slightest of delay in decision making or intervention can be
fatal for the patient. Once the expert help has been summoned (preferably by your
companion - medico or any paramedic), you can start the management as per your
capability and ensuring that your help (trying a half learnt intubation and causing oral
trauma and bleed making the job of the helper more difficult) does not cause any further
deterioration of condition of a patient already in trouble!
Means to Manage Obstructed Airway
The following section will touch upon the airway management maneuvers and devices
which all the doctors should know.3 Even when choosing out of these must know maneuvers
and devices, it is important for any doctor managing an airway problem to realize his
limitations and work within them instead of trying the best thing with which he has not
mastered well. A non-specialist trying to intubate instead of oxygenating and attempting to
ventilate the lungs with bag-mask-valve makes the job of the specialist (anesthesiologists,
intensivists and pulmonologists) MORE specialized and likelihood of patient survival less
probable!
(i) Manual methods
Head tilt-chin lift and jaw thrust are the manual methods described that do not require
any device to open the airway. These work by stretching the anterior structures of neck
thereby lifting the tongue and the epiglottis off posterior pharyngeal wall.
In performing the head tilt-chin lift maneuver to open the airway, emphasis is
placed on using the bony portion of the chin to better "lift" the chin upward. That is most
effectively done if the fingers are on the harder part of the chin (Figure 2). If the fingers
are pressing into the soft tissues, depending on the direction of the pressure, there is
some chance that the soft tissues may impede airflow in the mouth cavity. 3 In case of
doubtful C-spine, jaw thrust is the recommended method for opening the airway (Figure
3), together with manual in line stabilization to prevent any inadvertent movement of the
neck while applying jaw thrust.
189
(ii) Suctioning
Suction is used to clear the airway of oral secretions, gastric contents, blood (trauma) or
solid foreign body. It is carried out in the presence of audible or visible airway secretions
when the patient himself can not throw or swallow them out. This may happen due to
altered consciousness and depressed airway reflexes. Before attempting suction, it must
be understood that suctioning is NOT an innocuous procedure that can be taken lightly.
It has the potential of inducing damage to both the patient and the operator. The patient
can be subjected to severe stress (and hemodynamic changes thereof), hypoxemia,
injury and infection; and the operator may expose himself to the risk of infection and
being sprayed with patients secretions/blood. The procedure can be summarized as
follows: Check vacuum source, O2 source, sterile rinsing solution, lavage solution,
emergency drugs, resuscitative equipment; Hook the patient on to monitors (ECG and
pulse oximeter); Pre-oxygenate by increasing inspired oxygen concentration; Choose
appropriate size of suction catheter (outer diameter of the suction catheter should be
less than the inner diameter of the artificial airway, if in place) as a bigger catheter
may cause hypoxia & atelectasis; Use sterile technique (gloves & hand washing); If
aspirating through an endotracheal/tracheostomy tube, instill 2-4ml of lidocaine through
the tube and inject IV 1.5mg/kg preservative free lidocaine (Xylocard) about 90 seconds
before aspiration; Advance the catheter (blindly or under vision) up to the secretions or
past the distal tip of the artificial airway without vacuum; Apply/actuate suction and
remove the catheter in a rotating fashion; Limit time of suctioning to 10-15 seconds and
discontinuation of ventilation and oxygenation to 20 seconds; Re-oxygenate (and
ventilate, if applicable) after removal of the catheter; Rinse the catheter with rinsing
solution; Repeat suctioning until secretions have been adequately removed and reoxygenate after every short attempt; Dispose off the catheter after suctioning; If signs of
distress or hemodynamic instability (dysrhythmia, SpO2<90% etc) develop, immediately
discontinue the procedure and reestablish ventilation and oxygenation; Instill 5-10 ml of
sterile normal saline or nebulize with normal saline, for viscous secretions.
190
191
C. Combitube
Combitube (Figure 6) is a double lumen tube with a pharyngeal lumen with blocked
distal end and perforations at pharyngeal level and a tracheo-esophageal lumen with
open upper and lower end. With patient's head in neutral position (not in sniffing
position), the back of the tongue and jaw are grasped between thumb and forefinger
and the jaw is lifted. The Combitube is then gently inserted in a curved, downward
movement until the printed ring-marks lie between the incisor teeth or alveolar ridges.
Oropharyngeal balloon and distal cuff are inflated with recommended volumes of air.
With blind insertion, there is a high probability of esophageal placement of the
Combitube. Therefore, test ventilation is started via the longer, blue tube No. 1. If by
chance Combitube enters trachea, ventilation is changed to the shorter, clear tube
No. 2, leading to the tracheo-esophageal lumen.
Source: www.combitube.org
193
laryngoscopy again. After successful tracheal intubation and cuff inflation, the
confirmation of intubation is required.
Figure 7: Laryngeal mask airway (LMA) and the steps of its placement.6
194
Transtracheal ventilation can be given using a jet ventilator or without it (as shown here in A & B) by
inserting a large bore needle (IV cannula) through the cricothyroid membrane into the trachea. (H- hyoid bone; TC
thyroid cartilage; CC cricoid cartilage; CM cricothyroid membrane)
Figure 8:
(vi) Cricothyrotomy
Cricothyrotomy is the technique of identifying the cricothyroid membrane (lying in the
space between the thyroid and cricoid cartilages it can be identified by palpating a notch,
slight indentation or 'dip' in the skin inferior to the laryngeal prominence9) and placing a
tube in the trachea through it either by incising it, enlarging the incision and placing an
ETT or by using the Seldingers technique.
(vii) Bag and Mask
Bag mask ventilation (BMV)10, 11 should be and usually is the first response to inadequate
oxygenation and ventilation in a patient and it reduces the urgency to intubate. The
ability to ventilate a patients lungs using a bag-mask system is arguably the most
important skill for every intensivist and may be life saving for the patient. The skill
requires one hand to maintain mask seal and airway patency while the other hand
presses the bag to ventilate the patients lungs. The technique of BMV can be
summarized as: Place the appropriate mask on the patients face so that its nasal notch
(or apex) lies over the nasal bridge and the lower portion of the masks cuff rests in the
hollow above the chins bump and below the base of the teeth; Place your thumb and
index finger on the cephalad and caudad sides of the connector or orifice that connects
the mask with the bag to form a C; Place the other three fingers below the body of the
mandible forming an E. Gently press the mask with thumb and index finger on to the
face and pull the lower jaw up with the other three fingers while maintaining the head tilt.
Mould the mask gently but firmly on to the patients face to maintain air-tight seal while
the other hand presses the bag. In case of difficulty in BMV, head repositioning, use of
195
How will you know whether he is right or wrong? You can do that by using the look,
listen and feel method of detecting airway obstruction and its location (Refer 2 above)
What are the common causes of airway obstruction in such patients? The
commonest causes are the tongue and epiglottis falling back and obstructing the
oropharynx. Of course, there may be swelling, secretions, blood or some foreign
body like a pack left behind.
How can you relieve them till expert help arrives? You may use the manual methods
and nasopharyngeal airway (better avoid oropharyngeal airway because of the repair
inside the mouth) for the soft tissue obstruction, suction for secretions, and removal
under vision for any foreign body. If increasing swelling is the cause, it is better for an
expert to intervene early to secure the airway before it becomes an emergency!
Case 2: A forty five year lady is wheeled into the surgery postoperative ward after
laparoscopic cholecystectomy at around 4 pm. The surgery resident visits her at 4.30 pm
and, finding her complaining of pain, gives tramadol 100mg IM but does not enter on the
treatment sheet. The nurse in the postoperative ward comes to the patient for BP check at
4.40 pm. The patient complains of pain and she gives her another shot of IM tramadol 100
mg and makes an entry. The anesthesiology resident comes to see her before leaving the
OT for the day at 4.50 pm and instructs the staff to give IM diclofenac 75 mg to the patient to
supplement the tramadol as she is still in some pain. You (the surgery resident on night duty)
are summoned by the nurse on duty at around 6 pm saying that the patient is not OK. You
find her extremely sleepy, arousable only on painful stimuli. Her respiration is noisy and
strenuous, the SpO2 is 82% and pulse and BP are 124bpm and 140/96mmHg respectively.
How will you proceed?
196
Start O2 through simple face mask @ 10-15 lpm if not running while
asking the assistant (paramedic) to arrange for suction and airways, and
the nurse to call for the anesthesiologist/intensivist
Try to open the airway using the head tilt-chin lift; if respiration becomes
comfortable and quiet but worsens again on leaving the jaw, introduce an
appropriate size OPA/NPA (if OPA not tolerated)
If head tilt-chin lift does not make the respiration quiet, do oral suction
keeping the off-oxygen time such that SpO2 remains above 90%
In any case, ensure that the patient is monitored closely till she is alert
enough to can take care of her own airway. Nursing the patient in the
Recovery position wherein the patients airway remains open and the
secretions drain away from respiratory passage may be nearly impossible
to attain in adult post-operative patients. However, lateral position with
head extended might be possible in this case
Case 3: A 30 year lady underwent total thyroidectomy over almost 5 hours for huge Ca.
thyroid. On your evening round you find her very restless, making sharp noises with each
effort to breathe. Her chest and abdomen are moving up and down deeply but in a rather
unnatural manner. The monitor shows a pulse rate of 146 bpm with multiple abnormal
looking complexes, a BP of 160/80mmHg and SpO2 of 78%. How will you manage her?
Start O2 through simple face mask @ 10-15 lpm if not running while
asking the assistant (paramedic) to arrange for suction, airways, difficult
airway tray, and the nurse to call for the anesthesiologist/intensivist and
then come back and attach the monitors (especially SpO2 if not already
attached)
Try to open the airway using the head tilt-chin lift; if respiration becomes
comfortable and quiet but worsens again on leaving the jaw, introduce an
appropriate size OPA or NPA (if OPA not tolerated)
197
If head tilt-chin lift does not make the respiration quiet, do oral suction
keeping the off-oxygen time such that SpO2 remains above 90%
Parathyroid removal?
3 (a): In the next 5 minutes, as you grope for answers, the chest and abdominal movements
continue but the sound disappears, pulse rate rises to 170 bpm, BP is 90/60, SpO2 shows
poor signal and the lady throws a convulsion. How do you react now?
The airway is now fully obstructed and the patient has most probably suffered
from hypoxic convulsion. The suggested approach (expert help yet to arrive):
o
198
Summary
While tracheal intubation sounds the most glamorous airway management skill to
every medico other than the anesthesiologists/intensivist (they love fiberoptic scopes!), it is
important that the surgical colleagues identify their own needs, hone their ability to quickly
recognize airway obstruction and hypoxia, and concentrate on simpler and equally effective
short term options. They should then constantly update their skills through interaction with
their anesthesiology colleagues and attending hands-on workshops. When an airway
emergency arises, call for help and Airway Cart early. Right from the time of airway related
problem to the final outcome of the patient, it is important to realize that oxygen
supplementation needs to be kept in mind whenever airway management is being carried
out (missed out on a number of occasions when giving artificial ventilation in an emergency).
References
1. Kumar R, Kumar S, Misra A, Singh R.
Anatomy of airway and recognizing airway obstruction in
AIRWAY 2005 All about Airway! Management, Maneuvers and Gadgets; Edited by Kumar R,
Kumar S. New Delhi. Department of Anesthesiology, Intensive Care & Perioperative Medicine
MAMC & LN Hospital; pp 1-5.
2. Holinger LD: Etiology of stridor, Ann Otol Rhinol Laryngol 1980; 89:397400.
3. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency
Cardiovascular Care. Supplement to Circulation 2005; volume 112: Issue 24.
4. Understanding Anesthesia Equipment. 4
Wilkins, Philadelphia.
th
5. Roberts K, Whalley H, Bleetman A The nasopharyngeal airway: dispelling myths and establishing
the facts. Emerg Med J 2005;22:394396.
6. LMA Airway Instruction Manual 2004. San Diego.
7. Chong CF, Wang TL, Chang H. Percutaneous transtracheal ventilation without a jet ventilator.
Am J Emerg Med 2003; 21(6): 507-508.
8. Patel RG. Percutaneous Transtracheal Jet Ventilation: A Safe, Quick, and Temporary Way to
Provide Oxygenation and Ventilation When Conventional Methods Are Unsuccessful. Chest
1999;116:1689-1694.
9. Milner SM, Bennett JDC. Emergency cricothyrotomy. J of Laryn and Otol 1991;105:883-5.
10. Frederic Adnet. Difficult Mask Ventilation: An Underestimated Aspect of the Problem of the
Difficult Airway? Anesthesiology 2000; 92:12178.
199
Introduction
Focus on the nutritional status of the surgical patient has been steadily increasing.
More and more surgeons now realize that adequate nutrition is more important than other
external factors like antibiotics. No major or minor surgery is successful if the nutritional
aspect of treatment is ignored. Though newer modalities like Total Parenteral Nutrition have
emerged, yet oral or enteral nutrition continues to be the modality of choice to feed the
patient.
Response to Injury
At the site of injury ATP is used to breakdown glucose and lactate is generated. At
the same time, more and more amino acids are provided to the site of injury. These amino
acids are diverted from the liver, muscles, kidney and gut to the site of injury.
According to the integrated concept of trauma or sepsis, hormones like epinephrine,
steroids and glucagon are activated at a macro level, there is increased production of IL-1,
IL-2, IL-6, TNF and other cytokines by macrophages. Thus the body has immense nutritional
demand for both the repair work at injury site, as well as due to stress hormones and
inflammatory cytokines and interleukins.
Effects of malnutrition1
Malnutrition has an adverse effect on the immune function and tissue repair capacity.
Various studies have shown that there is a strong correlation between serum albumin at time
of admission and morbidity or mortality. There is an impaired response of the lymphocytes to
antigens, reduction of circulating T cells and reduced level of circulating complement
components1.
Assessment of Nutritional Status
Clinical Assessment
-
A careful history about recent weight loss and dietary intake is a must. Also history of
prolonged illness, vomiting and diarrhea is necessary.
Anthropometric measurements, BMI and expected weight for built and age are useful
indicators of the degree of malnutrition. The NRS (Nutritional Risk Screening, 2002) has
proposed the following comprehensive approach based upon clinical, anthropometeric
and biochemical parameters: -
200
201
Biochemical assessment
-
Serum albumin has traditionally been used to assess the nutritional status of the patient
but the drawback is that it fails to indicate the recent change in nutritional status as it has
a long half-life. Serum transferrin, pre-albumin (transthyretin), thyroid binding globulin,
retinol-binding globulins are proteins which have a short half-life and hence are more
accurate pointers of any recent change in the nutritional status and also serve as
markers of nutritional restitution.
Plasma concentrations
In healthy subjects
Albumin (ALB)
20 d
42+-2 g/l
Transferrin (TRF)
8d
Transthyretin (TTR)
2d
310+-35 mg/1
1/2d
62+-7 mg/1
202
203
204
conditions, the body shifts from glucose metabolism to fat metabolism and starts
using ketone bodies in preference to dextrose, thereby limiting glucose utilization.
Lipid solutions
These provide 9 cal/g. they are isotonic and can be infused peripherally. They are
very useful in stressed patient. The disadvantages are that they cause
immunosuppression by increased E2 prostraglandin production, hepatotoxicity, and
lung injury. Caution must be exercised in mixing lipids with other solutions as the
microglobules of these solutions might get disrupted. Optimal intake is one that
provides 15-30% of total calorie requirement by lipids; triglycerides should be
maintained at <250 mg/dl.
Amino Acids Solutions
These are directly used to manufacture proteins but can provide 4 cal/g if oxidized.
However, adequate caloric protection must be given to prevent oxidation of amino
acids. Glutamine and argenine solutions are especially useful in stressed patient as
these are also considered immuno-nutrients.
All in one solutions
Amino acids, dextrose and lipid formulations are mixed and given together. The
advantages are that risk of infection is reduced, it allows dilution, reduced nursing
time and administration of
Home TPN is possible.
Micronutrient and Multivitamin Support 7, 8, 9
These are present in small quantities in all tissues and are essential for cellular
function. Marked deficiencies of micronutrients are seen in stressed patients and
these are given at 5-10 times the recommended Dietary Allowances to compensate
for increased demand. These micronutrients are not mixed with TPN and given
separately, orally if possible. Multivitamin injections are commercially available for
parenteral administration, if required.
Composition of Nutritional Support
The Basal Energy Expenditure is calculated and the
Stress Factor is added.
The BEE is calculated by Harris-Benedict Equation
BEE (male) = 66+(13.7 x wt.) + (5 x Ht. In cm) (6.8 x age in yrs)
BEE (female) = 66.5 + (9.6 x wt.) + (1.7 x ht in cm) (4.7 x age in yrs)
205
Percentage increase
Malnourished patient
+10%
+10%
+10%
Bedridden
no change
+5%
Mobile
+10%
Postoperative
+15%
Sepsis / trauma
+25%
Burns
+35%
Decrease:
Situation
Percentage decrease
Obesity
-10%
-10%
Female sex
-10%
Amino acids must be spared and calorie requirements fulfilled by lipid and carbohydrates
given in a ratio of 30:70 or 40:60 depending on the stress condition. Patients on ventilators
must be given more lipids because increased CO2 production results from carbohydrates,
which makes it difficult to wean them off.
-
A caloric to nitrogen ratio of 150:1 for minor and 100:1 for major surgeries should be
maintained.
Complications of TPN
General Complications
Gallstones: Gallstones are likely to develop in patients on long-term TPN. This is not a
direct complication of TPN, but is because of the absence of gut stimulation, which
allows gall bladder stasis and stones to form. It can be prevented by partial parenteral
nutrition or by regular (expensive) injection of Cholecystokinin.
206
Oxidation of glucose produces more carbon dioxide than does the oxidation of a
combination of glucose and lipid. Although this is not a problem in patients
breathing normally, in patients with borderline hypercapnea (eg. weaning off
ventilator, ARDS) it can tip the balance.
Patients fed on dextrose alone are more likely to develop a fatty liver, as has
been explained earlier.
Excessive lipid infusions can be hepatotoxic. Ideally, not more than 40 percent of the
total daily calories should be of lipid origin. Acute over dosage is manifested by fever,
nausea, vomiting, dyspnea and hypercoagulability.
Serum triglyceride levels can rise rapidly if an individuals capacity to clear them is
compromised. Blood levels should be checked regularly.
Accumulation of unmetabolised free fatty acids (FFA) in the blood increases PGE2
production, causing immunosuppression.
Pulmonary dysfunction may result from the release of vasoactive amines produced
because of excessive PGE2 levels. Medium chain triglycerides (MCT) can avoid
207
some of these problems since they can be metabolized faster, leading to less
accumulation in the blood stream and lesser PGE2 production. Since all essential
fatty acids have long chains, infusion of some long chain triglycerides (LCT) also is
essential. The ideal mixture is a 50-50 ratio of LCT and MCT. Currently, only one
company markets such a product worldwide (lipofundin, Braun, Germany).
Complications Specific to Access Lines
Enteral feeding line related
Nasogastric tube increases the risk of gastric content aspiration, especially in an
unconscious patient. Where such a risk is present, feeding into the jejunum via a
nasojejunal tube may help. Prolonged use of either of these tubes can lead to
esophageal ulceration. A feeding gastrostomy (or jejunostomy) is the solution in such
cases.
Central line Related
Currently, most TPN-related complications are related to the central venous line.
Complications include injury to adjacent nerves and vessels, pneumothorax, air
embolism, infusion of TPN into the pleural cavity via a misplaced line and infection of
the central line. The position of all central venous lines should be confirmed by a
chest x-ray prior to the commencement of the infusion. Central lines should be
handled with aspetic precautions. A subcutaneously tunneled infusion line with a
Dacron cuff (Hickman line) is used for long-term or home TPN. Its use in routine TPN
is not justified.
Peripheral line related
Thrombophlebitis remains the most common complication of peripheral TPN. The
use of a glyceryl trinitrate patch just distal (towards the hand end) of the infusion site
is claimed to dilate the vein, increase the blood flow and dilute the infused TPN
solution more rapidly, leading to a lower incidence of thrombophlebitis. Peripheral
TPN cannulae should be treated with the same aseptic precautions as central lines.
Rationale for Use of Anabolic Agents 10, 11
The successful correction of PEM and prevention of a severe protein deficiency in
the presence of catabolic illness requires the restoration of the normal protein partitioning
process (to restore lean body mass and wound healing). However, the process means the
use of protein for protein synthesis, not energy. Restoration of the key components of
nutrition is essential before considering use of an anabolic agent (Table 8).
208
A limiting factor to restoration of lean mass and improving wound healing is the output of the
protein synthesis pathway, which is dependent on adequate substrate plus an anabolic
stimulus. Body composition studies during correction of PEM have demonstrated that a
significant portion of weight gain after unintentional weight loss from catabolic disease
represents the addition of body fat and extra-cellular fluid, not added protein mass due to
decreased anabolic activity. Even in the recovery phase, endogenous anabolic activity
remains depressed. This is especially true in elderly patients, those with chronic illness or
patients with a significant involuntary weight loss. Adequacy of substrate (1.5g/kg/d protein)
may not be sufficient to jump-start a rapid restoration of lean body mass.
The action of all anabolic agents currently in clinical use is twofold. First, amino acids
are driven into the protein synthesis pathway. Second, catabolic activity is decreased.
Anabolic hormones are being used with increasing frequency in populations with lean mass
loss or existing PEM, along with optimal nutrition and the added anabolic stimulus of
resistance exercise. The most commonly used anabolic agents are described.
Human growth hormone (HGH) 12, 13, 14
HGH is a potent anabolic hormone that has a host of metabolic effects, some due to
direct hormone activity on tissues, especially in the liver. Other effects are due to the release
of insulin-like growth factor-1, which has potent wound healing effects. The primary stimuli
for HGH release are starvation and intense exercise. The plasma HGH level is decreased
after severe injury or sepsis, thereby decreasing normal anabolic activity. Numerous studies
of exogenous HGH use in patients with trauma or burns and other injuries have
demonstrated its efficacy for improving anabolism and the wound-healing rate. The
mechanism for improved outcomes appears to be related to maintenance of lean body
mass. The average dose of HGH used is 0.1 to 0.2mg/kg of body weight, or about ten times
the normal endogenous production. A number of complications have been reported; the
most common is hyperglycemia, due to anti-insulin activity. Insulin supplementation is often
required in addition.
209
Testosterone
Testosterone levels are decreased immediately after severe trauma or critical illness and
throughout the recovery period, eliminating another anabolic stimulus during a period of
catabolism. Exogenously administered (oral or parenteral) testosterone is rapidly
metabolized in the liver, resulting in a half-life of approximately ten minutes, which is not
practical for clinical use.
Oxandrolone 15, 16, 17
Oxandrolone (Oxadrin, Bio-Technology General Corp., Iselin, NJ) is an orally
administered 17beta -hydroxy-17alpha methyl ester of testosterone and is cleared primarily
by the kidney. Hepatotoxicity is minimal. Oxandrolone is the only steroid in which a carbon
atom within the phenanthrene nucleus has been replaced by oxygen. This alteration appears
to be responsible for its potent anabolic activity, which is five to ten times that of
methyltestosterone. In addition, its androgenic activity is considerably less than testosterone,
minimizing this complication common to other testosterone derivatives.
Oxandrolone is the only oral anabolic steroid that is FDA approved for restoration of
weight loss after severe trauma, major surgical procedures, or infections. Weight gain is
primarily lean body mass.
Clinical trials have shown benefit in a variety of patient populations. Lean mass gains
with anabolic agents are four times that seen with optimum nutrition alone. As with other
anabolic agents, adequate calorie and protein intake is necessary for an optimum effect.
Resistance Exercise18, 19
Resistance exercise is a potent anabolic stimulus. When initiated in the catabolic
state, resistance exercise diminishes the degree of protein loss. Increasing lean body mass
in the elderly and chronically ill population by this approach can markedly decrease
disability. Large-muscle exercise should be given priority, because this training can
significantly reduce muscle loss and accelerate weight gain. In an injury or wound patient
population in whom catabolism is pronounced, an aggressive and early program of
resistance exercise that continues through the recovery phase is of major importance as an
additional anabolic stimulus.
An Approach to malnourished surgical patient:
210
Having identified such a patient, nutritional risk qualification may be carried out,
keeping in mind the fact that a weight loss of 20% with physiological disturbance
carries a substantial risk of nutritional complications.
Assess the stress factor- any catabolic stress should be sought for and quantified.
Greater the stress, greater the risk for nutritional complications.
Set the goal for nutritional therapy- Nutritional therapy comes at a cost and may have
some inherent risk. Only those patients in whom a useful prolongation of life is the
goal of therapy should be offered nutritional therapy. When such a prolongation is not
expected in view of natural history of disease, nutritional therapy should be with held.
1. Eremin O, Broom J. Nutrition and the immune response. In Eremin O, Sewell HF (eds). The
immunological basis of surgical science and practice. Oxford University Press, 1992; 134-44.
2. Buzby GP, Bbuin G, Cong CL et al. Perioperative total parenteral nutrition in surgical patients. N
Engl I Med, 325:525.
3. Detsky AS, Baker JP, Rourke IC et al. Perioperative parenteral nutrition: a meta analysis. Ann
Inter Med, 107:195-203.
4. Moore FA, Moore EE, Jones TN. TEN vs TPN following major abdominal trauma reduced septic
morbidity. J Trauma 1989; 29:216.
5. AGA Technical reviews, 2001.
6. Mc Clave et al. Gastroenterol Clin North Am 1989; 27:421-434.
7. Food and nutrition Board National Research Council. Recommended dietary allowances. Nat
Acad Science, Wash DC 1980.
8. Berger M, Cavadine C, Cheolero R, et al. Influence of large intakes of trace elements on recovery
after major burns. Nutrition 1994; 10:327-34.
9. Prasad AS. Zinc: An overview. Nutrition 1995; 11:93-99.
10. Demling R, DeSanti L. Anticatabolic and anabolic strategies in critical illness. Shock 1008;
10:155-60.
11. Streat S. Aggressive nutritional support does not prevent protein loss despite fat gain in septic
intensive care patients. J Trauma 1987; 27:262-6.
12. Kaiser F, Silver H. Morley. The effect of recombinant human growth hormone on malnourished
older individuals. Am Geriatric Soc 1991; 39:235-40.
13. Galzen C, Scheltinger M. Growth hormone alternates the abnormal distribution of body water in
critically ill surgical patients. Surgery 1992; 112:181-6.
14. Demling R, DeSanti L. Comparison of the anabolic effects and complications of human growth
hormone and the testosterone analog, oxandrolone, after severe burn injury. Burns 1999 in press.
15. Demling R, DeSanti L. Oxandarolone, an anabolic steroid, significantly increases the rate of
weight gain in the recovery phase after major burns. J Trauma 1997; 43:47-50.
211
212
The use of blood / blood components in most elective surgeries has decreased
because of careful assessment and management of patients prior to the surgery. Nowadays
there is minimum blood loss during surgery because of meticulous surgical techniques, use
of tourniquets, use of vasoconstrictors, use of antifibrinolytic drugs and good anaesthetic
techniques.
The use of blood /blood components in elective surgeries is inconsistent, varies
greatly between the hospitals, individual doctors and between the countries. These
variations depend upon the diagnosis /indication for surgery, differences in surgical
techniques, knowledge of clinicians/patients on the use of blood /blood components and the
availability of blood /blood components. There must always be a sound physiological reason
for transfusion in any patient, because the transfusion exposes the patients to several types
of risks including the possibility of transmission of infectious agents.1, 2
Guidelines for use of blood /blood components in surgery & haemorrage
1,2,3,5
For effective and proper utilization of blood during the surgical procedures & haemorrage
Blood transfusion services should frame the guidelines for appropriate use of blood and
propagate them among the clinicians. While framing the guidelines following points should
be kept in mind.
1.
Blood or its components should be used only if other modes of therapy e.g. crystalloids /
colloids have proved ineffective and if the benefits of blood transfusion outweigh the risk
associated with it.
2.
An average healthy adult individual with normal cardiovascular system can withstand 10
% loss of blood with out any ill effect as is daily observed in the blood transfusio0n
centers.
3.
Healthy average adult can afford to lose 20% of blood volume with out any ill effect
provided the circulatory blood volume is maintained by crystalloids or colloid solutions.3
4.
Proper assessment, selection and management of patients before surgery will help to
reduce the morbidity and mortality.
5.
Adopt the policy of blood sparing techniques and avoid the use of
4
213
unnecessary single
6.
7.
Each blood transfusion service should frame its Maximum Surgical Blood Order
Schedules (MSBOS) to promote efficient utilization of blood.
8.
Adopt the policy of type and screen in all elective surgical cases.
Mostly the patients of elective surgery are anaemic and it is important to investigate
and treat the cause of anaemia to improve the general condition of the patient before
undergoing surgery.
Nutritional deficiencies of iron and folate together with parasitic and helminthic
infestations primarily contribute to the cause of anaemia in general population to be
identified & treated.
Patients who are already anaemic, a further reduction in oxygen delivery due to
acute blood loss or the effects of anaesthetic drugs may lead to decompensation.
Many clinicians now accept the haemoglobin level of 7.5 g/dl as transfusion trigger
or the preoperative haemoglobin threshold in a well-compensated patient presenting
for surgery. However, a higher preoperative haemoglobin level will be required for
elective surgery in following situations.
1. Inadequate compensation for the anaemia and the oxygen supply to the tissues
is insufficient, such as:
Evidence of angina
2. Patients with co-existing cardio respiratory disease like ischaemic heart disease or
Obstructive airways disease
3. Major surgery or anticipated significant blood loss.
Blood transfusion should rarely be used preoperatively to facilitate elective surgery.
Surgery and coagulation disorders
It is important to enquire about history of any abnormal bleeding tendency in patient
and his or her family, together with a drug history.
214
Cryo precipitate
Granulocyte concentrate
215
Hypoplastic anaemia
Advantages
Less Plasma proteins with packed cells so there are minimum anaphylactic
reactions.
216
improved vaccumised extractor (optipress) have been introduced by Baxter for preparation
of leucoreduced blood components by removing buffy coat. The efficiency of this method is
about 85 %.
Advantage:
The platelets harvested from Buffy will have better therapeutic viability.
Alternative blood group can be given at times if group specific blood is not available
e.g.
For AB the alternative blood in order of preference should be A, B & O
For A group ---------- O group
For B group ----------- O group
217
Dosage:
1 unit of platelet concentrate / 10 kg body weight e.g. for 60kg man 6 units of random donor
platelets concentrate.
Guidelines for platelet transfusions
Adults
A) Non-bleeding patients with failure of platelet production
B) Bleeding patients
Diffuse bleeding following cardiopulmonary bypass and platelet count not yet
available or <100,000/ul
2.
218
3.
4.
Administration:
1. No special transfusion sets required. However patients requiring multiple platelet
transfusion like aplastic anemia , leukemia platelet transfusion set having leucocyte
filter should be used preferably to prevent allo-immunization & refractoreness to
platelets
2. No cross matching required, however if contaminated with red cells cross match is
indicated.
3. Use group specific platelets, however group non-specific platelets can be used if
group specific platelets not available.
4. Platelet dont carry Rh antigen however in young ladies of child bearing age, dont
give Rh Positive platelets incase there is any RBC contamination.
Complications:
Allergic & febrile transfusion reactions are not uncommon, especially in patients receiving
multiple transfusions. Infection risks are same as for whole blood.
Fibrinogen 150-230
Liver disease
Massive blood loss
Over dose of anticoagulants e.g. (Warfarion & Dicumerol)
DIC (Disseminated intravascular coagulation)
TTP ( Thrombocytic Thrombocytic
219
Storage:
Stored at -20c below & before use should be thawed at 37c & once thawed should be
storage at 4 - 6c & used within 6 8 hrs.
Complications:
Cryoprecipitate
Definition:
It is the insoluble portion of plasma remaining after the fresh frozen plasma has been
thawed under controlled conditions at 4 degree C.
Description:
per pack.
Storage: At- 30c & below for 1 year.
Indications:
As an alternative factor VIII concentrate in the treatment of:
Vonwillibrand disease
Hemophilia A
220
It has been seen that a radiation dose between 15-25 Gy (1500-2500 rads) is effective to
abolish mitogen induced blast transformation and mixed lymphocyte culture activity with no
cellular damage to platelets and red blood cells.
Responsibilities of Clinician in case the Patient needs Transfusion
Inform and explain to the patient or relatives about the proposed transfusion of blood/blood
products (benefits & risks) and record the same in the patients file.
1. Ensure proper identity of the patient & correctly complete a blood request form.
2. Collect the blood sample from the right patient in the right sample tube & correctly
label the
3. Sample tube.
4. Order blood in advance, whenever possible.
5. Provide the blood bank with clean information on:
221
6. Ensure the correct storage of blood and blood products in the clinical area before
transfusion.
7. Formally check the identity of the patients, the product and the documentation at
the patients bedside before transfusion.
8. Correctly record transfusion in the patients notes:
Time of transfusion
References
1. Transfusion Medicine Technical Manuals, American Association of Blood Banks (AABB) Editor
Th
Mark E.Brecher, MD 15 Edition 2005
st
vol5, N0 6
5. Saran, R.K. and Makroo R.N. Transfusion medicine, Technical Manual. Directorate General of
Health Services, Ministry of Health & Family Welfare, Govt. of India (1991).
6. American Association of Blood Banks, Standards for Blood Banks and Transfusion Services. 17
Edition. Bethesda, American Association of Blood Banks, 1996.
th
222
223
As the stone progresses down the ureter, the pain tends to migrate caudally and medially.
Distal ureteral stones may be manifested by bladder instability, urinary frequency, dysuria
and/or pain radiating to the tip of the penis, or the labia or vulva. Some patient can present
with the features of chronic renal failure (anorexia, loss of WT, anaemia, pedal edema).some
patients presents with features of accelerated HT and others can present with urinary tract
infection or septicemia.
Pre-Operative Evaluation:
Urinalysis should be performed in all patients with suspected calculi. Besides the
typical microhematuria, important findings to note are the urine pH and the presence of
crystals, which may help to identify the stone composition. Patients with uric acid stones
usually present with an acidic urine, and those with stone formation resulting from infection
have an alkaline urine. Identification of bacteria is more important in planning therapy, and a
urine culture should be routinely performed. Limited pyuria is a fairly common response to
irritation caused by a stone and, in absence of bacteriuria, is not generally indicative of
coexistent urinary tract infection.
Abdominal Ultrasonography
It is readily available, quickly performed and sensitive to detect renal caculi.
However, it is virtually blind to ureteral stone. When ureteral stones are visualized by USG
the finding is reliable to the extent of 97%. USG is highly sensitive to Hydronephrosis which
is usually seen in the ureteral obstruction.
Routine PAC test are carried out Metabolic evaluation is required for selected
recurrent stone formers. Haemoglobin and Coagulation profile is routinely carried out prior to
percutaneous and ESWL surgeries. The patients in elderly age group are investigated for
their medical and Cardiological problems.
Plain Film Radiography
Plain X-Ray KUB is sufficient to document the size and location of calcium bearing
calculi i.e. Calcium oxalate and calcium phosphate stones. Pure uric acid, cystine or
Magnesium, ammonium phosphate are difficult to locate.
Intravenous Pyelography
The intravenous pyelogram provides useful information about the stone (size,
location, radio density) and its environment (calyceal anatomy, degree of obstruction), as
well as the contralateral renal unit (function, anomalies). Proper bowel preparation, well
224
ESWL
Percutaneous Nephrolithotomy
Ureteroscopy
Laparoscopy
Renal Anatomy
Obstructions / Stasis
Hydronephrosis
Ureteropelvic junction
obstruction
Calyceal diverticulum
Horseshoe kidney and
other ectopic/fusion
anomalies
Lower pole
225
Clinical (Patient)
Infection
Obesity
Body Habitus deformity
Coagulopathy
Juvenile
Elderly
Hypertension
Renal failure
ESWL :
Since the introduction of HM-3 Lithotriptor by dornier in which patients needed to be
immersed in water bath a variety of technological advancement has made it a simplified
technique. These are basically three types of generators, electro hydraulic (Spark Gap),
electromagnetic and Piezo-electric.
Electro hydraulic generators are based on shock wave generation under water when
high voltage current is passed across two electrodes. These shock waves are then
reflected by a parabola and focused on F2 point (where the stone is located in the body).
ADVANTAGE
1. This is relatively less pain full
2. Low initial cost.
DISADVANTAGE :
1. Substantial pressure fluctuation from shock to shock
2. Electrodes have a short life and needs to be changed after every setting.
They differ on the basis of shock wave generation. Electro-hydraulic Generators spark
gap technologies produces shock waves by an underwater spark discharge. The shock
waves are focused on to the stone and stone breakage is monitored under C-arm. Some
of the machines have incorporated C-arm while others have mobile C-arm. This
procedure can be carried out under cover of analgesies or without analgesia. The
requirement of analgesies is more in thinner patients then in fat persons.
Electromagnetic Generators produce magnetic pressure wave when an electromagnetic
coil is used to generate the shock wave. These shock waves are then focused on to the
stone. Piezoelectric generators have a Polarized Polycrystalline ceramic element which
on activation produces shock waves. These crystals are placed on the under surface of a
spherical dish in such a manner that shock waves are focused on to the stone.
Some Lithotriptors have ultrasound localisation to minimize the radiation hazard which is
useful in infants and children. However, it requires a trained operator and fail to locate
the stone in upper ureter. Also, the completeness of process cannot be ascertained.
The majority (80-85%) of simple renal stones can be managed by ESWL. (Chanssy,
1988, Krings el al 1992) However, Grasso and Colleagues (1995c) treated 121 patients
who were failure of ESWL. Several other authors also noticed the limitations of ESWL
and formulated guidelines for its use.
226
227
228
2. When stones are impacted and bigger than 2cm in size PCNL is preferable
technique.
3. Some centers are using flexible ureteroscope and Laser Lithotripsy for upper Ureteric
stones as well.
Distal-Ureteral Stone
Ureteroscopic stone removal is the treatment of choice with almost 100% success
rate. Pneumatic Lithotriptors are best suited even for larger stones and complete stone
clearance is achieved in majority of the patients in single sitting.
TECHNIQUE
The procedure is carried out under C-arm and the ureteric orifices are dilated with
ureteral balloons and ureteroscopy is carried out. Stones are broken and removed.
When Ureteric orifices are dilated a Ureteric DJ Stent is placed to avoid post operative
discomfort due to edema at the site of surgery.
In the Indian circumstances pneumatic Lithotriptor work excellent with minimum
complications at low cost. However, the usual complication with ureteroscopy are minor
mucosal injuries or perforation. Rarely we can encounter degloving Ureteric avulsion
injuries especially when the Ureteric dilatation was insufficient.
Retrograde Intrarenal Surgery (RIRS)
Retrograde Intrarenal Surgery is a new approach to the stone management. The first
series of 208 patients undergone RIRS was reported by Fuchs and collegues (1990).
They used DJ Stent for a period of 1-2 weeks prior to the procedure for adequate
dilatation of the ureter and easy insertion of ureteroscope.
INDICATIONS OF RIRS
1. Single stone smaller than 1cm
2. Up to 5 stone particles smaller than 5 mm.
3. Patient with radiolucent stone (smaller than 1.5cm)
4. Patient with concomitant ureteral and renal stones.
5. Renal stone patients with Intrarenal Stenosis.
6. Patient with Nephrocalcinosis or urinary diversion.
7. Patient who need complete stone removal (i.e Pilots)
8. Patient with bleeding disorders.
229
230
231
Bladder
Intrinsic
Bladder carcinoma
Bladder calculi
Bladder neck contracture
Cystocele
Primary bladder neck hypertrophy
Functional
Neurogenic bladder
Vesicoureteral reflux
Extrinsic
Pelvic lipomatosis
Urethra
Intrinsic
Urethral stricture
Extrinsic
Benign prostatic hyperplasia
232
Pathophysiology
Obstructive uropathy occurs when the flow of urine is blocked at some point in the
urinary tract, and urine accumulates above the obstruction. The urine accumulation
increases the pressure and dilates the affected regions of the renal pelvis, calyces, and
ureters . The dilated kidney is more predisposed to trauma. Increased ureteral pressure
also results in pyelotubular, pyelovenous and pyelolymphatic backflow increasing the risk of
systemic sepsis in the presence of infection. Hence, obstruction coexisting with infection
should be considered a urologic emergency.
The clinical profile of the patient varies according to (1) the time interval over which
the obstruction occurs (ie. Acute or chronic), (2) whether the obstruction is unilateral or
bilateral, (3) the cause of obstruction (ie. Intrinsic vs. extrinsic), (4) whether the obstruction is
complete or partial, (5) presence of intrarenal versus extrarenal collecting system, and (6)
presence or absence of infection. Acute urinary obstruction may
change in the collecting
obstructed to the same degree and duration as the extrarenal system, may not exhibit the
same degree of hydronephrosis; however the degree of renal damage may be worse.
Chronic obstruction can produce an enlarged, normal or small atrophic kidney, again
depending on the length and degree of obstruction, as well as the presence of an intrarenal
or extrarenal collecting system. Usually, the collecting system dilates with time and the
tissue between the calyces gets thinned out. Ultimately, the calyces coalesce with thin septa
between them and a rim or shell of parenchyma remaining peripherally.
Microscopic changes consist of dilatation of the tubular lumen and flattening of the
tubular epithelium. Fibrotic changes and increased collagen deposition are observed in the
peritubular interstitium.
Obstructive nephropathy can lead to kidney failure within a few weeks or a few years.
The nephron number averages approximately 6 lac per kidney with a standard deviation
greater than 2 lac. Partial ablation of renal mass due to any renal insult initiates a cycle of
progressive glomerular injury in the remnant kidney. In this setting, the injury is associated
with hyperfiltration, glomerular hypertrophy, and systemic hypertension. Obstruction
maintained for greater than 6 weeks results in hydronephrosis of the affected kidney with
significant loss of functional renal parenchyma5. Renal function also is affected by relatively
short-term obstructions6. Mustonen and colleagues (1999) found that glomerular and tubular
function partially improved during the first month following immediate correction of an
obstruction. However, months later, half the patients still showed glomerular damage,
233
234
important in this phase and many other aspects of obstructive nephropathy19,20,8. TGF, a
cytokine with important implications in the development of interstitial fibrosis, is released by
macrophages in response to a perceived inflammation. The balance between production and
degradation of interstitial matrix is controlled by TGF 8,9. In addition, TGF attracts
fibroblasts, contributing to development and proliferation of interstitial fibrosis 21,9. Recent
evidence suggests TGF is the primary force driving the increased immunologic response
and the up-regulation of the renin-angiotensin system during the fibrotic process22,21. TGF
stimulates the production of NF B, a factor associated with tissue inflammation, increased
angiotensin II production, and the release of tubule cell chemoattractants23.
Effects of obstructive uropathy on GFR
Three components determine the GFR: glomerular hydrostatic pressure, glomerular
colloid osmotic pressure, and Bowmans capsule pressure. An event impacting any one of
the three components changes the GFR. All of the components can be influenced by an
obstruction. During the first few hours following obstruction, renal blood flow in the
obstructed kidney increases secondary to preglomerular vasodilation of renal blood vessels1,
which increases GFR. As the GFR increases over the initial 1 to 2 hours, increased urine
formation begins to gradually increase ureteral pressure. About 4 hours into the obstruction,
renal blood flow declines while ureteral pressure increases1. Then, increased intrarenal
pressure activates the renin-angiotensin system and increases levels of vasoconstrictors
such as thromboxane A2, which results in decreased renal blood flow and a decrease in
ureteral pressure2,8,18. Angiotensin II exacerbates obstructive nephropathy by increasing
TGF , which promotes both fibrosis24 and nitric oxide degradation18. Normally, nitric oxide
protects the kidney from infiltration of macrophages into the interstitium and decreases the
production of the protein interstitial matrix, suggesting it may have antifibrotic effects in the
kidney4. Also, nitric oxide inhibits excessive vasoconstriction initiated by renin-angiotensin
activation in processes like obstructive. Bilateral ureteric obstruction (BUO) differs from
unilateral ureteric obstruction (UUO). While during UUO, the kidney passes through three
phases: pre-glomerular vasodilatation, post-glomerular vaso-constriction, and finally, preglomerular vasoconstriction; BUO passes through a phase of pre-glomerular vasodilation
and then a post-glomerular vasoconstricton and remains in this state. Therefore, BUO is
associated with progressive and persistent rise in ureteral pressure despite a decrease in
renal blood flow.
235
Postobstructive diuresis
This phenomenon refers to the marked polyuria that occurs after the relief of BUO or
obstruction of a solitary kidney. It is most often seen in patients who have chronic
obstruction, volume overload and sometimes uremic encephalopathy. Most patients exhibit
both solute diuresis (caused by retained urea, sodium and water) as well as a concentrating
defect. The mechanisms responsible for this inability to concentrate urine include high atrial
natriuretic peptide levels and impaired
decreased reabsorption of sodium chloride by the thick ascending loop of Henle and
decreased reabsorption of urea by the collecting tubule, (2) increased medullary blood flow
(solute washout), and (3) increased flow and solute concentration in the distal nephron. All
these cause impaired medullary gradient which is necessary for concentrating urine.
Clinical features
The signs and symptoms of urinary obstruction depend on the various parameters as
discussed above. The differentiation between acute or chronic obstruction is purely clinical.
Chronic obstruction is usually asymptomatic. When the obstruction is bilateral, patients may
present with uremia. Most acute obstructive uropathies, on the other hand, are associated
with significant pain or the abrupt diminution of urine flow. The severity of the pain depends
on the rate of distention more than the amount of dilation of the renal capsule25. Patients
describe a colic pain in the flank that increases with consumption of large amounts of fluid or
following diuretic administration. Anuria frequently occurs in acute obstruction and less
frequently in chronic situations26. Sometimes, in unilateral obstruction or partial bilateral
obstruction, the patient may notice significant increases in urinary output independent of fluid
intake related to the damaged kidneys inability to concentrate urine1.
The clinician needs to obtain a detailed history about the type and duration of
symptoms, hematuria, lower urinary tract symptoms, previous urinary tract infections (UTIs),
history of stone disease, family history of prostate or pelvic cancer, and urinary output
patterns. Presence of infection should always be considered as it may require emergent
drainage.
Examination may reveal elevated jugular venous pressure, pulmonary congestion,
hypertension, and peripheral edema, indicative of volume overload25. There may be a
palpable abdominal mass related to hydronephrosis. Hydronephrosis that causes the kidney
to expand enough to become palpable usually is related to a chronic condition26. The
bladder is likely to be palpable over the suprapubic region secondary obstruction low in the
urinary tract1. As hydronephrosis develops, the possibility of costovertebral angle tenderness
236
increases. Women presenting with suspected urinary obstruction should always receive a
complete pelvic examination, and both genders receive a rectal examination1.
Laboratory evaluation
Urinalysis results may be normal in both acute and chronic obstructions. Albuminuria
may be absent but is commonly present in the range of less than 1.5 g/24 hours reflecting
the increased glomerular permeability during urinary retention6. Even sparse albuminuria
indicates glomerular dysfunction27. Microglobulin alpha-1, a low weight molecular protein, is
an indicator of tubular dysfunction. Nearly all microglobulin alpha-1 filtered by the glomerulus
is reabsorbed by the proximal tubule6. In chronic obstructive uropathy where fibrosis
development has begun, small amounts of this protein may be present in the urine. With
renal calculus or tumor involvement, microscopic hematuria is possible, but gross hematuria
is unlikely28. Chronic obstruction leads to renal tubule damage, and the urinary chemistry
findings are similar to those in intrinsic renal failure. These findings include urinary sodium
greater than 20 mEq/L, fractional excretion of sodium (FE Na ) greater than 1%, urine to
plasma creatinine ratio of less than 20 and urine osmolality less than 350 mOsm/kg H2O
(Walsh et al., 1998). With acute obstruction the urinary chemistry values are similar to those
in prerenal azotemia. These findings include urinary sodium less than 20 mEq/L, FE Na less
than 1%, urine to plasma creatinine ratio of greater than 30 and urine osmolality greater than
500 mOsm/kg H2O. Microscopic evaluation of the urine may reveal erythrocytes, leukocytes,
and bacteria.
Blood tests include red blood cell count, hematocrit, hemoglobin, white blood cell
count, serum electrolytes (Na+, Cl-, K+, HCO3 -, Ca++, HPO4-, Mg++), creatinine, blood urea
nitrogen (BUN), uric acid, albumin and ABG. The white blood cell count assesses for
possible inflammation or infection secondary to obstruction or neoplasm as a cause ofthe
obstruction. The hematocrit is important to assess for anemia related to chronic renal
insufficiency28. Patients with increasing serum creatinine without significant proteinuria and
trace to moderate numbers of red blood cells in the urine should immediately be suspected
of having an obstruction 25.
Radiologic evaluation
Ultrasonography has become one of the most important tools for assessing urinary
tract obstruction because it is rapid, low cost, safe and sensitive. The test is 98% sensitive
for detecting hydronephrosis secondary to obstruction, but the specificity is 78 %
29
. Though
operator dependent, ultrasound detects the type and level of the lesion, shows
hydronephrosis, can indicate pyonephrosis (echoes within the collecting system) and tells
237
the thickness of the renal parenchyma as an indicator of duration and severity of obstruction.
The degree of hydronephrosis should not be equated with the duration of the obstruction.
Because up to 22% of cases of hydronephrosis are not obstructive, there is room for error 29.
Most false-positive interpretations occur when mild hydronephrosis is present. Dilation
without obstruction may be seen in vesicoureteral reflux, chronic massive diuresis,
extrarenal pelvis, calyceal diverticula, congenital megacalyces and ileal conduits.
Obstruction without dilation may be seen in intrarenal crystals, nephrocalcinosis, staghorn
calculi retroperitoneal obstruction and GUTB where whole of ureter and PCS is rendered
nondistensible and pipe stem like. Patients who have no ultrasound evidence of obstruction
but who have persisting symptoms are subjected to additional testing1.
Use of duplex Doppler ultrasonography allows determination of the renal resistive
index (RI), [peak systolic velocity lowest diastolic velocity] / peak systolic velocity. An RI in
the obstructed kidney that is 0.1 greater than the contralateral kidney is considered
significant enough to indicate obstruction.
A supine radiograph [KUB] of the abdomen can reveal radiopaque urinary tract
calculi as the cause of obstructive uropathy. The film is able to detect radiopaque calculi
representing 90% of calculi discovered in patients30. However alone it does not prove the
calculi to be the cause of obstruction, it misses out radiolucent calculi and radioopacity due
to any other cause can be mistaken for the urinary calculi.
Intravenous urogram (IVU) has been the gold standard for the detection of ureteral
obstruction. The significant difference in IVU compared with ultrasonography is that the IVU
shows both increased anatomic detail and functional attributes of the urinary system on both
sides 1. It tells about the exact site of obstruction, its cause, the degree of hydronephrosis,
the status of renal parenchyma, guides the best treatment option, and also helps in deciding
the best surgical approach for a particular patient. However, since the test uses intravenous
contrast material, a potential nephrotoxic substance to illuminate the renal system, the
usefulness of the test for patients already suspected of having obstructive nephropathy is
questionable29. Also poor renal function may render the test useless because of nonexcretion of contrast. In general, a serum creatinine level of less than 2 mg% is needed.
Another dilemma with IVU is the significant time requirement, up to several hours, for
performing serial delayed films. Still , IVU remains the most widely used imaging modality to
guide the management of patients of obstructed kidney, because of its low cost and easy
availaibility. A kidney which is non-visualised on IVU (absence of both nephrogram and
pyelogram even on delayed films taken after 24-72 hours) should be assessed with a renal
scan before labeling it as a non-functioning kidney (single kidney GFR which is not sufficient
238
to take care of body wastes).a kidney may be non-visualised on IVU because of renal
agenesis, post nephrectomy, poor function with or without obstruction, or even in the
presence of normal function during renal colic leading to renal artery spasm.
Non-contrast computerized tomography (CT) scan is an effective imaging tool for
acute renal obstruction. With spiral scanners, images can be performed effectively without
contrast media, take only 5 to 10 minutes to perform, and cost about the same as IVPs. In
terms of benefits, the CT equals the accuracy of the IVP in determining the presence of
obstruction, but surpasses the IVP in detecting the specific cause of the obstruction 31.
Various signs of obstruction on spiral CT include hydroureter, perinephric stranding,
hydronephrosis, periureteral edema and renal swelling. But a non-contrast CT does not give
any indication about the function of the kidneys. Contrast enhanced MRI with MR urogram
has high resolution and can delineate the pelvicalyceal system as well as the site and cause
of obstruction. It is highly useful in cases with poor renal function because of the relative
non-toxicity of the gadolinium contrast.
Renal scan and diuretic renography is the most reliable technique to quantitatively
assess the split and total renal function in the presence of hydronephrosis. It is a noninvasive study, can be done even in patients with deranged renal function, has no risk of
contrast induced nephrotoxicity and also has much less radiation exposure than IVP or CT
scan. It can also be used to measure differential function and, therefore, is useful for
treatment planning. Moreover, a functional obstruction can be differentiated from an
anatomic cause. It can be used to follow up a patient after relief of obstruction. Also, the
assessment of renal blood flow provides a sense of whether function may return upon relief
of the obstruction. However, images from these scans lack the resolution to define the site of
obstruction.
The current radiopharmaceutical agent most widely used is technetium 99m
diethylenetriamine pentaacetic acid (99mTc-DTPA). It is excreted by glomerular filtration and
is not secreted or reabsorbed by the renal tubules. Another much more expensive agent is
99mTc-mercaptoacetyl- triglyine (MAG3), which offers better anatomical resolution, is more
efficiently excreted by the kidney (glomerular + tubular secretion), can be used in case of
decreased renal function, and delivers a lower dose of radiation. Thus it is the agent of
choice. 99mTc labeled Levo-ethyl cysteine (99mTc-LLEC) is a newer agent which is
relatively less expensive and has properties somewhat similar to the MAG3.
This study involves injecting a radioisotope and monitoring its passage through the
upper urinary tract. The patient should be well hydrated and catheterised. If the patient has a
239
nephrostomy tube in situ , it need not be clamped if only function of kidney is under
consideration. The early uptake of the kidney can be measured and indicates unilateral
function. The clearance of the radiopharmaceutical agent from the renal pelvis with a T
less than 15 min is considered normal, between 15 to 20 min is equivocal and T
1/2
1/2
of
greater
than 20 min indicates obstruction. Lasix (1 mg/kg) is then administered after approximately
20 minutes into the study if washout appears delayed. It is called as F+20 technique of
diuretic renography. Progressive accumulation despite furosemide administration confirms
obstruction. However rapid emptying despite an initial delayed excretion indicates dilatation
without obstruction (functional obstruction). A partial excretory response may indicate either
partial obstruction or renal dysfunction with an inability to respond to diuretic. These can be
differentiated by F15 technique of diuretic renography ie. by administering the diuretic 15
min before the radiopharmaceutical agent. The equivocal response to diuretic due to poor
response to diuretic in the F+20 technique, gets converted to washout response in this F15
technique.
Renal scans may not very useful in the advanced CRF patients and may be
misleading. In order to know about the renal function, GFR estimation or 24 hour creatinine
clearance can be done. Also, in such cases multiple factors should be considered including
cortical thickness on USG, amount of urine produced per day from the affected kidney and
the specific gravity of the urine being produced all of which can be easily assessed
anywhere. However, renal scans still hold there place in helping in diagnosis in patients who
do not have very advanced CRF. And also to assess any improvement in function when the
scan is repeated after 4-6 weeks after decompression of the urinary system.
Whitaker test was considered gold standard for evaluation of upper urinary tract
dilatation, classically used for UPJ obstruction. But with the advent of diuretic renogram it is
not often utilized clinically. It is a invasive test requiring a percutaneously placed canula
inside the renal pelvis and a bladder catheter connected to a pressure transducer each. fluid
(saline + contrast) is pushed into the renal canula at the rate of 10ml/min. fluoroscopic
monitoring of the anatomic site of obstruction can also be done. Rise of pressure in the renal
pelvis to less than 15 cm H2O is nonobstructed, 15 to 22 cm H2O is equivocal and greater
than 22 cm H2O is diagnostic of obstruction.
During retrograde pyelogram the contrast remains extravascular and therefore does
not interfere with renal function. This procedure requires anesthesia and is associated with
the risk of introducing infection in a obstructed system. It now only has adjunctive role in the
operating room during ureterorenoscopy or DJ stenting.
240
Ureteral stent: For distal obstruction, cystoscopic placement of a ureteral stent can be
attempted. A small tube running the length of the ureter from the renal pelvis to the
bladder is placed endoscopically in the operation theatre, usually with fluoroscopic
guidance, by the urologist. Anesthesia (ie, significant IV sedation and/or general
anesthesia) is required.
Percutaneous
nephrostomy:
For
midureteral
or
proximal
ureteral
obstruction,
Urethral catheter: A catheter is placed through the urethral meatus and into the bladder.
Suprapubic catheter: A catheter is placed through the lower anterior abdominal wall (just
superior to the pubis) and directly into the bladder. It is placed percutaneously at the
241
bedside (in the emergency department) or during an open surgical procedure by the
urologist. Local (for percutaneous) or regional/general anesthesia (for open) is required.
Other measures to be performed when the patient is first seen include (1) Investigate and
begin treatment of the life-threatening complications of obstructive uropathy (eg, pulmonary
edema, hypovolemia, urosepsis, hyperkalemia). (2) Consult nephrology to provide emergent
hemodialysis if necessary (3) A transurethral bladder catheter should be placed to measure
the urinary output. But in cases of unilateral obstruction with no uremia, it is best avoided as
it may introduce infection in a obstructed system. A Foley catheter can also be therapeutic
for obstruction below the level of the bladder. A properly placed catheter which does not
drain any urine indicates that the obstruction is above the level of bladder. A suprapubic
cystostomy may be needed in patients of bladder outlet obstruction, if attempts at
catheterization fail. (4) Relief of pain with narcotics or NSAIDs. The possible nephrotoxicity
of NSAIDs should be kept in mind while prescribing these. (5) There are many newer
experimental approaches that are being tried to ameliorate or modify the interstitial damage
after urinary obstruction. Ureteral obstruction results in increased fibrosis (collagen
diposition, interstitial volume expansion, and immuno-histochemical identification of
collagens), macrophage infiltration, tubular apoptosis, and transformation of fibroblasts to
myofibroblasts. The various chemo-mediators involved in these processes eg. Ang II, TGF ,
or nitric oxide (NO) are being targeted to reduce and retard the renal damage associated
with obstruction. AT I or AT II receptor blockers, ACE inhibitors, 1D11 (a monoclonal
antibody to TGF ), arginine (a precursor of NO) are all being tried but need further studies
before their routine clinical use.
Definitive management
The first crucial decision to be made is whether to remove the kidney or relieve the
obstruction. Diuretic renography, ultra-sonography (cortical thickness) and possibly even CT
may help the clinician in deciding this, but the experience of the surgeon in assessing a
clinical situation and per-op findings is the first. At times, laboratory data may seem to favor
salvage, whereas experience of the urologist favors nephrectomy. Viceversa is also true.
There have been cases of return of renal function when the kidney was salvaged if cortical
thickness was adequate, even though pre-op renography depicted poor renal function32.
Time is also a significant predictor of prognosis for patients with obstructive uropathy.
Vaughan and Gillenwater showed little return in renal function in dogs with 40 days of UUO.
But the duration of renal obstruction alone should not be a deterrent for the surgeon to repair
the blockage and possible preservation of some renal function. This is because humans may
242
have increased protection from the effects of long term obstruction in comparison to animal
models. This is due to the obstruction being usually partial, higher lymphatic and venous
drainage and extrarenal pelvis, if present.
Patients of bilateral obstruction have a persistent and progressive rise in the ureteral
pressure despite a decrease in renal blood flow, unlike the unilateral obstruction. therefore
such patients may have a more rapid deterioration of renal function. But still, the renal failure
in such patients is potentially reversible and certainly improvable, if treated early. Similar is
the case of solitary kidney with ureteric obstruction. It is improper to condemn such patients
as end stage renal disease while the so called CRF may be potentially reversible or may be
prevented from progressing further. With proper pre-op stabilization, correction of metabolic
aberrations, dialysis and timely decompre-ssion it is possible to salvage many of these renal
units to an extent where the need of renal replacement therapy may be deferred. 33 And
relieving the obstruction may at least improve the status from anuric status to oliguric status
which would help in better fluid and electrolyte management in a dialysis dependent patient.
Patients of CRF who harbour a known cause of urinary obstruction in the absence of
hydronephrosis should be considered obstructed and the potential cause should be
alleviated at the earliest. Prolonged obstruction (irrespective of whether hydronephrosis is
present or not) causes irreversible tubular, glomerular and interstitial damage resembling
medical renal disease. Once irreversible damage sets in, the natural history of disease is
similar to those of patients of medical renal disease and the management may not be altered
significantly whether or not these patients have a cause of obstruction. Most of these
patients are candidates for renal replacement therapy.
Nephrectomy should be considered if there is permanent severe loss of ipsilateral
renal function (GFR of <10ml/min) or there is development of unmanageable complication in
hydronephrotic kidney, eg. severe recalcitrant infection (ie. pyonephrosis), or trauma to
hydronephrotic kidney. The issue of renal salvage is more pressing if the patient has bilateral
renal obstruction. Many a times a non functioning kidney due to a benign cause is detected
incidentally. Such a kidney warrants nephrectomy if it is associated with any of the
followilng intractable pain, stone disease, haematuria, recurrent infection, uncontrolled
hypertension, malignancy, tuberculosis or large hydronephrotic kidney liable to trauma.
Nephrectomy can be accomplished by both conventional open surgery or laparoscopic
techniques.
The definitive mangement, once the decision to preserve the kidney has been made,
depends upon the particular cause of obstruction and may include watchful waiting,
243
obstructed kidneys. The better functioning kidney should be preserved first if the patient is
asymptomatic or has equal symptoms on both sides. More experienced surgeons have also
repaired both sides at the same sitting in the past. But its routine application is questionable.
The timing of intervention is also critical. Any urinary tract obstruction patient should
be treated on priority basis because of progressively increasing renal loss with increasing
duration of obstruction, as discussed above. But the cases associated with infection should
be dealt with urgently. Minimal intervention in the form of percutaneous nephrostomy or DJ
stenting is the safest yet life saving procedure in such patients.
Summary
Obstructive nephropathy is a frequent but preventable disease. Clinicians must make
a concerted effort to educate patients, especially those at greatest risk, about the signs and
symptoms of obstruction of the renal system. Diuretic renogram has emerged as the best
available modality to assess the renal function and guide treatment. Obstructions need to be
identified and addressed before the progression to obstructive nephropathy. Newer
modalities are being tried at the molecular level targeting either Ang II, TGF , or nitric oxide
(NO) to prevent the fibrosis and inflammation associated with obstruction.
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Massague, J.I. (1990). The transforming growth factor-b family. Annals of Biochemistry, 6, 597641
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Harris, K.P.G., Schreiner, G.F., & Klahr, S. (1989). Effect of leukocyte deple-tion on the function
of the post-obstructed kidney. Kidney International, 36, 210 215
18.
Truong, L.D., Sheikh-Hamad, D., Chakraborty, S., & Suki, W. N . (1998). Cell apoptosis and
proliferation in obstructive uropathy. Seminars in Nephrology, 18(6), 641 651
19.
Kaneto, N., Morrissey, J., & Klahr, S. (1993). Increased expression of TGF -b1 mRNA in the
obstructed kidney of rats with unilateral ureteral ligation. Kidney International, 44 , 313 321
20.
Pimental, J.L., Sundell, C.L., & Wang, S. (1995). Role of angiotensin II in the expression and
regulation of trans-forming growth factor-b in obstructive nephropathy. Kidney International, 48,
1233 1246
21.
Becker, G.J., & Hewitson, T.D. (2000). The role of tubulointerstitial injury in chronic renal failure.
Current Opinion in Nephrology and Hypertension, 9(2) , 133 138
22.
Taal, M.W., Omer, S.A., Nadim, M.K., & Mackenzie, H.S. (2000). Cellular and molecular
mediators in common pathway mechanisms of chronic renal disease progression. Current
Opinions in Nephrology and Hypertension, 9(4), 323 331
23.
Morrissey, J.J., Ishidoya, S., McCraken, R., & Klahr, S. (1996). Nitric oxide generation
ameliorates the tubulointerstitial fibrosis of obstructive nephropathy. Journal of the American
Society of Nephrology, 7(10), 2202 2212
24.
Klahr, S., Ishidoya, S., & Morrissey, J. (1995). Role of angiotensin II in the tubulointerstitial fibrosis
of obstruc-tive nephropathy. American Journal of Kidney Disease, 21(1), 141 146
25.
Klahr, S., Bueskert, J., & Morrison, A. (1986). Urinary tract obstruction. In B.M. Brenner & F.C.
Rector (Eds) , The kidney (3th ed) (pp. 1443 - 1490 ) . Philadelphia: W.B. Saunders Company
26.
Yarger, W.E. (1991). Urinary tract obstruction. In B.M. Brenner & F.C. Rector (Eds.), The kidney
(4th ed) (pp. 1772 -1793). Philadelphia: Saunders
27.
Recker, F., Hofmann, W., Bex, A., & Tscholl, R. (1992). Quantitative determination of urinary
marker proteins: A model to detect intrarenal bioeffects after extracorporeal lithotripsy. The
Journal of Urology , 148(3 Pt. 2), 1000 1006
28.
Rahman, M., & Smith, M.C. (1998). Chronic renal insufficiency: A diagnostic and therapeutic
approach . Archives of Internal Medicine, 158 (16), 1743 1752
29.
Koelliker, S.L., & Cronan, J.J. (1997). Acute urinary tract obstruction: Imaging update. Urologic
Clinics of North America, 24(3), 571 582
30.
Dretler, S.P. (1990). Ureteral stone disease: Options for management. Urology Clinics of North
America, 17 , 217- 230
31.
Smith, R.C., Rosenfield, A.T., & Choe, K.A. (1995). Acute flank pain: Comparison of non-contrastenhanced CT and intervenous urography. Radiology, 194 , 789 794
245
32.
Shapiro SR, Bennett AH (1976). Recovery of renal function after prolonged unilateral ureteral
obstruction. J Urol, 115, 136-140
33.
Singh I, Gupta NP, Hemal AK, Aron M, Dogra PN, Seth A. Efficacy and out come of surgical
intervention in patients with nephrolithiasis and renal failure. Int Urol Nephrol 2001; 33: 293-8
246
Retroperitoneal tumors
Kim Mammen, Prerna Gupta
Christian Medical College, Ludhiana
Introduction
These are uncommon heterogeneous group of tumors arising either primarily in
retroperitoneum or representing metastases from elsewhere. The reported incidence of
retroperitoneal tumor (RPT) varies from 0.3 to 3%. Primary retroperitoneal tumor develop
independently from the cell lines distinct from major retroperitoneal organs. Tumor of
retroperitoneal organs are not included in retroperitoneal tumor traditionally.
Primary retroperitoneal tumors comprise a variety of lesions, with different treatments
and prognoses. These tumors originate from various tissues of the retroperitoneum such as
fat, muscle, arteries, veins, lymphatic and fibrous tissue. Tumors of kidney, ureter, adrenal,
duodenum, pancreas and metastatic tumors are traditionally not discussed as retroperitoneal
tumors.
Anatomy
The retroperitoneum or retroperitoneal space is an actual and potential space
between peritoneal cavity and posterior body wall, containing structures of mesodermal
ectodermal origin with their embryonic remnants. According to Melicow and Ackerman, the
retroperitoneum is a region of trunk covered anteriorly by parietal peritoneum and superiorly
bounded by 12th rib and diaphragm with the pelvic diaphragm and the fascia of levator ani
and coccygeus muscle forming the inferior boundary. Posteriorly, it is bounded by fascia of
the muscles of the abdominal wall.,
boundaries make RPT expand and invade anteriorly into the abdominal cavity. Besides
many vital structures, the potential space itself contains loose connective tissue, fat, nerves,
lymphatics and lymph nodes.
Etiology
The majority of RPT (75-90%) are malignant, 75% are mesodermal in origin, 24% are
of neuroectodermal origin and 1% are from embryonic remnants.
malignancy in this area is sarcoma, though lymphoma, extranodal germ cell tumor and
carcinoma also occur. The etiology of most sarcomas is not known. Rarely these tumors
are associated with a history of therapeutic radiation, except malignant fibrous histiocytomas
which are being diagnosed increasingly due to availability of immunohistocytochemistry
stains. Exposure to vinyl chloride, thorium dioxide and other agents has been linked with
247
Low Grade
34
6
3
4
High grade
23
27
4
2
Total
57(50%)
33(29%)
7(6%)
6(5%)
5(4%)
4(4%)
1(1%)
1(1%)
248
There is
tremendous histological variation within the same tumor. For this reason a small biopsy may
not give proper assessment of the malignant potential of the entire lesion.
249
Retroperitoneal tumors carry a bad prognosis. Malignant tumors present late and are
often inoperable at the time of presentation. Current chemotherapy is not effective and
radiation is limited by toxicity to adjacent structures.
recurrence because of variable histology in different parts of the tumor, occasional true
malignant degeneration and presence of microscopic tumor beyond the pseudocapsule.
Clinical Presentation
The most common age of onset is between 40-70 years with almost equal
involvement of both sexes. Between 70-90% of RPT are mainly of malignant nature and
remain asymptomatic in the early stage.
may
be
associated
with
several
paraneoplastic
syndromes.
250
LABORATORY TESTS:
retroperitoneal germ cell tumor besides liver and kidney function tests.
CT SCAN OR MRI OF ABDOMEN: MRI has a greater accuracy over that of CT scan in
defining tumor extent and respectability (100% vs. 80% respectively).
MRI also
demonstrates the extent of recurrent tumor and points out areas of desmoplastic reaction
within the mass.
MFH exhibits a
heterogeneous signal pattern with low intensity of T1W, and higher intensity of T2W
sequence e.g. Hemangiocytoma appears as a multiloculated cystic mass with areas of solid
tissue on MRI. MRI correctly identifies the presence or absence of lymphadenopathy from
germ cell tumor of testes in 80 to 88% of cases. In lymphoma, a positive FNAC obviates the
need for surgery while in others it may useless due to variegated histology of the tumor.
Standard metastatic evaluation including CT scan of chest, abdominal imaging and level of
liver enzymes should be carried out in all cases.
ANGIOGRAPHY - is an useful investigation in selected cases where the tumor is of very
large volume.
Staging
The prognosis of patients with RPT depends on tumor grade size, nodal status, local
invasion and distant metastasis.
American Joint
Committee on Cancer(AJCC) has recommended a staging protocol where RPT are staged
251
Treatment
The treatment of choice for these lesions is wide local excision.
Microscopic
extension tends to occur along fascial planes and may be as far as 6 to 7 cm beyond all
gross disease. Metastasis to the regional lymph nodes in uncommon. The best results have
been seen in those tumors in which a margin greater than 3 cm can be obtained. If this is not
feasible, preoperative adjuvant chemotherapy or radiotherapy should be given.
Surgery
Adequate blood (up to 6 units) should be arranged as blood loss may be
considerable. Complete bowel preparation is required and consent is must for the removal
of adjacent organs and fecal or urinary diversion. If hypotensive anesthesia is used, blood
loss decreases significantly.
Tumors at pelvic level are best approached through a long midline incision and
above it via a thorocoabdominal incision which can be extended in T-shaped fashion
252
anteriorly or posteriorly.
dissection in subadventitial plane along the lateral border of aorta or IVC, extending dorsally
between spine and psoas major/quadratus lumborum muscle. This critical step determines
whether tumor has traversed along a spinal nerve root into the spinal canal and its cord,
which renders the tumor incompletely respectable.
peritoneum laterally with a sufficient deep margin of normal body wall, to provide a plane of
dissection posteriorly to spinous process. If at this point the surgeon can touch his fingers
together bimanually via the dissection plane and find an absence of intervening tissue, the
RPT is completely respectable. Involved major blood vessels can be excised and replaced
with a vascular graft and for the IVC above renal veins, drainage can be provided through
portal or splenic vein. Major lymphatic channels should be ligated to prevent lymphocele
formation. Sometimes RPT are very tense due to liquifactive necrosis of tumor thus prone to
dehiscence, which is prevented by the decompression of cystic tumor area using a trocar
and purse string suture with an additional
Z stitch, to bury the punctured site.
Colon and small bowel is mobilized, ligating the inferior mesenteric artery, if
necessary. Based on the preoperative angiogram feeding vessels should be controlled early.
Both the ureters should be identified and protected. To prevent, ureteral ischemia, stripping
of ureteral adventitia should be avoided. Major lymphatic channel including cysterna chylli
should be ligated to prevent lymphocoele formation.
Surgical extirpation is the mainstay of successful treatment for retroperitoneal
tumors. Experience and surgical skill are important assets in dealing with very large tumors
in the retroperitoneum. Pre-operation angio-embolization may be useful for very large and
vascular tumors.
Radiation Therapy
Radiotherapy combined with operative resection is beneficial in reducing local
recurrence after resection and 3-5 cms margin should be included all around the gross
tumor. When radiation is used alone it has a failure rate of 80-85%. Maximum benefits are
obtained in patient with complete surgical excision, positive microscopic margin or
incomplete resection. A dose greater than 5500 c GY is required to lower the incidence of
local recurrence. Intraoperative radiotherapy (IORT) has been used increasingly to improve
the result but a study comparing IORT and postoperative external abeam radiotherapy
(IBRT) with postoperative radiotherapy showed that IORT reduces local recurrence as well
253
as radiation enteritis. The impracticality of the method of IORT makes this an unreasonable
choice. In future radio-sensitizer such iododeoxyuridine may improve the response.
Chemotherapy
A complete response rate is 15-35% have been reported with the use of Adriamycin
as a single agent.
combined with granulocyte macrophage colony stimulating factors (GM-CSF) have been
seen to result in a significant improvement in the response rate and it may be used for
disseminated disease.
Chemotherapy is appropriate for patients in whom the disease cannot be cured with
surgery. Adriamycin, Ifosphamide, high dose Methotrexate, Cytoxan, DTIC, VP-16,
Cisplatinum are among the most commonly used drugs. These drugs are used in
combination and can have moderate to severe toxic effects. More recently, Chemotherapy is
used as Neo-Adjuvant treatment with some success. The goal is to shrink the tumor prior to
surgery and increase the chance for cure. This approach at times uses concomitant
Radiation therapy as well. A new drug called Ecteinascidin has been shown to benefit some
patients with soft tissue sarcomas. It is still being tested and has not been submitted for
approval to the FDA.
Prognosis
After complete resection of primary RTP an actual 5 years survival rate is 74%
compared to 35% after partial resection.
primary tumor to 44% for recurrent disease. A local recurrence in the range of 40% to 82%
has been reported with the median time to recurrence of 15 months and 44 months for high
grade and low grade tumor. The completeness of resections and grade of tumor are primary
determinants of survival. Even partial resection improves survival and quality of life. The
use of adjunctive radiotherapy delays the progression of disease and does not improve
survival. A study by Potter et al reconfirmed the survival benefit after complete surgical
excision and identified tumor grade as independent predictor or survival.
Follow Up
Patients are evaluated with physical examination every 2-3 months. Abdominal pain
or symptoms indicate the need for a CT scan/MRI study.
254
References
1. Sitting KM, Rohr MS, McDonald JC. Abdominal wall, Umbilicus, Peritoneum, Mesentries,
Omentum and Retroperitoneum. In: Text Book of Surgery, Vol. 1, edited by Sabiston DC and
Lyerly HK, WB Saunders Company 1997; Page 809-824.
2. Daly JM, Adam JT, Fantini GA and Fisher JE. Abdominal Wall, Omentum, Mesentry and
Retroperitoneum, In: Principles of Surgery, 7th Edition by Schwartz, etc. Vol, II, McGraw Hill
Company 1999: Page 1580-84.
3. Testini M, Catalano Jr G, Macarini L, Paccione F. Diagnosis and surgical treatment of
retroperitoneal tumor. Int Surg 1996; 81: 88-93.
4. Marshall FF. Urological survey: Urological oncology: renal, ureteral and retroperitoneal tumors. J
Urol. 2006 Sep; 176 (3): 950-1.
5. Pierie JP, Betensky RA, Choudry U, Willett CG, Souba WW, Ott MJ. Outcomes in a series of 103
retroperitoneal sarcomas. Eur J Surg Oncol. 2006. Aug 17.
6. Buse S, Gilfrich C, Wagener N, Pfitzenmaier J, Haferkamp A, Hohenfellner M. Thoraco-abdominal
approach to large retroperitoneal tumors. BJU Int. 2006 Jul 28.
7. Raut CP, Pisters PW. Retroperitoneal sarcomas: Combined-modality treatment approaches. J
Surg Oncol. 2006 Jul 1; 94(1): 81-7.
8. Chew C, Reid R & ODwyer PJ. Value of biopsy in the assessment of a retroperitoneal mass.
Surgeon. 2006 Apr; 4 (2): 79-81.
255
Urethral Trauma
Madhu S. Agrawal, Sumit Bansal
SMS Hospital, Agra
"It is the urologist who has to share the burden of this ultimate disability with the patient
when the thoracic, the abdominal, and even the orthopedic aspects are probably long
forgotten..."
Mr. Richard Turner-Warwick (1977)
On pelvic fracture with associated urethral distraction injury
Relevant Anatomy: The male urethra may be divided into 2 portions. (Figure.1)The posterior
urethra includes the prostatic urethra, which extends from the bladder neck through the
prostate gland. It then joins the membranous urethra, which lies between the prostatic apex
and the perineal membrane. The anterior urethra begins at that point and includes 3
segments. The bulbar urethra courses through the proximal corpus spongiosum and ischial
cavernosus-bulbospongiosus muscles to reach the penile urethra. The penile urethra then
extends through the pendulous portion of the penis to the final segment, the fossa
navicularis. The fossa navicularis is invested by the spongy tissue of the glans penis.
Potential areas for injury can be
susceptible
to
blunt
force
injuries
because of its path along the perineum. Straddle-type injuries from falls or kicks to the
perineal area can result in bulbar trauma. Conversely, the penile urethra is less likely to be
injured from external violence because of its mobility, but iatrogenic injury from
catheterization or manipulation can occur, which is also possible in the fossa navicularis.
Classification: Urethral injuries can be classified into 2 broad categories based on the
anatomical site of the trauma:
A.
Trauma above the urogenital diaphragm (posterior urethra): most often involves
membranous urethra
256
B.
Trauma below urogenital diaphragm (anterior urethra): most often involves bulbar
urethra
fracture
Symptoms:
Patients usually complain of lower abdominal pain and inability
to urinate. A history of crushing injury to the pelvis is usually obtained.
Signs:
Blood at the urethral meatus is the single most important sign of urethral injury.1 The
importance of this finding cannot be overemphasized, because an attempt to pass a urethral
catheter may result in infection of the periprostatic and perivesical hematoma and
conversion of an incomplete laceration to a complete one. The presence of blood at the
external urethral meatus indicates that immediate urethrography is necessary to establish
the diagnosis.
Suprapubic tenderness and the presence of pelvic fracture are noted on physical
examination.2 A large developing pelvic hematoma may be palpated. Perineal or suprapubic
contusions are often noted. Rectal examination may reveal a large pelvic hematoma with the
prostate displaced superiorly (Figure.2). Rectal examination can be misleading, however,
because a tense pelvic hematoma may resemble the prostate on palpation. Superior
displacement of the prostate does not occur if the puboprostatic ligaments remain intact.
Partial disruption of the membranous urethra (currently 10% of cases) is not accompanied
by prostatic displacement.
Instrumental examination:
The only instrumentation involved should be for urethrography. Catheterization or
urethroscopy should not be done, because these procedures pose an increased risk of
hematoma, infection, and further damage to partial urethral disruptions.
Differential Diagnosis:
Bladder rupture may be associated with posterior urethral injuries in approximately
20% of cases. Cystography cannot be done preoperatively, since a urethral catheter should
257
258
diagnose
RUG.
urethral
trauma
patient
is
The
positioned
for
imaging
is
ideally
in
an
259
the penis stretched so that the meatus points cephalad. This produces a C configuration
from the bladder level to meatus tip (Figure 5). The Foley catheter is then placed inside the
urethra with the balloon inflated in the fossa navicularis. Approximately 20-30 mL of 30%
contrast material is injected into the urethra, with the exposure being made during the active
injection of the last few mL of contrast, allowing maximum filling of the deeper bulbar,
membranous, and prostatic urethral sections. The entire procedure should preferably be
performed under fluoroscopic control.
Classification of RUG findings:
The most accepted and unified classification of RUG findings for urethral injuries is the
Goldman classification, with its foundation in the earlier system developed by Colapinto and
McCallum.4,5 The Goldman classification of urethral trauma is defined entirely on the
anatomical findings of the injury and not on its mechanism. This system defines five major
types of urethral injuries as seen in RUG.
Type I urethral injury results when the puboprostatic ligament is ruptured, and the
prostate is allowed to move superiorly (Figure 6). The urethra remains intact however, and is
only severely stretched by the movement of the prostate. No extravasation of contrast
material is seen with radiography, and continuity is maintained with the bladder. True cases
of Type I urethral injuries are uncommon.
Type II urethral trauma is the classically described posterior urethral injury in which
the urethra is torn superior to the urogenital diaphragm (Figure 7). In such an injury,
contrast-agent extravasation is seen within the extra peritoneal pelvis, but contrast material
is not present within the perineum. Here, the urogenital diaphragm is intact, preventing the
spread of contrast material inferiorly. This type exists in approximately 15% of urethral
trauma cases resulting from pelvic crush injuries.
The most common type of urethral trauma has proven to be type III urethral
injury5.Type III urethral injury, like type II, shows disruption above the urogenital diaphragm
(Figure 8). Unlike type II, though, this injury extends through the urogenital diaphragm and
includes the proximal bulbous urethra. In this injury, extravasation can be found within the
extra peritoneal pelvis and within the perineum. The amount of contrast material found
above or below the urogenital diaphragm depends upon the exact location of the injury and
the degree of disruption to the perineal membrane.
Type II or III urethral injury can be further classified as partial or complete tear.5 With
RUG; partial tears are diagnosed when extravasation of contrast material occurs with the
260
presence of contrast material in the bladder. Complete tears are diagnosed when
extravasation is present and no contrast agent is present in the bladder or in the proximal
torn end of the urethra. The relative frequency of partial tears versus complete tears is highly
variable in the literature, and no reason for this variance has been agreed upon.
Type IV urethral trauma is a tear to the bladder neck that extends into the proximal
urethra (Figure 9). Contrast-agent extravasation is seen in the extra peritoneal pelvis around
the proximal urethra. Such injuries can damage the internal urethral sphincter, resulting in
incontinence.5Proper diagnosis is therefore essential to ensure adequate patient care.
Type V urethral trauma describes all cases that are isolated to the anterior urethra
(Figure.10). Such an injury occurs distal to the urogenital diaphragm and is more associated
with perineal crush or straddle injuries.3 The resulting urethral injury is usually a partial tear
of the bulbous urethra, though complete tears can also occur. In this case, contrast-agent
extravasation occurs inferior to the urogenital diaphragm. If the Buck fascia remains intact,
the extravasation is limited to its confines, i.e., the penile shaft. If the Buck fascia is
disrupted, the contrast material contained within the limits of the Colles fascia. 3 In this case,
contrast agent might be found in the lower abdomen and in the scrotum.
2. CT Scan:
Despite the prevalent use of CT as the initial screening modality for general acute
trauma, the literature has described few applications of CT in diagnosing urethral injuries
(Figure 11).
One report has shed new light into the important potential clinical value for CT in
diagnosing urethral trauma. In this retrospective review, Ali et al reviewed 97 patients
examined over an 11-year period. Seventeen patients had pelvic fractures and urethral injury
(confirmed during urethroscopy or surgery), 30 patients had pelvic fractures with no
associated urethral injury, and 50 patients had neither pelvic fracture nor urethral injury. As a
result of their investigation, the authors were able to identify findings specific for type I, II,
and III urethral injuries as well as findings highly associated with general urethral trauma.
A distance of 2 cm between the prostatic apex and urogenital diaphragm was specific
for type I urethral injuries. The CT findings specific for type II and type III urethral trauma
were contrast-agent extravasation above the urogenital diaphragm and extravasation below
the urogenital diaphragm, respectively. CT findings associated with but not specific for
urethral trauma were distortion or obscuration of the urogenital fat plane, hematoma of the
ischiocavernosus muscle, distortion or obscuration of the prostatic contour, distortion or
261
262
suggested that sonography demonstrates hematoma size and the extent of fluid
extravasation better than RUG. Other investigators have shown that sonourethrography can
more accurately measure stricture length than RUG. This information could prove useful for
planning surgical repair for specific cases.
Management
A. TRAUMA ABOVE UROGENITAL DIAPHRAGM
EMERGENCY MEASURES:
1. Resuscitation & care of vitals (A,B,C care)
2. Assessment &management of other injuries
pelvic
fracture.
to
delayed
repair,
263
making
secondary
repair
more
difficult.
2. URETHRAL REALIGNMENT OVER CATHETER (RAIL-ROADING):
The definition of primary realignment of urethral distraction injury means immediate
"indirect" or endoscopy-assisted stenting of the distraction with a urethral catheter, without
any pelvic dissection or sutures.8 This procedure can
be completed quickly, with minimal morbidity.
13, 14
. The
suprapubic catheter is left after the urethral catheter is removed because many of these
264
patients go on to develop symptomatic urethral stricture. If the patient voids satisfactorily via
the urethra, the suprapubic catheter can be removed 7 to 14 days later.
Limitations of rail-roading:
Catheter may obstruct the urethra & exudates in long term, leading to urethritis and
stricture in hitherto uninvolved anterior urethra
Splinting does not prevent stricture formation. It has also been shown that the
prostate invariably comes down spontaneously as hematoma is absorbed.
approach
or
involves
manipulation.
no
urethral
Percutaneous
265
heals spontaneously, and the suprapubic cystostomy can be removed within 2-3 weeks.
The cystostomy tube should not be removed before voiding cystourethrography shows that
no extravasation persists.21
B. Delayed Urethral Reconstruction:
Reconstruction of the urethra after prostatic disruption can be undertaken after 3 months,
assuming there is no pelvic abscess or other evidence of persistent pelvic infection (Figure
15).
Before
reconstruction,
combined
apex of the prostate. 16F silicone urethral catheter should be left in place along with a
suprapubic cystostomy. Catheters are removed within a month, and the patient is then able
to void.
Advantages:
1. Simplifies initial management of serious injury
2. Well within the abilities of occasional operator
3. Pelvic hematoma undisturbed, avoids blood loss, infection
4. Avoids converting partial to complete tear
5. Avoids surgery if urethral tear is incomplete
6. Allows preoperative assessment of impotence
7. Avoids complication of prolonged urethral catheterization - urethritis, epididymitis,
stricture
8. Results of delayed anastomotic repair excellent
9. Lower incidence of complication (restricture, impotence, incontinence)
B. TRAUMA BELOW UROGENITAL DIAPHRAGM
1. Urethral contusionThe patient with urethral contusion shows no evidence of extravasation, and the urethra
266
remains intact. After urethrography, the patient is allowed to void; and if the voiding occurs
normally, without pain or bleeding, no additional treatment is necessary. If bleeding persists,
urethral catheter drainage can be done.
2. Urethral lacerationsInstrumentation of the urethra following urethrography should be avoided. A small midline
incision in the suprapubic area readily exposes the dome of the bladder so that a suprapubic
cystostomy tube can be inserted, allowing complete urinary diversion while the urethral
laceration heals. Percutaneous cystostomy may also be used in such injuries. If only minor
extravasation is noted on the urethrogram, a voiding study can be performed within days
after suprapubic catheter drainage to search for extravasation. In more extensive injuries,
one should wait 2-3 weeks before doing a voiding study through the suprapubic catheter.
Healing at the site of injury may result in stricture formation. Most of these strictures are not
severe and do not require surgical reconstruction.
The suprapubic cystostomy catheter may be removed if no extravasation is
documented. Follow-up with documentation of urinary flow rates will show whether there is
urethral obstruction from stricture.
3. Urethral laceration with extensive urinary extravasationAfter major laceration, urinary extravasation may involve the perineum, scrotum, and lower
abdomen. Drainage of these areas is indicated. Suprapubic cystostomy for urinary diversion
is required. Infection and abscess formation are common and require antibiotic therapy.
4. Immediate repairImmediate repair of urethral lacerations can be performed, but the procedure is difficult and
the incidence of associated stricture is high.
Complications
1. Impotence:
Impotence is found in 13% to 30% of patients with pelvic fracture and urethral distraction
injury who are treated with early catheter placement only8,
9, 13, 17
. In a population of
patients who ultimately required open repair and who presumably had more severe,
complete urethral distraction, the incidence was much higher (48% to 72%) 22,23. Although
not completely impotent, a further 32% of patients in this population reported poorer
erections after injury23. Some patients with impotence immediately after injury recover
267
erectile function, some as long as a year or two later16, 24. This phenomenon may be why
some authors have reported improvement in potency after completion of open
urethroplasty 3 months after the injury25,
26
repair is 30-80% (mean, about 50%). This figure can be reduced to 30-35% by
suprapubic drainage with delayed urethral reconstruction.
The related complication of anejaculation, likely secondary to bladder neck scarring, is
found in 15% of urethral distraction injury patients17.
2. Incontinence:
Most patients with significant urethral distraction injury also have injury to the external
(striated) sphincter. Presumably, continence is then provided by the bladder neck 26.
Accordingly, patients with open bladder neck before urethroplasty have a significantly
higher rate (53%) of incontinence than those with a closed bladder neck27 .The overall
rate of incontinence is low (2% to 4%)
8, 28
problem to treat. In some reports, as many as 10% have an areflexic bladder secondary
to the original injury, resulting in the need for intermittent catheterization28. A minority of
patients (6%) complains of mild urge or stress incontinence. Incontinence in primary
reanastomosis is noted in one-third of patients. Delayed reconstruction reduces the
incidence to less than 5%.
3. Stricture:
Stricture following primary repair and anastomosis occurs in about 50% of cases. If the
preferred suprapubic cystostomy approach with delayed repair is used, the incidence of
stricture can be reduced to about 5%. After urethral reconstruction for posterior urethral
rupture, 12% to 15% of patients have initial stricture development at the anastomosis26,
29
urethrotomy)
30
.Ultimately, patients treated with this approach have a 97% success rate,
5 Goldman, SM; Sandler, CM; Corriere, JN Jr; McGuire, EJ: Blunt urethral trauma: a unified,
anatomical mechanical classification. J Urol 1997 Jan; 157(1): 85-9.
6 .Riccabona, M: Contrast ultrasound of the urethra in children. Eur Radiol 2003 Jul; 13(7): 1494-5.
268
7. Bearcroft, PW; Berman, LH: Sonography in the evaluation of the male anterior urethra. Clin Radiol
1994 Sep; 49(9): 621-6.
8. Elliott, DS; Barrett, DM: Long-term follow up and evaluation of primary realignment of posterior
urethral disruptions.J Urol 1997; 157:814816.
9. Kotkin, L; Koch, MO: Impotence and incontinence after immediate realignment of posterior urethral
trauma: Result of injury or management? J Urol 1996; 155:16001603.
10. Al-Ali, IH; Husain, I: Disrupting injuries of the membranous urethrathe case for early surgery and
catheter splinting.Br J Urol 1983; 55:716720.
11. Herschorn, S; Thijssen, A; Radomski, SB: The value of immediate or early catheterization of the
traumatized posterior urethra.J Urol 1992; 148:14281431.
12. Gheiler, EL; Frontera, JR: Immediate primary realignment of prostatomembranous urethral
disruptions using endourologic techniques. Urology 1997; 49:596599.
13. Routt, ML; Simonian, PT; Defalco, AJ; et al: Internal fixation in pelvic fractures and primary repairs
of associated genitourinary disruptions: A team approach.J Trauma 1996; 40:784790.
14. Jepson, BR; Boullier, JA; Moore, RG; Parra, RO: Traumatic posterior urethral injury and early
primary endoscopic realignment: Evaluation of long-term follow-up. Urology 1999; 53:12051210.
15. Follis, HW; Koch, MO; McDougal, WS: Immediate management of prostatomembranous urethral
disruptions.J Urol 1992; 147:12591262.
16. Morehouse, DD; Belitsky, P; Mackinnon, K: Rupture of the posterior urethra.J Urol 1972; 107:255
258.
17. Asci, R; Sarikaya, S; Buyukalpelli, R; et al: Voiding and sexual dysfunctions after pelvic fracture
urethral injuries treated with either initial cystostomy and delayed urethroplasty or immediate
primary urethral realignment. Scand J Urol Nephrol 1999; 33:228233.
18. Morey, AF; McAninch. JW: Reconstruction of posterior urethral
analysis in 82 patients. J Urol 1997; 157:506.
19. Kantor, A; Sclafani, SJ; Scalea, T; et al: The role of interventional radiology in the management of
genitourinary trauma. Urol Clin North Am 1989 May; 16(2): 255-65.
20. Clark, WR; Patterson, DE; Williams, HJ Jr: Primary radiologic realignment of membranous urethral
disruptions. Urology 1992 Feb; 39(2): 182-4.
21. Podesta, ML; Jordan, GH: Pelvic fracture urethral injuries in girls. J UroI2001; 165:1660.
22. Dhabuwala, CB; Hamid, S; Katsikas, DM; Pierce, JM Jr: Impotence following delayed repair of
prostatomembranous urethral disruption.J Urol 1990; 144:677678.
23.Corriere,JN Jr; Rudy,DC; Benson,GS : Voiding and erectile function after delayed one-stage repair
of posterior urethral disruptions in 50 men with a fractured pelvis.J Trauma 1994; 37:587589.
24. Turner-Warwick, R: A personal view of the immediate management of pelvic fracture urethral
injuries. Urol Clin North Am 1977; 4:8193.
25. Koraitim, MM: The lessons of 145 posttraumatic posterior urethral strictures treated in 17 years.
26. Morey, AF; McAninch, JW: Reconstruction of traumatic posterior urethral strictures.Tech Urol
1997; 3:103107.
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urethral distraction defects.J Urol 1999; 162:347351.
28. Corriere,JN Jr; Rudy,DC; Benson,GS : Voiding and erectile function after delayed one-stage
repair of posterior urethral disruptions in 50 men with a fractured pelvis.J Trauma 1994; 37:587
589.
29. Mundy, AR: Urethroplasty for posterior urethral strictures. Br J Urol 1996; 78:243247.
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269
Displaced pelvic fractures result from high energy absorption & may be a component
of poly-trauma. The situation is usually life threatening requiring aggressive resuscitation
protocols.
Anatomy: Pelvis is a ring structure consisting of 3 bones namely the iliac, ischial & pubic
bones. The stability of this ring is derived purely from its ligamentous connections. The
interosseous sacroiliac, the ant. & post. SI ligaments, sacrotuberous, sacrospinous & the
iliolumbar ligaments are important stabilisers.
Relations: The iliac blood vessels & the lumbosacral plexus form important anterior relations
of the sacroiliac joint & are therefore liable to get injured in pelvic disruptions.
Haemorrhage: Life threatening bleeding can occur following pelvic injuries. It is usually the
low pressure venous channels & the broad cancellous Fracture surfaces which are the usual
culprits & not the major blood vessels. Constant movement of the unstable fractured
fragments leads to repeated clot dislodgement leading ultimately to coagulation failure &
death. Moreover ligamentous disruption leads to opening up of the retroperitoneal space &
loss of tamponade effect allowing large amounts of blood to collect in the flanks.
Associated intra-abdominal bleeding may have a compounding effect extraperitoneal bleed. Peritoneal lavage, USG or abdominal CT may help in diagnosis.
Classification (Tile):
A. Stable
B. Rotationally unstable- open book
C. Rotationally & vertically unstable.
Diagnosis- Clinical
-
Soft tissue- Flank or buttock contusion, abrasions & swelling, at times frank
degloving- Morel-Lavalle lesion.
270
Diagnosis- Radiological
-
Plain X- ray pelvis AP view is sufficient for emergency management- >2.5cm pubic
symphysis widening suggestive of SI ligament disruption.
Outlet & inlet views may later be done for better visualisation of pelvic displacement/
rotation & sacral fractures
Associated injuries:
1. Urological
2. Neurological
3. Visceral
Open pelvic fractures:
Pelvic fractures may be associated with perineal wounds or rectal tears necessitating
aggressive debridement in former & diversion colostomy in the latter. Mortality rates may be
as high as 50% in such situations.
Management:
Stabilisation of Pelvis is a life saving manoeuvre which prevents repeated clot
dislodgement. Temporary measures include using a sheet as a pelvic binder or pneumatic
anti-shock garment.
External fixation: In the hospital, external fixation is the most accepted mode of quickly
stabilising the pelvis apart from being minimally invasive. It is ideally suited to the
horizontally unstable pelvic fractures. In vertical shear injuries it may be combined with
skeletal traction pending internal fixation.
The types of frames in vogue are:
1. Anterior frame which involves pin insertion in the iliac crest.
2. Anti-shock C-clamp (Ganz). Applies direct pressure over the SI joint
Selective embolisation:
If bleeding does not stop after Ex. Fix. Application, an angiography is performed to identify
arterial bleeders and these are stemmed by steel coils / gel foam injection.
Supportive therapy: Blood & volume replacement
Post-fixation care: Logrolling, non wt. bearing walker ambulation.
Removal at 6-8weeks
Shift to internal fixation after 7-10 days.
271
History
Amputation is the most ancient of surgical procedures. Early surgical amputation was a
crude procedure by which a limb was rapidly severed from an unanaesthetized
patient.
The open stump was then crushed or dipped in boiling oil to attain hemostasis. This
procedure was associated with a high mortality rate. For those who survived, the resulting
stump was poorly suited for prosthetic fitting.
Indications
Absolute Irreversible ischemia in a diseased or traumatized limb. Overall, indications of
amputations have been classified as
1.
2.
3.
A).
severe trauma,
burns, frostbite.
Dangerous
malignant tumours,
lethal sepsis,
crush injury.
Damn Nuisance
common indication for amputation. Approximately half of amputations for peripheral vascular
disease are performed on patients with diabetes. Most significant predictor of amputation in
272
Trauma
Trauma is the leading indication for amputations in younger patients. Several scoring
2.
3.
4.
5.
Out of these Mangled Extremity Severity Score (MESS) is most acceptable scoring system
where grading is based on :
1. Energy that causes the injury.
2. Limb ischemia
3. Shock
4. Age
Score of six or less consistent with a salvageable limb. However it should be emphasized
that no scoring system can replace experience and good clinical judgement.
C). Infection
Open amputation is indicated in this setting and may be performed using one of the
two methods. A Guillotine amputation may be performed with later revision to more proximal
level after infection is under control. Alternatively an open amputation may be performed at
the definitive level by initially inverting the flaps and packing the wound open with secondary
273
closure at 10-14 days. In acute setting, the most worrisome infections are those produced by
gas forming infections.
D). Tumours :
Indications include
1. Primary malignancy.
2. Palliative measure in patients with metastatic disease.
3.
2. Non-end bearing: Weight is not taken over at the end of the stump. Scar can be terminal.
Examples: above knee, below knee amputations.
274
Objectives
1. Securing rapid tissue healing.
2. Preserving an adequate length of stump.
3. Attain maximal function of residual limb.
4. Rehabilitation of person as a whole.
Principles of Amputations
1. Clean operative field.
Pre-operative aseptic skin care should be taken. Fresh wounds should be cleaned &
debrided. Old wounds should display healthy granulation tissue.
2. Tourniquet.
Tourniquet is highly desirable except in ischemic limbs. It makes the amputation easier. Limb
should be exsanguinated before inflation. For infections or malignant growths, expressing
blood is inadvisable;
275
3. Level of amputation
As much of the length as is consistent with good function should be preserved. Trade
off lies between increased function with more distal level of amputation and decreased
complication rates with a more proximal level of amputation.
Too short stump leads to slipping out of prosthesis, whereas too long stump is
associated with inadequate circulation become painful, ulcerate. It is also associated with
complicated incorporation of joint in prosthesis.
Surgery should be performed through as normal tissue as possible to enhance
wound healing and at a level most suited for prosthesis. With modern prosthesis, any level of
amputation acceptable.
Ideal Level : Certain sites are preferred, determined by types of prosthesis, function of part,
muscle balance and adedquacy of circulation.
Transtibial
Minimal useful length- 9 cm or flex the knee to right angle; the residual tibia should extends
at least 3 fingerbreadths beyond the insertion of med. Hamstrings.
Fibula is divided 1cm prox. to the tibia
276
Transfemoral
Shortest length for effective use of prosthesis 8 cm. Ideal length is 13 cms.
Transradial
Preserve as much length as possible. Even very short below elbow stump is preferable to
an elbow disarticulation.
Transhumeral
Atleast 3.8 cm proximal to elbow joint for fitting an elbow lock mechanism.
Clinical findings :
1. tissue appearance,
2. skin temp,
3. presence/ absence of edema after elevation,
4. hair growth,
277
5. presence of pulses,
6. sensation level
Lab findings
1. Doppler study
2. Themography
3. Laser doppler flowmetry
4. Transcutaneus O2 measurements
Surgical findings
1. Adequate bleeding
2. Tissue viability
4. Skin flaps
Ends should be covered with good mobile skin of adequate thickness and normal
sensation. With introduction of modern total contact prosthesis location of scar is
unimportant. Avoid adherence to underlying bone & redundant skin. Their combined length
should equal one and a half time the width of the limb at the site of amputation.
Flap length : depending on site of amputation
Upper ext :
Above wrist ant/post equal flaps,
Below wrist : long ant flap- use tough palmer skin over stump.
Lower ext :
Hip : Raquet incision scar away from faecal contamination & pressure area over ischial
tuberosity.
Above knee : ong ant/ short post
Below knee :
Circulation adequate equal ant/post flaps to allow scar to lie transversely immediately
behind tibia
278
Ischemic limb more vascular posterior flap longer, scar anterior above the bone end.
279
7. Blood vessels :
Major blood vessels isolated, doubly ligated with non- absorbable sutures & then cut.
Tourniquet is released before closure & hemostasis achieved.
8. Drain :
For 48 -72 hours,
Prevent post op hematoma & infection.
9. Bone :
Periosteum cut at the saw line. Bone cut transversely except in end bearing stumps where it
is cut parallel to ground. Bone edges are rounded off with a file.
Post Operative Regimen
Following surgery, the amputee is actively involved in three stages of rehabilitation:
Absolute bed rest with limb elevation-for conventional prosthesis with adequate
vascularity.
Immediate upright posture for ischaemic limb
280
Prosthesis
Silicone & gel material more comfortable.
Should
fit comfortably,
function well,
look presentable,
be fitted as soon as possible patient uses much better.
Complications
Immediate
1. Post op hemorrhage.
Early
1. Secondary hemorrhage from infection.
2. Ischemia, suturing under increased tension breakdown of skin flap, ulceration.
3. Gas gangreneclostridia, spores from perineum.
Delayed
1. Skin : eczema,
tender purulent lumps in groin
ulceration due to poor circulation.
2. Muscle : too much muscle left at endunstable cushion, feeling of insecurity,
prevent proper use of prosthesis.
3. Artery : poor circultationcold,blue stump, liable to ulcerate.
4. Nerve : painful/ tender neuroma,
stump hyperaesthesia,
phantom limb.
5. Joint : stiffness/ deformity,
fixed flex/ abd at hip in A/K stumps,
fixed flexion at knee in B/K stumps..
6. Bone : spur formation.
7. Prosthetic fit : abnormal.
Amputations in children
For children ( Krajbich):
1. Preserve length
2. Preserve important growth plates
281
282
Trauma is one of the leading cause of death & disability in both industrialized &
developing countries. About 60% of all Blunt Abdominal Trauma (BAT) are caused by
automobile accidents. Other causes are assaults, falls, pedestrian struck & recreational
activities. The abdomen can be arbitrarily divided into 4 areas:
The first is the intrathoracic abdomen, which is the portion of the upper abdomen that
lies beneath the rib cage. Its contents include the diaphragm, liver, spleen, and stomach.
The second is the pelvic abdomen, which is defined by the bony pelvis. Its contents
include the urinary bladder, urethra, rectum, small intestine, and, in females, the ovaries,
fallopian tubes, and uterus. Injury to these structures may be extraperitoneal in nature and
therefore difficult to diagnose.
The third is the retroperitoneal abdomen, which contains the kidneys, ureters,
pancreas, aorta, and vena cava. Injuries to these structures are very difficult to diagnose
based on physical examination findings. Evaluation of the structures in this region may
require a CT scan, angiography, and an intravenous pyelogram.
The fourth is the true abdomen, which contains the small and large intestines, the
uterus (if gravid), and the bladder (when distended). Perforation of these organs is
associated with significant physical findings and usually manifests with pain and tenderness
from peritonitis. Plain x-ray films are helpful if free air is present. Additionally, DPL is a useful
adjunct.
Mechanism of Injury
Mechanisms of blunt injury abdomen include shearing, crushing and compression
forces. Rapid deceleration causes differential movement among adjacent structures. As a
result, shear forces are generated and cause hollow, solid, visceral organs and vascular
pedicles to tear, especially at relatively fixed points of attachment. Youth have a better
tolerance than old because of more elastic tissues and firm abdominal muscles.
The crushing forces are generated when intra-abdominal contents are crushed
between the anterior abdominal wall and the vertebral column or posterior thoracic cage.
The duodenum, pancreas, spleen, liver and kidneys are especially vulnerable.
283
External compression forces result when a sudden and dramatic rise in intraabdominal pressure occurs and culminates in rupture of a hollow viscous organ (in
accordance with the principles of Boyles law).
Initial Assessment & Resuscitation
As soon as the patient arrives in the emergency department a quick initial assessment
with simultaneous resuscitation is started. The goal of the primary survey, as directed by the
Advanced Trauma Life Support (ATLS) protocol, is to identify and expediently treat lifethreatening injuries. The protocol includes the following:
Breathing
Circulation
Disability
Exposure
The initial clinical assessment of patients with BAT is often difficult and notably
inaccurate. Associated injuries often cause tenderness and spasm in the abdominal wall and
make diagnosis difficult. Lower rib fractures, pelvic fractures, and abdominal wall contusions
may mimic the signs of peritonitis.
Powell et al reported that clinical evaluation alone has an accuracy rate of only 65% for
detecting the presence or absence of intraperitoneal blood. In general, accuracy increases if
the patient is examined repeatedly and at frequent intervals.
The greatest compromise of the physical examination occurs in the setting of
unconsciousness as in head injury, alcohol abuse,spinal injuries or concomitant psychiatric
illness .
The most reliable signs and symptoms in alert patients are pain, tenderness,
gastrointestinal hemorrhage, hypovolemia, and evidence of peritoneal irritation. However,
large amounts of blood can accumulate in the peritoneal and pelvic cavities without any
significant or early changes in the physical examination findings.
Detailed Assessment of the Abdomen
The abdominal examination must be systematic. The abdomen is inspected for
abrasions or ecchymosis. The seat belt sign (a contusion or abrasion across the lower
abdomen), is highly correlated with intraperitoneal pathology. Visual inspection for
abdominal distention, which may be due to pneumoperitoneum, gastric dilatation, or ileus
284
produced by peritoneal irritation, is important. Ecchymosis involving the flanks (Grey Turner
sign) or the umbilicus (Cullen sign) indicates retroperitoneal hemorrhage, but this is usually
delayed for several hours to days. Rib fractures involving the lower chest may be associated
with splenic or liver injuries. Auscultation of bowel sounds in the thorax may indicate the
presence of a diaphragmatic injury. Palpation may reveal local or generalized tenderness,
guarding, rigidity, or rebound tenderness, which suggests peritoneal irritation.
A rectal examination should be performed to search for evidence of bony penetration
resulting from a pelvic fracture, and the stool should be evaluated for gross or occult blood.
The evaluation of rectal tone is important for determining the patient's neurologic status, and
palpation of a high-riding prostate suggests urethral injury.
A nasogastric tube should be placed routinely (in the absence of contraindications,
eg, basilar skull fracture) to decompress the stomach and to assess for the presence of
blood. If the patient has evidence of a maxillofacial injury, an orogastric tube is preferred.
As the assessment continues, a Foley catheter is placed and a sample of urine is
sent for analysis for microscopic hematuria. If injury to the urethra or bladder is suggested
because of an associated pelvic fracture, then a retrograde urethrogram is performed before
catheterization.
Laboratory Investigations
Serum amylase and serum lipase: The serum amylase or lipase level is neither
sensitive nor specific as a marker for major pancreatic or enteric injury. Normal levels
do not exclude a major pancreatic injury. Elevated levels may be caused by injuries
to the head and face or by an assortment of nontraumatic causes (eg, alcohol,
narcotics, various other drugs). Amylase or lipase levels may be elevated because of
pancreatic ischemia caused by systemic hypotension that accompanies trauma.
However, persistent hyperamylasemia or hyperlipasemia should raise the suggestion
of significant intra-abdominal injury and is an indication for aggressive radiographic
and surgical investigation.
285
Chest Radiograph
Chest radiograph is an integral part of abdominal examination. In presence of shock
resuscitation measures take precedence over X-ray studies. When laparotomy is clearly
indicated, the time is not wasted for X-rays.
Abdominal Radiograph
Double wall sign Both walls of bowel inner & outer are sharply outlined when there
is air inside and outside the bowel
Ultrasonography
Ultrasound examination is emerging as a fast and noninvasive diagnostic modality that
is especially applicable in blunt abdominal trauma. Focused assessment by sonography
in trauma (FAST) includes study of the subhepatic space, the left subphrenic space
(spleen), the suprapubic and pelvic regions, and a subxiphoid view of the pericardium.
FAST examination relies on hemoperitoneum to identify patients with injury. The study is
considered abnormal if fluid is detected.
Strength: Non-invasive,useful in resuscitation room being portable, Weakness: Not
always available, highly operator dependent , low sensitivity for free fluid less than 500
ml false negatives include retroperitoneal & hollow viscera injury .
286
287
useful when the patient will be inaccessible for a long period of time (for example during
prolonged neurosurgical interventions).
Weaknesses: Significant retroperitoneal injuries may be undetected with DPL. DPL
leaves fluid in the abdomen, making subsequent CT or ultrasound less reliable. DPL is
highly invasive and should be considered a surgical procedure. Injuries sometimes occur
during DPL.
Laparoscopy
Laparoscopy is still awaiting a true delineation of utility. In blunt trauma, diagnostic
laparoscopy offers no clear advantage over less invasive modalities such as DPL or CT
scan and complications can occur from trocar misplacement. The most important
limitation in addition to being invasive is, its inability to reliably identify hollow viscus and
retroperitoneal injuries, even in the hands of experienced laparoscopists.
In the
uncooperative trauma patient, laparoscopy usually requires general anesthesia and a trip
to the operating room. The effect upon intracranial pressure in cases of head trauma is
not completely delineated.
MANAGEMENT
Non-Operative Management of Abdominal Trauma (NOMAT)
Nonoperative management strategies based on CT scan diagnosis and the
hemodynamic stability of the patient are now being used in the treatment of adult solid
organ injury, primarily the liver and spleen. Eligibility criteria include patients who are
haemodynamically stable, conscious and
hollow viscera injury excluded and without any indication for laparotomy or coagulation
defect.
NOMAT consists of:
Nasogastric aspiration
288
Operative Management
A midline incision is usually preferred. When the abdomen is opened, hemorrhage
control is accomplished by removing blood and clots, packing all 4 quadrants, and
clamping vascular structures. Obvious hollow viscus injuries are sutured. After intraabdominal injuries have been repaired and hemorrhage has been controlled by packing,
a thorough exploration of the abdomen is then performed to evaluate the entire contents
of the abdomen.
SPECIFIC MANAGEMENT
Splenic Trauma
It is the most frequently injured in BAT. Non-operative management is instituted
when there is haemodynamic stability ,negative abdominal examination ,absence of contrast
extravasations on CT ,absence of other clear indication for exploratory laparotomy. Injuries
to solid organs such as spleen , liver and kidneys are graded on the basis of subcapsular
hematomas, capsular tears, parenchymal lacerations and avulsion from the pedicle, in an
ascending order.
Operative management is done for
o
289
Surgical Management
The priorities of surgery are to stop haemorrhage, remove dead or devitalised liver
tissue, and ligate or repair damaged blood vessels and bile ducts.Most liver injuries have
stopped bleeding spontaneously by the time of surgery. These wounds do not require
suturing but should be drained to prevent bile collections. Liver bleeding can usually be
stopped by compressing the liver with abdominal packs while experienced surgical and
anaesthetic help is summoned. If visibility is obscured by continued bleeding, the hepatic
artery and portal vein should be temporarily clamped with a vascular clamp to allow accurate
identification of the site of bleeding. The Pringle maneuver will stop bleeding unless there is
an injury to the retrohepatic vena cava or hepatic veins. If bleeding cannot be stopped the
area should be packed; absorbable gauze mesh can be wrapped around an injured lobe and
sutured to maintain pressure and tamponade bleeding. The abdomen is then closed without
drainage and the packing removed under general anaesthesia two to three days later.
Packing is also used if a coagulopathy develops or to allow the patient to be transferred to a
tertiary referral unit for definitive management.
Patients with blunt injuries associated with substantial amounts of parenchymal
destruction may require resectional debridement. Rarely, a severe crushing injury
necessitates a formal hepatic lobectomy. The most difficult problems are lacerations of the
vena cava and major hepatic veins behind the liver because temporary clamping of the
inflow vessels does not slow blood loss from hepatic veins. Advanced operative techniques
including total hepatic vascular isolation by clamping the portal vein and the vena cava
above and below the liver or lobectomy may be required. The mortality after blunt hepatic
injury is 10% when only the liver is injured.
290
Injury to Duodenum
Most common mechanism is a motor vehicle accident causing steering wheel blow
and handle bar injuries to epigastrium.
Early recognition requires high index of suspicion because clinical features tend to be
non-specific & plain skiagram of abdomen are usually not helpful
CT has been added to the diagnostic algorithm for subtle duodenal injury. It is very
sensitive to the presence of small amounts of retroperitoneal air, blood, or contrast
agent extravasated from the injured duodenum, especially in children
Most of injuries are accompanied by other intra-abdominal injuries owing to its close
anatomic relationship with other solid organs & major vessels Early diagnosis of
duodenal rupture is essential, the delay of which is associated with increased
morbidity and mortality. The diagnosis of this injury remains problematic, because the
signs and the symptoms (tachycardia, vomiting and rise in temperature) of
retroperitoneal viscus are notoriously subtle.A delay in diagnosis for longer than 24
hours results in a thickened, friable and inflamed bowel wall. Primary repair alone is
unlikely to be successful, as it may lead to duodenal dehiscence, a lateral duodenal
fistula and other lethal complications.
Management
The degree of duodenal injury, diagnosis time and surgeon preference, often
determines the type of technique using repair. Although most duodenal injuries can be
managed successfully by simple repair, othe available techniques include tube
duodenostomy
and
duodenojejunostomy
pyloric
and
exclusion,
with
or
pancreaticoduodenctomy.Most
without
significant
gastrojejunostomy,
complication
is
291
Diagnosis
Blunt trauma to the pancreas may be clinically occult and parenchymal and duct
injury may not be recognised during initial evaluation or even surgery. A high index of
suspicion is therefore necessary in patients with severe upper abdominal injuries. Abdominal
radiographs may show retroperitoneal air and a ruptured duodenum. Serum amylase activity
is a poor indicator. It can be normal in patients with severe pancreatic damage and increased
in patients with no demonstrable injury to the pancreas. Contrast enhanced computed
tomography is the best investigation. Features of pancreatic injury include pancreatic
oedema or swelling and fluid collections within or behind the peritoneum or in the lesser
peritoneal sac. Endoscopic retrograde cholangiopancreatography can be use to assess the
integrity of the main ducts in stable patients.
Intraoperative Evaluation
Pancreatic injury is usually diagnosed at laparotomy. The injury may be obvious in
patients with a major fracture of the body or neck of the pancreas or associated duodenal
injury. Other clues to pancreatic injury are retroperitoneal bile staining, fat necrosis,
peripancreatic oedema, or subcapsular haematoma. The pancreas should be fully mobilised
and exposed to rule out a duct injury. Failure to detect a major injury to the pancreatic duct is
an important cause of postoperative morbidity.
Management
Haemodynamically stable patients with minor injuries of the body or tail of the
pancreas who have no visible damage to the duct can be managed by external drainage of
the injury site with soft silastic drains. Major injuries of the body and tail of the pancreas that
affect the duct should be treated by distal pancreatectomy. Patients with injuries to the head
of the pancreas without devitalisation of pancreatic tissue can be managed by external
drainage provided that any associated duodenal injury is amenable to simple repair.
Pancreatoduodenectomy as a primary procedure is restricted to stabilised patients with
disruption of the ampulla of Vater or major devitalising injuries of the pancreatic head and
duodenum. Injuries of this severity occur after blunt trauma or gunshot wounds but are
uncommon with stabwounds.
Injury to Small & Large Intestine
Small bowel laceration/perforation occurs in 3% to 5% of cases of blunt abdominal
trauma. The classic triad of small bowel injury (rigid abdomen, tenderness, absent bowel
292
sounds) occurs in only one-third of patients. The detection of this subset of trauma patients
has improved markedly with CT, which has led to a decrease in the number of nontherapeutic laparotomies performed in the setting of blunt abdominal trauma. Common CT
signs of small bowel perforation in order of decreasing frequency include: peritoneal free
fluid (80%), bowel wall thickening (60%), free air (40%), and contrast extravasation (15%).
Free air and contrast extravasation are found in only half of patients with small-bowel
perforation, but are each nearly 100% specific for bowel perforation.
Blunt injury to the colon is rare. Few studies of adequate size and design exist to
allow clinically useful conclusions. Colonic injury after blunt trauma is rare and difficult to
diagnose. No diagnostic test or combination of findings reliably excluded blunt colonic injury.
Management
Small intestinal perforation may be closed by primary closure or resection-
anastomosis
Colonic perforations:
Primary closure
Resection
&
colostomy
in
delayed
diagnosis,prolonged
293
Whatever the type of injury, the investigation for the staging of a renal injury begins with
excretory urogram. This exam also shows if the opposite kidney has a normal function. The
CT scanning can distinguish better a major from minor injury, can identify extravasation that
were not demonstrated in excretory urogram. Arteriography can be used when there is no
CT scan available or when the CT is not a definitive exam, and it may reveal the actual
bleeding vessel, show occlusion of the main renal artery or its branches, and also renal
lacerations.
Exploration is required in: Vascular injury of renal pedicle .Only 30-40% of kidneys with
arterial injuries can be salvaged. Before performing a nephrectomy, assess the viability of
the contralateral kidney, deep corticomedullary lacerations with extravasation and large
perinephric hematoma.The surgical exploration is best done through a trans abdominal
transperitoneal approach, trying to make the best wide exposure and an early vascular
control .
Urinary Blader and Urethral Injuries
Management
BLADDER
URETHRA
Primary repair
Secondary repair
Gastric Injuries
294
Management
Most perforations are closed primarily, in case of major tissue loss Gastric resection is
done.
Diaphragmatic Injuries
Diaphragmatic
injuries
are
notoriously
difficult
to
diagnose.
CT
scan
is
confirmatory.Small diaphragmatic injuries on the right side may heal without incident, and
the liver protects against potential hernias. Small injuries on the left side may result in
symptomatic diaphragmatic hernias. Acute diaphragmatic defects are best approached
through the abdomen. Laparoscopic repair may be feasible for delayed repair.
Pelvic Fractures
"Bad" pelvic fractures should undergo external fixation prior to laparotomy, as
significant bleeding may result when the abdomen is opened (and the pelvis spreads open
like a book). External fixation controls a significant amount of bleeding; angiography and
embolization may occasionally be required. Direct surgical exploration of pelvic hematomas
is generally followed by disaster.
Further Reading
Asher WM, Parvin S, Virgillo RW, Haber K: Echographic evaluation of splenic injury after
blunt trauma. Radiology 1976 Feb; 118(2): 411-5
Chiu WC, Cushing BM, Rodriguez A, et al: Abdominal injuries without hemoperitoneum: a
potential limitation of focused abdominal sonography for trauma (FAST). J Trauma 1997 Apr;
42(4): 617-23; discussion 623-5.
Cryer HG, Larmon B: Patient Care Phase: Prehospital and Resuscitation Care. In: Greenfield
LJ, Mulholland MW, Oldham KT, Zelenock GB, Lillemoe KD, eds. Surgery: Scientific
Principles and Practice. 2nd ed. Philadelphia, Pa: Lippincott-Raven; 1997:280-4.
Davis JJ, Cohn I Jr, Nance FC: Diagnosis and management of blunt abdominal trauma. Ann
Surg 1976 Jun; 183(6): 672-8.
Digiacomo JC, Hoff WC, Rotondo MF: Barrier precautions in trauma resuscitation: Real-time
analysis utilizing videotape review. Am J Emerg 1997; 15: 34-39.
Fabian TC, Croce MA, Stewart RM, et al: A prospective analysis of diagnostic laparoscopy in
trauma. Ann Surg 1993 May; 217(5): 557-64; discussion 564-5.
Goldberg BB, Clearfield HR, Goodman GA, Morales JO: Ultrasonic determination of ascites.
Arch Intern Med 1973 Feb; 131(2): 217-20.
Gross M, Lynch F, Canty T, et al: Management of pediatric liver injuries: a 13-year experience
at a pediatric trauma center. J Pediatr Surg 1999 May; 34(5): 811-6; discussion 816-7.
Han DC, Rozycki GS, Schmidt JA, Feliciano DV: Ultrasound training during ATLS: an early
start for surgical interns. J Trauma 1996 Aug; 41(2): 208-13.
295
Ivatury RR, Simon RJ, Weksler B, et al: Laparoscopy in the evaluation of the intrathoracic
abdomen after penetrating injury. J Trauma 1992 Jul; 33(1): 101-8; discussion 109.
Jui J, Modesitt S, Fleming D, et al: Multicenter HIV and hepatitis B seroprevalence study. J
Emerg Med 1990 May-Jun; 8(3): 243-51.
Murray CJ, Lopez AD: Mortality by cause for eight regions of the world: Global Burden of
Disease Study. Lancet 1997 May 3; 349(9061): 1269-76.
Murray CJ, Lopez AD: Alternative projections of mortality and disability by cause 1990-2020:
Global Burden of Disease Study. Lancet 1997 May 24; 349(9064): 1498-504.
Neuhof H, Cohen I: Abdominal puncture in the diagnosis of acute intraperitoneal disease. Ann
Surg 1926; 83: 454-62.
Ortega AE, Tang E, Froes ET, et al: Laparoscopic evaluation of penetrating thoracoabdominal
traumatic injuries. Surg Endosc 1996 Jan; 10(1): 19-22.
Perry JF: A five-year survey of 152 acute abdominal injuries. J Trauma 1965 Jan; 147: 53-61.
Powell DC, Bivins BA, Bell RM: Diagnostic peritoneal lavage. Surg Gynecol Obstet 1982 Aug;
155(2): 257-64.
Pryor JP, Pryor RJ, Stafford PW: Initial phase of trauma management and fluid resuscitation.
Trauma Reports 2002; 3(3): 1-12.
Root HD, Hauser CW, McKinley CR: Diagnostic peritoneal lavage. Surgery 1965 May; 57:
633-7.
Rosen P, Barkin RM, eds: Emergency Medicine: Concepts and Clinical Practice. Vol 1. 4th
ed. St. Louis, Mo: Mosby-Year Book; 1998:555-61.
Rozycki GS, Ochsner MG, Feliciano DV, et al: Early detection of hemoperitoneum by
ultrasound examination of the right upper quadrant: a multicenter study. J Trauma 1998 Nov;
45(5): 878-83.
Rozycki GS, Ochsner MG, Schmidt JA, et al: A prospective study of surgeon-performed
ultrasound as the primary adjuvant modality for injured patient assessment. J Trauma 1995
Sep; 39(3): 492-8; discussion 498-500.
Simpson RL, Turner VF: Diagnostic, percutaneous peritoneal lavage in blunt abdominal
trauma: rationale, technique and results. Aust N Z J Surg 1986 Feb; 56(2): 103-7.
Smith RS, Fry WR, Morabito DJ, et al: Therapeutic laparoscopy in trauma. Am J Surg 1995
Dec; 170(6): 632-6; discussion 636-7.
van der Spuy JW: South African road traffic statistics: 1950-1994. Trauma Emerg Med 1996;
13(1): 35-8.
296
Traumatic Brain Injury (TBI) is now emerging as the leading cause of mortality across
the world. According to WHO, TBI has already exceeded cancer as the cause of mortality. It
is projected that by year 2020 it may even exceed stroke or even heart attack if no proper
attention is warranted. Approximately 2 million population suffers from TBI in United State
annually of these 70000-90000 have permanent long term disability.(1)
In India the similar statistics are not available, however nearly 50000 accidents are
reported in Delhi per year. Nearly 2000 of them are fatal. The fatal accidents are definitely
declining among metropolitan cities however more and more people are found with some
kind of disability particularly after mild brain Injury.
Pathophysiology: Over the past one decade the basic science development has provided a
much deep insight to understanding of Pathophysiology of TBI. Foremost is the neuronal
dysfunction which come as a result of direct impact or shearing phenomenon to brain. This
force result in indiscriminate release of neurotransmitter and ionic influx resulting in alteration
of cerebral metabolism. The primary impact results in macroscopic injuries like contusions ,
fracture, hematoma or microscopic injury e.g Diffuse Axonal Injury (DAI), Ischemic cytotoxic
oedema, Blood Brain Barrier Disruption and phasic inflammatory recruitment.(2)
Secondary biochemical reactions is considered as three step process. Firstly there is
disruption of calcium homeostasis. A sudden rise of intracellular calcium occurs which
activate a number of enzymes which eventually destroy cell structures. Secondly there are
release of free radicals which mediated per oxidation mechanisms.(3) Finally intracellular
acidosis is a major mechanism which results I ischemia. There are emerging trends that
inflammatory response mediated by cytokines may result in chronic inflammatory
response.(2)
It is also observed that following TBI , cerebral blood flow shows a triphasic response
which has an important bearing in development of oedema as well as can be an important
determinant\ant in deciding fluid therapy .(4-6)
Types of Head Injury:
International classification of disease (ICD-10) has classified head injury in S00 code. Some
of the common TBI as seen frequently are:
297
Fractures It can be as a result of direct contact injury or rarely counter coup effect.
Various type of fractures are depressed fracture , linear fracture, compound fracture ,
comminuted fractures.
Coup injury is at the site of direct contact of head with an object or ground .Counter coup
injury result due to transmission of effect of acceleration and indirect contact of
opposite end with a solid ground . The wave of injury may oscillate to and fro which
may get concentrated in between coup and counter coup zone to produce
intermediate coup injury.
Hematoma : Epidural hematoma , Subdural hematoma , intracerebral hematoma and
contusion of the brain are common injuries of moderate to severe head injury.
Diffuse axonal injury - DAI is the most prevent form of TBI. It results due to transmission
of wave form of acceleration deceleration and torsional affect of an injury. This is one
of the most discussed form of injury in present days due to its role in production of
Post concussion syndrome.
Vascular injury to brain Various arterial and venous injuries can occur resulting in
dissection thrombosis of vessels. It can also produce Carotico cavernous fistula
(CCF) or dural AV fistula. Cerebral ischemia , infarction of brain can be as a result of
direct vascular injury or as a result of post traumatic vasospasm.
Post concussion syndromes (PCS) is an organic illness where patient presents with
hetrogenous group of symptoms such as headache, memory impairment, confusion,
lethargy, vertigo, etc. It can continue up to two years and has medico legal
implication in head injury.
Monitoring in Acute Head Injury
Modern concepts of monitoring of TBI is entirely based upon understanding of
pathophysiology of head injury. This in fact plays an important role in deciding mode of
treatment.
Monitoring direct arterial pressure with arterial lines along with measurement of
Intracranial pressure (ICP) helps in calculating Cerebral perfusion pressure. More over
manipulation of MAP will also require placement of CVP line. The temperature, pulse rate,
oxygenation ABG , are inherent monitoring parameters for all head injury of moderate to
severe nature.(3)
298
Glasgow Coma Scale (GCS)- It is the most informative scoring system in monitoring head
injury patient. The best score is recorded which may have fallacious impression. The score
is not applicable in children. It doesnot take into account pupil size and reaction which is
essential in all head injury charting. The major benefit of GCS is its objectivity with no
observer variation.
Intracranial Pressure Recording
It is essential to monitor ICP to regulate CPP in all severe head injury. It is also
known that episodic rise of ICP can occur in presence of normal CT scan. Intraventricular
catheter devices are ideal for ICP measurement. It is also a predictor of decreasing level of
consciousness, and even helps in making a favorable surgical decision in presence of
equivocal hematoma .Most studies recommend monitoring for 48-72 hrs in predicting
outcome and guiding therapy.
Transcranial Doppler (TCD)
Based upon Doppler shift principle TCD offers a useful tool in monitoring flow velocity
in the brain. Systolic flow mean flow diastolic flow, pulsatile index are Doppler parameter for
predicting good flow and thus are predictor of CBF. An oligemic or hyperemic response
mediate drug delivery, fluid intake. Bing non invasive this is becoming an essential tool in all
neuro ICU. 2 Hz probe is used in temporal window which can insinuate virtually all major
vessels in circle of Willis. Normal flow velocity in Middle cerebral velocity is 35-45 cms/ sec
in adults. Being non invasive in can be repeated as many time as desired or even 24 hrs
monitoring is possible with TCD.
Jugular Venous Oxymetry.
Jugular venous sampling is a indirect measure of oxygen concentration of the brain.
Normal Jugular bulb oxygen saturation is around 65-70% (Sjv02). Reduction in Sjvo2 or
increase in arterio jugular difference in oxygen concentration above 9 ml/dl suggest
inadequate CBF. Both these parameter have been found to have a close relation with poor
outcome(3).
Brain Oxymetry.
Near Infrared spectroscopy ( NIRS) similar to pulse oxymetry is a non invasive bed
side devise that can monitor oxygen concentration of the brain from scalp. It measures ox
hemoglobin concentration of tissue which may be useful in detecting neuronal hypoxia. A
detective device is applied over the scalp . Its sensor detect oxygenation of a selected area
299
of focused brain hence may not be reflective for entire brain. Normal brain oxygen
concentration detected by brain oxymeter if around 92-96 %.(3)
Plain X Rays
The role of conventional radiology is getting debatable in recent time. It is only indicated in
open fractures. Positive radiology does not correlate with occurrence of intracranial lesion
with certainty. Both WHO and European Federation of Neurological societies (EFNS
guidelines) do not recommend skull radiology as a screening tool for Mild Head Injury(MHI)
(7)
None the less observation in our country indicate that plain radiology should be done
in all severe head injury and in all MLC cases.
All patients should be subjected to plain X rays of Cervical spine as screening to rule
out spine fractures or atlanto axial dislocation.
CT Scan:
This is still considered as primary investigation in case of Head Injury. It picks up
fracture, contusions, haematoma. Several studies have shown that prevalence of intracranial
abnormalities vary from 5-8% with GCS of 15. There are WHO guidelines for indication of
CT Scan in head Injury.(8) These guideline are based upon patient age, history,
examination, GCS, plain X Ray findings etc. However Medico legal indication for CT scan
has not been incorporated in WHO guidelines.
3 D reconstruction offers a better picture particularly for suspected atlanto axial
dislocation associated with TBI.
Newer Developments in Imaging
Normal CT Scan does not rule out TBI. MRI Brain certainly yield more information
than CT scan in MHI. However it has not become popular primarily due to cost , non
availability and limited value in severe head injury.(9)
MRI nonetheless picks up major pathology in Diffuse axonal Injury which are missed
on CT scan e.g. Contusions in corpus callosum, brain stem, basal ganglion etc.
SPECT scan is another upcoming modality which pick up deformed brain function by
detecting altered brain glucose and oxygen metabolism. This is certainly useful in post
concussion syndromes in MHI to support the patient claims as organic illness rather than
functional in origin.(10)
300
Management:
General Measurements- It is of utmost importance to maintain a proper CBF and
oxygenation in all TBI. Universal data support to maintain normotension and normal Po2 ans
Pco2 . A systolic BP of less than 90 mmHg has deleterious effect in brain perfusion. Hypoxia
with PaO2 less than 60mmHg ameliorate already compromised brain. CVP should be kept
around 8-10 cms of water. Normal ABG is desirable. Hyponatrememia increase oedema and
trigger seizures. Hyperglycemia is associated with worsening of neurological status.
Hyperthermia (fever) also adds to brain oedema. Systemic infection should be appropriately
dealt.
Fluid Therapy :
Fluid replacement is guided by clinical and laboratory findings.
In general Dextrose fluids are avoided as it tend to produce brain swelling and lead to
hyperglycemia. It is normally recommended to use 30-40ml/Kg as maintenance. Serum
osmolality should be maintained at 290-300 mosm/l.to minimize fluid influx to exaggerate
oedema. Isotonic saline with osmolality of 308 is good choice. Hypertonic saline raise
plasma sodium and osmolality with reduction of ICP. Hypertonic saline withdraw the fluids
from the cells hence decreases oedema, increase intravascular volume, improve BP and
cardiac output. It also has vasodilator effect thus may improve microcirculation. Hypertonic
saline are given as single bolos therapy or continuous infusion with good results In common
3% saline is used however renal failure and hyperosmolar coma may worsen the patient.
Central pontine demyelination is also reported with these solutions (11). For pediatric
patients, 1.6% saline when compared to ringer lactate results in lower ICP , less need for
barbiturate , low incidence of pulmonary complications. (12)Albumen preparations is one of
the corner stone in Lund protocol. Hetastarch should be used with caution as it lead to
hemostasis and intracranial hemorrhage.
Nutrition:
Generally an overlooked entity which is often ignored due to lack of awareness. TBI
have high nutritional requirement which should be instituted with in 24hrs.Enteral feed is
preferred as it has low incidence of hyperglycemia and has protective effect on gastric
mucosa to prevent ulceration. Antacid prophylaxis is also supplemented for the same
reasons.
Antiepileptic Drugs (AED):
Seizure may occur early within 7 days or late (after 7 days) with reported incidence
between 4-25% and 9-42% respectively.(13)
301
Incidence of post traumatic seizures are maximum in patients with GCS less 10,
presence of contusions, haematoma particularly frontal, penetrating injury, or depressed
fracture
Once started phenytoin or any other AED is continued for 3 yrs conventionally.
However there are no consensus on this issue. It is also reported that seizures soon after
head injury without any evidence of predisposing pathology as elaborated above need no
AED. Such immediate seizures are due to hypoxia or disturbance of auto regulation.
Pharmacological Neuroprotection
Neuroprotection involves reduction of ICP by decreasing brain metabolism. This
results in improving CBF, anticonvulsant action free radical scavenging, drugs induced
inverse steal, antagonism of voltage sensitive calcium or sodium channels and potentiation
of GABAergic transmission. Various drugs which are currently used are Barbiturates,
Etomidate, Propofol, Ketamine 16 as intravenous agents. Inhalation agents such as
Isoflurane,Servoflurane, Desflurane are on trail. Some of the other drugs used are calcium
blocker, Glutamate antagonist, Magnesium, Antioxidants, Trilizad maleate, Lidocain, Super
oxide desmutase, Tromethamine.
Steroids- There are no convincing reports that steroids offer any kind of benefit. A recent
Cochrane review concluded that neither moderate benefit nor adverse effect of steroid can
be confirmed and a large population based trail is needed to explore the benefit of steroids.
References
1.
Mc Carthy ML, Serpi T, Kufera JA,Demeter LA,Paidas C. Factors influencing admission among
children with a traumatic brain injury.Acad.Emerg.Med2002:9:68-693.
2.
3.
4.
5.
6.
7.
Vos PE, Battistin L, Birbamer G et al: EFNS guideline on mild traumatic brain injury:Report of an
EFNS task force. Eur J Neurol 2002;9:207-219.
8.
Borg J, Holm L,Cassidy DJ etal: Diagnostic procedure in mild traumatic brain injury- Results of
WHO collaboration centre task force on mild traumatic brain injury. J Rehab Med 2004
(suppl.);43:61-75.
302
9.
Hoffman PAM, Stapert SZ, Kroonengurg V etal. MR imaging, Single photon imaging CT, and
neruocognitive performance after mild traumatic brain injury. Am. J Neurorad. 2001;22:441-449.
10.
11.
Quereshi AL Saurez JI, Bhardwaj A et al. Use of hypertonic saline (3% saline/ acetate infusion in
treatment of cerebral oedema;effects on ontracranial pressure and lateral displacement of brain.
Crit. Care Med.1998;26:1119-1122.
12.
Simma RM, Burger R , Falk M,Fanconi S. A prospective randomosed and controlled study of fluid
management in children with severe head injury ;lactate ringer solution versus hypertonic saline
Crit. Care Med.1998;26 :1263-1270.
13.
Schierhout G, Robert I.Prophalactic antiepileptic agents after head injury; a systemic review. J
Neurol. Neurosurg Psychiat 1998;64:108-112.
303
304
11. Acidosis
C. T. Scan Findings
1. Tense infiltration of the retro peritoneum out of proportion to peritoneal disease.
2. Extrinsic compression of the inferior vena cava by retroperitoneal hemorrhage or
exudates.
3. Massive abdominal distension with an increased ratio of AP to transverse abdominal
diameter.
4. Direct renal compression or displacement.
5. Bowel wall thickening with enhancement.
6. Bilateral inguinal herniation.
etc.
3. Recurrent ACS in which the patient has recovered from the ACS once but because of
secondary insults the cycle begins again. This verity is associated with very high mortality
rate
Pathophysiology and the march of events:
The normal intra-abdominal pressure ranges between 0 and 5 mmHg. When it is
mildly increased to between 10 and 15 mmHg, cardiac index is usually maintained or even
increased because abdominal viscera are mildly squeezed and venous return increases.
Respiratory and renal symptoms are unlikely to occur. Hepatosplanchnic blood flow may
decrease At this point; intravascular volume optimization will probably correct these
alterations. When intra-abdominal pressure is moderately increased to between 15 and 25
mmHg the full syndrome may be observed, but usually responds to aggressive fluid
resuscitation, and surgical decompression should be considered. At high pressures (< 25
mmHg) surgical decompression associated with fluid resuscitation and transient use of
305
306
307
further leads to anaerobic cell metabolism, lactic acidosis, free radicals generation, and
translocation of bacteria from the gut, which contributes to later septic complications and
multiorgan dysfunction syndrome. Small bowel ischemia and elevated portal venous
pressure causes visceral edema, which further increases the volume of the abdominal
contents in the peritoneal cavity and raises the IAP to an alarming level.
Effects of ACS on Abdominal Wall
Increased IAP has been shown to reduce the abdominal wall blood flow by the direct
compressive effect of IAH, leading to local ischemia and edema. Blood flow to the rectus is
reduced by 60% at an IAP of 10 mm of Hg or more As collagen deposits and resistance to
infection are directly proportional to tissue perfusion and oxygenation, elevated IAP
adversely affects the wound healing.
Intracranial Effects of IAP
The elevated IAP increases the intra cranial pressure and reduces the cerebral
perfusion pressure secondary to elevated intrathoracic pressure and elevated central venous
pressure with impaired cerebral venous outflow.
Systemic reperfusion injury:
Rapid decompression of the abdomen results in acute hypovolemia as a result of
decompression of the mesenteric vascular bed and release of lactic acid into the blood
stream. This is also a sequel of abrupt drop in central filling pressure and systemic vascular
resistance. Supra-ventricular arrhythmias and episodes of systole have also been reported.
The factor responsible for these adverse events is the rapid washout and systemic
circulation of lactic acids, potassium, and other by products of anaerobic metabolism, from
the reperfused viscera and lower extremities.
Gut ischemia promotes regional production of inflammatory mediators, expression of
cell adhesion molecules on endothelial and immune cell surface and increases the
procoagulatory property of vascular endothelial surface. During reperfusion, gut injury may
be amplified by increased production of free oxygen radicals and exhaustion of endogenous
antioxidant defence mechanism. Translocation of bacteria and toxins through the leaky gut
mucosa again amplify or perpetuate systemic inflammation, leading to multiple organ
dysfunction syndrome and death in critically ill patients.
Diagnosis:
The diagnosis of ACS depends on a very high degree of suspicion and recognition of the
patients at risk, identification of clinical syndrome and lastly measurement of IAP. C. T. scan
of
abdomen
can
help
to
establish
the
308
diagnosis
in
few
cases
of
ACS.
Patients at Risk
1. Abdominal trauma
2. Hemorrhage
3. Peritonitis
4. Emergency aortic surgery
5. Intra abdominal packing
6. Forced abdominal closure
Management:
Measuring the IAP?
At the bedside IAP is best measured through the urinary bladder catheter connected
to a manometer or a pressure transducer. In fact, all that is required is a Foley catheter:
disconnecting it from the urine bag; instilling 100 ml of normal saline into the bladder and
elevating the disconnected catheter perpendicular to the supine patient and his bed. The
height of the water-urine column in the catheter is the IAP in cm H2O (=0.735mm Hg). The
levels will fluctuate with the patients respiratory cycle-up during respiration, down during
expiration-following the movements of the diaphragm. A neurogenic or small contracted
bladder may render the measurements invalid. The blocked catheter or the presence of a
pelvic hematoma may cause errors in measurements. Accurate measurements are best
achieved in the supine position because the Trendelenburg position (or its reverse) may
affect intra-bladder pressure.
The indications of abdominal decompression
The decision to decompress the abdomen should not be taken based upon isolated
measurements of IAP without taking into account the whole clinical picture. Early or mild
physiological abnormalities caused by IAHT can be managed by fluid administration or after
load reduction.
Established ACS, however, mandates an emergency decompressive laprotomy,
which, when performed in the well-resuscitated patient, promptly restores normal physiology.
To prevent hemodynamic decompensation intravascular volume should be restored, oxygen
delivery maximized, and hypothermia and coagulation defects corrected. Following
decompression, the abdominal skin and fascial edges are left open using one of the
temporary abdominal closure devices (TACD)
309
Decompression in the intensive care unit may be indicated in few cases, where the
hemodynamic or pulmonary instability precludes safe transport to the operating
room.
N.B:
systemic reperfusion injury. Rapid infusion of few liters of crystalloids within few
minutes of post decompression is required to restore hemodynamic stability.
310
and treatment of IAHT may reduce these complications in patients with borderline
IAHT [5,6].
Surgical Techniques in the prevention and management of ACS:
There are three different types of advanced treatment techniques for the management of
ACS.
1. Laparostomies or open abdomen techniques
2. On demand re-laparotomies
3. Staged abdominal repair (STAR)
In order to avoid IAHT and ACS, forceful closure of the abdomen in patients having
massive retroperitoneal hematoma, visceral edema, severe intra-abdominal infection,
or a need for haemostatic packing, should be avoided.
311
Leaving the fascia open, closing only the skin with sutures or towel clips to protect
the bulging viscera, has also been recommended.
Occasionally, however, the skin closure alone may produce IAP of 50mmHg or more.
Certainly, leaving both fascia and skin unsutured maximal reduction in IAP may result
in fistula and evisceration.
Bridging the fascial gap with a Temporary abdominal closure device (TACD)[fig.4, 5]
circumvents these problems. Various devices include
Zipper Laparostomy,
Urobag zipper laparostomy.
The author has utilized these techniques in patients with intra-abdominal sepsis
with gratifying results. The distinct advantages of Urobag Zipper Laparostomy
over classical marlex zipper were lower incidence of bowel fistulae and also the
fact that urobag being non-adhesive and transparent allows a better visualization
of the peritoneal cavity with lower incidence of device induced fistulae[1,2]. .
A good rule of thumb is that if, when looking at the abdomen horizontally, the guts
can be seen above the level of the wound, the abdomen should be left open and
temporary abdominal closure (TAC) utilized. It is better to anticipate the development
of abdominal compartment syndrome and use an alternate wound closure technique to
prevent its occurrence in these cases.
Mortality/Morbidity of ACS:
The morbidity of ACS is attributed to its effects on multiple organ systems. Because
of this, ACS has a high mortality rate even with treatment. Furthermore, ACS is often a
sequel to severe injuries that independently carry high morbidity and mortality rates. In the
early 1990s Eddy and Morris documented an ACS mortality rate of 68%, this has been
reflected in the subsequent literature, with similar mortality rates of 25-75% [2-6].
Summary:
IAHT is yet another factor to consider in the overall management of the emergency
abdominal patient. It may be obvious-
crying for abdominal decompression. More
commonly, however, it is relatively silent but contributing to SIRS (systemic
inflammatory response syndrome), organ dysfunction and death.
312
The exact clinical conditions that define abdominal compartment syndrome (ACS)
are controversial; however, organ dysfunction caused by intra-abdominal
hypertension (IAH) is considered to be ACS.
Management includes immediate decompression in severe cases and the intraabdominal pressure using the indirect method measuring the intracystic pressure,
which is as sensitive as the direct method, helps in the decision-making regarding the
degree of urgency and the extent of intervention.
References
1. Chintamani, Singhal V .Temporary closure of open abdominal wounds by modified sandwich
vacuum pack technique Br J Surg. 2003 Nov 90(11) 1452-1453
2. Chintamani, Singhal V.Urobag Zipper laparostomy in intraperitoneal sepsis Trop Doct. 2003
Apr; 33(2): 123-4. 9 [The Journal Of The Royal Society Of Medicine UK]
3. Chintamani, Borah C, Krishna SV, Anuj M, Bhatnagar D. The role of APACHE-II triaging in
optimum management of small bowel perforations. Trop Doct 2001 Oct; 31(4): 198- 201
[Journal of the Royal Society Of Medicine UK]
4. Burch JM, Moore EE, Moore FA, Franciose R: The abdominal compartment syndrome.
Surg Clin North Am 1996, 76:833-842.
5. Nathens AB, Brenneman FD, Boulanger BR: The abdominal compartment syndrome. Can J
Surg 1997, 40:254-262
6. Watson RA, Howdieshell TR: Abdominal compartment syndrome. Southern Med J 1998,
91:326-332.
313
Neonatal intestinal obstruction results from a variety of causes but with similar clinical
features. The collective incidence is about 1 in 1500 live births. Although congenital causes
such as duodenal atresia, jejuno-ileal atresia, malrotation, meconeum ileus and
Hirschsprungs disease form bulk of the cases, paralytic obstruction due to necrotising
enterocolitis (NEC) and related disorders is increasing with better survival of pre-term
babies. Correct diagnosis requires an understanding of the Pathophysiology, application of
clinical skills and focussed radiological imaging. Prenatal diagnosis is possible with
ultrasound and the expectant mothers can be referred to tertiary care centres for post natal
management of babies. This chapter gives a brief overview of the important conditions with
stress upon diagnosis, Pathophysiology and initial management. Principles of surgical
treatment are briefly discussed. The target audience is general surgical trainees and
practising surgeons.
Causes of Neonatal Intestinal Obstruction simplified:
A.
Mechanical Obstruction:
Intraluminal:
Meconeum ileus, Inspissated milk syndrome
Affecting bowel wall:
Atresias, Hirschsprungs disease, Anorectal malformations
Extrinsic bowel compression
Malrotation, Duplication cysts, Hernias
B.
The most common causes are: Duodenal atresia, jejuno-ileal atresia, Hirschsprungs
disease, meconeum ileus, malrotation and necrotising enterocolitis. Oesophageal atresia
and anorectal malformations (imperforate anus), though fall in the gambit of intestinal
obstruction, are not covered in this chapter as they require specific management. Functional
obstruction due to metabolic causes is also excluded.
314
Prenatal diagnosis
Antenatal ultrasound picks up bowel lesions well because the foetal bowel is gasless.
Since meconeum is comprised of swallowed amniotic fluid, polyhydramnios occurs in about
50-60% cases especially in proximal atresias. Identification of dilated gut loop with
polyhydramnios is sometimes a reason for amniocentesis to rule out Downs syndrome
because of 30% association between Downs and duodenal atresia. Dilated proximal
oesophagus points towards oesophageal atresia. Bowel in chest suggests diaphragmatic
hernia. Flecks of calcification and echogenic bowel wall suggest antenatal bowel perforation
leading to aseptic chemical meconeum peritonitis.
Post natal diagnosis
The cardinal features of intestinal obstruction in neonate are: bile stained vomiting,
abdominal distension and failure / delay in passing meconeum. A truly bile stained vomits is
green in colour. It occurs in all obstructions below the ampulla of vater. Yellow vomit,
resulting from concentration of carotene pigment from the colostrums, is a frequent reason of
referral but it is usually self limiting and does not merit investigation in the first instance.
Persistent vomiting merits investigation irrespective of colour.
Extent of distension is related to the level of obstruction. Gastric, duodenal and
proximal jejunal obstruction produces minimal distension. Hirschsprungs disease presents
with massive distension as both the large and small bowel distend. Ileal atresia causes
moderate distension. Timing of distension is also important. Most atresias and
Hirschsprungs disease do not cause distension at birth. It develops over the first few days of
life as the child swallows air. If a baby is distended at birth it should point towards either
congenital mass (duplication cysts, hydrocolpos, teratomas) or complicated meconeum
peritonitis (Giant cystic meconeum peritonitis). Meconeum filled distended loops can
sometimes be felt in meconeum ileus.
Most term babies pass the first meconeum within 24 hrs. It is delayed in most cases
of Hirschsprungs disease. A neonate with intestinal atresias may continue to pass good
meconeum for initial few days because of the intestinal secretions in the distal gut. In
meconeum disease few pellets of meconeum may be passed in response to rectal
stimulation or enema. NEC is typically associated with blood and mucus in stools.
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Imaging
Plain film of the abdomen in two planes is the most important investigation, although
it is not possible to distinguish small bowel from large bowel loops in babies. Pyloric,
duodenal and jejuno-ileal atresia show a characteristic appearance on plain x ray.
Decision to perform contrast studies should be taken in light of the findings on plain
X-ray and clinical picture. In general if the plain film shows much gas a lower GI contrast is
more useful. If there is less gas on plain film an upper GI study will give more information.
Free gas is a contraindication for contrast study. For malrotation an upper GI series is more
useful while for HD and meconeum disease a contrast enema is a better investigation.
Contrast enema should initially be done with water soluble non ionic contrast. If the
contrast reaches the dilated proximal bowel it rules out atresia. If the entire large bowel is
collapsed (microcolon) the differential diagnosis is meconeum disease, and total colonic
aganglionosis. The contrast should then be changed to gastrograffin which contains a
surface active agent (Tween 80) to help decompress the bowel by loosening the thick
meconeum. This is often therapeutic in meconeum disease. Since Gastrograffin causes fluid
shift into the bowel lumen, the baby should be well hydrated before gastrograffin enema... A
hypovolemic child and /or free gas on X-ray are absolute contraindications of gastrograffin
enema.
Pathophysiology and its implication in fluid management
Mechanical obstruction leads to accumulation of intestinal secretions in the proximal
segment, increased bacterial proliferation due to stasis and compromised mucosal gut
barrier. This leads to intramural fluid extravasation followed by leaking serosa. These fluid
shifts in the third space lead to hypovolemia and acidosis. This sets in a chain of events
resulting in spasm of mesenteric vessels and gut ischemia. Bacterial overgrowth occurring in
the static fluid in presence of mucosal ulceration leads to bacterial translocation in the
circulation causing septicaemia and further fluid imbalance by peripheral vasodilatation.
Hypovolemia is the key factor in triggering the disruptive forces on the gut barrier. The total
third space loss is contributed by fluid sequestered in the lumen, loss of fluid in the
oedematous gut wall and weeping serosal surface. These losses cannot be measured but
can only be estimated. It is important, therefore, that fluid resuscitation begins as early as
possible after diagnosis. Following a focussed examination a nasogastric tube should be
passed, IV line started, samples taken for basic blood investigations and fluid resuscitation
should begin. Remember that other than loss of airway integrity, there is no more urgent
state than that of a neonate in hypovolemia state. A normovolemic baby can tolerate a rapid
316
expansion of blood volume by 25% without any ill effects on circulation. Since the total blood
volume in an infant is 8% of body weight i.e. 80 ml per kilo, a bolus of 20ml per kilo of normal
saline would be appropriate. This would cause small urinary response in a volume depleted
baby while it will not cause failure in a normovolemic one. A severely dehydrated neonate
may require as many as 4 -5 boluses to produce good urine out put (minimum 1ml/kg/hr and
desired 1.5 ml/kg/hr). Urine out put should be the guide to fluid replacement. Blood pressure
is not a good guide because it may remain normal even with 30% volume depletion. Rapid
volume expansion can be achieved within 2-3 hrs.
Components of fluid therapy are:
1. Maintenance: 60ml/kg/day in a term baby on day I
2. Replace existing deficiencies: 20ml/kilo Bolus of N saline. Repeat if minimal urinary
response. Consider 5% HAS. Use 50% colloid and 50% crystalloids.
3. Replace ongoing measurable losses: Nasogastric aspirate to be replaced volume by
volume with N saline.
Simple anatomical mechanical obstruction such as intestinal atresia should be
distinguished from paralytic functional obstruction occurring in septic baby or NEC.
Chronology of events pertaining to abdominal signs helps. In primary obstructive lesions the
initial abdominal symptoms occur in an otherwise healthy and active newborn, while in
paralytic obstruction of sepsis the abdominal symptoms occur late in a setting of ill baby with
other systemic symptoms.
A focussed discussion on specific causes of neonatal intestinal obstruction follows:
Malrotation
Malrotation of midgut is an anatomical abnormality that allows the mid gut to twist
clockwise around the superior mesenteric vascular pedicle. The mid gut extends from 2nd
part of the duodenum to mid transverse colon. During early embryonic life the mid gut
develops rapidly and extrudes into the umbilical cord temporarily. From 7th week onwards, as
it starts returning to the peritoneal cavity, it is disposed as a single large loop based on SMA
pedicle The upper segment i.e. duodeno-jejunal loop is the pre- axial loop and the lower
segment i.e. ileo-caecal loop is the post-axial loop. The whole assembly undergoes a 270
degree counter clockwise turn as it enters the peritoneal cavity. As a result the duodenal
loop passes under the SMA and transverse colon lies in front. The DJ gets fixed in left upper
quadrant at trans-pyloric level and the ICJ gets fixed in the right lower quadrant with the root
of mesentery running obliquely between these two points. The rotation and fixation occurs
simultaneously. In malrotation somehow the contraclockwise rotation stops at 90 degree with
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simultaneous arrest of fixation. The DJ stays right of the midline; the caecum stays high in
the midline, close to Duodenum, with peritoneal bands running between them (Ladd bands).
The entire midgut hangs from this narrow pedicle making it prone to volve. Malrotation is not
synonymous with midgut volvulus. The former is the anatomical abnormality as described
above. It may remain asymptomatic for the entire life or it may lead to chronic duodenal
obstruction of intermittent nature. Mid gut volvulus is a dire emergency that occurs in a
setting of malrotation when the mid gut rotates clockwise around the narrow pedicle of SMA.
This, if not derotated urgently can potentially lead to ischemic necrosis of the entire mid gut
with disastrous consequences. On the other hand a prompt surgery can give a normal life to
the patient with minimal long term complications. In most patients of malrotation volvulus
develops in the first week of life. Volvulus after first month is rare although the predisposing
anatomical abnormality remains life long and volvulus can potentially occur at any age.
Bilious vomiting in a neonate with malrotation is almost always due to volvulus.
Typically the child is well at birth, takes feeds well and passes milk stools. Suddenly on the
third or fourth day he /she develop bile stained vomiting with minimal or no distension. The
child would deteriorate fast to go into shock. Examination reveals a soft abdomen with
possibly a mass in the central abdomen representing the volved gut. Plain film will show gas
in stomach and duodenum and perhaps proximal jejunum but there would be paucity of
distal gas. A soft tissue shadow may be evident in the central abdomen representing the
fluid filled but gas repleted volved midgut. A contrast upper GI series will show a typical cork
screw appearance (Spiral sign) in the proximal jejunum and duodenum. Ultrasound will show
Superior mesenteric vein on the left of SMA (Normally SMV is on the right of SMA). This is a
life threatening emergency requiring fast resuscitation with NG tube, IV fluids and an urgent
laparotomy. Usually there is no time for radiological investigations. The urgency in derotating
the gut is so much that laparotomy is a part of resuscitation. At operation Ladds procedure
is performed which includes:
1. Devolving the midgut by rotating it anticlockwise to undo the twisted mesentery.
2. Division of Ladds bands i.e. the peritoneal bands between the caecum on the left and
duodenum on the right.
3. Widening the mesentery so that further volvulus does not occur.
4. Fixing the gut in a position of non rotation. DJ and small gut on right and ICJ and large gut
on the left.
5. Inversion appendicectomy to avoid diagnostic difficulty if the patient were to suffer from
appendicitis in future.
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If the midgut is found non viable at laparotomy it is wise to derotate it and leave it in
situ. A re-look operation is then done 48 hrs later with the hope that a part of gut would have
regained vascularity. The dead gut would have clearly demarcated by then allowing
minimum resection.
Post-operative adhesions that invariably develop help in fixing the gut in its new
position and therefore, prevent recurrence. This is perhaps a unique situation where
adhesions are desired rather than feared after a laparotomy.
Although uncommon, a neonate with malrotation can present with duodenal
obstruction because of Ladds bands without volvulus. The baby is hemodynamically stable
enough to undergo contrast upper GI study which reveals the DJ junction in an abnormal
location. The normal DJ should be on the left of the spine, going upwards and reaching the
level of the pylorus. In malrotation the DJ is on the right side and duodenum does not cross
the spine, consequently the proximal small bowel loops are on the right side. Lower GI
contrast study to see the position of the caecum is less helpful because the caecum may be
sub hepatic in normal babies without malrotation.
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the proximal segment is dilated in a bulbous fashion for some distance. The distal segment
is collapsed. The child may continue to pass meconeum for few days before developing
distension and bile stained vomiting. The treatment is excision of the dilated portion with end
to end anastomosis. Although there is a significant disparity in the lumen to preclude end to
end anastomosis, disparity of up to 1:4 can be tackled by simple
cheating and end to end
anastomosis is possible. It is preferable to
end to back anastomosis. The dilated proximal
portion and few cm of the distal segment should be excised as they lack normal motility, and
help reduce lumen disparity. An important part of the operation is checking for more
obstruction distally in the form of stenosis or multiple atresias. This is done by injecting
saline in the distal segment and checking for its flow across the entire distal gut including
rectum and anal canal. While it is easy to detect distal atresias, stenosis may be missed if
only air is injected. Saline injection will result in a
waist at the level of stenosis.
Meconeum Disease of neonate
Meconeum ileus, meconeum plug syndrome and meconeum peritonitis constitute
meconeum disease of the neonate. The basic feature is distal small bowel obstruction by
thick and sticky tenacious meconeum resulting from pancreatic deficiency. In the west it is
commonly associated with cystic fibrosis. The more common meconeum ileus presents with
abdominal distension setting within few hrs (sometimes at birth) and early onset bilious
vomiting. Meconeum filled loops are often palpable. The child is otherwise healthy and
active. Plain X-ray shows a typical ground glass appearance with fewer air fluid levels than
the degree of distension would suggest. Contrast enema shows microcolon. Gastrograffin
enema is usually therapeutic, failing which, surgery is required. Resection or enterostomy
may be required. At times anastomosis with a venting safety valve (Bishop Koop or Santuli's
type anastomosis) are required.
Meconeum plug syndrome is a milder variant, frequently associated with diabetic
mothers. It is also known as small left colon syndrome. There is a thick meconeum plug
usually at splenic flexure which causes obstruction. Gastrograffin enema is diagnostic as
well as therapeutic. Rectal biopsy should be taken in these cases to exclude HD because of
a known association. Meconeum peritonitis occurs as a result of antenatal perforation. It is a
sterile chemical peritonitis and may cause meconeum cyst formation with presentation as a
mass and distension at birth. Plain X-ray may show dense calcification. Usually a laparotomy
is required.
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321
with congenital cardiac malformations or are septic. The gut symptoms develop secondarily
over an already existing illness of systemic nature such as temperature instability, poor
perfusion, lethargy, seizures and acidosis. Typical scenario is a sick baby in the nursery who
suddenly develops abdominal distension and bilious aspirates from the Nasogastric tube.
There may be blood stained stools. Abdominal wall erythema develops late and heralds gut
gangrene. X rays show variable picture, but typical features are dilated loops, haziness
because of free fluid, fixed loop, intramural gas, portal vein gas and free gas. Bowel
ischemia will lead to intramural gas and finally perforation. Management is largely
conservative: antibiotics, intravenous alimentation, nasogastric decompression, fluids and
supportive therapy. Indications of surgery are: perforation, fixed loop, sudden drop in platelet
count, and demonstration of intra-abdominal abscess. At operation gangrenous bowel
should be resected, abscess drained and anastomosis done between healthy bowel ends.
Very often it is not possible to achieve anastomosis because of widespread disease and the
bowel is of dubious viability. Stoma should be formed in that situation. Sometimes the gut is
left is situ after lavage and a second look operation is done 48 hrs later with a view to
salvage as much of gut as possible. Long term complications are many and beyond the
scope of this chapter.
Summary:
1. Common causes of neonatal obstruction are: duodenal atresia, jejuno-ileal atresia,
malrotation, Hirschsprungs disease, meconeum ileus and NEC.
2. Bile stained vomiting is always considered surgical unless proved otherwise. Yellow
vomit is self limiting and should not be confused with bilious vomiting which is green.
3. Degree of distension is variable and may be completely absent in proximal
obstructions. Higher the obstruction, lesser the distension but sooner the onset of
vomiting.
4. Plain X-ray in two planes is the most important investigation.
5. After a focussed examination Nasogastric tube should be passed and IV fluid
resuscitation started. Investigations are done once the baby is stabilised.
6. Contrast enema should only be done in a fluid resuscitated baby.
7. 95% term babies pass first meconeum within 24 hrs. Delayed meconeum, global
distension, late onset vomiting and response to rectal irrigation are characteristic of
HD.
8. Malrotation can present with life threatening midgut volvulus. Urgent laparotomy is a
part of resuscitation in that situation.
9. NEC presents with intestinal symptoms occurring in a background of systemic illness.
rd
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Enterocutaneous Fistula
Col RP Choubey
Army Hospital (R&R) Delhi Cantt
Complicated fistula
many tracts.
Etiology
Majority of enterocutaneous fistulas are caused by surgery and result from
breakdown of an anastomosis or necrosis of an ischemic segment of bowel. Spontaneous
enterocutaneous fistulas may result from inflammatory bowel disease, irradiation, perforation
of duodenal ulcer and gastrointestinal or gynaecological malignancies.
Problems of enterocutaneous fistulas
1.
Fluid and electrolyte imbalance: Depending upon the site of fistula and the
amount of discharge, the patient may have imbalance of fluid and electrolytes
and hypovolemia.
323
2.
3.
4.
and
324
the morale of the patient .Postural drainage so as to enable the effluent to drain with
out excoriating the skin is also helpful in certain situations.
3. Sepsis : Uncontrolled fistula out put can lead to intra abdominal collection which
may get infected to form intra abdominal abscess. Unexplained fever and raised
leukocyte count are some of the indicators of such sepsis. All attempts should be
made to detect these with ultrasound or CECT of the abdomen and these should be
promptly drained. Primary treatment of anastomotic leak so as to convert the
uncontrolled leak into a controlled osteomy by intestinal diversion has found favour
with many workers.
4. Nutrition: One of the key factors in overall outcome of the cases of enterocutaneous
fistulas is maintenance of good nutrition. Malnutrition occurs in enterocutaneous
fistulas due to the following factors :
i) loss of protein rich intestinal secretions
ii) inadequate nutrient intake
iii) ongoing sepsis with ketabolism
Patients may be administered nutritional support enterally or parentrally. The dictum is , If
the gut works , use it. Enteral route is usually preferred .A minimum of 100 cms of jejunum
or 150 cms of ileum is required for successful enteral feeding. The enteral nutrition
has
many physiological and metabolic benefits. Luminal nutrients like glutamine and short chain
fatty acids are used by epithelial cells of small intestine and colon respectively for trophic
benefit. Enteral feeding also stimulates manufacture of immunoglobins in the gut which
prevent bacterial translocation and improve the overall immune function of these critically ill
patients. The enteral feeding is also safer and cheaper to administer . Patients with fistula
of proximal intestine can also be fed enterally by placement of feeding tube distal to the
fistula. The problem in these patients is the lack of all bilio pancreatic secretions and hence
they require a low fat elemental diets. Re infusion of gastrointestinal secretions collected
from the proximal fistula via the feeding tube is one method described to improve digestion
as well as to manage the fluid , electrolyte and endogenous protein loss.
Parentral nutrition , if to be given , usually is required to be given through a central vein as
the incidence of thrombophlebitis is high if the
glucose amino acid fluids is done through peripheral vein. In planning TPN for the patients
with enterocutaneous fistula , one should also consider the co morbid conditions in the
patient.
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Once the general condition of the patient stabilizes and immediate problems taken
care of , a fistulogram is done to define the tract and anatomy of the distal bowel. It may also
demonstrate presence of an abscess cavity in case of a complex fistula. Majority of the
enterocutaneous fistulas where there is no distal obstruction ,where the sepsis has been
well controlled and nutrition has been taken care of , will close spontaneously. However
fistulas resulting due to complete disruption of an anastomosis or those associated with
conditions like inflammatory bowel disease , malignancy , post irradiation , presence of
foreign body in the vicinity or having presence of distal obstruction are unlikely to close
spontaneously.
Drugs to decrease fistula out put:
A randomized , prospective , placebo controlled , double blind study on administration of
octreotide (a somatostatin analogue) in enterocutaneous fistulas was studied by Sancho et
al in 1995 .They concluded that patients free of sepsis but with persistent fistula despite 7
days of TPN
may benefit from octreotide and achieve early closure . Similar use of
therapeutic doses of H 2 antagonists or proton pump inhibitors help to reduce gastric acidity
and indirectly lessen pancreato biliary secretions and thereby reduce fistula out put. Fujita
et al have found that high collagenase activity in the bowel wall following an anastomotic
leak leads to delay of healing of fistula. Factor XIII which promotes cross linking of fibrin
during early phase of wound healing has been found to significantly accelerate healing of
anastomotic leak especially of non healing fistulae. Date et al have found good response in
healing of long standing enterocutaneous fistulae even in non IBD patients with infusion of
Anti TNF alpha antibody (Infliximab).
Definitive therapy:
If after six weeks of nutritional support spontaneous closure has not occurred or if the patient
has developed uncontrolled sepsis at any time , operative intervention becomes necessary.
If an abscess is detected it should be drained by per cutaneous drainage or by open
drainage. An uncontrolled sepsis may also necessitate to convert the fistula into a ostomy
and a mucous fistula. Even under the best of conditions operative repair of enterocutaneous
fistula may be unsuccessful.
Conclusion :
Achieving the goals of treatment of enterocutaneous fistula
restoration of intestinal continuity is not an easy task, particularly when the patient
is
malnourished , potentially septic and is recovering from a complicated surgery. The usual
326
management after the initial resuscitation is based on maintaining the nutrition ( as far as
possible by enteral route ) control of sepsis , stoma care and eventually a surgical
intervention
327
Male Sterilization
R.C.M.Kaza, Baljit Kaur
India with its population of one billion is in urgent need of population control
measures. National family welfare program is in operation since 1952 and Government of
India runs an extensive campaign for family welfare annually. Despite that the couple
protection rate is 46% (National Census 1991). This result in 78% pregnancies being
unplanned and 25% unwanted. They add to the population burden and worse still many
women seek termination of these pregnancies resulting in avoidable morbidity. Eleven
million abortions are done in India and 20,000 women die as a result.(NFHS survey 1995)
The world scenario is no better with millions of women dying following abortions in
unwanted and unintended pregnancies, It is an emergency since India is projected to be the
most populous nation by 2040 AD.
There is increasing emphasis world over on male participation in Reproductive
health. This results in better contraceptive prevalence, their continuation and increased
acceptance of contraception. Responsible men also take better care of their progeny. Men
have only two options to control fertility. Condom is a temporary method, and Male
sterilization is the permanent method. Male sterlization is an index of male participation in
family welfare and is simpler and more effective than female sterilization.
Male sterilization can be achieved with or without surgery. Surgical methods include
an Incisional method and the No scalpel method (NSV). Currently The No Scalpel method is
the Gold standard for Vasectomy (Campbell 2002)
Vasectomy essentially involves two steps:
1. Approach to the vas deferens
2. Occlusion of the vas
The first can be achieved either by incising the scrotum after administering a local
anesthetic or percutaneously through a small 2mm puncture as in No Scalpel method. The
NSV procedure which is the method of choice will be described.
The occlusion of vas is done traditionally by ligation and excision of a segment of
vas. It may also be done by cautersing the lumen of vas that results in a fibrotic occluded
segment of vas. Ligature is not applied in this situation. Recently thermal cautery is also
being used. Electrically operated cautery produces heat at the local site and the current
spreads for a certain distance which results in loss of a longer segment of vas than desired.
328
Thermal cautery is a battery operated unit where power from dry cells heats a loupe of wire
to red heat and that is introduced into the lumen of vas to burn the mucosa. Only the mucosa
in contact with the loupe is destroyed. The net effect is the same as electrical cautery without
the loss of extra vas segment.
The differences between a conventional/incisional vasectomy and No scalpel
vasectomy are as shown in this table.
Steps
9.Dressing
Conventional
vasectomy
Into the incision site and a
chord block
With two fingers
With fingers only
2cm incision on both sides
of scrotum
Layer dissection in multiple
steps
Excision Ligation with silk
or Cautery of lumina
Dealt through a second
incision
Two incisions closed by
stitches
Bulky with scrotal support
10.Ambulation
Late; 7 days
1.Local administration
2.Vas identification
3. Vas fixation
4.Vas approach
5.Vas dissection
6.Vas occlusion
7.Vas on second side
8.Skin closure
No scalpel Vasectomy
Skin wheal in the midline
and perivasal block
Three finger technique
Vas fixation forceps
Single midline 2mm
puncture
Single step dissection of all
layers.
Excision Ligation with silk
or Cautery of lumina
Dealt through the same
midline puncture.
Single midline puncture
with no stitches.
Small band aid. Scrotal
support optional
Immediate with restrictions
for two days.
The advantages of NSV are obvious. The effort of minimizing the access results in various
other
Minimals. (Kaza 2006) They are:
1. Minimal scrotal handling because of three finger technique of palpation of vas
2. Minimal pain because of effective perivasal administration of anesthetic and
minimal handling
3. Minimal dissection because of fixation of minimal tissue in ring forceps and one
step dissection of all layers of vas.
4. Minimal time taken for surgery
5. Minimal dressing only a band aid.
6. Minimal restrictions - only two days
7. Minimal drugs
8. Minimal complications
9. Minimal Follow up
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10. Minimal instruments only two special instruments along with a scissors
330
This is the best method of quickly identifying, isolating and fixing Vas deferens where the
middle finger placed posteriorly acts as a platform against which the vas is fixed by thumb
and stretched by index finger.
The skin wheal for anaesthetizing the skin is raised in midline at the junction of upper 1/3 rd
and lower 2/3rd of anterior scrotal raphe. The needle is advanced perivasally upto its full
length towards inguinal ring and 2cc local is given. No local to be given while removing
withdrawing needle.
Vas is fixed with ring forceps placed perpendicular and parallel to its axis.
331
The tips of dissection forceps are opened and first one blade and then two blades are
inserted into the lumen of vas and opened thrice so that all layers in front of vas are
dissected away in one step.
332
vas or by use of intraluminal thermal cautery/ electrical cautery. The ligature should be only
tight enough to occlude the lumen of the vas. Too tight will cut through the vas and to loose
will result in slip ligature.
Thermal Cautery : A battery operated cautery pencil is used that has tip approx 1 cm long.
The exposed vas is hemi sliced to enable introduction of the tip of t thermal cautery into the
lumen of the vas on either side laving a 1 cm segment to be resected. The luminal mucosa
of the vas is coagulated enough to cause occlusion by fibrosis.
coagulated & 1 cm segment resected. This results in segment occlusion of vas. It is being
practiced in selected centers only in India.
Internal spermatic fascia is interposed between two cut ends of vas. The ligated abdominal
end of vas is reduced into scrotum and drawn up into wound when it comes out covered by
internal spermatic fascia. This is promptly ligated with the abdominal end. This exteriorizes
the abdominal end out of the cord.
333
334
(h) The client must be told that he does not become sterile immediately after the operation
and that he or his wife will have to use another method of contraception for at least 20
ejaculations or for three months (whichever is earlier) following vasectomy. The client must
use condom, if his wife is not using contraception.
(i) The client should report to the doctor or a clinic if there is excessive pain, fainting, fever,
bleeding, increase in scrotal size or pus discharge from the operated site.
(j) Return to the clinic (in cases of conventional vasectomy) for removal of stitches and
postoperative check-up in seven days.
(k) Report to the clinic for semen analysis after 3 months.
(l) If there are many questions, contact the health personnel or doctor at any time.
(m) The client must be provided with instructions on where to go if complications (such as
infections, swelling of the scrotum, fever, increase in pain, bleeding from the wound ) arise.
Complications of Vasectomy:
Vasectomy has some immediate and delayed complications albeit very low. Some of the
complications that can occur are briefly discussed.
Intraoperative complications:
Intraoperative complications such as vasovagal reaction, bleeding due to vascular injuries
can all be prevented by counseling and careful surgical technique. Vasovagal reaction can
be prevented by explaining the procedure to the client in advance , effective block, gentle
surgical technique and reassuring the client during the surgical procedure (Engender
Haealth )True xylocaine toxicity is rare and can be avoided by proper administration of local
anaesthesia as per guidelines.
Infection and haematoma:
They are unusual. The percentages of these complications in both the methods of
vasectomy are as under:
Study
Incsional vasectomy
Kendrick et al 1987
Nirapathpongporn 1990
Sokal et al
No of vasectomies
% with infections
65,155
523
627
3.5%
1.3%
1.3%
2%
1.7%
10.7%
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No Scalpel Vasectomy
Nirapathpongporn 1990
Li et al 1991
Sokal et al
680
179,741
606
0.2%
0.9%
0.2%
0.3%
0.1%
1.7%
Sloughing of the vassal ends after ligature can also result in a leak and
granuloma. Most of the granulomas are asymptomatic. Granulomas occurring early within 23 weeks can be painful (Peterson et al)
Long term effects of vasectomy:
Extensive research has been undertaken on the long term effects of vasectomy. Five
large scale cohort studies have examined the incidence of number of diseases in
336
vasectomised and non vasectomised men. ( Massey et al) Results of large scale well
designed epidemiological studies in men have consistently shown no adverse effects of
vasectomy in terms of heart disease, testicular or prostatic cancer, immune complex
disorders and a host of other conditions. (engender health) Vasectomy appears to be largely
safe and highly effective method of contraception, certainly with risks no greater than those
for any of the contraceptive methods used by women.
NSV is the gold standard for vasectomy today and if possible all vasectomies should
be performed this way. Training is mandatory for experienced surgeons as well. It is now a
part of the national programme and state trainers exist in most states. Government of India
funds and supports both the training and service activities.
337
questioned. Medical grade silicone plugs(vasoc) were formed in place with reasonable
success but their safety efficacy and the technically demanding nature of the procedure was
questioned.
Devices that stay in place in the vas have also been tried which can be removed to
reestablish patency. But the devices quite often have not stayed in place in the muscular
wall of vas.
Selected references:
1.
2.
3.
4.
5.
6.
Engender Health 2002 Male sterilization Contraceptive Sterilization: global issues and trends
161;177
7.
Kendrick JS 1987 Complications of vasectomies in the United States Journal of Family Practice
25(3):245-248
8.
9.
Mark A Barone Belinda Irsula Mario Chen-Mok et al 2004 Effectiveness of vasectomy using
Cautery BMC urology 4:10
10.
David Sokal Belinda Irsula Melissa Hays et al 2004 Vasectomy by ligation Excision
without fascial interposition; a randomized controlled trial BMC Med 2:6
11.
Peterson HB Huber DH Belker AM 1990 Vasectomy : An appraisal for the Obstetriciangynecologist Obstetrics and Gynecology 76:568-572
12.
Massey FJ 1984 vasectomy and health: Results from a large cohort study Journal of American
medical association 252(8): 1023-1029
13.
Xiao 1987 Chemical Vas Occlusion in the peoples republic of china Fertility regulation today and
tomorrow ed E Diczfalusy M Bygdeman, New york raven press 265-274
14.
Zhao SC 1990 Vas deferens occlusion by percutaeous injection of polyurethane elastomer plugs:
clinical experience and reversibility Contraception 41(5) 453-459
338
with or
Introduction
According to WHO, Universal Work Precautions are simple infection control
measures that reduce the risk of transmission of blood borne pathogens through exposure to
blood or body fluids among patients and health care workers. Under the
universal
precautions principle, blood and body fluids from all persons should be considered as
infected with HIV, regardless of the known or supposed status of the person. Improving the
safety of injections is an important component of universal precautions.
In 1987 the Centre for Disease Control and Prevention (CDC) in Atlanta proposed a
new concept for isolation precautions called "Universal Precautions," originally designed to
protect health care workers (HCWs) from exposure to blood borne pathogens. Universal
Precautions (i.e., using certain work practices and barrier equipment when exposure to any
blood or other potentially infectious materials is likely) would minimize the risk of
transmission of blood borne infections.
In January 1996, the CDC proposed that Universal Precautions be renamed
Standard Precautions. The term Standard Precautions combines the major features of
Universal Precautions and Body Substance Isolation (designed to reduce the risk of
transmission of pathogens from moist body substances).
Universal Precautions apply to the following:
1) blood
2) all body fluids, secretions, and excretions except sweat, regardless of
whether or not they contain visible blood
3) non-intact skin
4) mucous membranes
5) any unfixed tissue or organ (other than intact skin) from a human (living
or dead)
6) HIV-containing cell or tissue cultures, organ cultures, or HIV- or HBVcontaining culture medium or other solutions, and
7) blood, organs, or other tissues from experimental animals infected with
HIV or HBV.
Surgical Specialties and invasive procedures
Doctors practicing surgical specialties or performing invasive procedures are
especially at risk because of the possibility of needle stick injuries during surgery. Certain
specialties expose the HCW to splash of body fluids. This happens commonly during
339
deliveries. Dentists are exposed to vapours of body fluids during certain dental procedures
which require the use of high speed drills. Cardiac and vascular surgeons are exposed to
direct splash of blood during the performance of procedures on heart or major blood vessels.
Risk of transmission of HIV, HBV and HCV
Risks of transmission of three important blood borne viruses, namely, human
immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV),
underlines the necessity for Universal Precautions.
Hepatitis B Virus can be transmitted parenterally, sexually, and perinatally. Although
percutaneous inoculation is the most common mechanism for occupational infection, HCWs
are also at risk when blood or other potentially infectious materials contaminate mucous
membranes or non-intact skin. Even microscopic breaks in the skin may permit infection with
HBV. Initial symptoms of hepatitis B infection range from none (asymptomatic) to nausea,
malaise,
and
jaundice,
with
the
development
of
acute
or
chronic
hepatitis.
HIV is also transmitted parenterally, sexually, and peri-natally. HIV adversely affects the
immune system, with several stages of disease progression. Within a month after exposure,
an individual may experience an acute retroviral syndrome (a mononucleosis-like
syndrome), with signs and symptoms that can include fever, lymphadenopathy, myalgia,
arthralgia, diarrhea, fatigue, and rash. Individuals may be asymptomatic for months to years
after infection, although they can transmit the virus to others. Most HIV-infected persons will
eventually develop acquired immunodeficiency syndrome (AIDS), which can result in fatal
opportunistic infections or neoplastic processes.
Occupational infection with HIV may occur after an adverse exposure to blood or
other potentially infectious materials (contaminated with blood) from an individual infected
with this virus. The risk of infection following an adverse exposure is very low when
compared with HBV and is estimated to be about three HIV infections per 1000 exposures.
Hepatitis C virus (HCV) is another blood borne infection that represents an occupational
risk. HCV accounts for the majority of hepatitis formerly called non-A, non-B hepatitis. Like
HBV, this virus is transmitted parenterally but less efficiently.
Occupational Exposures
Occupational exposure means reasonably anticipated skin, eye, mucous membrane,
or parenteral contact with blood or other potentially infectious body fluids. Other potentially
infectious body fluids include the following human body fluids:
340
semen
vaginal secretions
amniotic fluid
peritoneal fluid
pericardial fluid
pleural fluid
sputum
dental procedures
cerebrospinal fluid
synovial fluid
any body fluid that is visibly contaminated with blood.
341
membranes, non-intact skin, and contaminated items. Wear gloves whenever you can
reasonably anticipate contact with blood or other potentially infectious materials, and
contaminated items, or when handling or touching contaminated items or surfaces.
Gloves should be worn particularly during the performance of the following day to day
procedures:
1. putting an IV drip
2. giving an IV injection
3. doing the dressing of a wound
4. draining an abscess however small
5. stitching a laceration
6. removing stitches
7. doing any procedures in minor or major operation theatre
Gloves do not need to be worn in the following situations
1. examination of a patient with intact skin
2. giving an intra-muscular injection
Disposable (single-use) gloves should never be washed and reused. Remove gloves
immediately after use, before touching non-contaminated items such as door handles,
telephones, computers, equipment etc.
Wash hands thoroughly immediately after removal of gloves to avoid transfer of microorganisms to other environments. Wearing gloves does not replace the need for hand
washing, because gloves may have small, in-apparent defects or may be torn during use,
and hands can become contaminated during removal of gloves.
B : Wearing of Cap and Mask
Cap and mask must be worn
1. when entering an operation theatre minor or major
2. performing a minor surgical procedure
3. performing a major surgical procedure
4. during wound dressings in the ward
5. performing all dental procedures
6. during delivery of a baby or any other obstetrical procedure
C : Eye Protection
Means of eye-protection such as plastic glasses with solid side shields, goggles,
masks with clear visors, and chin-length face shields, should be worn whenever splashes,
342
spray, spatter, or droplets of blood or other potentially infectious materials may be generated
toward the eyes, nose, or mouth. In these situations, wear either: (1) mask and eye
protection or (2) a chin-length face shield. Personal eyewear or wearing of plane glasses is
not adequate as a barrier unless side panels are present.
D : Water proof apron to protect the body
Water proof apron must be worn whenever performing a surgical procedure. It is a
common experience during major surgical procedures to find the blood or body fluids flowing
off the sides of the body of the patient. This happens particularly during major or prolonged
abdominal procedures. Blood soaked fluids thus come in contact with the trunk of the
surgeon and his assistant. If the surgeon is not wearing a plastic apron to protect himself,
blood then comes in contact with surgeons body. It is a common experience with all
surgeons to find the OT dress and their own underclothes soaked in blood after a major
surgical procedure if they are not wearing a protective plastic apron.
It is also absolutely required to wear plastic apron while receiving casualties in the casualty
department. Road traffic accident patients often have multiple injuries and blood may be
flowing off the body when the patients are brought in. The casualty doctors therefore must
be adequately protected by wearing a plastic apron, adequately protective foot wear and
must use gloves before handing such patients.
E : Adequately protective foot wear
It is commonly seen that the residents wear chappals while on duty in operation
theatre or casualty department. This is a disastrous situation which requires rectification.
Feet of HCWs are as prone to being exposed to potentially contaminated blood or body
fluids from a patient as are their hands or the trunk. Patients are often brought into the
casualty after road accidents or other reasons of injury. Their blood or body fluids can
spatter the floor as they lie on the stretchers.
Adequate foot wear should be the wearing of complete canvas shoes or the gum
boots. Gum boots are particularly required while performing endo-urological procedures.
Here we always have the blood contaminated irrigation fluids falling onto the floor where the
urologist is standing to perform the procedure. Trans Urethral Resection of prostate or a
bladder tumour is one of the commonly performed procedures and the returning irrigation
fluid always contains blood. The feet of the surgeon are therefore exposed to acquire a
blood borne virus if there is the slightest breach of the skin of the surgeon.
343
344
It is obvious that the transmission rate is lowest with HIV and several times higher with
Hepatitis B Virus.
Prevention of Needle Stick Injuries
It is universally agreed that majority of needle stick injuries are preventable. More
than 80% of needle stick injuries can be prevented by using safer needles. In India, use of
blunt tipped needle is easiest to achieve. These needles are now easily available and are
cost effective. However, advances in needle designs have made it possible to eliminate
sharps from many uses-such as iv piggybacks, use of blunt needles or retract the needle so
it's no longer a danger.
Placing sharps containers within reach and at eye level in
operation theatres and by the bed side in every patient room
reduces the risk of injury. Disposable knife blades and needles can
easily be disposed right away after use thereby preventing the
need to be handled by more than one HCW.
Operation Theatre precautions to prevent needle stick injuries
There are several measures that should to be taken to avoid actual injury in the operation
theatre and these should be considered seriously:
no more than one person should work in an open wound/cavity (unless essential). It
is often seen that besides the surgeons hand, there are also the hands of one or two
assistants in the abdominal wound. This crams the space and if suturing is being
done at depth, there is a greater chance of sustaining a needle stick injury.
use the hands-off technique: the needle is not handled by more than one person
,i.e., the surgeon. The assistants must be in hands-off position so that they do not
come in contact with the needle at all.
announce to your colleague or the nurse assisting you that the needle is being
returned in the needle holder.
ensure needles and sharps are not left exposed, these must be placed in a kidney
tray and not handed back hand to hand during a surgical procedure.
345
use instruments rather than fingers for retracting the wound and suturing. In spite of
repeatedly highlighting this point, it is still observed that residents frequently use
hands to retract a wound for the sake of expediency.
use instruments when handling needles. It is accepted universally that the needle
should only be held only with a needle holder. A change in the position of the needle
should also be effected only with the use of instruments like toothed forceps.
direct needles and instruments away from your own, or assistants hand.
donot bend or snap used needles. This process may lead to needle stick injury.
Never re-cap a used needle. This may lead to accidental needle stick injury if the cap
is missed while capping the needle.
Place used needles into a clearly labelled and puncture-proof sharps approved
container.
Never use a hand held curved needle for suturing skin. It is a practice with some
institutions to provide large hand held needles for suturing wounds, especially after a
cut down procedure to access a vein.
Special Points
Single vs Double gloves
There has been a considerable debate on this issue over the years. Those preferring
to use a single pair of gloves argue that two pairs of gloves substantially reduce the feel
during surgery. However, the proponents of using two pairs of gloves have traditionally
argued that wearing two gloves offers extra protection against needle stick injuries.
According to Tanner and Parkinson (The Cochrane Library, Issue 3, 30 August 2006.
Chichester, UK: John Wiley & Sons, Ltd ) wearing of two pairs of gloves offers additional
protection against needle stick injuries. The summary and conclusions of their article are as
follows :
Two layers of surgical gloves can reduce the number of breaks to the innermost glove that
might allow cross-infection between the surgical team and patient
Surgical operations are undertaken within a clean environment and with members of the
surgical team wearing sterile gloves. Sterile surgical gloves aim to protect the patient from
contamination with bacteria from members of the surgical team and protect the surgical team
346
from the body fluids of the patient. Double-gloving (wearing two sets of gloves) is becoming
more common, especially for surgery where sharp surfaces are formed (such as orthopaedic
or dental surgery). The review found that a second pair of gloves does protect the inner pair,
without apparently affecting surgical performance. A glove liner between the two pairs of
gloves reduces breaks to the inner glove even further, and extra-thick gloves seem to be as
good as two pairs.
The addition of a second pair of surgical gloves significantly reduces perforations to
innermost gloves. Triple gloving, knitted outer gloves and glove liners also significantly
reduce perforations to the innermost glove.
Hand washing and gloving practice amongst HCWs an interesting study from Saudi
Arabia
In an article published in August 2006, Basurrah and Madani have made some
interesting observations with regard to the hand washing and gloving practices of various
categories of medical staff in a tertiary care hospital in Riyadh ( Saudi Arabia ).
The authors evaluated the adherence to handwashing and gloving practice among
health care workers (HCWs) in 5 medical and 5 surgical wards of a 1250-bed hospital in
Riyadh. Nurses, consultants, residents, interns, and medical students attending these wards
were each unobtrusively observed for handwashing and gloving practice. Each HCW was
observed only once for all handwashing and gloving opportunities during a single patient
encounter. 312 handwashing opportunites for 230 HCWs were observed. The study
population comprised 110 nurses, 76 residents, 23 medical students, 11 interns, and 10
consultants. Female subjects constituted 56.1% of the population. The ratio of handwashing
sinks to beds was 1:6-7.
The overall frequency of handwashing was 6.7% before patient contact and 23.7%
after patient contact.
Adherence to handwashing was 70.0% among medical students, 69.2% among
interns, 18.8% among nurses, 12.5% among residents, and 9.1% among consultants. The
duration of handwashing was suboptimal for all HCWs (average of 4.7 seconds).
Adherence to wearing gloves for performing procedures was on an average 75.5%.
The authors concluded and advised as follows :
Poor adherence to handwashing is a worldwide problem.
347
Strategies to improve hand hygiene practice should be multifaceted and should include
increasing the availability and accessibility of handwashing sinks and alcohol-based hand
rubs.
It is therefore easily conceivable that such practices as elucidated in the foregoing
article are in operation in other countries including India. We therefore need to educate
ourselves and our staff of all catgories to pay special attention to the absolute basics of
Universal Precautions to minimise the risk of acquiring some of the deadly viral diseases. To
assume that Universal Precautions are being followed by everybody in our surroundings will
be a folly. We need to repeatedly ensure that HCWs are following the Precautions every
time and without any exception. We and our medical colleagues stand exposed to danger of
acquiring blood borne viruses if we fail to meet this challenge.
In Conclusion
A surgeon requires all the means of barrier precautions (Universal Work Precautions)
being made available to him. There must be no exceptions to the use of barrier precautions
as described above while looking after patients in the wards or the operation theatres.
A change in the attitude to the surgery is required to ensure that there is no
accidental sharp injury, especially a needle stick or a scalpel blade injury in the operation
theatre or a surgical ward. Surgery needs to be performed in a controlled and deliberate
manner. Attention must also be paid to the details of sequence of all procedures.
If a needle stick or sharps injury does occur during the course of the professional
work, it must be reported immediately. Appropriate steps must be taken for counseling,
testing and starting The Post Exposure Prophylaxis (PEP) if indicated.
References
Tanner J, Parkinson H : Double gloving to reduce surgical cross-infection (Cochrane Review). The
Cochrane Database of Systematic Reviews 2006, Issue 3. Art. No.: CD003087.
DOI:10.1002/14651858.CD003087.
Basurrah M, Madani T : Handwashing and gloving practice among health care workers in medical and
surgical wards in a tertiary care centre in Riyadh, Saudi Arabia, Scandinavian Journal of Infectious
Diseases, Volume 38, Number 8, August 2006, pp. 620-624(5)
348
The central part of the gland is called the adrenal medulla and produces catecholaminesepinephrine and norepinephrine.
The outside part of the gland surrounding the medulla is the adrenal cortex. This part of
the adrenal gland is responsible for producing steroid hormones in the body. The several
types of steroids hormones produced by the adrenal glandsare:
-
Mineralocorticoids (aldosterone): that help regulate the sodium levels in the body by
controlling the absorption and excretion of salt and water in the kidneys, which in turn
helps to regulate blood pressure.
The adrenal cortex also produces several sex hormones-androgens (in males) and
precursors to estrogen (critical for females).
Adrenal cortical tumors
Adrenal tumors can either be benign or malignant. Malignant tumors grow in
uncontrolled manner and invade adjacent tissues and metastasise through the blood stream
or through the lymphatics.
The most common tumor of the adrenal gland is actually a benign tumor called an
adrenal adenoma . The most common malignant tumors found in the adrenal gland are
secondaries that have metastasized from melanomas, lung cancers, and breast cancers.
Cancers can arise directly from the adrenal cortex. These cancers can either be
functioning or non-functioning. Functioning adrenal cortical cancers are more common than
non-functioning cancers. Cancers can also arise within the adrenal medulla, the most
common of which are pheochromocytomas and, rarely, lymphoma.
Incidence/risk
Each year approximately 500 cases of adrenal cortical cancers are diagnosed in the
United States. These occur most commonly in patients between the ages of 30 and 50.
349
Children under the age of 5 develop adrenal cortical cancers at a higher rate than the rest of
the population. Males are more likely to develop non-functioning adrenal carcinomas, while
females are more likely to develop functioning adrenal carcinomas.
Familial history may be noted in patients with Multiple Endocrine Neoplasia, but
cortical tumors are not known to run in families.
Clinical features of adrenal cortical tumors
Both adrenal adenomas and adrenal cortical cancers can be produce excess steroid
hormones. Symptoms vary depending on the steroid that is produced. The following are the
commonly observed conditions in the presence of hypersecretion of mineralocorticoidd or
steroid hormones.
Conn's syndrome (known as primary hyperaldosteronism): Conn's syndrome most
commonly occurs with adrenal adenomas, but it can also rarely occur in the setting of
adrenal hyperplasia and adrenal cortical cancers.
Hypersecretion of aldosterone may result in hypernatremia, hypervolemia, and a
hypokalemic alkalosis manifested by episodic weakness, paresthesias, transient paralysis,
and tetany. Diastolic hypertension and a hypokalemic nephropathy with polyuria and
polydipsia are also common. Secondary Aldosteronism, an increased production of
aldosterone by the adrenal cortex is caused by stimuli originating outside the adrenal, is
related to hypertension and edematous disorders (eg, cardiac failure, cirrhosis with ascites,
the nephrotic syndrome).
Cushing's syndrome (hypercortisolism) : This syndrome is a constellation of clinical
abnormalities due to chronic exposure to excesses of cortisol (the major adrenocorticoid) or
related corticosteroids.
Hyperfunction of the adrenal cortex may be ACTH-dependent, or it may be
independent of ACTH regulation, eg, production of cortisol by an adrenocortical adenoma or
carcinoma.
Therapeutic administration of exogenous cortisol or related synthetic analogs
suppresses adrenocortical function and mimics ACTH-independent hyperfunction.
ACTH-dependent hyperfunction of the adrenal cortex may be due to (1)
hypersecretion of ACTH by the pituitary gland; (2) secretion of ACTH by a nonpituitary
tumor, such as small cell carcinoma of the lung (the ectopic ACTH syndrome); or (3)
administration of exogenous ACTH.
350
Whereas the term Cushing's syndrome has been applied to the clinical picture
resulting from cortisol excess regardless of the cause, hyperfunction of the adrenal cortex
resulting from pituitary ACTH excess has frequently been referred to as Cushing's disease,
implying a particular physiologic abnormality. Patients with Cushing's disease may have a
basophilic or a chromophobe adenoma of the pituitary gland.
Clinical manifestations include rounded "moon" facies with a plethoric appearance.
There is truncal obesity with prominent supraclavicular and dorsal cervical fat pads ("buffalo
hump"); the distal extremities and fingers are usually quite slender. Muscle wasting and
weakness are present. The skin is thin and atrophic, with poor wound healing and easy
bruising. Purple striae may appear on the abdomen. Hypertension, renal calculi,
osteoporosis, glucose intolerance, reduced resistance to infection, and psychiatric
disturbances are common. Cessation of linear growth is characteristic in children. Females
usually have menstrual irregularities.
Virilism: In adrenal tumors, an increased production of androgens, in addition to cortisol,
may lead to hypertrichosis and other signs of virilism in the female. Virilization in women
also results in deepened voice, loss of hair, and increase in the size of the clitoris. Women
can have irregular menstrual periods or stop menstruating altogether, and men can
experience sexual impotence.
In children, excessive cortisol can lead to premature sexual development and
maturation (precocious puberty). These can be called as adrenal virilism or a drenogenital
Syndrome
Adrenal tumors can also cause symptoms when they assume a large size. Patients
with large adrenal tumors may experience feelings of abdominal fullness or localized pain.
Patients may feel early satiety and experience weight loss. In some cases of large adrenal
tumors, patients may actually feel a mass in their abdomen.
Investigations and Diagnosis
Laboratory evaluation
Functioning adrenal cortical cancers and adenomas are frequently diagnosed
because of the symptoms caused by the excess steroids hormones secreted by these
tumors.
Patients with Cushing's syndrome need to be evaluated to see if the syndrome is
caused by a lesion in the adrenal glands or by excess production of ACTH from the pituitary
adenoma or an ectopic tumor somewhere else in the body.
351
Plasma cortisol is normally 5 to 25 g/dL in the early morning hours (6 to 8 am) and
declines gradually to < 10 g/dL in the evenings. Patients with Cushing's syndrome usually
have elevated morning cortisol levels and lack the normal diurnal decline in cortisol
production, so that evening plasma cortisol levels are above normal and total 24-h cortisol
production is elevated.
Free urinary cortisol, is the best assay for urinary excretion (normal 20 to 100 g /
24h), is elevated > 120 g/24 h in Cushing's patients.
The dexamethasone test (screening test), in which 1 mg of dexamethasone is
administered orally at 11 to 12 pm and plasma cortisol is measured at 7 to 8 am the next
morning, has been used to screen for Cushing's syndrome. Most normal patients will
suppress their morning plasma cortisol to <= 5 g/dL after this test, whereas most patients
with nonpituitary Cushing's syndrome will have a morning cortisol level of at least 9 g/dL
and will maintain their plasma cortisol at its original level.
Low dose Dexamethasone test: Giving oral dexamethasone 0.5 mg q 6 h for 2 days to
normal subjects leads to inhibition of ACTH secretion. Consequently, urinary-free cortisol will
usually decrease to 50% or less than the pretreatment level but, in any case, to < 10 g/24 h
on the 2nd day. In patients with Cushing's disease, pituitary ACTH secretion is relatively
resistant to suppression, thus urinary-free cortisol will not decrease in a normal fashion.
High dose Dexamethasone Test : When the oral dose of dexamethasone is increased to 2
mg q 6 h for 2 days, urinary-free cortisol will usually decrease by at least 50% from the
baseline values in patients with Cushing's disease, which is dependent on pituitary ACTH.
In patients with adrenal tumors, cortisol production is independent of ACTH, thus
dexamethasone will have no suppressive effect. In patients with ectopic ACTH syndrome,
the production of ACTH by the ectopic tumor is almost always unaffected by
dexamethasone, hence urinary steroids remain unchanged. The dexamethasone test
distinguishes a pituitary abnormality from other forms of Cushing's syndrome.
The overnight metyrapone test and the ACTH stimulation test are other tests that
are used less commonly now.
In contrast to adrenal hyperplasia, dexamethasone administration either does not
suppress or only partially suppresses androgen excretion in virilizing adenomas or
adenocarcinomas.
352
rapidly growing cells within the body e.g. cancer cells are rapidly dividing and growing, they
take up more radioactive glucose than the surrounding tissue. PET scans have been very
useful in detect a number of different types of cancers. Its use in adrenal cancers is still
being studied.
353
Biopsy
A small piece of the tumor is taken through a needle for histological examination. In
the case of adrenal tumors, this procedure is usually performed while the patient is
undergoing a CT scan or ultrasound to guide the biopsy.
Staging of adrenal cortical cancers
In addition to diagnosing adrenal cortical cancers, the radiographic imaging
performed also helps to determine the stage of the patient. In general, patients with adrenal
cortical cancer are divided into one of four stages.
Stage I: The cancer is smaller than 5 cm and has not spread outside of the adrenal gland.
Stage II: The cancer is larger than 5 cm and has not spread outside of the adrenal gland.
Stage III: The cancer has spread into the fat surrounding the adrenal gland or has spread to
lymph nodes near the adrenal gland.
Stage IV: The cancer has spread to other parts of the body, has spread into other organs
near the adrenal gland, or has spread into both the fat around the adrenal gland and the
lymph nodes near the adrenal gland.
Although this system of cancer staging is quite complicated, it is designed to help the
management.
Treatment
Incidentalomas : Most adrenal adenomas are detected on a CT scan or MRI scan that is
performed for an unrelated reason. It is only necessary to treat them if they are causing
symptoms. Otherwise, they can be followed with repeated scans periodically.
Symptomatic tumors: In the event that an adenoma does need to be treated, surgical
removal is the most frequent treatment used. In many cases, this can be performed using a
laparoscopic procedure.
Occasionally, because of the size or location of the adenoma, a laparoscopic procedure
cannot be performed, and a large incision will need to be made in the abdomen in order to
remove the tumor.
354
Surgery
Currently, the only known curative treatment for adrenal cortical cancers is complete
resection of the tumor. Unfortunately, this is only possible in a limited number of patients with
this disease. At least half of patients with adrenal cortical cancers have metastases or
cancer invading into other organs, such that a complete resection of the cancer is not
possible. The best results with surgical resection have been with an en bloc resection,
meaning that the entire tumor is removed in one piece. This also includes removing the
entire kidney on the same side as the adrenal cancer.
Occasionally, adrenal cancers will grow into the inferior vena cava. Even in these
cases, complete resections of the cancer can sometimes be performed. Even in cases
where the tumor cannot be removed in its entirety, surgical removal of as much tumor as
possible can improve symptoms, particularly if they are due to excessive steroid secretion.
Treatment
Treatment is directed at correcting the hyperfunction of the pituitary gland or the
adrenal cortex; the precise approach depends on the underlying abnormality.
Initially, the patient's general condition should be supported by appropriate
administration of K and a high protein intake.
When the pituitary is the source of excessive ACTH secretion, the standard approach
is to perform a transsphenoidal exploration of the pituitary and excise a tumor, if one is
found. This surgical procedure is demanding and should be performed only in experienced
centers. The operation is successful in about 70% of cases and works best with
microadenomas < 1 cm in diameter.
If no tumor is found, the next step is supervoltage irradiation of the pituitary,
delivering 40 to 50 Gy. In children, pituitary irradiation may reduce secretion of growth
hormone and may cause precocious puberty occasionally. Response to irradiation may
require several months.
Bilateral adrenalectomy is reserved for patients with pituitary hyperadrenocorticism
who do not respond to both pituitary operation and irradiation.
Adrenalectomy requires steroid replacement for the remainder of the patient's life, in
the same pattern as is required for primary adrenal failure.
355
356
Radiation Therapy
Radiation Therapy is used in a number of cancers as both the main method of
treatment or in combination with surgery. Radiation therapy is not part of the routine
management of adrenal cancers, particularly in cases where the cancer is completely
removed by surgery. Radiation has been tried in cases where surgical removal of the cancer
is incomplete or in cases where the cancer recurs after surgery. In these cases, the radiation
is usually delivered for a total of 5 to 7 weeks but results remain poor.
Shortly after treatment for functional (secreting) adrenal tumors, samples will be
drawn to measure hormone levels in the body. If the hormone levels have returned to normal
after therapy, regular follow-up will occur. You will be followed every 3-6 months for several
years after treatment.
In the majority of cases of hyperaldosteronism, symptoms resolve with surgical
removal of the adenoma; however, 30% of patients will have repeat episodes of high blood
pressure even after the adenoma is removed. If the adrenal adenoma produces cortisol, the
patient should take steroids by mouth before and for some time after the surgery until the
body is able to produce these steroids on its own again.
Treatment of secondaries
In most cases, when other cancers spread to the adrenal glands, they are treated
with chemotherapy.
In the case of non-functional (non-secreting) adenomas and adrenal cortical cancers,
periodic follow-up MRI or CT of the abdomen will be obtained for the first few years
Results of treatment for adrenal cortical cancers
Adrenal cortical cancers are curable only in cases where the entire tumor is removed
at surgery. These tend to be aggressive cancers, even after complete surgical removal is
performed; they have a tendency to recur. The 5-year overall survival describes the
percentage of patients who are alive at 5 years after cancer treatment.
Stage I and II: After en bloc resection for stage I and II adrenal cortical cancers, the 5-year
overall survival rate is 40-60%.
Stage III and IV: For stage III cancers, the 5-year overall survival is 20%. For stage IV
patients, the 5-year overall survival is 10%.
357
1.
2.
3.
4.
Suggested readings:
Harrisonss Principles of internal Medicine.
Textbook of Endocrinology
Merck Manual
Endocrine web.
358
359
Nodular hyperplasia
Adrenal medullary tumours
Pheochromocytoma
Neuroblastoma
Ganglioneuroma
Miscellaneous
Adrenal cyst
Myelolioma
Metastasis
Connective tissue tumours
Infection
Granulomas
In a recent systematic review that combined studies using the broadest definitions,
adenomas
accounted for
41%,
metastasis
19%,
adrenocortical
carcinoma
10%,
myelolipoma 9% and pheochromocytoma 8%, with other usually benign lesions such as
adrenal cysts comprising the remainder.
The size of the lesion affects the distribution of etiologies. Among lesions larger than
6 cm, adrenal carcinomas comprised 25%and metastasis 18%, while adenomas accounted
for only 18%; for tumours under 4 cm, adrenal carcinomas comprised 2% and
adenomas65%; and for tumours of 46 cm, adrenocortical carcinoma constituted 6%.
Bilateral adrenal masses are found in about 1015% of cases. When masses are
bilateral, several diagnoses are morelikely, including metastatic disease, congenital adrenal
hyperplasia,
lymphoma,
infection
(e.g.,
tuberculosis,fungal),
hemorrhage,
360
diameter and solidity, and none about its functional status. However, ultrasound can be a
simple, effective tool for follow-up.
The CT scan is most commonly used in the assessment of AI. Adrenal adenomas
are usually small, well defined homogeneous lesions, with evident margins and large
intracytoplasmic lipid content. The presence of hemorrhage, calcifications or necrosis is
common but nonspecific. Large size, irregular shapes, vague contour, invasion into
surrounding structures and high signal intensity usually denote malignancy. High signal
intensity can be expressed in either Hounsfield units (HU) (with an intensity higher than 10 or
20 units being used as diagnostic threshold) or in signal-lesion (SL) to signal-fat (SF) ratio
(with SL/SF ratio above 1.5 suggesting malignancy). More recently, excellent results have
been observed for the identification of adenomas by 1015-min-delayed enhanced CT, since
that adenomas are characterized by rapid washout of IV contrast. Using this method, a
washout of 4050% is highly suggestive of a benign mass with sensitivity and specificity of
96% and 100% respectively, whereas low washout percentages strongly suggest metastasis
(for an overall accuracy of 96%).
The accuracy of MRI to the differentiation between benign and malignant tumors is
comparable to that of CT scan. Usually, malignant masses are hypointense on T1-weighted
images and hyperintense on T2-weighted images, with strong enhancement after contrast
injection and delayed washout. More recent studies have used the lipid content of
adenomas, which causes a loss in signal intensity on chemical-shift MRI. However, MRI may
be helpful in the diagnosis of pheochromocytoma, where it outperforms CT scanning. High
signal intensity on T2-weighted MRI is suggestive of pheochromocytoma.
Hormonal evaluation
Available evidence suggests that
1. Overnight (1-mg) dexamethasone suppression test and determination of fractionated
urinary and/or plasma metanephrines should be performed. Exceptions will include
patients with imaging characteristics of myelolipoma or an adrenal cyst. The rationale
for
the
1-mg
dexamethasone
suppression
test
is
to
detect
subclinical
361
362
363
10. Thompson NW & Cheung PSY. 1987 .Diagnosis and treatment of functioning and nonfunctioning
adrenocortical neoplasms including incidentalomas. Surgical Clinics of North America 67 423-436.
THYROID INCIDENTALOMA
Introduction
During the past decade, improved technology and increasing use of sensitive, high
frequency ultrasonography has led to the identification of nonpalpable thyroid nodules during
nonthyroidal ultrasonographic examination of the neck . The discovery of one or more
nodules within an otherwise clinically normal thyroid gland raises concern about malignancy
and creates a difficult treatment decision for clinician and patient. These lesions, which are
referred to as "incidentalomas," are small and nonpalpable and are incidentally discovered
on ultrasonography. Although most authorities recommend fine-needle aspiration biopsy for
palpable nodules, the optimal method for treating nonpalpable nodules is a matter of
controversy.
Prevalence
In 1955, Mayo clinic series of autopsy from 821 patients showed that 406 glands
(49.5%) contained one or more nodules; 306 of these (37.3% of 821) were multinodular, and
100 (12.2% of 821) contained single nodules. Of the 406 nodular glands, 144 (35.5%) had
nodules that were larger than 2.0 cm in diameter. In another autopsy series of 215 patients
who did not have thyroid disease,documented nodules in the thyroids of 70 patients (32.5%).
One series reported that in 151 patients with a clinical diagnosis of a solitary thyroid
nodule, ultrasonography showed that 73 (48%) had other nodules. Among the patients in
whom subclinical nodules were discovered on ultrasonography, 49 (67%) had two nodules
and the other 24 (33%) had three or more nodules that had escaped clinical detection. In that
report , 89% of clinically palpable nodules were 1 cm in diameter or larger. In 72% of patients
with more than one nodule, nodules that had not been identified by palpation were smaller
than 1 cm in diameter. In a retrospective analysis,results of clinical examination with those of
ultrasonography and found that only 12 of 32 (38%) clinically "solitary" nodules were truly
solitary on ultrasonographic examination; 15 patients (47%) had several nodules, and 5 had
normal glands.
From these studies, it is clear that thyroid incidentalomas are common in apparently
normal glands and in glands with solitary nodules and that they are detected on thyroid
364
365
larger than 1.5 cm in diameter, a history of head or neck irradiation (particularly in childhood),
a strong family history of thyroid cancer, or ultrasonographic findings that suggest
malignancy, the next appropriate step is ultrasonographically guided biopsy. Treatment
should then be determined on the basis of the cytologic diagnosis. Thyroxine suppressive
therapy is not advisable for either a cytologically proven benign nodule that is larger than 1.5
cm in diameter or a benign-appearing nodule that is smaller than 1.5 cm in diameter
detected ultrasonographically . Therefore, most nonpalpable nodules do not require
immediate treatment and should be followed up simply with palpation. FNAC should be done
if and when the nodules become palpable and managed accordingly.
Suggested reading
1. Rojeski MT, Gharib H. Nodular thyroid disease. Evaluation and management. N Engl J Med. 1985;
313:428-36
2. Scheible W, Leopold GR, Woo VL, Gosink BB. High-resolution real-time ultrasonography of thyroid
nodules. Radiology. 1979; 133:413-7.
3. Carroll BA. Asymptomatic thyroid nodules: incidental sonographic detection. AJR Am J Roentgenol.
1982; 138:499-501.
4. Tomimori E, Pedrinola F, Cavaliere H, Knobel M, Medeiros-Neto G. Prevalence of incidental thyroid
disease in a relatively low iodine intake area. Thyroid. 1995; 5:273-6
5. Komorowski RA, Hanson GA. Occult thyroid pathology in the young adult: an autopsy study of 138
patients without clinical thyroid disease. Hum Pathol. 1988; 19:689-96.
6. Kuma K, Matsuzuka F, Yokozawa T, Miyauchi A, Sugawara M. Fate of untreated benign thyroid
nodules: results of long-term follow-up. World J Surg. 1994; 18:495-8.
7. S. R. Steele, M. J. Martin, P. S. Mullenix, K. S. Azarow, and C. A. Andersen. The Significance of
Incidental Thyroid Abnormalities Identified During Carotid Duplex Ultrasonography. Arch Surg,
October 1, 2005; 140(10): 981 - 985.
366
INTRODUCTION
Organ transplantation, from being an experimental procedure just 50 years ago, has
evolved to become the treatment of choice for end stage organ failure resulting from almost
any of a wide variety of causes. Transplant of the kidney, liver, pancreas, intestine, heart and
lungs has now become common place in all parts of the world. The optimal treatment of end
stage renal failure is transplantation, since it enhances both quality of life and survival
compared with dialysis. The combination of pancreatic and renal transplantation has similar
benefits, whilst transplantation of other organs is truly life-saving since no long-term
biomechanical support is available.
Transplant is the act of transferring an organ, tissue or cell from one place to another.
Transplants are divided into following categories:
Autograft (autologous transplant)
Transplantation of an individuals own tissue to another site, e.g. the use of patients own
skin to cover third-degree burns or a saphenous vein femoro-popliteal graft.
Isograft (syngeneic or isogeneic transplant)
Transplantation of tissue between genetically identical members of the same species e.g.
Kidney transplant between identical twins or grafts between mice of the same inbred strain.
Allograft (allogeneic transplant)
Transplantation of tissue between genetically non-identical member of the same species eg.
Cadaveric renal transplant or graft between mice of different inbred strains.
Xenograft (xenogeneic transplant)
Transplantation of tissue between members of different species e.g. Baboon kidney into a
human.
TRANSPLANT IMMUNOBIOLOGY
It is only after a basic understanding of transplant immunobiology that the obstacle of
transplant rejection can be overcome. The success of transplants today is due in large part
to control of the rejection process, thanks to an ever-deepening understanding of the
immune process triggered by a transplant.
367
As with bodys reaction to an infection, graft rejection is triggered when specific cells of the
transplant recipient, namely T & B lymphocytes, recognize foreign antigens.
Transplant Antigens
The main genes involved in triggering rejection are coded for by a group of genes
known as major histocompatibility complex (MHC). These antigens and hence genes define
the
foreign nature of one individual to another within same species. MHC complex is known
as the human leucocyte antigen (HLA) system. It comprises a series of genes located on
chromosome 6. The HLA antigens are grouped into two classes, which differ in their
structure and cellular distribution. Class I molecules (named HLA-A, B and C) are found on
the membrane of all nucleated cells. Class II molecules (named HLA-DR, DP and DQ) are
generally expressed by antigen presenting cells (APCs) such as B lymphocytes, monocytes
and dendritic cells.
HLA molecules can initiate rejection and graft damage, via either humoral or cellular
mechanism. Humoral rejection occurs if the recipient has circulating antibodies specific to
the donors HLA from prior exposure (i.e., blood transfusion, previous transplant, or
pregnancy), or if post transplant, the recipient develops antibodies specific to the donors
HLA. The antibodies then bind to the donors recognized foreign antigens, activating the
complement cascade and leading to cell lysis. The blood group antigens of the ABO system,
though not part of the HLA system, may also trigger this form of humoral rejection.
Cellular rejection is the more common type of rejection after organ transplants.
Mediated by T lymphocytes, it results from their activation and proliferation after exposure to
donor MHC molecules.
Allorecognition and Destruction
The recognition of foreign HLA antigens by the recipient T-cells is referred to as
allorecognition. This process may occur by either a direct or an indirect pathway. In the
direct pathway, the receipients T cells directly interact with donor HLA molecules, leading to
the generation of activated cytotoxic T Cells. In the indirect pathway the recipients own
APCs first process the donors antigens (which may be shed from the parenchymal cells of
the graft into the recipients circulation, or alternatively may be encountered by the recipients
APC in the graft itself); then the recipients APCs present the donors antigens to the
recipient T cells, leading to the activation of those T cells.
Regardless of the method of presentation of foreign MHC, the subsequent steps are
similar. Binding of the T cells to the foreign molecule occurs at the T-cells receptor (TCR)
368
CD3 complex on the surface of the lymphocyte. This binding leads to transduction of a signal
to the cell, named signal1.
This signal by itself, however, is not sufficient to result in T-cell activation. Full
activation requires transduction of a second signal that is not antigen dependent. Signal 2 is
provided by the binding of accessory molecules on the T-cell to corresponding molecules
(ligands) on the APC. An example is CD 25 on the T lymphocytes binding with its ligand B 7
on the surface of the APC. Transmission of signal 1 and 2 to the cell nucleus leads to
interleukin-2 (IL-2) gene expression and to production of IL-2 cytokine. IL-2 then permits the
entire cascade of T-cell activation to proceed, leading to proliferation and differentiation of
these cells into cells capable of causing damage to the graft. T-cell activation is key in
initiating the rejection process, but B-cell activation and antibody production also play a role.
There are three main types of clinical rejection (explained in relation to kidney transplant)
TYPE
Hyperacute
Rejection
TIME
It occurs from
the time of
revascularisation
of the Kidney to
48 hrs. post
operatively
CAUSE
Pre-existing
antibodies to
donor
antigens
PRESENTATION
Kidney appears
blue and flaccid
urine output ceases
Acute
Rejection
It occurs usually
within 6 weeks
after transplant
Immune
response to
foreign tissue
Fever, malaise
elevated WBC,
acute hypertension
graft tenderness
manifestation of
deteriorating renal
function.
Chronic
Rejection
Occurs months
to year after
transplantation
Antibody
immune
response to
foreign tissue
Progressives
azotemia,
proteinuria,
hypertension,fever,
graft tenderness,
anaemia, malaise
TREATMENT
The transplant
cannot be saved and
the kidney is
removed
Prevent by crossmatching before
surgery.
Treatment is usually
initiated with high
doses of steroid. If
steroids are not
effective, treatment
is instituted with a
monoclonal antibody
called OKT3.
Loss of graft will
occur. Requires retransplantation or
dialysis.
IMMUNOSUPPRESSION
The success of modern transplantation is in large part due to the successful
development of effective immunosuppressive agents. Without these agents, only transplant
between genetically identical individuals would be possible. From just two drugs available in
369
1960s, the therapeutic armamentarium for transplant patients has broadened significantly till
now, with a variety of drug combinations and protocols available. Immunosuppressive drugs
are generally used in combination with others rather than alone.
Induction Immunosuppression refers to the drugs administered immediately posttransplant to
induce
immunosuppression.
Biologic
agents
are
used
for
this.
Maintainance
Immunophilin Binders
a. Calcineurin Inhibitors
i. Cyclosporine
ii. Tacrolimus (FK 506)
b. Noninhibitors of Calcineurin
i. Sirolimus (rapamycin)
II.
Antimetabolites
a. Inhibitors of de novo purine synthesis
i. Azathioprine
ii. Mycophenolate mofetil(MMF)
b. Inhibitors of de novo pyrimidine synthesis
i. Leflunomide
III.
Biologic Agents
a. Polyclonal antibodies
i. ATGAM
ii. Thymoglobulin
b. Monoclonal antibodies
i. OKT3
ii. IL-2R(humanized)
IV.
Others
a. Deoxyspergualin
b. Corticosteroids
c. FTY720
370
II.
Deceased donors
Living donor
DECEASED DONOR
Determination Of Brain Stem Death
Most extrarenal transplant and half of renal transplants are from deceased donor.
Deceased donors meet criteria of brain death, but whose organs are being perfused by lifesupport measures.
Criteria for brain death
When testing for brain death, hypothermia, medication side effects, drug overdose
and intoxication must be excluded.
Management Of Donor
Once the diagnosis of brain death has been established, the process of organ
donation can be initiated. The goal is to preserve organ function and optimize peripheral
oxygen delivery. Donor is provided with
Cardiovascular support
-
ionotropics)
Respiratory support
-
Maintain oxygenation
Hypothermia correction
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Investigations blood group, cytotoxic cross match, tissue type Virology, metabolic profile
Criteria For Donor Selection
Absolute Contraindication for organ donation:
CIS cervix)
Normal urinalysis
2. Liver
Age 0-75yrs
3. Heart
Age 0-65yrs
Normal ECG
Relative CI
-
Prolonged hypotension
Chest trauma
4. Lung
Age 0-60yrs
CXR normal
5. Pancreas
Age 10-45yrs
No h/o DM
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Relative contraindications
-
Gross obesity
PVD
IHD
Procedure
After dissection of the organs to be procured, they are perfused in situ via
Heart and lung are excised followed by liver and pancreas and then kidney.
Adequate length of donor iliac artery is excised for use in reconstructing the arterial
supply of the pancreas
Organs are further flushed with perfusion solution and are then placed in
bags.
LIVING DONORS
Living donors are being used for all transplants except heart transplants
Advantages
1.
2.
4.
Receiving organ from closely matched relative also has immunologic benefit
Disadvantages
1.
2.
0.05% - nephrectomy
Kidney
I.
373
II.
or CT
Procedure
Nephrectomy can be performed by
B)
Flank incision
Anterior approach
Liver
I.
II.
Adult recipient
-
Main complications
C)
Pancreas
Organ preservation
Purpose of organ preservation is to deliver to recipient a viable graft that will exhibit
primary function.
The most common methods involve the use of hypothermia and pharmacologic
inhibition to slow down metabolic process in the organ once it has been removed from
deceased donor.
Effect of cold storage on organs
Hypothermia storage of 4C dramatically reduces metabolic activity by a factor of 1.52 for each 10C fall in temperature.
However, in absence of energy inflow into cells, there is switch from aerobic to
anaerobic metabolism, resulting in accumulation of end products. On reperfusion, these
byproducts generate free radicals resulting in ischaemia reperfusion injury.
374
Hypothermia also contributes to cellular swelling because the membrane ion pumps
are slow to function.
Organ preservation fluids
These fluids have been developed to improve organ preservation by ameliorating
some of the detrimental effects of hypothermia alone.
In principle, chemical composition of preservation fluid is similar to intracellular
electrolytes
They contain impermeants such as sucrose and raffinose and large anions such as
lactobionate or gluconate, which are included to provide osmotic forces and thus limit cell
swelling.
Other principal constituents are buffers which reduce intracellular acidosis and
minimize the loss of potassium from cells.
Preservation time
Liver 16hrs
Pancreas 24hrs
KIDNEY TRANSPLANTATION
A kidney transplant now represents the treatment of choice for patients with end stage
renal disease (ESRD). Very few absolute contraindications to kidney transplant exist.
Therefore, most patients with ESRD should be considered as potential transplant
candidates.
Contraindications to renal transplant:
Strong Contraindications
Relative Contraindications
1.
Unresolved malignancy
1.
Obesity or malnutrition
2.
Ongoing metabolic disease 2.
UTI
3.
Active Sepsis
3.
Severe peripheral vascular disease
4.
Active tuberculosis
4.
Poorly controlled diabetes
5.
Severe vasculitis
5.
Prior malignancy
6.
End stage vascular disease 6.
History of non-compliance
7.
Active AIDS
7.
Inadequate social support
8.
Active Drug Abuse
8.
Life expectancy < 5 years
9.
Active lupus
9.
Emotional instability
10.
Recent MI
10.
Decreased mental capacity
11.
Insufficient financial resource
375
Preoperative Evaluation
Pretransplant evaluation should identify any factors that would contraindicate a transplant or
any risk factors that could be minimized pretransplant. It can be done in four parts.
1. Medical Evaluation
2. Surgical Evaluation
376
3. Immunologic Evaluation
4. Psychosocial evaluation
Surgical procedure
The surgical technique for kidney transplant has changed very little from the original
pelvic operation described in the 1950s.
With the standard approach, the dissection is extraperitoneal (to allow for easy
access for percutaneous renal biopsy).Right iliac fossa is chosen because of more
superficial location of the iliac vein on this side, however, left iliac fossa should be used if the
recipient may be a candidate for future transplant, if it is a second transplant or if there is
significant arterial disease on the right side.
The internal iliac Artery can be used as the inflow vessel, with an end to end
anastomosis, or the external iliac Artery can be used with an end to side anastomosis.
The donor renal vein is anastomosed end to side to the external iliac vein.
After the vascular anastomosis is completed and the kidney perfused, urinary
continuity can be restored by a number of will described techniques. (The important principle
is to attach the ureter to the bladder mucosa in a tension free manner and to cover the distal
1cm of ureter with a submucosal tunnel, thus protecting against reflux from voiding).
Early Postoperative Care
The immediate post operative care of all recipients involves
Stablizing the major organs systems (eg. Cardiovascular, pulmonary and renal).
377
Optimize immunosuppression.
Screen and monitor for complications that are directly or indirectly related to
immunosuppressive medications.
Results
1 and 5 year Graft survival rates from deceased donor are 88% and 63% respectively and
from living donor are 94% and 76% respectively.
Complications
Potential complications include
1.
2.
3.
4.
5.
Current Concepts
The dramatic improvement in outcomes for renal transplant has made it the renal
replacement modality of choice for virtually all patients with ESRD.
Renal transplantation, even with marginal kidneys is cost effective and cost efficient
as compared to dialysis.
The disparity between the demand for and the supply of available organs has led to
acceptability of more and more borderline donors:
Ectopic kidney
378
HTN
PANCREAS TRANSPLANTATION
Diabetes mellitus is a very common medical condition with immense medical, social
and financial costs. However, even though exogenous insulin can prevent the acute
metabolic complications and decrease the incidence of secondary complications associated
with diabetes, it cannot provide a homeostatic environment comparable to that afforded by a
functioning pancreas. Only a functioning pancreas can provide immediate insulin responses
to the moment to moment changes in glucose levels.
A successful pancreas transplant can establish normoglycemia and insulin
independence in diabetic recipients. A pancreas transplant also has the potential to halt
progression of some secondary complications of diabetes and can substantially enhance the
quality of life, more than that achieved by exogenous insulin administration. Currently the
main drawback of a pancreas transplant is the need for immunosuppression. Pancreatic
transplants are now preferentially performed in diabetic patients with kidney failure who are
also candidates for a kidney transplant, as they already require immunosuppression to
prevent kidney rejection. However, a pancreas transplant alone (PTA) is appropriate for non
uremic diabetics if their day to day quality of life is so poor (e.g. Labile diabetes with
ketoacidosis and / or hypoglycemic episodes, or progression of severe diabetic retinopathy,
nephropathy, neuropathy and / or enteropathy) that chronic immunosuppression is justified
to achieve insulin independence.
Pre-operative evaluation
Pre-operative evaluation for pancreas transplant recipients does not differ
substantially from that for diabetic kidney transplant recipients. Examination of the
cardiovascular system is most important which includes coronary angiography. Detailed
neurologic, ophthalmologic, metabolic and kidney function testing may be needed to assess
the degree of progression of secondary complications.
Once a patient is determined to be a good candidate for a pancreas transplant, with
no obvious contraindications, it is important to decide which type of pancreas transplant is
best for that individual. First the degree of kidney dysfunction and the need for a kidney
transplant must be determined. Patients with stable kidney function are candidates for PTA.
379
However patients with moderate kidney insufficiency will likely require a kidney transplant as
well.
For patients requiring both a kidney and a pancreas transplant, various options currently
possible are:
1. Deceased-donor, simultaneous pancreas- kidney transplant (SPK)
It is the most common option worldwide. The recipient has the advantage of
undergoing both transplants at the same time. There is immunologic advantage,
as acute rejection rates are significantly lower for SPK( versus PTA) recipients.
2. Living-donor kidney transplant, following weeks to months later by a deceased
donor pancreas transplant( pancreas after kidney (PAK) transplant)
Advantages are that if a living donor is available for the kidney transplant, then this is
a good option for uremic diabetic patients and by performing the two operations
sequentially instead of simultaneously, the overall surgical complication risk may be
decreased. Disadvantage is that the long term pancreas graft survival rates for PAK
recipients are somewhat inferior to SPK transplants.
3. Simultaneous deceased-donor pancreas and living-donor kidney transplant(SPLK)
Candidates with a suitable living donor for the kidney transplant who have not yet
progressed to dialysis can be placed on the deceased donor pancreas transplant
waiting list. Advantages are use of living donors for the kidney, shorter waiting times
and single operation. Disadvantages are that it is technically more difficult to
organize, as it requires using two full surgical teams and two full operating rooms. It
may also create difficult timing issues for the living donor, who must come in quickly
for an emergent operation.
4. Living-donor, simultaneous pancreas-kidney transplant
It is a potential option which is especially useful for candidates with a high level of
preformed antibodies. Disadvantage is the difficulty in arranging a single individual
suitable to donate both kidney and hemipancreas. It also involves the substantial
surgical risk to the living donor.
Surgical Procedure
The initial preparation of the donor pancreas is a crucial component of a successful
transplant. Direct physical examination of the pancreas often is the best or the only way to
confirm its suitability. Before implantation, a surgical procedure is carried out to remove the
spleen and any excess duodenum and to ligate blood vessels at the root of mesentery. The
inflow vessels to the graft are the splenic and superior mesenteric arteries; outflow is via the
portal vein. Arterial reconstruction is performed before implanting the graft into the recipient.
380
The donors superior mesenteric and splenic arteries are connected, most commonly using
reversed segment of donor iliac artery as a Y-graft; doing so allows for a single arterial
anastomosis in the recipient.
The pancreas graft is then implanted via an anastomosis of the aforementioned arterial
graft to the recipients common iliac artery or distal aorta, and, via a venous anastomosis of
the donor portal vein to the recipient iliac vein (for systemic drainage), or to the superior
mesenteric vein (for portal drainage). If both a kidney and a pancreas are transplanted, they
are placed in a intraperitoneal position, with the kidney usually in the left iliac fossa and
pancreas in the right iliac fossa. Once the pancreas is revascularized, a drainage procedure
must be performed to handle the exocrine pancreatic secretions. Options include
anastomosing the donor duodenum to the recipient bladder or to the small bowel.
Bladder drainage
Main advantage is the ability to directly measure enzyme activity in the pancreatic
graft exocrine secretions by measuring the amount of amylase in urine. The leak rate
is the same whether pancreas is drained to the bladder or to the bowel, but the
consequences of a bladder leak are much less severe than those associated with
bowel leak. Disadvantages are complications such as dehydration and acidosis and
local problems with the bladder such as hemorrhage, infection and stones.
Enteric drainage
It is more physiologic and has fewer long term complications. Disadvantage is that
the ability to monitor for rejection is decreased, as urinary amylase is absent.
Rejection in SPK transplant recipients always affects both the kidney and pancreas
and serum creatinine levels can be used as a marker in such cases. Hence enteric
drainage is preferred for SPK transplants. If kidney and pancreas are from different
donors or if a PTA is performed, then bladder drainage is preferred.
for
which
transplantation
of
exocrine
pancreas
appears
unnecessary.
381
Patient Selection
C-peptide negative
Donor criteria
Donor criteria for islet isolation are similar to those for solid pancreas transplantation.
Surgical technique for removal of pancreas is also same as that for solid pancreas
transplantation i.e., keeping capsule intact to avoid handling of the pancreas.
Islet isolation is a complex process and involves
Resulting purified islet preparation is then washed, counted and assayed to make
sure it meets product release criteria.
Surgical procedure
Purified islet cells are injected into the portal vein of the recipient. Portal vein is cannulated
either under radiologic guidance or at laparotomy via a mesenteric or omental vein. Islet
cells then engraft in the hepatic parenchyma and secrete Insulin, which drains into the
circulation.
Complications
Portal Hypertension
Hepatic abscess
Bacteremia
382
Disadvantages of the procedure is the need for long term immunosuppression and islet cell
rejection can be difficult to monitor and diagnose. One possible method of avoiding
immunosuppression is to surround the islets with a semipermeable membrane, process
called as microencapsulation. The process allows small molecules such as glucose and
oxygen to reach islet cells and would allow insulin to reach systemic circulation from there
but would prevent immune cells and large molecules such as antibodies from reaching the
islet cells. Significant improved results have also been reported by using steroid free
immunosuppression and injecting islet cells from multiple donors.
These recent success reports have stimulated a flurry of islet transplant activity at centers
across the world.
LIVER TRANSPLANTATION
The field of liver transplantation has undergone remarkable advances in the last two
decades and from essentially an experimental procedure in the early 1980s, a liver
transplant is now the treatment of choice for patients with acute and chronic failure. Patient
survival also at 1 year post-transplant has increased from 30% in 1980s to more than 85% at
present.
The major reasons for this change include refined surgical and preservation
2.
Ascitis, and / or
Marked asthenia
383
3.
Cirrhosis
Biliary atresia
LT indicated when
4.
Liver failure
B.
Age
Serum bilirubin
Controversial indications
5.
No viral replication
Routine
prophylaxis
with
anti-HBs
immunoglobulin
postoperatively
6.
7.
Alcohol cirrhosis
Accepted indication if:
8.
Hepatocellular carcinoma
Accepted indication if:
without transplantation)
9.
384
10.
Hemochromatosis
Wilsons disease
1-antitrypsin
deficiency
Tyrosenemia
Cystic fibrosis
Cryptogenic cirrhosis
Amyloidosis
Patients with well compensated cirrhosis are not candidates for transplant. It is only patients
with de-compensated cirrhosis who have poor prognosis without a transplant. Signs and
symptoms of de-compensated cirrhosis are:
1.
Hepatic encephalopathy
2.
Ascitis
3.
4.
5.
Hepatorenal syndrome
2.
3.
4.
5.
Cholangiocarcinoma
6.
7.
HIV infection
8.
Sepsis
9.
Malignancy
10.
Preoperative Evaluation
Once the indications for a transplant and the absence of contraindications have been
established, a careful search for underlying medical disorders of the cardiovascular,
pulmonary, neurologic, genitourinary and gastrointestinal systems must be made. Serologic
evaluation to screen for the presence of underlying viral infections is important. Unique to
385
patients with chronic liver disease, the pretreatment evaluation must assess for any
evidence of hepatopulmonary syndrome, pulmonary hypertension and hepatorenal
syndrome.
Though hepatorenal
386
387
Older donors
Steatotic grafts
As a rule, these alternatives best suit good-risk recipients. Patient in poor general at the time
of transplantation should receive optimal grafts.
Postoperative Care
The immediate postoperative care for liver transplant involves:
Stabilizing the major organ systems (e.g., cardiovascular, pulmonary, and renal)
Evaluating graft function and achieving adequate immunosuppression
Monitoring and treating complications directly or indirectly related to transplant
Results
Liver transplantation is an established treatment for acute and chronic liver disease, with 5year survival rates > 70% for most indications.
INTESTINAL TRANSPLANTATION
Least frequently performed of all transplants with the highest rejection rate and the lowest
graft survival rates.
Why intestinal transplant not increased?
Medical alternative exist for patients with intestinal failure, namely, long term TPN.
Intestinal lumen is filled with potential infective pathogens that can gain access to
the recipients circulation if there is mucosal breakdown. ( which can occur during
acute rejection episode)
388
Indications
Irreversible intestinal failure that is not successfully managed by TPN or has life
threatening complications (e.g. hepatic dysfunction, recurrent sepsis due to central access)
Currently patients who are stable while receiving TPN without such complication are
generally not considered to be suitable transplant candidates because their estimated
annual survival rate is higher with TPN.
Contraindications
Malignancy
Active infection
Donor
Graft may be from living or deceased donor.
Living donor- 200 cm of distal small bowel is used. Inflow to graft is made via
ileocolic artery and outflow via ileocolic vein.
For combined liver and intestinal transplant, graft is procured intact with an aortic conduit
that contains both celiac and superior mesenteric artery.
Recipient
Infrarenal aorta can be used as the inflow vessel and venous drainage is via portal
vein. GI continuity can be achieved through various methods.
Stoma is made for endoscopic access to perform biopsy which is only reliable
method to monitor or diagnose rejection.
Results and Complications
1 and 3 year graft survival rates are 60% and 40% respectively.
Potential complications include- enteric leak, abdominal abscess, respiratory infections and
life threatening hemorrhage.
Most of mortality after small bowel transplantation is due to sepsis and multiorgan failure.
FUTURE OF TRANSPLANT
Problems with current status of transplant
Requirement for long term or life long Immurosuppression and its complications like
malignancies and infections.
389
Tolerance
Development
of
state
of
donor
specific
hyporeactivity
in
absence
of
immunosuppressive medications.
Xenotransplantation
Hindrances are
- Formidable immunologic barrier between species.
- Risk of transmission of infections (zoonoses).
- Ethical problems.
Successful xenotransplants for humans would probably involve use of the Pig.
Cellular transplant
Involve the injection of cells that have the potential to replace cells in an organ that has
been damaged by disease
Organogenesis
Growing organs de novo from primitive cells or stem cells.
References
1.
Ball ST, Dallman MJ. Transplantation immunology. Curr Opin Nephrol Hypertens
1995; 4 : 465.
2.
John L.R.Forsythe.Transplantation : A Companion to Specialist Surgical Practice. 3
Edition Elsevior Saunders 2005.
rd
3.
Rose SM, Turka L, kerr L et al. Advances in immune-based therapies to improve solid
organ graft survival. Adv Intern Med 2001; 47: 293.
4.
Vander Werf WJ, D;Alessandro Am, Hoffmann RM et al. Procurement, preservation
and transport of cadaver kidneys. Surg Clin North Am 1998; 78: 41.
5.
DAlessandro Am, Southard JH, Love RB et al. Organ preservation. Surg Clin North
Am 1994; 74 : 1083.
6.
Schaubel D, Desmeules M, Mao Y, et al. Survival experience among elderly endstage renal disease patients. A controlled comparison of transplantation and dialysis.
Transplantation 1995; 60 : 1389.
7.
Wolfe RA, Ashby VB, Milford DL, et al. Comparison of mortality in all patients on
dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric
transplant. N Engl J Med 1990; 341 : 1725.
th
8.
Bunicardi FC, et al. Schwartzs Principles of surgery. 8 Edition Mcgraw Hill medical
publishing division. 2005. 295-332.
9.
Kasiske BL, Ramos EL, Gaston RS et al. The evaluation of renal transplant
candidates: clinical practice guidelines. J Am Soc Nephrol 1995; 6 : 1.
390
10.
Terasaki PI, Cecka JM, Gjertson DW et al. High survival rates of kidney transplants
from spousal and living unrelated donors. Engl J Med 1995; 333 : 333.
11.
Friedman A. Strategies to improve outcomes after renal transplantation. N Engl J
Med 2002; 346 : 2089.
12.
Matas AJ, Humar A, Payne WD et al. Decreased acute rejection in kidney transplant
recipients is associated with decreased chronic rejection. Ann Surg 1999; 230 : 493,
Discussion 498.
13.
Sutherland DE, Gruessner RW, Najarian JS et al. Solitary pancreas transplants. A
new era. Transplant Proc 1998; 30 : 280.
14.
Humar A, Ramcharan T, Kandaswamy R. et al. Pancreas after kidney transplant Am
J Surg 2001; 182 : 155.
15.
Farney AC, Cho E, Schwitzer E et al. Simultaneous cadaver pancreas living donor
kidney transplantation : A new approach for the type 1 diabetic uremic patient. Ann Surg
2000; 232 : 696.
16.
Krishnamurthi V, Philosophe B, Bartlett ST. Pancreas transplantation. Contemporary
surgical techniques. Urol Clin North Am 2001; 28 : 833.
17.
Humar A, kandaswamy R, Granger D et al. Decreased survival risks of pancreas
transplantation in the modern era. Ann Surg 2000; 231 : 269.
18.
McChesney LP. Advances in pancreas transplantation for the treatment of diabetes.
Dis on 1999; 45 : 88.
19.
Wiesner RH. Current indications, contraindications and timing for liver transplantation
in Busutill RW, Klintmalm GB (eds). Transplantation of the Liver, Philadelphia WB Saunders
1996, p.71.
20.
Fan ST, Lo CM, Liu CL. Technical refinement in adult-toadult living donor liver
transplantation using right lobe graft. Ann Surg 2000; 231 : 126.
21.
Humanr A, Ramcharan T, Sielaff T et al. Split liver transplantation for 2 adult
recipients. An initial experience. Am J Transplant 2001; 1 : 366.
22.
Everson GT, Kam I. Immediate postoperative care, in Maddrey WC, Schiff ER, Sorrell
MF (eds). Transplantation of the Liver. Baltimore Lippincott Williams and Wilkins, 2001, p.
131.
23.
Buchman Al, Scolapio J, Fryer J. AGA technical review on short bowel syndrome and
intestinal transplantation. Gastroenterology 2003; 123 : 111.
24.
Kato T, Ruiz P, Thompson JF et al. Intestinal and multivisceral transplantation. World
J Surg 2002; 26 : 226.
25.
Abu-Elmagd K, Bond G, Reyes J et al. Intestinal transplantation coming of age. Adv
Surg 2002; 36 : 226.
26.
Dooldeniya MD, Warrens AN. Xenotransplantation. Where are we today? J R Med
2003; 96 : 111.
391
Hodgkins Disease
S.K.Jain, Amit Gupta
Maulana Azad Medical College, New Delhi,
NATURAL HISTORY AND CLINICAL PRESENTATION
More then 80%of patients with HD present with cervical lymph node involvement and
more then 50% have mediastinal disease.
Some patients may note systemic symptoms such as unexplained fevers, drenching
night sweats weight loss, generalized pruritus , and alcohol-induced pain in tissues
involved by HD.
The theory of contiguity of spread and the development of treatment programs, including
presumptive treatment of uninvolved sites, were important conceptual advances in the
treatment of HD.
Nearly all patients with hepatic or bone marrow involvement by HD have extensive
Involvement of the spleen.
One third of patients present with one of the three B symptoms: fever, night sweats, or
10% weight loss in the past 6 months. Fevers may present in the classic waxing and
waning PEL-Epstein pattern. Night sweats may be drenching, requiring a change of
bedclothes.
HD may be diagnosed during pregnancy, and many women become pregnant after
successful treatment.
DIAGNOSTIC WORKUP
Diagnostic and staging procedures commonly used for HD are listed in Table 52 -1.
Important factors such as patient age and presence of concurrent disease influence the
selection of staging studies.
The retroperitoneal lymph nodes are best evaluated by bipedal lymphangiography, the
sensitivity; specificity& overall accuracy of the lymph angiogram are 85 %, 98%, and
95%, respectively. The lymph angiogram is especially helpful for sub diaphragmatic
presentation: however, it is generally not available outside major academic centers &
not useful but still used in some centers in 1. Design of radiation portals 2. in detection of
sub diaphragmatic disease 3. Follow up of patients after completion of chemotherapy.
Computed tomography (CT) scan is less sensitive, specific, and accurate (5%, 92%, and
87%, respectively) for detection of disease in the retroperitoneal nodes.
392
High dose gallium (8-10mci) with single-photon emission CT provides the most
valuable images and may be most helpful in evaluation of the mediastinum or hilar
nodular involvement
Approximately two-thirds of patients who have positive restaging gallium scans after
completion of chemotherapy have a relapse, compared with less than 20% of those
with negative studies.
There are more data available about FDG-PET in the initial staging of non-Hodgkins
lymphoma than for HD. It seems a reliable technique for detection of bone marrow
involvement. The published data indicate that PET is highly sensitive, at least for
differentiating residual fibrosis and a viable tumor. Some canters are increasingly using
PET scan in initial evaluation & to monitor response. Persistently positive scans can
allow the early identification resistant or residual disease.
The primary role of staging laparotomy is in patients who are candidates for treatment
with irradiation alone i.e. early stage disease
393
Radiological studies
Standard
Chest radiograph: poster anterior and lateral
Computed tomography of thorax for disease detection and treatment planning
purposes
Computed tomography of abdomen and pelvis
Complementary
Bipedal lymphangiography is unnecessary if multi agent chemotherapy is used as
part of standard approach
Gallium scan
Special tests
Standard
Cytological examination of effusions, if present
Bone marrow, needle biopsy (if sub diaphragmatic disease or presence of B
symptoms or anemia or leucopenia or thrombocytopenia)
Optional
Per cutaneous liver biopsy
Peritoneo-scopy
Staging laparotomy with splenectomy, liver biopsy, selected lymph node
biopsies, and Open bone marrow biopsy only in cases of early HD where
treatment alone with irradiation is planned.
Chemotherapy (children, the elderly. Any person with intercurrent medical problem, bulky
mediastinal disease, clinical stage III to IV disease or marrow involvement).
Lowrisk populations for sub diaphragmatic extension are(a) patients with clinical disease
limited to intrathoracic sites (yield approximately0%) (b) woman with stage I disease (yield
approximately 6%), (c) men with stage I disease and lymphocyte predominance or inter
follicular histology (yield approximately 4%), and (d) woman with stage II disease and with
three or fewer sites of clinical involvement and who are younger then 27 years of age (yield
approximately 9%).
STAGING SYSTEM
The Ann Arbor staging system for HD. Used since 1971 is outlined in Table -2. The
Lymphoid regions defined in this system are shown in Figure -1.
The Ann Arbor system includes designation of a clinical stage, based on the result of the
Initial biopsy and clinical staging studies, and a pathologic stage, based on the result of
any subsequent biopsies.
Inadequacies of the Ann Arbor system include failure to consider bulk of disease and
lack of a more precise of the E lesion
394
Description
II
III
IV
Note : Absence or presence of fever, night sweats, or unexplained loss of _ >10% of body
weight the 6 months before diagnosis is denoted by the suffix letter A or B, respectively,
Patients are assigned a clinical stage based on the initial biopsy and all subsequent non
surgical staging sub staging procedures such as bone marrow biopsy, staging laparotomy,
and splenectomy,
PATHOLOGIC CLASSIFICATION
- They secrete power cytokines including IL1, IL6, TNF & activated nuclear factor kappa
(NFkB)
395
FIG 1. Lymphoid region as defined in the Ann Arbor staging system, notes that the cervical,
supraclavicular, occipital, and preauricular nodes are included in a single region. The mediastinum
and
pulmonary
hila
make
up
three
regions.
from
Hoppe
RT.
The
non-Hodgkins
lymphomas:pathology, staging, and treatment. Curr Probl Cancer 11:379,1987, with permission.)
FREQUENCY
Age adjusted incidence: - 2.7 cases per 100000 populations.
Accounts for 2 percent of neoplasm affecting the general population.
More common in males.
85 % of cases in pediatric age group are m,ales.
Bimodal age distribution in both sexes peaking in young adults (aged 15-34 years) & older
individuals (more than 85 years )
Cellular Classification
Five histologic subtypes of HD are defined by WHO modification of the Revised
European American Lymphoma (REAL) classification..
1. Lymphocyte rich classic Hodgkins disease (5%) is often diagnosed in young
people. Patients Frequently present with early- stage disease, and systemic
symptoms are uncommon(less then 10%) the natural history is the most favorable of
the histological subtypes.
396
After the extent of disease has been determined, histologic subtype seems to have little
additional impact on prognosis.
Ann Arbor stage is the most important prognostic factor influencing therapy.
GENERAL MANAGEMENT
Radiation Therapy
Irradiation is the most effective single agent for the treatment of patients with HD. Actual
relapse-free survival at 5 years for all stages ranges from 94% to 45%.
Chemotherapy
397
mustard),
vincristine
sulfate
(oneovin),
procarbazine
Combined-modality therapy has the advantage of treating all sites of disease at the
outset (especially important in stage III or IV), in addition to reducing bulky disease to
facilitate subsequent irradiation (especially in the mediastinum).
For patients with relatively limited disease, management with staging laparotomy and
sub total lymphoid irradiation is being challenged by programs using clinical staging only
followed by treatment with chemotherapy alone or combined-modality therapy.
HODGKINS DESEASE
and adjuvant radiotherapy for Partial response or after Complete response, followed by
peripheral blood stem cell support. The usefulness of radiotherapy after chemotherapyinduced complete remission is not yet established.
RADIATION THERAPY TECHNIQUES
Evenly weighted opposed-field treatments are generally used: all fields are treated daily
with fractions of 1.5 to 1.8 Gy.
Mantle
398
The field extends from the inferior portion of the mandible nearly to the level of the
insertion of the diaphragm.
In addition to lung blocks, blocks can be placed over the occipital region and spinal
Cord posteriorly, the larynx anteriorly, and the humeral heads both anteriorly, and
posteriorly.
Spinal cord shielding may not be necessary with compensated fields if the prescribed
Tumor does is only 36Gy, but should be used when the prescribed does is more then
40Gy.
For significant mediastinal disease with sub carinal extension or pericardial involvement
the entire cardiac silhouette is irradiated to 15 Gy, with a black placed over the apex of
the heart thereafter.
After a dose of 30 to 35Gy has been delivered, a block is placed in the sub carinal region
(approximately5cm below the carina), shielding additional pericardium and myocardium.
If the pulmonary hilar lymph nodes are involved and a patient is being treated with
irradiation alone, a37% transmission lung block can be used to deliver 15.0to16.5Gy to
the lung.
When the mediastinal mass is large , treatment may be given slowly (1.25 to 1.50 Gy per
day to a total dose of 15Gy). Therapy is interrupted for 7to 14 days to permit further
regression of disease and redesign of the lung block.
Pre-auricular Field
The pre-auricular field can be treated with opposed lateral or unilateral photons or,
preferably, with a unilateral 6-to 9-Me V electron filed to spare the contra lateral Parotid.
In some cases, the primary site of enlarged nodes may include bulky high cervical
nodes, which extend very near the upper border of the typical mantle field. In this setting
large, Opposed lateral Waldeyr fields can be used to encompass the upper cervical and
adjacent
The classic sub diaphragmatic irradiation field for HD is the inverted Y which includes the
retroperitoneal and pelvic lymph nodes.
For retroperitoneal nodes only, the inferior border of the sub diaphragmatic field is drawn
at the L4-5 Interspace (para aortic/splenic pedicle field ) or below the bifurcation of the
aorta to include the common iliac nodes (spade field).
399
If the spleen is intact, the entire spleen, not just the splenic hilar region, is included in the
field action. When the sub diaphragmatic field does not include the pelvis, the term
subtotal lymphoidbe irradiation is used
Low dose hepatic irradiation may be used for splenic involvement if irradiation alone is
being used as primary treatment or in combined modality programs when the liver is
involved .A 50% transmission block delivers 20 to 22 Gy to the liver during the same
period in which the Para-aortic nodes receive 40 to 44 Gy.
In women, the ovaries normally overlie the iliac lymph nodes. To avoid radiation
induced amenorrhea, an oophoropexy must be performed. The surgeon marks the
ovaries with radiopaque sutures or clips and places them medially and as low as
possible behind the uterine body. A double thickness (10 half-value layer) midline block
is then used; its location is guided by the position of the opacified nodes and transposed
ovaries. When the ovaries are at least 2 cm from the edge of this block, the dose is
decreased to 8% of that delivered to the iliac.
Use of a double-thickness midline block and specially constructed testicular shield can
reduce testicular dose from 10% to from 0.75% to 3.00%.
Most patients with stage I to II disease can be managed effectively with irradiation alone
90% of these patients have supradiaphragmatic disease.
Eligibility criteria include one or two sites of disease only, no bulky mediastinal
involvement, and asymptomatic status with erythrocyte sedimentation rate less than 50
mm per hour or B symptoms with erythrocyte sedimentation rate less than 30 mm per
hour.
If Staging includes a laparotomy, patients with pathologic stage IB or IIB can be treated
effectively with irradiation alone.
400
For people older than 65 to 70 years of age, treatment should be tailored to respect their
quality of life without threatening their
normal survival. Although late effects of
treatment are the major problem in childhood, it is immediate intolerance that is
problematic in the elderly.
HD is diagnosed during
pregnancy because
If there is limited disease (e.g., stage IA), an involved field irradiation (neck-field) could
allow staging to be postponed until delivery.
During the final three months, fetal development is advanced enough to allow an induced
premature delivery or to wait a few weeks until childbirth. A close discussion with the
pediatrician and the obstetrician allows the adequate moment for the delivery to be
chosen.
Some chemotherapeutic agents do not cross the placenta (e.g., vincristine suflate or
vinblastine sulfate), and may be useful if treatment is necessary.
The pathologic pattern is different, with a high frequency of mixed cellularity type, and
the response to chemotherapy is not as good as in human immunodeficiency virusnegative patients. Three major prognostic factors are no acquired immunodeficiency
syndrome before HD diagnosis, CD4 counts more than 250 to 300, and response to HD
treatment.
FOLLOW UP
401
SEQUELAE OF TREATMENT
Radiation pericarditis after well executed mantle therapy is seen is less than 5% of
patients and can be managed with conservative medical treatment.
A staging laparotomy is not indicated in patients with stage I or II Hodgkins Disease with
Bulky Mediastinal Involvement if combined modality therapy is planned.
The recommended dose of radiation varies from 25 to 40 Gy, but most data cite radiation
doses or at least 36 Gy.
The irradiation fields should confine to the area of residual disease with adequate margin
not the initial volume of disease before chemotherapy.
402
If the iliac nodes are involved, a staging laparotomy may be performed to define
appropriate therapy more precisely.
In general, the outcome of treatment for patients with subbiaphragmatic disease is same
to that for patients with supra-dlaphragmatic disease.
Only the most favorable subgroup of stage IIIA Patients, those with anatomic subsutie III
A
Most patients with stage IIIA disease may be treated effectively with combined modern
therapy.
Systemic chemotherapy is the mainstay of treatment for patients with advanced stage
References
403
1. Biti GP, Cimino GP, Cimino G, Cartoni C, et al. Extended- field radiotherapy is superior to
MOPP chemoder for the treatment of pathologic stage I-IIA Hodgkins disease: 8 years
update of an Italian protective randomized study. J Clin Oncol 1992;10:378-382.
2. Carbone pp, Kaplan HS, Musshoff K. Report of the Committee on HodgkinsDisease
staging sification. Cancer Res 1971:1:1860-1861.
3. Castellino RA, Hoppe RT, Blank N, et al. Computed tomography, lymphography, and
stagine arotomy: correlations in initial staging of Hodgkin disease . AJR Am J Roentgenol
1984;143-37.
4. Connors JM, Klimo p. is it an E lesion or stage IV? An unsettled issue in Hodgkins
deseaes steging J Clin oncol 1984;2:1421-1483.
5. De Vita VT Jr, Hubbard SM, Longo DL. The chemotherapy of lymphomas:looking back
me forward: the Richard and Hinda Rosnthal Foundation Award lecture, Cancer Res
1987;47-5824.
6. Duhmke E, Diehi V,Loeffler M, et al, Randomized trial with early stage Hodgkins
desease 30 Gy vs. 40 Gy extended- field radio0therapy alome. Int J Radiat Oncol Biol
Phys1996;36-305
7. Eghbali H, Soubeyran P, Tchen N, et al. Current treatment of Hodgkin disease. Crit Rer
Hematol 2000;35(I):49-73.
8. Fabian CJ, Mansfield P, Tchen N, et al. Low dese involved field radiation after in
advanced Hodgkin disease: a Southwest Oncology Group randomized study.Ann
1994:120;903-912.
9. Font D , Israel O. The role of Ga-67 scintigraphy in evaluation the result of therapy of
lympathy patients. Semin Nuel Med 1995;25:60-71.
10. Glatstein E, Trueblood HW, Enright LP, et al, Surgical of abdominal involvement lected
patients with Hodgkins disease. Radiology 1970;425-432.
404
Gastrointestinal Lymphoma
Narinder Teckchandani
Prof. N.S.Hadke
405
involvement of the contiguous lymph nodes necessitating direction of treatment to that site.
It was Dawson et al who first established the criteria for diagnosing primary GI lymphoma5 :
1) absence of palpable peripheral lymphadenopathy on general physical examination.
2) normal peripheral blood smear and bone marrow biopsy.
3) absence of mediastinal lymphadenopathy on chest X-ray.
4) disease grossly confined to the affected small bowel segment as confirmed by diagnostic
imaging, endoscopy or laparotomy.
5) regional lymphadenopathy only.
6) absence of hepatic or splenic tumour involvement except via. direct extension from the
primary bowel involvement.
The lymphoid tissue of the gut is termed mucosa-associated lymphoid tissue (MALT).
Malignant transformation of any of the immune cell types in gastrointestinal lymphoid tissue
leads to lymphoma of this tissue. Usually this lymphoma arises from B cells derived from the
MALT marginal zone. Thus, the term MALT lymphoma has become synonymous with
marginal zone B cell lymphoma. Lymphomas that arise from gastrointestinal lymphoid tissue
but do not have marginal zone features are designated as particular clinicopathologic entities
using the terminology of the REAL classification.6
Gastrointestinal lymphomas most commonly involve the stomach or small intestine,
although the oral pharynx, esophagus, colon, or rectum may be involved uncommonly. In
developed countries, the stomach is the most common site of involvement (approximately
60% of cases) but in the Middle East, the small intestine is the most common site of
gastrointestinal involvement.7
STAGING:
Ann Arbor staging with Musshoff and Blackledge modifications is used for staging of primary
intestinal lymphomas:8
Stage I: Limited local disease confined to intestine.
Stage II: Intestinal lymphoma confined below the diaphragm. It is subgrouped as:
II 1: Regional lymph node involvement
II 2: Distant lymph node involvement
StageIII: Intestinal lymphoma with involvement on both sides of diaphragm.
StageIV: Widespread dissemination including the liver, spleen and the bone marrow.
406
The diagnosis of lymphoma requires expert pathologic study. Sufficient tissue should
be obtained for analysis. In the gastrointestinal tract this often means multiple endoscopic
biopsies, laparotomy or laparoscopy. Fine needle aspiration alone does not provide
adequate tissue for complete classification. Pathologic workup should include light
microscopy and immunophenotypic analysis.8
It should be noted that the best treatment for many gastrointestinal lymphomas
remains controversial. Whereas many large controlled trials have defined precisely the best
treatment for many nodal lymphomas, this is not the case for gastrointestinal lymphomas.
The treatment recommendations for GI lymphomas are usually based on small case series
or extrapolation from results with nodal lymphomas and traditional practices.7
With these general principles applying to all GI lymphomas, we proceed to discussion
of site-specific clinicopathologic varieties.
GASTRIC LYMPHOMAS
These are mostly B cell lymphomas, and lymphomas of T cell origin have rarely been
reported.
a) Marginal zone B cell lymphoma of MALT: It represents approximately 40% of gastric
lymphomas. The incidence varies according to the incidence of H. pylori in the
population being assessed.
Gastric tissue does not normally contain MALT but may acquire it in response to chronic
H. pylori infection. Malignant transformation occurs in a small percentage of patients with
acquired gastric MALT and results in a lymphoma with generally indolent behaviour.9
Eradication of the infection with anti- H. pylori drugs leads to regression of this lymphoma
in most cases.9
Under the REAL classification system of lymphomas, this variety of NHL is termed
extranodal marginal zone B cell lymphoma, but the disease is still commonly referred to
as gastric MALT lymphoma or primary low-grade gastric B cell lymphoma.8
The clinical symptoms often simulate those of gastritis or benign peptic ulcer. As would
be expected in a tumour that requires chronic inflammatory activity induced by H. pylori,
the peak incidence of gastic low-grade MALT lymphoma is in the sixth and seventh
decades.9
Low-grade gastric MALT lymphomas are most commonly located in the antrum
(41%) but may be multifocal in 33% of cases. Lesions may appear as ulcers (in
407
47% of cases), erosions (in 23%), or simply as erythema (in 30%). 10 The mucosa
involved by this lymphoma is often relatively flat but often the endoscopist demonstrates
relatively subtle features such as nodulation, rugal fold thickening and/ or non-specific
gastritis. By the same token, macroscopic examination by the pathologist at the time of
resection may be relatively unrewarding, with a flat, somewhat firm and infiltrated lesion
being the only demonstrable abnormality. Deep infiltration, mass formation and
ulceration are usually not a substantial feature of this disease.11 Grossly, advanced
cases present as giant convolutions mimicking hypertrophic gastritis or gastric polyps.
One particular property of low-grade MALT lymphoma of the stomach is multifocality.
Whilst there may be a pre-dominant lesion, small foci of lymphoma can often be
demonstrated remote from the main mass. This multifocality is of importance in those
cases treated by surgery. Absence of demonstrable tumour at resection lines, in a partial
gastrectomy specimen, does not guarantee complete excision.12 The diagnosis of lowgrade MALT lymphoma of the stomach demands extensive biopsy mapping at the time
of endoscopy to detect such multifocality. If surgery is contemplated, the multifocality
may well be an indication for total gastrectomy.
Antibiotics aimed at eradicating H. pylori have become the mainstay of the therapy for
low-grade gastric MALT lymphoma and the current literature is sufficient to suggest that
more toxic therapies such as radiation, chemotherapy, or surgery be reserved for
disease not responding to antibiotics or for more advanced disease with deep
penetration of stomach wall or extragastric spread.13,14
b) Diffuse large B cell lymphoma: More than 50% of gastric lymphomas are diffuse large
B cell lymphomas. The histogenesis of diffuse large B cell lymphoma may be de novo or
due to transformation of low-grade MALT lymphoma.15
The antrum is the commonest site but no part of the stomach is immune. Like MALT, it
has a predilection for the distal half of the stomach, with a tendency to spare the pylorus.
It may grossly appear as large ulcers, protruded tumours or multiple shallow ulcers.
Large cell lymphomas typically invade the muscularis propria layer or more deeply and
are in general, more aggressive.16
High-grade lymphoma is usually, but not exclusively, associated with a mass lesion in
the stomach. Patients may have a large palpable mass and still be in excellent physical
condition. The gross or radiographic distinction from carcinoma may be very difficult.
Mass lesions are likely to show ulceration but occasionally more diffuse infiltration with
an intact mucosa is seen. Unlike low-grade tumours, local lymph node involvement is
408
common and at least 50% of tumours will be at least stage II. At times, free perforation
into the abdominal cavity occurs.11
This lymphoma should be managed with curative intent in the same way as nodal diffuse
large B-cell lymphoma, although there is data showing that in some patients antiHelicobacter therapy may yield remissions.14,16 The optimal management of diffuse large
B cell lymphoma of the stomach is controversial. The traditional approach for localized
disease has been surgery alone or surgery followed by radiation or chemotherapy for
patients with poor prognostic features. This approach has had the advantage of
providing diagnostic and staging information and has avoided the risk of perforation or
bleeding that may result from primary treatment with chemotherapy or radiation.16
Pseudolymphoma of the stomach is a condition traditionally regarded as of
inflammatory nature, although it is notoriously difficult to distinguish from lymphoma
radiographically or grossly. It presents in most cases in association with a gastric
ulceration or erosion and is accompanied by extensive fibrosis. Microscopically, the
features favoring a diagnosis of pseudolymphoma are said to be the presence of clearly
reactive germinal centres throughout the lesion, a mixed population of inflammatory cells
(including mature lymphocytes and plasma cells), proliferation of blood vessels, and a
polyclonal pattern of immunoglobulin stain.10,11
RADIOLOGICAL DIAGNOSIS
Low-grade MALT lymphomas often produce focal and subtle gastric changes on barium
studies compared with the more obvious changes of advanced tumours. The tumour may be
polypoid, ulcerating or infiltrative, and so often has a radiological appearance identical to that
of a gastric carcinoma, although some times an ulcerating lymphoma may resemble a
benign gastric ulcer. The diagnosis of lymphoma may be suggested if there are giant
cavitating lesions or multiple polypoid tumours, particularly if they show central ulceration
giving them a bulls eye appearance or if there is extensive infiltration producing
pronounced thickening of the gastric folds.17 Diffuse submucosal infiltration thickens the
gastric wall to produce an appearance that resembles linitis plastica. Most lymphomas
produce little in the way of a desmoplastic reaction, and therefore distensibility of the
stomach is generally preserved, with the exception of the occasional patient (about 10%)
who has Hodgkins disease. Antral tumours frequently spread to the duodenum. Less often,
fundal tumours spread to involve the oesophagus. CT features which suggest lymphoma
rather than gastric carcinoma include a bulky homogenous tumour with pronounced
409
thickening of the gastric wall, preservation of the perigastric fat plane, transpyloric spread,
multicentricity, wide-spread nodal disease and splenic enlargement.17
UPPER GI ENDOSCOPY
Upper GI endoscopy is extremely useful in gastric lymphomas as it enables localization,
direct visualization, biopsy and, in case of medical treatment, follow-up of gastric lesions.
SMALL INTESTINE LYMPHOMAS:
Lymphomas accounts for the third most common neoplasm arising in the small intestine,
accounting for approximately 15% to 20% of all malignant small bowel tumours. 18 Although
partial small intestine obstruction is the most common mode of presentation, 10% of patients
with small bowel lymphoma present with bowel perforation.19
Primary small intestine lymphomas are most commonly located in the ileum, which contains
the highest concentration of lymphoid tissue in the intestine. However, T-cell lymphomas,
such as those complicating enteropathy, are most common in the jejunum.20
The small intestine shows a characteristic diffuse thickening with proximal, aneurysmal,
dilatation and there is usually mesenteric lymphadenopathy.21 The cirumferential thickening
of the small bowel may cause functional obstruction, or mechanical obstruction due to its
structuring. Ulceration and the destructive infiltration of the intestinal wall without much
desmoplastic reaction may result in perforation. Grossly, the presence of diffusely thickened
folds with small nodules or discrete tumor growths heralds the emergence of a high-grade
malignancy, which proves rapidly fatal in most instances.20
Sometimes, multifocality with lymphomatous polyposis has been described and is
characterized by multiple small polypoid tumours throught the small bowel. These are
composed of monotonous neoplastic mantle or follicular cells, which have a centrocyte-like
morphology.20,21
The clinician must keep a high index of suspicion for lymphoma being mistreated with
antitubercular drugs in patients with small bowel mass and mesenteric lymphadenopathy
who are empirically given antitubercular therapy in endemic countries. In such patients
possibility of lymphoma must be considered if there is a failure to respond to antitubercular
treatment by the end of one month of therapy.22
Under the most recent classification schemes (WHO as well as REAL classifications)
lymphomas arising in the small intestine are of five types:
410
a) Diffuse large B cell lymphoma (or adult western type): It represents about 55% cases
of small bowel lymphoma and is the most common
developing most often in the ileocecal region. Morphologically, these tumours are
composed of diffuse large B cells with large nuclei that are twice the size of a normal
lymphocyte. HIV as well as general immunodepressed states, have been found to be risk
factors for the development of this lymphoma.19
These tumours commonly occur in adult males, with a median age of 54-61 years.
Treatment consists primarily of surgical resection followed by adjuvant radiation or
chemotherapy.18
b) MALT Lymphoma (or Mediterranean type or Immunoproliferative small intestinal
disease): It constitutes 20% of small intestine lymphoma cases. These lymphomas are
characterized by marginal zone cells similar to those of Peyers patches and mesenteric
nodal tissue. It is associated with the production of an unusual heavy chain protein,
called Alpha-heavy chain.22 It is especially common in Mediterranean countries due to
poor sanitation and low socio-economic status. Thus, it can be proposed that, in a way
analogous to H. pylori-associated gastric MALT, lymphocytes in intestinal MALT may be
stimulated by infectious agents and proliferate in response. Patients are usually younger,
in second or third decade of life and present with symptoms of malabsorption.22
Treatment is multimodality, including surgical resection and adjuvant chemoradiation
therapy. Survival from MALT lymphoma arising in the small intestine has been reported to
be better than that arising in the stomach.23
c) Enteropathy associated T-cell lymphomas of the small intestine: It accounts for 15%
of small bowel lymphomas. It has been found to arise in the setting of malabsorption and
steatorrhea and is closely associated with celiac disease. It has been estimated to arise
in approximately 5% to 10% of all patients with celiac disease.24 Treatment consists of
surgery and chemotherapy. The prognosis for this lymphoma is very poor.25
d) Burkitts Lymphoma: It accounts for about 5% of small bowel lymphomas.26 Burkitts
lymphoma cells are monomorphic, medium-sized cells with round nuclei and abundant
basophilic cytoplasm. It is most common in children and accounts for one-third of all
paediatric lymphomas. One-fourth of the patients present with a mass in the right lower
quadrant of abdomen. It is a rapidly growing tumour with a short doubling time.
Treatment consists primarily of chemotherapy.26
411
412
bowel lumen is not usually found in adenocarcinomsa. With aggressive large cell
lymphomas, there can often be findings of cavitary masses that appear arising from the
mesentery. Carcinoid tumours appear as ill-defined, homogenous masses with displaced
small bowel loops. There is soft-tissue stranding and mesenteric desmoplastic reaction.
Sarcoma/ GIST present as homogenous, hypervascular masses with central liquefactive
necrosis.27
CAPSULE ENDOSCOPY
The introduction of the video capsule endoscope into clinical practice has permitted
complete examination of the entire small bowel mucosa. The 11 mm X 26 mm video capsule
is swallowed with water. The capsule takes two images per second for about 8 hours. These
images are transmitted to the recorder belted around the waist of the patient. Recorded
images are downloaded to a workstation. Review of the video, selection of representative
images, and generation of a report takes 30 to 90 minutes. The role of video capsule
endoscopy in the diagnosis of small bowel neoplasms is currently being defined and with
increasing experience, it is bound to become a very useful investigation modality.
COLORECTAL LYMPHOMA
The majority of colorectal lymphomas are non-Hodgkins type. B cell diffuse large cell
histologic type is the most common. Approximately, 15% of GI lymphomas arise in the large
bowel, and the majority are situated in the cecum or the rectum.28 Presentation is similar to
that of colorectal carcinoma, and the diagnosis is made on histologic examination of a biopsy
specimen. Patients with colorectal lymphoma are often treated initially with surgery followed
by chemotherapy and/ or radiation.28,29
OTHER SITES
Primary NHL rarely occurs in oropharynx and esophagus. The histologic type is
usually diffuse large cell lymphoma.30 Owing to the extreme rarity of primary lymphoma at
these sites data regarding their optimal management are lacking. A combined modality
approach including chemotherapy surgery and/ or radiotherapy has been suggested by
some investigators.30
Gastrointestinal lymphomas may mimic practically all conditions in the GI tract. A
biopsy (endoscopic/ image guided/ open surgical resection) must be considered whenever
lymphoma is suspected to be the cause of gastrointestinal complaints in a patient. A high
index of suspicion by the clinician is necessary to avoid delaying or missing the diagnosis of
this potentially curable entity.
413
References
1. Picker L, Siegelman M. Lymphoid tissues and organs. In: Fundamental Immunology. 4
Philadelphia: Lippincott Raven; 1999. p. 479-532.
th
ed.
2. Harris NL, Jaffe ES, Stein H. A revised EuropeanAmerican classification of lymphoid neoplasms:
A proposal from the International Lymphoma study Group. Blood 1994;84:1361-92.
3. Zucca E, Roggero E, Bertoni F, Cavalli F. Primary extranodal non-Hodgkins lymphomas:
Gastrointestinal, cutaneous and genitourinary lymphomas. Ann Oncol. 1997;8:727-37.
4. Isaacson P. Gastrointestinal lymphomas of T- and B-cell types. Mod Pathol 1999;12:151-8.
5. Zucca E, Cavalli F. Gut lymphomas. Clin Haematol 1996;9:727-41.
6. Pugh W, Mc Bride J. The Pathologic Basis
Lymphomas. In: Hematology - Basic Principles
Livingstone; 2000. p. 1263-93.
7. Gray GM, Rosenberg SA, Cooper AD et al. Lymphomas involving the gastrointestinal tract.
Gastroenterology 1992;52:143.
8. Rohatiner A, D Amore F, Coiffier B et al. Report on a workshop convened to discuss
the pathological and staging classification of gastrointestinal tract lymphoma. Ann Oncol
1994;5:397-400.
9. Isaacson PG. Gastric MALT lymphoma: From concept to cure. Ann Oncol 1999;36:139-47.
10. Day DW, Jass JR, Price AB, Shepherd NA, Sloan JM, Talbot IC. Non-epithelial tumors of the
th
stomach. In: Morson and Dawsons Gastrointestinal Pathology. 4 ed. Hong Kong: Blackwell
Publishing; 2003. p. 196-203.
11. Rosai J. Gastrointestinal tract. In: Rosai and Ackermans Surgical Pathology. 9
Elsevier; 2004. p.680-4.
th
ed. Missouri:
12. Zucca E, Bertoni F, Roggero E, Cavalli F. The gastric marginal zone B-cell lymphoma of MALT
type. Blood 2000;96:410-9.
13. Zaki M, Schubert ML. Helicobacter pylori and gastric lymphoma. Gastroenterology 1995;108:
610-2.
14. Parsonnet J, Hansen S, Rodriguez et al. Helicobacter pylori infection and gastric lymphoma. N
Engl J Med 1994;330:1267-71.
15. De Wolf-Peeters C, Achten R. The histogenesis of large cell gastric lymphomas. Histopathology
1999;34:71-5.
16. Ibrahim EM, Ezzat AA, Raja MA et al. Primary gastric non-Hodgkins lymphoma: clinical features,
management and prognosis of 185 patients of diffuse large B-cell lymphoma. Ann Oncol
1999;10:1441-9.
17. David Sutton. The stomach and duodenum. In: Textbook of Radiology and Imaging. 6
London: Churchill Livingstone; 1998. p. 598-9.
th
ed.
18. Rawls RA, Vega KJ, Trotman BW. Small bowel lymphoma. Curr Treat Options Gastroenterol
2003;6:27.
19. Domizio P, Owen RA, Shepherd NA, Talbot IC, Norton AJ. Primary lymphoma of the small
intestine. A clinicopathological study of 119 cases. Am J Surg Pathol 1993;17:429-42.
20. Day DW, Jass JR, Price AB, Shepherd NA, Sloan JM, Talbot IC. Non-epithelial tumors of the
th
small intestine. In: Morson and Dawsons Gastrointestinal Pathology. 4 ed. Hong Kong:
Blackwell Publishing; 2003. p. 376-382.
th
21. Rosai J. Gastrointestinal tract. In: Rosai and Ackermans Surgical Pathology. 9 ed. Missouri:
Elsevier; 2004. p. 735-6.
414
22. Fine K, Stone M. -Heavy chain disease, Mediterranean lymphoma, and immunoproliferative
small intestine disease: A review of clinicopathological features, pathogenesis, and differential
diagnosis. Am J Gastroenterol 1999;94:1139-52.
23. Nakamura S, Matsumoto K, Jakeshita M et al. A clinicopathologic study of primary small intestinal
lymphoma: Prognostic significance of MALT-derived lymphoma. Cancer 2000;88:286.
24. Green PH, Fleischauer A N. Bhagat G et al. Risk of malignancy in patients with celiac disease.
Am J Med 2003;115:149-53.
25. Gale J, Simmonds PD, Mead GM, Sweetenham JW, Wright DH. Enteropathy-associated
intestinal T-cell lymphoma: Clinical features and treatment of 31 patients in a single center. J Clin
Oncol 2000;18:795-803-12.
26. Bishop PC, Rao VK, Wilson WH. Burkitts lymphoma: Molecular pathogenesis and treatment.
Cancer Invest 2000;18:574-83.
27. David Sutton. The small bowel and peritoneal cavity. In: Textbook of Radiology and Imaging. 6
ed. London: Churchill Livingstone; 1998. p. 625-6.
th
28. Fan CW, Changehien CR, Wang JX, et al. Primary colorectal lymphoma. Dis Colon Rectum
2000;43:1277-82.
29. Doolabh N, Anthony T, Simmang C, et al. Primary colonic lymphoma. J Surg Oncol 2000;74:25762.
30. Okerbloom JA, Armitage JO, Zetterman R, Linder J. Esophageal involvement by non-Hodgkins
lymphoma. Am J Med 1984;77:359-61.
415
Definition or comment
Onset:
Acute
Acute on chronic
Chronic
Complete
Limb threatened
Irreversible
Limb non-viable
Claudication
2.
Rest Pain
3.
Ulceration
4.
Gangrene
416
In contrast, the Symptoms and signs of acute limb ischaemia are as follows:
Table No 2: Symptoms & Signs of Acute Ischaemia
Symptoms or signs
Comment
Pain
Pallor
Pulseless
Perishing cold
Paraesthesia*
Paralysis*
*Anaesthesia and paralysis are the key to diagnosing complete ischaemia that requires
emergency surgical treatment
417
Platelets effects
Lipid effect
Coagulation effects
2.
418
3.
Temporal arteritis or giant cell arteritis is diease affecting the temporal vessels in
Spinal Claudication
Pain brought on by weight bearing or taking
first step
Pain classically radiated down the back of
leg with associated numbness or tingling or
altered sensation
Is brought on by extension of spine and
relieved by flexion,
simian stance
419
Clinical Presentation
Aorto-Iliac Disease
Calf claudication
Calf claudication
Pain starts but if the patient continues to walk the metabolites increase the
muscle blood flow and sweep away the P- substance produced by exercise and pain
disappears.
Grade 2
Pain continues but the patient can still walk with effort.
Grade 3
Grade 4
Rest pain
burning felt in the foot at rest, made worse by lying down or elevation of the foot. The pain
is felt first in the most distal part of the leg, in the toes and the instep of the foot. It is due to
the ischaemia of the skin and subcutaneous tissues, which are richly supplied by nerves.
Characteristically, the pain is worse at night largely due to absence of gravity effect in the
supine position aiding blood flow to the limb and partly due to lower blood pressure and
heart rate while sleeping leading to decreased blood flow to the limb. The patient might
attempt to overcome this somewhat by using
gravity aid and hanging the foot out of the
bed or by sleeping in chair. This attitude leads to pedal oedema and thereby worsening of
microvascular perfusion. Paradoxically, a limb with rest pain may appear bright red due to
accumulation of vasodilator metabolites. Rest pain is completely different from night cramps
commonly seen in the elderly.
420
No clinical symptoms
Stage 2
Intermittent claudication
Stage 3
Stage 4
Clinical Examination:
Physical examination involves inspection of the extremities for signs of chronic
ischaemia like thin, shiny skin, loss of hair and subcutaneous fat, presence of brittle nails
with transverse ridges and areas of minor ulceration and differentiation from signs of acute
arterial occlusion like pallor, pulselessness, poikilothermia, pain, paraesthesia and paralysis.
All the peripheral pulses have to be palpated with care and recorded. It is important to know
the site of palpation of each pulse. It is important to note temperature difference between two
limbs if any, skin changes of ischemia, muscle wasting, Capillary and Venous Refilling,
Buergers Angle, perform Buergers Test, and differentiate an arterial ulcer from a venous
ulcer. Similarly, dry gangrene has to be differentiated from wet gangrene. It is possible for
patients with proximal stenosis to have a palpable distal pulse at rest and it is important to
look for their disappearance on exercise. It is also important to perform a detailed and
appropriate neurological assessment to differentiate spinal from vascular claudication.
421
Investigations:
General:
1.
Blood : Routine examination of blood including a hemoglobin percent (low Hb% can
decrease claudication distances and aggravate rest pain), blood sugar examination as
diabetics have worse prognosis, are essential. Erythrocyte sedimentation rate (ESR) is
usually raised in Buergers disease. In patients with high suspicion of underlying connective
tissue disorders, specific test like RA factor, LE cell phenomenon etc. may be carried out.
Lipid profile is mandatory in elderly patients with atherosclerosis.
2.
3.
Plain X-ray of the abdomen will show the presence of arterial calcification and flecks
ECG: an abnormality in ECG may influence the decision for surgery, in patients with
Hand Held Doppler ultrasound2 blood flow detection uses a continuous wave
ultrasound signal, beamed at an artery and the reflected beam is picked up by a receiver.
The changes of frequency in the reflected beam, as compared with the transmitted beam,
are due to the
Doppler shift, resulting from passage of beam through moving blood. These
frequency changes are converted to audio signals. This investigation may be used
effectively in cases where a differential diagnosis of atherosclerosis is entertained showing
the site of block and extent of distal run-off. A 8-10 MHz continuous waver Doppler
ultrasound probe is used to assess the posterior tibial (PT), dorsalis pedis (DP) and peroneal
arteries. A normal pedal pulse produces a Doppler signal with 2 or 3 distinct phases with a
clear sharp sounding systolic peak. The reduction in the pitch of this signal and a lack of the
phasic components is recongnised as abnormal finding. In low arterial flow conditions, it
becomes difficult to differentiate between arterial from venous flow. In such a situation,
application of compression in the distal part of the limb would tend to augment in case of a
venous signal but will leave the arterial signal unaffected.
422
6.
This measurement gives the quantitative assessment of the global limb arterial perfusion.
Patient lies supine, all measurements are at the level of the heart and only after resting for
10-15 minutes. A standard BP cuff of 15-20 cm width is positioned in the ankle just above
the malleoli. A 8-10 MHz Doppler ultrasound probe is used to hear the pedal Doppler signals
and inflated above the systolic pressure for the signals to disappear. The point at which the
Doppler signals first returns on gradually lowering the pressure marks the systolic pressure
at the ankle level. Normally an average of 2 measurement for each of the arteries namely
dorsalis pedis and posterior tibial is used to denote the ankle pressure. Similar procedure is
done for brachial artery. The ratio of the highest recorded systolic pressure at the ankle to
the brachial systolic pressure at the arm forms the ABPI. The ankle brachial index is
interpreted in the manner as given in Table 4. As a thumb rule, patients with ABPI of 0.8
or 0.9 have moderate peripheral vascular disease, those between 0.5 to 0.8 suffer from
intermittent claudication and those with < 0.5 may suffer from rest pain, ulceration or
gangrene.
TABLE 10 Ankle Brachial Pressure Index34
ABI
Interpretation
1.1 0.1
Normal
0.6 0.2
Intermittent claudication
0.3 0.1
0.1 0.1
Toe Pressures Using Photoplethysmograph: These are used when the arterial
disease is suspected between the ankle and the toes. The measurement is done using a
an occlusion cuff of 2-3 cm diameter placed around the great toe or 2nd or 3rd toe and
the digital pulse is recorded by a photoelectric cell placed on the toe. The measurements
are recorded on a strip chart recorder with cuff pressures being recorded simultaneously.
Toe pressures are normally lower than the brachial or the tibial arteries at the ankle due
to high resistance created by small digital arteries. Toe pressures are also indicated as
a percentage of the brachial artery pressure referred to as the Toe Brachial Index (TBI).
Normal ratio is 0.8-0.9. Patients with claudication have TBI of 0.2-0.5 and those with CLI
have TBI<0.2
423
8.
Pole Test: This is used to determine the adequacy of lower limb bolld flow in patients
with incompressible vessels or who are unable to tolerate an ankle pressure cuff. It
involves listening to the pedal pulse using the hand held Doppler probe while the patients
leg is raised against a pole. The height at which the Doppler signal disappears is
reflected by the markings in mm Hg in a caliberated pole directly. A maximum of 60-70
mm Hg only can be recorded since the test is limited by the height upto which the patient
is able to lift the leg.
9.
10.
Walk Test: The basis of this test is that measurement of ABPI before and after a
patient has walked can expose less severe or compensated peripheral vascular disease.
The walk can be standard or graded ( incline) using a tread mill. A reduction in ABPI of
>20% indicates presence of severe arterial disease. In normal limbs, there is a rise or
status quo in the ABPI. As a rough guide, post exercise ABPI of 0.8-0.9 confirms
claudication caused by moderate disease, 0.5-0.7 indicates significant disease and <0.5
denote severe arterial insufficiency.
Duplex imaging2 gives accurate information on the size of artery, the flow rate,
turbulence and the presence of stenosis. The combination of Doppler and color mapping
allows easy recognition of stenotic sites. This has been achieved by the use of pulsed or
continuous wave Doppler and the two- dimensional images produced by the B- scan
made either singly or in combination. Peak systolic velocity at the site of stenosis is
compared to that measured proximally to obtain a peak systolic velocity ratio (PVR) and
relates to the degree of stenosis. A 2x increase in PVR at a stenosis corresponds to 50%
reduction in diameter on arteriography. This modality is non invasive and has now
become the mainstay of assessment of arterial insufficiency, and has largely replaced
routine use of conventional arteriography. This requires detailed assessment of each
major arterial segment i.e Aorta, Iliacs, Femoropopliteal and infrapopliteal segments.
This investigation has virtually become the first line investigation to localize the
level of block with a great deal of accuracy.
12.
424
arteries over a guidewire and produce intravascular ultrasound images which give
details of arterial walls, luminal contents and dimensions. This is not a routine
investigation for peripheral arterial disease and as yet is not cost effective.
13.
14.
15.
425
Treatment:
The management of atherosclerotic occlusive peripheral arterial disease is divided into
three parts as follows:
1.
2.
3.
The following flow chart is a useful aid memoire on the management of this condition.
FlowChart 1: Treatment Pathway for chronic lower limb ischemia. From: Beard JD, Gaines PA.
Treatment of chronic lower limb ischemia. In: Vascular & Endovascular surgery. Beard JD & Gaines
PA (eds). 2
nd
426
Management of Diabetes
Use of anti-oxidants treatment for homocystinemia
Anti-platelet therapy
B. Treatment of Intermittent Caudication
Intervention is based on several factors which are
quality of life issues more than
claudication distance. Also the presence of co-morbid conditions significantly alters
intervention.
Table 12: Factors affecting intervention in Claudication
Favour of Intervention
Against Intervention
Severe symptoms
Short history
Job affected
Still smoking
Aorto-iliac disease
Femoro-distal disease
Stenosis/short occlusion
Unilateral Symptoms
Multi-level disease
a)
Exercise programmes have shown that encouraging the patients to walk to near
maximum pain tolerance had beneficial results in more distal disease such a femoral
block as compared to angioplasty. In proximal disease, angioplasty has been found
to be superior to exercise though long term well controlled studies are limited in
literature.
b)
c)
d)
427
PTFE in graft patency at 2 years for below knee level, the results are equivocal for
above knee level but favour the use of vein. ii) Supra-inguinal bypass Aortobifemoral bypass has >90% patency at 1 year but higher mortality. Cross femoral or
ilio-femoral by pass have similar success rates for unilateral disease with lower
mortality rates. Axillo-bifemoral grafts have a lower patency rate and are not
justifiable for claudication.
Fig 1: Types of Supra-inguinal Bypass surgery. From: Beard JD, Gaines PA. Treatment of chronic
lower limb ischemia. In: Vascular & Endovascular surgery. Beard JD & Gaines PA (eds). 2
nd
edition.
50-75% of patients tend to benefit from endovascular intervention and this should be
offered as the first choice. However it is prone to higher complication rate as compared to
claudicants due to risk of embolization and dissection.
b)
Both supra and infra inguinal bypass surgery is possible in this group of patients
where co-existent morbid conditions are absent. Whereas, PTFE is preferred for the
428
former, autologous saphenous vein is preferred for the latter. The patency rates for
femoro-popliteal bypass are 10% lower for CLI as compared to claudicants.
c)
Drugs: Prostacycline analogues are expensive and when used have shown significant
reduction in death and amputation in short term (6 months).
d)
e)
f)
Pain Relief Morphine sulphate has been used for chronic pain relief.
Amputations These are ideal for those with extensive tissue loss, poor case for
revascularization and presence of severe co-morbid conditions along with the above.
References
1.
Beard JD, Gaines PA. Treatment of chronic lower limb ischemia. In: Vascular & Endovascular
nd
surgery. Beard JD & Gaines PA (eds). 2 edition. WB Saunders. London. 2001. Pp 55-88.
2.
London NJM, Cleveland TJ. Assessment of Chronic lower limb ischemia. In: Vascular &
nd
Endovascular surgery. Beard JD & Gaines PA (eds). 2 edition.. WB Saunders. London. 2001 Pp
27-53.
3.
Leng GC, Fowkes FGR. Epidemiology and risk factors for peripheral arterial disease. In:
nd
Vascular & Endovascular surgery. Beard JD & Gaines PA (eds). 2 edition. WB Saunders.
London. 2001.Pp 1-26.
4.
5.
Belkin MJ, Whittemore AD, Donaldson MC, Conte MS, Gravereaux E. Peripheral Arterial
Occlusive disease. In: Sabiston Textbook of surgery. Townsend CM, Beauchamp RD, Evers BM,
th
Mattox KL (eds). 17 edition. Saunders. Philadelphia. 2004. pp1989-2029.
6.
Simon JC, Lloyd MT, John MP. Non operative treatment of chronic lower limb ischaemia. In:
Current problems in Surgery. Wells SA (ed). Jan 1991. pp 45-46.
7.
Olin JW, Lie JT. Thromboangiitis obliterans (Buergers disease). In : Loscalzo J, Creager MA,
nd
Dzau VJ, eds. Vascular Medicine. 2 ed. Boston:Little,Brown,1996 pp1033-1049.
8.
Boyd AM. The natural course of atherosclerosis of the lower extremities. Angiology
1960;11:10-14.
9.
Tenant WG, Ruckley CV. The critically ischaemic limb. In: Recent advances in surgery (18).
Taylor I, Johnson CD (eds). Churchill Livingston. Edinburgh. 1995;pp 117-139.
429
Fig 2: Types of Infra-inguinal Bypass surgery. From: Beard JD, Gaines PA. Treatment of chronic
lower limb ischemia. In: Vascular & Endovascular surgery. Beard JD & Gaines PA (eds). 2
WB Saunders. London. 2001:Pp 55-88
430
nd
edition..
Diabetic foot ulcers are very common, with an annual incidence of 2% to 3% and a
prevalence of 4% to 10%1. Clinical studies show that foot ulcers precede 85% of nontraumatic lower extremity amputations among diabetic patients1. Needing a first amputation
is a poor prognostic sign in diabetic patients; 28% to 51% of these patients require a second
amputation within 5 years 1. The presence of peripheral diabetic complications leading to
amputation is also associated with systemic complications. The 5-year mortality rate after
lower extremity amputation ranges from 39% to 68% 1. In view of these alarming figures,
diabetic foot becomes a major cause of morbidity and sometimes mortality in these patients.
Pathogenesis
Sensory neuropathy, ischemia, injury, hypergycemia and infection are the predominant
pathogenic factors in development of foot ulcers in diabetic patients 2. 33% of diabetic foot
ulcerations are neuropathic, 33% are ischaemic and 33% are of a mixed nature 2.
The mechanisms of factors leading to diabetic foot include:
1. Neuropathy
Damage of sympathetic nerve fibres is recognised early in diabetes due to peripheral
neuropathy. It is well documented (e.g. Tooke, 1995)
431
5,2
. In patients
with diabetic foot ulcers, peripheral sensory neuropathy is found in 80% of cases 2.
Ulceration develops because patients lack protective sensations to warn them of injury to
the foot. As a result, puncture wounds may go unnoticed, foreign bodies may remain in
subcutaneous tissues, or poorly fitting shoes may continue to be worn until pressure
necrosis develops. Other factors in ulceration are ischemia, callus formation, and
edema2.
Motor involvement causes weakness of the intrinsic muscles causing imbalance between
the long flexors and extensors, causing a cavus foot and claw toes. The weight bearing
contribution of the toes decreases and the fat pad under the metatarsal heads is drawn
forwards, decreasing cushioning and increasing vertical and shear forces. The
metatarsal and heel pads are atrophied 5.
2. Ischaemia
Microvascular pathology
It has also been assumed to play a role in diabetic neuropathy, and in the so-called
diabetic foot. The histology of affected diabetic tissue reveals a PAS positive, thickened
capillary basement membrane. Electron microscopy of skeletal muscle capillaries
reveals reduplication of the basal lamina 6.
The structural changes which occur in the microcirculation do not seem to account for
all the full extent of the disease, leading to the concept of
functional
.Functional
microangiopathy may result from nonenzymatic glycosylation which affects many blood
components including hemoglobin, red blood cell membrane, fibronectin, fibrinogen,
and platelets 6.
Glucosylation of the red blood cell has been shown to inhibit the cell pliability and to
decrease the ability of this cell to pass through pores smaller than 7 microns. The
lumen of some capillaries may be as narrow as 3 microns and ordinarily red blood cells
will elongate into a more sausage like configuration to traverse this loop. Stiffened
membranes will certainly inhibit or limit this passage 7. In addition to stiffened red blood
432
cells, diabetics also have increased plasma concentration of fibrinogen and capillary
leakage leading to loss of albumen and water. There is an increased tendency for
diabetic platelets to aggregate. The end result is increased whole blood or plasma
viscosity and sluggish microcirculation 7.
The pathogenesis is accentuated by the peripheral vascular disease, which occurs in
these patients. It is seen that Atherosclerosis appears earlier, progresses quicker and
shows less male bias in diabetics. Vessels in the lower limb most involved are distal
superficial femoral, tibial and peroneal vessels 8.
3. Injury
Mechanical stress is the precipitator of ulceration in both the neuropathic and ischaemic
foot. The most common sites are the curve of the 1st and 5th metatarsal heads. The sole
of the foot has a relatively good blood supply and tends not to ulcerate early 8. In the
neuropathic foot ulceration precipitated by direct high-pressure injury (unfelt) or
gradually through repetitive stress. Callosities develop under metatarsal heads and the
heel. Subcutaneous tissue trapped between bone and thick unpliable skin producing
high shear forces, leading to sterile deep haematoma. This deep ulcer then tracks to
the skin leading to sinus tract or ulcer, Charcot foot/ Neuroarthropathy is a rare
outcome seen in diabetics following the action of
various factors, mainly neuropathy. This is
described as a chronic painless degenerative
process affecting the weight-bearing joints of the
foot. Only in 1 % of diabetics are seen with
charcots foot
collapse
of
the
arch,
etc.
Anatomic
bearing,
excessive
pressure,
and
ulceration .
4. Hyperglycemia
Hypergycemia
affects
host
immunologic
defenses.
Granulocyte
adherence,
433
diapedesis
10,11
and often do not have leukocytosis in the presence of acute soft tissue
or bone infection.12
5. Infections
The spectrum of foot infections in diabetes ranges from simple superficial cellulitis to
chronic osteomyelitis. Infections in patients with diabetes are difficult to treat because
these patients have impaired microvascular circulation, which limits the access of
phagocytic cells to the infected area and results in a poor concentration of antibiotics in
the infected tissues 9. For this reason, cellulitis is the most easily treatable and
reversible form of foot infections in patients with diabetes. Deep skin and soft tissue
infections also usually are curable, but they can be life threatening and result in
substantial long-term morbidity 9.
Patients with diabetes also can have a combined infection involving bone and soft
tissue called fetid foot
13
13
Recent clinical trials for the treatment of such wounds have used a period of at least 8 weeks
during which there have not been signs of active healing or attaining closure 5..
The evaluation of diabetic ulcer should determine the etiology of the ulcer and ascertain
whether the lesion is neuropathic, ischemic, or neuro-ischemic 14
1. Neuropathic ulcer - Under metatarsal head, surrounded by thick hyperkeratosis,
pink punched out base, readily bleeds, painless. Foot warm with palpable pulses and
distended veins 14.
2. Ischaemic ulcer - not surrounded by hyperkeratosis, dull fibrotic base, doesnt bleed
easily, painful to touch 14.
3. Infection - Surrounding cellulitis, discharge, erythem. Generally, limb-threatening
infections can be defined by cellulitis extending beyond 2 cm from the ulcer
perimeter, as well as deep abscess, osteomyelitis, or critical ischemia
434
14
Presence of edema
Temperature gradient
Dermal thermometry
435
Two-point discrimination
Pain: pinprick
Clonus testing
Babinski test
Rhomberg's test
Biomechanical
abnormalities:
orthopedic
deformities
(hammertoes,
Gait evaluation
3.
4.
Ulcer classificaton
Most classification systems primarily focus on the depth of the ulceration and neglect
or inconsistently include infection and peripheral arterial occlusive disease. To make a
classification system clinically relevant, it should be easy to use, reproducible, and effective
to accurately communicate the status of wounds in persons with diabetes mellitus. There are
a variety of variables that could be included in such a system, such as faulty wound healing,
patient compliance, quality of wound granulation tissue, host immunity, nutritional status, and
co-morbidities 15.
Shea, in 1975 was one of the first to propose a standard wound classification system 15.
This scheme was designed to assess decubitus ulcerations and was the model used for
formation of subsequent classification systems, including the International Association for
Enterostomal Therapy system16. One of the most commonly cited diabetic wound
classification systems was first described by Meggitt in 1976 and popularized by Wagner in
1981 17,18.
436
II
III
Pre or postulcerative
lesion completely
epithelialized
Wound
penetrating to
tendon or capsule
Wound
penetrating to
bone or joint
Pre or postulcerative
lesion, completely
epithelialized with
infection
Wound
penetrating to
tendon or capsule
with infection
Wound
penetrating to
bone or joint with
infection
Pre or postulcerative
lesion, completely
C
epithelialized with
ischemia
Wound
penetrating to
tendon or capsule
with ischemia
Wound
penetrating to
bone or joint with
ischemia
Pre or postulcerative
lesion, completely
D epithelialized with
infection and
ischemia
Wound
penetrating to
tendon or capsule
with infection and
ischemia
Wound
penetrating to
bone or joint with
infection and
ischemia
437
The criteria for each of the stages are based on clinical and laboratory data.
1. Clean ulcers are defined as wounds without local or systemic signs of infection
21
2. Wounds with frank purulence and/or two or more of the following local signs may be
classified as
infected. These signs include warmth, erythema, lymphangitis,
lymphadenopathy, edema, pain, and loss of function 21.
3. The working diagnosis of lower extremity ischemia is made by a combination of
clinical signs and symptoms plus non-invasive vascular studies. Clinical signs and
symptoms may include claudication, rest-pain, absent pulses, atrophic integument,
absence of pedal hair, dependent rubor or pallor on elevation. Non invasive criteria
include transcutaneous oxygen measurements of < 40hg
21,22
signs coupled with one or more of the above non-invasive values provides a working
diagnosis of lower extremity vascular insufficiency22.
The natural history of diabetic foot has been divided using The Simple Staging
System23 covers the whole spectrum of diabetic foot disease but nevertheless emphasises
the foot ulcer as a pivotal event demanding urgent and aggressive management. The natural
history of the diabetic foot can be divided into six stages, each based on significant events in
the development of complications, as follows:
Significant events in the natural history of the diabetic foot on the road to amputation
1 The diabetic foot may have no risk factors for ulceration (stage 1).
2 Neuropathy, ischaemia, deformity, oedema and callus are the most well known risk factors
for ulceration (stage 2).
3 Ulceration is a pivotal event on the road to amputation requiring urgent and aggressive
management (stage 3).
4 Infection delays healing and can destroy tissue with alarming rapidity (stage 4).
5 Necrosis is the result of tissue destruction from infection and ischemia (stage 5).
6 There comes a time when the foot is destroyed and major amputation is inevitable; this is
the final stage (stage 6) 23.
Laboratory Testing
Clinical laboratory tests that may be necessary in the appropriate clinical situations
may include: fasting and postparandial blood glucose, glycohemoglobin (HbA1C), complete
438
blood count (CBC) with or without differential, erythrocyte sedimentation rate (ESR), serum
chemistries, wound and blood cultures, and urinalysis 5.
Imaging Studies
Plain radiographs should be the initial imaging study in diabetic patients with signs
and symptoms of a diabetic foot disorder. X-ray findings in a diabetic foot infection, such as
osteomyelitis, may not demonstrate any osseous changes on radiographs for up to 14 days.
Plain radiographs may be indicated in the detection of osteomyelitis, osteolysis, fractures,
dislocations seen in neuropathic arthropathy, medial arterial calcification, and soft-tissue gas
5
Computed tomography (CT) scans may be indicated in the assessment of suspected bone
and joint pathology not evident on plain radiographs. This study offers high anatomic detail
and resolution of bone with osseous fragmentation and joint subluxation being well
visualized 5.
Technetium bone scans are often used in diabetic foot infections although this modality lacks
specificity, especially in the neuropathic patient. Three-phase bone scans may be indicated
in the early detection of osseous pathology such as osteomyelitis, fractures, and Charcot
arthropathy. However, such imaging tests are best utilized to confirm clinical suspicion and
have higher specificity when combined with other scintigraphic techniques such as white
blood cell scans 2,5.
Gallium 67 citrate is another nuclear medicine technique that is not used as frequently today
due to more accurate alternative imaging studies. This study can be used in concert with
technetium bone scans to aid in the diagnosis of osteomyelitis and also may be of value in
the presence of acute osteoarthropathy 2,5.
Indium-111 leukocyte scans, TcGG-labeled white-cell scan (HMPO), or other variations of
white blood cell scintigraphy are useful in differentiating between osteomyelitis and
neuropathic arthropathy due to their relatively high sensitivity and specificity. These tests are
expensive and time consuming, but are available at most hospitals when early identification
of bone infection is required 2,5.
Magnetic resonance imaging (MRI) is often used in evaluating soft-tissue and bone
pathologies. This scan may be indicated to aid in the diagnosis of osteomyelitis, deep
abscess, septic joint, and tendon rupture. It is a readily available modality which has a very
high sensitivity for bone infection and can also be used for surgical planning. Despite its high
439
cost, magnetic resonance imaging has gained wide acceptance in the management of
patients with diabetic foot infections 5.
Vascular examination
Noninvasive arterial studies (NIAS) should be performed to determine lower extremity
perfusion. Such studies may include Doppler segmental arterial pressures, and waveform
analysis, ankle-brachial indices (ABI), toe pressures, and transcutaneous oxygen tension
(TcPO2) 22,24.
TABLE 2 Noninvasive Vascular Tests 22,24
Test
Abnormal value
appropriate
assessment
for
potential
revascularization.
Digital
subtraction
440
can cause areas of increased pressure and ulcer formation. Those with loss of
protective sensation or severe foot deformity should be seen every 2 to 3 months 7.
4. Any foot lesions should be assessed for infection, debrided of devitalized tissue, and
examined radiographically for foreign body, soft-tissue gas, and bony abnormalities
Early and appropriate referral to specialists, including podiatrists, neurologists, and
vascular and orthopedic surgeons, can reduce the risk of these outcomes 7.
5. Poorly designed or ill-fitting shoes can cause serious problems in diabetic patients with
neuropathy. Patients with significant foot deformity may benefit from referral to a
pedorthist or orthotist for prescription of depth inlays or custom-designed shoes.
Abnormal weight distribution also should be addressed, most often with orthotic devices,
special shoes, or surgical correction 25.
6. Tissue Load Management - The goal of load management is to create an environment
that enhances soft tissue viability and promotes healing of the pressure ulcer. The
vigilant use of proper positioning and support surfaces are important. It is important to
avoid positioning patients on a pressure ulcer. To use devices like pillows or foam to
keep the heels off the bed, keep knees and ankles from touching and to maintain the
head of the bed at the lowest degree medically necessary and to move a sitting or lying
down patient at least once an hour 5.
Treatment
First and foremost good control of diabetes mellitus.
Eliminate infection- Augmentin is a good broadspectrum antibiotic but not to be used on
everyone with a positive culture swab. Other measures to be taken include removal of
infected bone, drainage of abscesses, allow autoamputation in dry gangrene and
debride /amputate in wet gangrene as the case may be 12.
Debridment - Various traditional and newer methods of debridment are being used, which
include1. Autolytic Debridement: Autolysis uses the body's own enzymes and moisture to rehydrate, and provide absorption, desloughing and debriding capacities to necrotic
and fibrotic tissue. Soft autolytic debridement can be achieved with the use of
occlusive or semi-occlusive dressings like hydrocolloids, hydrogels and transparent
films, which maintain wound fluid in contact with the necrotic tissue. It has a
441
26
Agents like Growth factors (e.g. Becaplermin) and Bioengineered skin grafts (Apligraf,
Dermagraft) Human fibroblasts (delivers growth factors and other agents directly to
the wound) 26 are used to augment wound healing
2. Whirlpool treatment -This treatment modality is often administered twice daily for 20
minutes. Water temperature range from 33.5 C to 35.5 0C = 92 F to 96 F. The
main action of whirlpool are to cause vasodilitation ,softening and loosening of
necrotic tissue,wound cleansing, exudate removal and reduced infection and pain
management . Effects of warm water and mechanical effects of whirlpool mediate
these actions 27.
4. Hyperbaric Oxygen (HBO) - In a hypoxic environment, wound healing is halted by
decreased fibroblast proliferation collagen production, and capillary angiogenesis
.Hypoxia also allows growth of anaerobic organisms. Hyperbaric oxygen therapy
442
30
and amputations
22
vascular surgeries. This includes combination of revascularisation and free flap for patients
with extensive tissue loss
31
Bagdade JD, Root RK, Bulger RJ. Impaired leukocyte function in patients with poorly
controlled diabetes. Diabetes. 1974; 23:9-17.
10. Molinar DM, Palumbo PH, Wilson WR, Ritts RE. Leukocyte chemotaxis in diabetic patients
and their first-degree relatives. Diabetes 1976; 25:880-889.
443
11. Eneroth M, Apelqvist J, Stenstrom A. Clinical characteristics and outcome in 223 diabetic
patients with deep foot infections. Foot Ankle Int 1997; 18:716-22.
12. McMahon MM, Bistrian BR. Host defenses and susceptibility to infection in patients with
diabetes mellitus. Infect Dis Clin North Am, 1995; 9(1): 1-7.
13. Boyko EJ, Ahroni JH, Stensel V, Forsberg RC, Davignon DR, Smith DG. A prospective study
of risk factors for diabetic foot ulcer: the Seattle Diabetic Foot Study. Diabetes Care 1999;
22:1036-42.
14. Knighton DR, Ciresi KF, Fiegel VD, Austin LL ,Butler EL. Classification and treatment of
chronic nonhealing wounds: successful treatment with autologous platelet- derived wound
healing factors (PDWHF). Ann Surg. 1986; 204:332-330.
15. Shea JD. Pressure sores: classification and management. Clinical Orthopaedics and Related
Research. 1975; 112:89-100.
16. Doughty D. Management of pressure sores. Journal of Enterostomal Therapy. 1984; 15:3944.
17. Meggitt B. Surgical management of the diabetic foot. Br J Hosp Med. 1976; 16:227- 332.
18. Wagner FW. The dysvascular foot: a system for diagnosis and treatment. Foot and Ankle.
1981; 2:64-122.
19. Forrest RD, Gamborg-Neilsen P. Wound assessment in clinical practice: a critical review of
methods and their application. Acta Med Scand. 1984; 687:69-74.
20. Pecoraro RE, Reiber GE. Classification of wounds in diabetic amputees. Wounds. 1990; 2:6573.
21.
Giacalone VF, Krych SM, Harkless LB. The university of Texas health science center at san
antonio: experience with foot surgery in diabetics. Journal of Foot and Ankle Surgery. 1994;
33:590-597.
22. Orchard TJ, Strandness DE. Assessment of peripheral vascular disease in diabetes: report
and recommendation of an international workshop. Diabetes Care.1993; 83:685-695.
23. Foster A. Simple Staging System: a tool for diagnosis and management. The Diabetic Foot
journal. 2000; 3 (2): 56-62.
24. Apelqvist J, Castenfors J, Larsson J. Prognostic value of ankle and toe blood pressure levels
in outcome of diabetic foot ulcers. Diabetes Care. 1989; 12:373-378.
25. Viswanathan V, Madhavan S, Gnanasundaram S. Effectiveness of different types of footwear
insoles for the diabetic neuropathic foot: a follow-up study. Diabetes Care 2004; 27(2): 474477.
26. Agency for Health Care Policy and Research (AHCPR) Clinical Practice Guideline. Wound
Care Information Network. . Available at http://www.medicaledu.com.
27. Sussman, C, Byl N. Whirlpool, Wound Care Collaborative Practice Manual for Physical
Therapists and Nurses, Sussman, C. And Bates-Jensen, BM, Aspen Publishers 1998.
28. La Van FB, Hunt TK: Oxygen and wound healing, Clinics in Plast Surg 1990; 17 (3): 463-472.
29. Dyson M, Smalley D. Effects of ultrasound on wound contraction. In Millner R and Corket U
(eds): Ultrasound Interactions in Biology and Medicine. Plenum, New York, 1983, p 151.
30. Lee JS, Lu M, Lee VS, Russell D, Bahr C, Lee ET. Lower-extremity amputation. Incidence,
risk factors, and mortality in the Oklahoma Indian Diabetes Study. Diabetes 1993; 42:876-82.
31.Hickey NC, Thomson IA, Shearman CP, Simms MH: Aggressive arterial reconstruction for
critical lower leg ischaemia. Br J Surg. 1991; 78: 1476-1478.
444
and serotonin
7,8
have
sometimes been detected in MTC. Several hormonal products of MTC may result in
significant clinical manifestations. CGRP may be responsible for episodes of flushing and
diaorrhea
19
prostaglandins 12.
Clinical Presentation :
There are three principle components to the primary diagnosis of MTC : detection,
staging and evaluation for hereditary disease.
As previously stated, 80% of MTC occur sporadically , presenting with painless,
progressive nodule in the thyroid gland affecting predominantly the patients in 5th or 6th
decade of life with female to male preponderance as 1.5:1. At the time of presentation as
palpable nodule, nearly 50% of patients have lymph node metastasis and approximately
10% have lung, liver or bony metastasis. Local effects viz. dysphagia, recurrent laryngeal
nerve palsy, tracheal obstruction causing stridor is seen only in
445
Fine Needle Aspiration Cytology (FNAC) shows highly cellular smears constituted by
heterogeneous oval, spindle shaped or plasmacytoid cells lacking papillary or follicular
pattern and devoid of colloid. Calcitonin immuno-histochemical staining on the specimen
confirms the cytological diagnosis. Elevated basal serum calcitonin levels further
corroborates the diagnosis of MTC.
Having confirmed the diagnosis of MTC, the next important task is the staging of the
tumor. There is no consensus regarding the staging work up protocol. Several imaging
methods have been found to be useful in assessing the extent of disease. CT Scan, MRI
and ultra-sonography will help in detecting local invasion or regional lymphadenopathy. CT
or MRI are recommended for detecting mediastinal and lung metastasis. Early liver
metastasis are of milliary pattern and hence CT is not useful for their detection. Nuclear
medicine
studies including
dimercaptosuccinic acid
14
131
and
In-octeotride
131
13
I-metaiodobenzylguanidine
15
limited role in the primary work up, but may be useful in identifying residual disease.
According to TNM classification, the staging of the MTC is as follows:
TheT Stage :
T1- tumor 1 cm. or less within the thyroid gland
T2- tumor sized 1-4 cms. within the thyroid gland
T3- tumor sized greater than 4 cms. within the thyroid gland
T4-tumor of any size extending outside of thyroid gland itself
The N Stage:
N0- No spread to lymph nodes
N1a-Ipsilateral neck nodes involvement
N1b-Bilateral or Contra lateral lymph node involvement
The M Stage :
M0- No tumor spread to other organs
M1- Tumor spread to other organs
Stage I: T1N0M0
Stage II : T2N0M0
Stage IV : any M1
The last but not the least task in diagnostic work-up for MTC is the evaluation for
hereditable
disease.
Screening
test
for
pheochromocytoma
either
with
urinary
catecholamines or metanephrines is the least one should do not only to rule out the
hereditary possibility but also to avoid the harmful effects of high levels of circulating
446
catecholamines during thyroidectomy Although a strong argument can be made for doing
germline ret analysis in all patients with apparently sporadic MTC16, further studies are
needed to determine the diagnostic yield and cost effectiveness of such an approach.
Hereditary MTC has three variantsMEN 2A: MTC, Pheochromocytoma, Hyperparathyriodism
MEN 2B : MTC, Pheocromocytoma, Mucosal neuromas
FMTC : Isolated Familial Medullary Thyroid Carcinoma
MEN 2A is the most common type of hereditary MTC with C Cell hyperplasia and
MTC as its cardinal lesion in95% of individuals. Pheochromocytoma and
hyperparathyroidism are less penetrant with life time incidence of 40% to 60%
and 10% to 25% on an average respectively15.
The thyroid tumors in MEN 2B are usually more aggressive, with widespread
metastasis at an early age as compared to MEN 2A. Pheochromocytoma appears at an
earlier age and are almost bilateral (versus a 50% bilateral incidence in MEN 2A ).
Pre-symptomatic diagnosis of inherited MTC has historically relied on three different
techniques : biochemical screening, family linkage studies and more recently , germline ret
analysis. Biochemical screening using pentagastrin (0.5 ug/kg) or pentagastrin plus calcium
(elemental calcium 2mg/kg) over one minute to stimulate calcitonin secretion on yearly
basis starting at the age of 6 years in individuals at risk was the main stay of diagnosis of
hereditary MTC .Its place has now been taken by techniques to identify ret gene mutations in
germline ( usually white blood cells) DNA. This has made the identification of affected
individuals in the family relatively simple and accurate.
Treatment:
Surgery is the primary modality of treatment of MTC whether sporadic or inherited.
Pheochromocytoma must be carefully excluded and if present treated surgically before
embarking on the surgical management of MTC to avoid intra-operative catecholamine
crisis.17
All patients with palpable disease localized to thyroid must undergo total
thyroidectomy with central node dissection from the hyoid bone to the innominate veins and
ipsilateral mid jugular node sampling and if found positive ,then functional ipsilateral lymph
node dissection preserving jugular vein, sternocleidomastoid muscle and accessory nerve is
recommended. Some surgeons recommend ipsilateral prophylactic or therapeutic functional
neck dissection if the primary tumor is more than 1 cm and when the central nodes are
447
positive18. A prophylactic contra-lateral neck dissection should be done when the primary
tumor is bilateral and when there is extensive lymph adenopathy on the side of the primary
tumor
18
19
single gland disease and excision may be performed if other parathyroid glands are not
found to be hyperplastic on biopsy. All unresected parathyroid glands should be marked with
clips because patients with MEN 2A have high risk of persistent or recurrent primary
hyperparathyroidism19. Patients with FMTC should have a continued follow up for
pheochromocytoma and primary hyperparathyroidism.
Prophylactic Thyroidedctomy :
Prophylactic thyroidectomy has been recommended in hereditary MTC.
MEN 2A. In most centers , thyroidectomy is performed in patients by the age of 5
years or when a mutation is identified 20,21.
FMTC : Some centers recommend management similar to that of MEN 2A
MEN 2B : In most centers , surgery is performed with in first 6 months of life,
preferably within first month , because of early age of MTC onset and particularly
aggressive behavior 17.
Treatment of Residual Disease :
By definition the surgical cure of MTC means normal post operative serum calcitonin
levels. Elevation of post operative calcitonin levels or rising levels indicate
persistent or recurrent disease.
The incidence of persistent hyper calcitonemia after thyroidectomy is 50% in non
palpable microscopic disease and 80% with palpable MTC
22
due to
448
The natural course of the disease in absence of overt metastasis is slow progression
.In patients with hypercalcitonemia with no other evident disease, there is 86% survival at 10
years
24
. In another study it was found that 5 year survival was 95% in patients with lymph
node metastasis alone compared to 41% survival in those with extranodal disease 25.
Reoperation for minimal residual disease with curative intent is controversial.
MTC imaging with anti-CEA Mabs could be very useful in determining the ideal
26
23
advanced MTC does have a role in controlling compression on vital structures in the
mediastinum and in large liver metastasis for poorly controlled diarrhea and flushing.
Cytoreductive procedures such as radiofrequency ablation or cryoablation for liver
metastases should be considered in symptomatic patients to reduce tumor burden.18
Radio-iodine has no role in the residual disease as the MTC cells do not concentrate
radio-iodine. External beam radiotherapy may give some relief
27,28
26
to
be
of
some
benefit
in
reliving
the
symptoms
of
paraneoplastic
18
syndrome .However, they are better managed by medical management but their treatment
by and large remains frustating.
Monoclonal antibodies to CEA have been found to be unsuccessful.
Prognostic Factors
Screening for MTC and early treatment ( total thyroidectomy with central node
clearance ) gives nearly 100% cure rate
30
with out clinical or radiological evidence of residual tumor after apparently curative surgery
enjoy a long term survival but have occult metastasis30. Age at presentation and clinical
staging have been found to independent predictors of survival30.
449
Patients without capsular invasion have been shown to have 92 % survival at 10 years
compared to only 67% in those with capsular invasion. Calcitonin immunostaining is another
important prognostic indicator
32
cells is attended with 87% survival as compared to only less than 60% in those with less
than 10% staining. Calcitonin levels per se are not of much predictive value.
450
The field of minimally access surgery has experienced an explosive growth in the last
2 decades. Few major breakthroughs have marked the development of laparoscopic
surgery-Lens scopes (1870-88), rod lens system of J Hopkins (1950s), fiber optic cold light
transmission (1960s) and the computer chip video camera (1980s) The gynecologists were
the first to embrace the endoscopic technology, while the same did not gain a strong
foothold among the surgeons. It was Kurt Semm, a German gynecologist who performed the
first laparoscopic appendicectomy during a gynecological procedure in 19831.
LAPAROSCOPIC CHOLECYSTECTOMY
It was Philips Mouret who performed the first laparoscopic cholecystectomy in 1987 at
Lyon in France2. Since than Laparoscopic cholecystectomy has become widely accepted
as the procedure of choice for the patient with symptomatic cholelithiasis. Growing
expertise in the field of laparoscopy has enabled surgeons to apply the principles of open
surgery to laparoscopy. Technique like fundus first3 and subtotal cholecystectomy are
being increasingly practiced, there by decreasing the rate of conversion to open surgery.
Also, acute cholecystitis, which in the past was a relative contraindication to laparoscopic
surgery, is also being done by minimally invasive technique.
LAPAROSCOPIC CBD EXPLORATION
The advent of laparoscopic cholecystectomy had created a dilemma for treating patients
with known/suspected choledocholithiasis. Approximately 10% of patients who undergo
laparoscopic cholecystectomy harbour common bile duct stones4,5. Prior to the
development of laparoscopic cholecystectomy the management of these patients
included CBD exploration at the time of cholecystectomy6. Clearance rate of >90% was
accepted as the standard of care.
Many surgeons are now routinely performing common bile exploration and questioning
the wisdom of preoperative endoscopic retrograde cholngiography with or without
sphinterotomy.
Advantages of this laparoscopic CBD exploration include a single hospital admission,
shorter hospital stay, quicker recovery, reduced morbidity and mortality, decreased cost
and higher success rate of 95 to 100%7,8. Various approaches have been used for CBD
exploration: TRANSCYSTIC DUCT APPROACH The indications are the presence of a
451
small (<0.8 cm) stone in the CBD, presence of a limited number of CBD stones (<5), the
absence of stone in the common hepatic duct and the cystic duct joining the CBD on its
lateral or posterior (not the medial) aspect. CHOLEDOCHOTOMY Is done in the
presence of one or more of following:Larger (>01.0 cm) ductal stones in a dilated CBD. several CBD stones (>5), stones in the
common hepatic duct and Unfavourable anatomy of the cystic duct joining the CBD on
its left side after a spiral course posterior to the common hepatic duct. 9,10.
CHOLEDOCHODUODENOSTOMY Indications are multiple stones with dilated duct >1.5
cm, single large stone >1.5 cm in CBD, unretrieved intra hepatic stone, stricture of lower
end CBD, impacted stone.
LAPAROSCOPIC HERNIA REPAIR
The first laparoscopic inguinal hernia repair was performed by an enthusiastic gynecologist,
Ger, in 1982, by approximating the internal ring with stainless steel clips. Since than various
techniques have been described for hernia repair:
Intra Peritoneal Onlay Mesh (IPOM) Is being done for ventral hernia, Trans abdominal
preperitoneal (TAPP) Is being done by beginners and for failed Total Extra Peritoneal
(TEP), TEP For small reducible hernia.
After laparoscopic herniorrhaphy patients returned to work quicker and had less persistent
pain and numbness. The disadvantages of laparoscopic approach are longer duration of
operation, higher cost, requirement of GA, longer learning curve and more serious
complications (bowel and vascular). At present best indications of the inguinal hernia repair
by laparoscopy are bilateral, recurrent hernias after open repair, presence of inguinal hernia
in a patient who required a laparoscopy for another procedure.
LAPAROSCOPIC ESOPHAGUS AND GE JUNCTION SURGERY
The surgical treatment of medically recalcitrant GERD has been studied since the
introduction of Laproscopic Nissen Fundo Plication in 1991.11 Increasing number of patients
have opted for surgical treatment since the advent of Minimal assess surgery (MAS) with its
obvious advantages. Various other procedures are being performed like Hellers myotomy,
transhiatal
esophagectomy,
thoraco
laparoscopic
452
esophagectomy,
laparoscopic
453
SPLENECTOMY
Since the mid 90s laparoscopic splenectomy has steadily developed as the approach of
choice for most elective splenectomies. Initially, it was being performed for normal sized
spleens, but now is being performed for large sized spleens also. The absolute contra
indications are bleeding diathesis and massive splenomegaly (28-30 cm longitudinal
diameter and 3000 gm in weight).
A meta-analysis of 2490 patients comparing laparoscopic splenectomy with open
splenectomy found laparoscopic splenectomy to be associated with fewer pulmonary, wound
and infectious complications19.
HEPATIC AND PANCREATIC SURGERY
With available technology, laparoscopic hepatic surgery is becoming increasingly
popular. Laparoscopy is an ideal way to treat simple cysts and hydatid cysts. Peripherally
situated benign tumors have been successfully managed by wedge or segmental excision at
many centers world wide. Anatomical hepatic resection like right and left hepatectomy, donor
hepatectomy and radio frequency ablation for hepatic malignancy is being performed
laparoscopically
Palliative procedure of bypass of patient in unresectable pancreatic cancer have been
performed laparoscopically including cholecystojejunostomy20 and gastrojejunostomy21.
Whether these procedures achieved better cost effective palliation than the currently
employed technique will need to be evaluated.
Other procedures that are also being performed are pancreaticoduodenectomy (PD)
distal PD
23
22
and pancreaticojejunostomy.
ADRENAL SURGERY
In many respects, adrenal gland are ideally suited to laparoscopic excision, since
most adrenal tumors are small (<6 cm) and pathologically benign. Recently a variety of
minimal access surgeries have been utilized for performing adrenalectomy 24-27.
PYELOLITHOTOMY
The development of retroperitoneoscopic surgery i has been slow compared with that of
transperitoneal laparoscopic surgery due to the inability to establish quick adequate
pneumoperitoneum with direct introduction of a needle into the retroperitoneum. However,
with the advent of balloon dissection technique by Gaur28 in 1992 has opened new horizon in
454
455
laparoscopic centers world wide38. Offered at only a few centers, laparoscopic radical
nephrectomy is almost exclusively performed by the transperitoneal approach39,40.
Laparoscopic radical nephrectomy is a viable treatment option for a small or a medium sized
(< 8 cm) renal tumor without lymphatic or venous extension38. Recently radical nephrectomy
has also been performed by the retroperitoneal laparoscopic approach38,40,41,42
VASCULAR SURGERY
LUMBAR SYMPATHECTOMY
In recent years there have been increasing reports of lumbar sympathectomy being
carried out laparoscopically.Initially, these procedures were carried out transabdominally
with reflection of colon43 but most surgeons now use an extraperitoneal technique with
balloon inflation to dissect extraperitoneal space.If one presumes that this technique can
produce a complete and lasting lumbar sympathectomy with safety and decreased
morbidity,it may reduce the reluctance the perform the surgery for some indications(
frostbite, hyperhidrosis) in which gain is relatively insignificant for open surgical procedure.
AORTOILIAC OCCLUSIVE DISEASE AND ANEURYSM
The use of laparoscopic techniques in intraabdominal vascular surgery my have the
potential to provide the usual benefits of minimum access surgery. Either laparoscopy
assisted or totally laparoscopic aorto-bifemoral bypass grafts have been reported44.
However, experience today indicates that the challenges of obtaining adequate vascular
exposure and control, as well as the technical demands of achieving secure anastomosis,
have provided considerable obstacles and led to long operating time and limited application
in clinical practice.
Abdominal aortic aneurysm is another surgery being performed laparoscopically. In this
technique, aneurysm neck and iliac arteries are dissected laparoscopically followed by
standard endo-aneurysmorhapphy through minilaparotomy
THORACOSCOPIC SURGERY
CERVICOTHORACIC SYMPATHECTOMY
Endoscopic sympathectomy essentially replaced the open surgical approach, with the open
procedure being limited to unique circumstances in which an endoscopic approaach is
contraindicated.
456
RECENT ADVANCES
In future, the modern day surgeons will be able to go through are complete unified
real time investigation that includes CT, USG and MRI, with the help of Virtual Reality
trainers, he will be able to rehearse on the 3 dimensional reconstructed images of the
particular patient and plan the surgery accurately. If any doubt arises, the image can be
beamed live to the expert and discuss about the problems and if needed, the expert can
guide the surgeon by telesurgery.
ROBOTICS
A number of inherent pitfalls of laparoscopy hinder the performance of certain
laparoscopic operation even after the surgeon has accumulated years of experience. These
pitfalls include an unstable video camera platform, limited motion (degrees of freedom) of
straight laparoscopic instruments, 2 dimensional imaging and poor ergonomics for the
surgeons. Inexperienced or bored laparoscopic camera holders move the camera frequently
and rotate it away from the horizon. The long, straight laparoscopic instruments are limited in
their motion by the trocars. Similarly, the standard 2 dimensional video imaging used in
most laparoscopic operations impedes the surgeons depth perception, compounding
limitations of laparoscopic instruments. The major breakthrough came when in August 1993
Dr. Jonathan Sackier, formerly of Cedars Sinai Medical Center performed the worlds first
laparoscopic cholecystectomy using robotic assistance45. In September 2001, professor J
Marescaux and his team were the first to do telesurgery ( operation Lindbergh)46 its
advantages are 3 D visualization, improved dexterity, greater surgical precision, improved
access, increased range of motion and reproducibility.
References
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2. Litynski Z, High lights in History of Laparoscopy. Frankfurt: B Bernert Verlag, 1996.
3. Mahmud S, Masaud M, Canna K; Fundus-first laparoscopic cholecystectomy; Surg Endosc.2002
Apr;16(4):581-4, Epub 2001 Dec 17.
4. Nahrwold D (1986) The biliary system. In Sabiston X (Eds.) Textbook of surgery. WE Saunders.
Philadelphia.
457
5. Way Lw, Admirand WJ, Dunphy JE (1972) Management of choledocholithiasis. Ann Surg 176:
347-359.
6. Beal J (1984) Historical perspective of gallstone disease. Surg Gynecol Obstet 158:181-189.
7. Hunter JG. Laparoscopic transcystic common bile duct exploration. Am J Surg 1992;163:53-56.
8. Carroll BJ, Phillips EH, daykhovsky L, et al. Laparoscopic choledochoscopy: an effective
approach to the common duct. J Laparoendosc Surg 1992;2:15-21.
9. De Paula AL, Hashiba K, Bafutto M, et al. Laparoscopic antegrade sphincterotomy. Surg
Laparosc Endosc Percutan Tech. 1993;3:157-160.
10. Curet MJ, Pitcher DE, Martin DT, Zucker KA. Laparoscopic antegrade sphincterotomy. A new
technique for the management of complex choledocholithiasis. Ann Surg. 1995;221:149-155.
11. Dallemagne B, Weerts JM, Jehes C, Markiewicz S, Lombard R. Laparoscopic Nissen
fundoplication : preliminary report. Surg Laparosc Endosc 1991;1:138-43.
12. Frantzides CT, Ludwig KA, Quebbeman EJ, Burhop J. Laparoscopic highly selective vagotomy:
technique and case report. Surg Laparosc Endosc 1992;2:348-352.
13. Helms B, czarnetzki D. Laparoscopic proximal selective vagotomy. Minim Invasive Ther
1992;1(suppl1):118.
14. Legrand M, Detroz B, Honore P, Jacquet N. Laparoscopic highly selective vagotomy. Minim
Invasive Ther 1992;1(suppl1):90.
15. Bailey RW, Flowers JL, Graham SM, Zucker KA. Combined laparoscopic cholecystectomy and
selective vagotomy. Surg Laparosc Endosc 1991;1:45-49.
16. Kathhouda N, Mouiel J. A new technique of surgical treatment of chronic duodenal ulcer without
laparotomy by videocoelioscopy. Am J Surg 1991;161:361-364.
17. Uyama I, Sugioka A, Fujita J, et al. Completely laparoscopic proximal gastrectomy with jejunal
interposition and lymphadenectomy. J Am Coll Surg 2000;191(1):114-9.
18. Ziprin P. Ridgway PF, Peck DH, Darzi AW. The theories and realities of port-site metastases: a
critical appraisal. J Am Coll Surg 2002;195(3):395-408.
19. Winslow ER, Brunt LM. Perioperative outcomes of laparoscopic versus open splenectomy:a
metaanalysis with an emphasis on complications, Surgery.2003 Oct;134(4):647-53.
20. Fletcher DR, Jones RM. Laparoscopic cholecystojejunostomy as palliation for obstructive
jaundice in inoperable carcinoma of pancreas. Surg Endosc 1992;6:147-149.
21. Mouiel J, Katkhouda N, White S, Dumas R. Endolaparoscopic palliation of pancreatic cancer.
Surg Laparosc Endosc 1992;3:241-243.
22. Gagner M, Pomp A (1994) Laparoscopic pylorus-preserving pancreaticoduodenectomy. Surg
Endosc 8:408-410.
23. Cuschieri A, Jacomowics JJ, Van Spreeuwel J (1996) Laparoscopic distal 70% pancreatectomy
and splenectomy for chronic pancreatitis. Ann Surg 5:168-179.
24. Brunt LM, Molmenti EP, Kerbl J, et al. Retroperitoneal endoscopic
experimental study. Surg Laparosc Endosc 1993;3:300-306.
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458
29. Gaur DD, Agarwal DK, Purohit KC, Darshne AS. Retroperitoneal laparoscopic pyelolithotomy. J
Urol.1994;151(4):927-929.
30. Micali S, Moore RG, Averch TD, et al. The role of laparoscopy in the management of renal and
ureteric calculi. J Urol. 1997;157:463-466.
31. Hemal AK, Goel A, Kumar M, Gupta NP. Evaluation of laparoscopic retroperitoneal surgery in
urinary stone disease. J Endourol 2001;15(7):701-705.
32. Chander J,Suryavanshi M,Lal P,Singh L,Ramteke VK.Retreperitoneoscopic Pyelolithotomy for
management of renal calculi.JSLS 2005:9(1):97-101
33. Eterovic D, Juretic-Kuscic L, Capkum V, Dujie Z. Pyelolithotomy improves while extracorporeal
lithotiripsy impairs kidney function. J Urol. 1999;161:39-44.
34. Gaur DD, Trivedi S, Prabhudesai MR, Gopichand M. Retroperitoneal laparoscopic pyelolithotomy
for staghorn calculus. J Laparoendosc Adv Surg Tech A.2002;12(4):299-303.
35. Ramakumar S, Lancini V, Chan DY, Parsons JK, Kavoussi LR, Jarrett TW. Laparoscopic
pyeloplasty with concomitant pyelolithotomy. J Urol 2002;167(3):1378-80.
36. Harmon WJ, Kleer E, Segura JW. Laparoscopic pyelolithotomy for calculus removal in a pelvic
kidney. J Urol. 1996;155:2019-2020.
37. Valdivia-Uria JG, Abril Baquero G, Monzon Alegesque F, et al. Laparoscopic management of
complex lithiasis in horse shoe kidneys. Actas Urol Esp. 1994;18(suppl):346-350.
38. Abbou C, Gasman D, Saini F, et al: Radical nephrectomies: A retroperitoneal approach [abstract
no. 1113.]. J Urol 157:286, 1997.
39. Clayman R, Elbahnasy A, Elashry O, et al: Laparoscopic vs. open radical/total nephrectomy for
renal cell carcinoma [abstract no. 1280]. J Urol 157:328. 1997
40. Ono Y, Katoh N, Kinukawa T, et al: Laparoscopic radical nephrectomy:4 years of experience
[abstract no. 157:120,1997.
41. Gill IS, Grune MT, Pomeroy BD: Retroperitoneoscopic radical nephrectomy for renal tumors in
endstage kidneys [abstract no.P6-15]. J Endourol 11:S127, 1997.
42. Ono Y, Katoh N, Kinukawa T, et al: Laparoscopic radical nephrectomy via the retroperitoneal
approach [abstract no. V-38] J Urol 155:297A, 1996.
43. Kathouda N,Wattansini Chaigoon S,Tang E,et al: LAP Lumbar Sympathectomy. Surg Endosc
11:257,1977
44. Ahn SS,Niyama DT,Rud Kin GH,et al :LAP Aortobifemoral bypass.J Vascular Surgery26:128132,1997
45. Sackier JM, Wooters C, Jacobs L, Halverson A, Uecker D, Wang Y, Voice Activation of a surgical
Robotic Assistant. Am J Surg, 1997;174:406-409.
46. Butner SE, Ghodussi M, Wang Y.:Robotic Surgery. The Transatlantic Case, submitted for
publication to 2002 IEEE International Conference on Robotics and Automation, Washington D.C.
459
CHOLELITHIASIS has plagued mankind for over 2000 years. During last several
centuries numerous innovative and creative techniques have been introduced in an effort to
manage patients with symptomatic gallstone disease. The treatment for symptomatic
gallstone disease remained relatively primitive and ineffective until the late 1800s.
John Stough Bobbs of Indianapolis is credited with performing the first operation on
biliary tract in 1867 when he made cholecystostomy, removed gallstones and sutured the
gall bladder closed. Karl Langenbuch is credited with the first cholecystectomy in
1881.Despite the efficacy of this technique physicians have long pursued for less invasive
alternatives. For last 15 years, laparoscopic cholecystectomy has revolutionized the
management of symptomatic gallstone disease.
Over last few years there has been a change in clinicopathological presentation
diagnostic modalities and therapeutic options for biliary calculus disease.
INCIDENCE
There has been an increase in the incidence of gallstone disease all over the world.
--A study conducted at St Georges hospital, London showed that there was an increase in
hospital admissions for cholelithiasis( 30% for males & 64% for females ) in year 1990/2000
as compared to year 1980/1990.
--The prevalence of gall stones in Japan has also risen since early twentieth century from 2
to 7%.1
AETIOLOGY
A change in the trend of gallsone disease from fat, fertile, female of forty to young, asthenic
female in twenties is being noticed.The factors responsible being3 :
Early use of oral contraceptives
Less intake of fat
Higher content of bilirubin and calcium
Low content of phosphorous in bile.
OBESITY still remains a major risk factor in women and statistically significant in men4.
Apart from this, other risk factors being
460
--Age
--Diabetes Mellitus
--Hemolytic diseases
--Pregnancy
--Long term parenteral nutrition
--After vagotomy
--Ethnic background
PATHOPHYSIOLOGY
With present pathophysiological information relating to the formation of gallstones,the
classification into pure and mixed stones is outdated.The accepted current classification
recognizes three main types of gallstones cholesterol, black pigment and brown pigment
stones1.
The pathogenesis of cholesterol stones has been extensively investigated and recent
developments found following factors responsible5: Lithogenic liver(supersaturation of bile with cholesterol)
Guilty gall bladder(gallblader dysmotility and stasis)
Indolent intestines(prolongation of large bowel transit time)
DIAGNOSIS
Epigastric/right upper quadrant pain occurring for 30 to 60 mins after meals -- Suspicion of
gallstone disease.
DIAGNOSTIC MODALITIES
1. Ultrasonography-investigation of choice -90 to 95 % sensitive
2. Radionucleotide scan(HIDA Scan)
3. MRCP
-90 to 95% sensitive and 90 to 100% specific
-detects stones as small as 2 mm in CBD
4. ERCP
-Diagnostic and therapeutic in managing CBD stones
5. Intraoperative cholangiogram (IOC)
-Can safely be omitted without increased incidence of retained stones in following
patients:
No h/o pancreatitis
Normal liver functions
461
462
463
patients. It has been concluded that because of the conditions benign natural history , a wait
and see policy has been recommended in all asymptomatic patients except following9: 1.Diabetes mellitus
2.Acromegaly(on somatostatin therapy)
3.Life expectency > 20 years
4.Calculi > 3 cms/gallbladder wall > 3mm.
5.Individuals from areas with high prevalence of gallbladder cancer.
6.Chronically obliterated cystic duct.
7.Non- functioning gallbladder.
8.Porcelain gallbladder.
9.Gallbladder polyp > 10 mm.
References
1. Alferd Cushieri. Disorders of biliary tract. Essential Surgical Practice 2004;375-452.
2. Shaffer EA. Epiemiology and risk factors for gallstone disease; has the paradigm changedin the
21st century? Curr Gastroenterol Rep 2005 May ;7(2): 132-40.
3. Gupta RL, Sharma SB , Kumar SP. Changing trends in gallbladder stone disease -an observation.
Indian J Med Sci 1998 Jul ; 52(7):309-16.
4. Ostrowska L, Czapska D, Karzewski JK. Body weight gain as a major factor of cholelithiasis in
women and an important risk factor in man. Rocz Akad Med Biolymst .2005 ;50 Suppl 1 :54-6.
5. Dowling RH . Review: pathogenesis of gallstones. Aliment Pharmacol Ther .2000 May ;14 Suppl 2
:39-47.
6. Peter Shamamiam , Michael Grasso. Management of complex biliary tract calculi with a holmium
laser. J Gastrointest Surg 2004;8:191-199.
7. G.Saomani , V.Durante, M.R. Magnolia.ombined endoscopic treatment for cholelithiasis associated
with choledocholithiasis. Surg Endosc 2005; 19 : 910-914.
8. Gupta SK , Shukla VK . Silent gallstones :a therapeutic dilemma. Trop Gastroenterrol . 2005 AprJun; 25(2) :65-8.
9. Picci R , Perri SG ,Dalla Torre A. Therapy of asymptomatic gallstones: indications and limits. Chir
Ital .2005 Jan-Feb;57(1): 35-45.
464
INTRODUCTION
Gallstone disease is one of the most common problem affecting digestive
tract.Autopsy reports have shown a prevalence of gallstones from 11% to 36% with an
average value of 18.9% for women & 9.5% for men.Incidence of asymptomatic gallstones84.9% for women & 87% for men.Prevalence of gallstones in females is approximately twice
that of male population.Highest prevalence is seen in pima indian tribe of Arizona and it is
rare in Africa.The aim of this review is to discuss
cholecystolithiasis(gallstones).Natural
history,surgical
management
of
465
Black pigment stones--Forms in gallbladder & accounts for 25% of stones in the west,although their prevalence is
higher in Asian countries.Composed of bilirubin polymers without calcium palmitate,varying
amount of cholesterol(3-25%) & a matrix of organic material. Associated infection is present
in less than 20% of cases.They are usually multiple,small,irregular & dark green to black in
colour.Their consistency is hard & they have a layered cut surface. They are found in
situations where there is excessive hemolysis & where hepatic function is deranged(as in
cirrhosis).In these cases fraction of bilirubin escaping conjugation increases.the resultant
excess unconjugated bilirubin is vulnerable to polymerization and co-precipitation with free
ionized calcium.Vast majority occurs in patients without detectable chronic hemolysis.
Brown pigment stones--In contradiction to the above type,these stones form in the bile ducts(primary ductal calculi)
& associated with infection of the biliary tract. In the far east,those earthy brown pigment
stones occur more frequently than cholesterol rich stones. Attributed to bacterial infection
and occasionally to parasitic warms(Ascaris lumbricoides,Clonorchis sinensis and even
Schistosoma japonicum) in the biliary tree.Scanning electron microscopy of fresh specimen
demonstrates bacteria inside crevices & pits of those amorphous soft stones in
98%.Contains calcium bilirubinate,calcium palmitate and only small amount of cholesterol
bound
in
matrix
of
small
amount
of
organic
material.Mikes
Classical
debris,dead
bacteria
&
amorphous
material
to
form
typical
466
467
this, considerable quantities of cholesterol are carried in normal bile as a clear one phase
solution.In the past,it was assumed that the lipophillic cholesterol was solubilized in the bile
by the combined detergent action of bile acids & phospholipids.In 1950s, Isaksson &
colleagues(1954)defined cholesterol solubility in bile by Isaksson Ratio.(ratio of bile acids &
phospholipids:cholesterol).They showed that the ratio was high in stone free control subjects
& low in gallstones carriers.In 1960s, Small,Dervichian & colleagues used classical
physiochemical methods to characterize more accurately how cholesterol was solubilized by
bile acids & phospholipids in water.They fixed the percentage of water in bile as 90%(the
proportion normally found in bile) and used as triangular co-ordinates to prepare phase
diagrams which defines the maximum solubility of cholesterol in model bile.
But for several reasons we now know that there are limitations to this approach First, many investigators were unable to reproduce Admirand and Smalls original findings.
Many stone free individuals had supersaturated bile and there was a large degree of overlap
in saturation indices between control subjects & gallstone patients.
Second, as a result specificity of demonstrating supersaturated bile was low.The factor
which distinguished best between stone-free control & gallstone patient was not
supersaturated bile,but the nucleation time.
Third, in dilute hepatic bile, cholesterol is not transported as micelles rather as small
phospholipid/cholesterol liposomes or vesicles.
THE TRIPLE DEFECT IN CHOLESTEROL GALLSTONE FORMATION--1. Supersaturation with cholesterol :
The presence of supersaturated bile is prerequisite for the development of
gallstone;without it they cannot form. But its a non specific finding.Supersaturation is
common in stone free individuals. Lithogenic index is the ratio of the actual amount of
cholesterol that can be dissolved in the bile sample using triangular co-ordinate
plots(Thomes & Hoffman 1973).A lithogenic index of >1 indicates supersaturated
bile(with respect to cholesterol).The normal ratio : conc bile salts + conc
phospholipids/conc cholesterol=10:1.
1.
Nucleation defect :
468
3.
Anti-nucleators
Apolipoprotein
A-I&A-II
Apoliporotein B
Lectin-bound protein
Phospholipids.
Serpins
(in high conc.).
Ursode-oxycholic acid.
Fatty acids.
Bile acids
conjugates.
Gall-bladder stasis :
octriotide
injury,vagotomy,gastrectomy,obesity,rapid
treatment,high
weight
spinal
loss,gastric
cord
bypass
469
Role of bacteria--With the advent of electron microscopy, several investigators have noted the
presence of chains of cocci on the outer surface & in the interior of split
gallstones,often nestling in the clefts between sheets of crystals.Swidsinski (1998)
used nested PCR techniques to look for bacteria DNA in gallstone.On routine
bacteriological culture, only 9% of gallstones from 100 patients were positive
although bacterial DNA was found in the stones from 82 of the remaining 91
patients(90%)4.Most mixed cholesterol stones had bacterial DNA sequences
whereas only 1 in 7(14%) pure cholesterol stones yielded a PCR product(Lee et al
1999)5.
Role of non cholesterol material at the core of cholesterol stones--In the centre of cholesterol stones there is often a non-cholesterol pigment rich core
or nucleus which consists of calcium bilirubinate,calcium carbonate& mucin.Most
common calcium salt in gallstones is calcium carbonate.Calcium salt precipitate
out of the solution when product of their cation concentration times their anion
concentration exceeds the solubility product (or ksp) of the salt.Hepatic bile is
almost invariably supersaturated with calcium carbonate as compared to
unsaturated bile in gallbladder,but stones forms in gallbladder because additional
factors such as stasis is equally important.In patients who form calcified gallstones,
although gallbladder bile is supersaturated with calcium carbonate,the cation
concentration(Ca++) is normal.The factor responsible for supersaturation is high
anion (CO3=) concentration.In turn ,the explanation for the high carbonate ion
concentration seems to be defective acid secretion by a diseased gallbladder
mucosa.Impaired hydrogen ion secretion results in a raised pH within the
gallbladder lumen.This is in turn responsible for a low(Co2), a high [CO3=] and
therefore a high [Ca++] *[CO3=]product in gallbladder bile.
470
positive paternal family history & presence of gallstone disease in women.In Chilean
Amerindians & Hispanics (who have a high prevalence of gallstones) cholesterol
lithogenic genes are found frequently7.Most convincing evidence that bile-lipid
secretion is at least partly under genetic control comes from two separate groups of
studies in experimental animals.
Transgenic animals : Smit & colleagues (1993) showed that deletion of mdr-2
gene caused liver disease with bile duct proliferation & portal inflammation
incompatible with life.The correspponding gene in humans is called the mdr-3
gene.The relevance of these observations to human gallstone disease is
uncertain.However it clearly establishes that in animals and perhaps in men bile
lipid secretion can be influenced markedly by genes.
Recent developments in cholesterol microcrystal nucleation--1. Identification of new pro - & anti nucleating factors:
2. Role of aspirin& NSAIDs : though some researchers found that
in high
471
releasing
peptide,VIP,peptide
yy
and
calcitonin-gene
related
peptile(CGRP).In gallstone carriers there are strong and weak contractors and in
weak contractors,CCK receptor structure of the gallbladder myocetes is
altered.The defect in gallbladder contraction does not involve an intracellular signal
transduction pathway-but rather sarcolemmal membrane.
MODELS OF HUMAN GALLSTONE DISEASE--1.
2.
develops
rapidly
in
obese
individuals
undergoing
rapid
weight
in
those
receiving
oral
urso-deoxycholic
acid
in
different
doses(300mg,600mg,1200mg/day).
3.
472
4.
is
relatively
longlasting
analogue
of
native
human
473
Iron deficiency-Johnston et al13(1997) showed that iron deficient diet leads to lower 7alpha hydroxylase levels,high saturation indices and more cholesterol crystals per high
powered field.
Role
of
Apoliprotein
E4---This
apoliprotein
increases
intestinal
cholesterol
474
bilirubin glucuronide , the water soluble form of bilirubin in bile, to free unconjugated bilirubin.
The latter is water insoluble & combines with ionized calcium in bile to form calcium
bilirubinate leading to stone formation.Up-regulated cholesterogenesis & down- regulated
bile acid synthesis in the liver may be one of the etiologic factors responsible for the
formation of hepatic bile substantially supersaturated with cholesterol ,which leads to
subsequent formation of cholesterol- rich stones.The most important factors for the formation
of intra-hepatic calcium bilirubinate stones are considered to be biliary stasis, bacterial
infection and biliary mucin.Chronic proliferative inflammation is suggested to precede bile
duct deformations and the development of intrahepatic stone formation may make strictures
which promote further growth of initial stones through alternations of bile flow.A study on the
biliary dynamics in patients with intrahepatic stones revealed that biliary stasis might exist
not only in affected but in unaffected intrahepatic bile ducts compared with normal subjects.
Further more , the time activity curves in the bile ducts of the left lobe were significantly
longer than in those of right lobe, even in normal subjects.the prolongation in the left
intrahepatic bile ducts could explain why involvement of the left lobe are prominent.The
abnormality of the sphincter of oddi probably plays little role in etiology of intrahepatic
stones.
Metabolic factors like cholesterol supersaturation and microscopic cholesterol crystals play
an important etiological role in intrahepatic cholesterol stones like cholesterol gallbladder
stones.Activity of the Apolipoprotein A-1 which is one of the inhibiting factors of cholesterol
nucleation in bile is reported to decrease in the hepatic segments containing cholesterol
stones.
Bibliography
1.Rajagopal S U, Keightley A , Bills P,Walters J R F,Murphy G M, Dowling R H 1989 Predictive
value of pre-treatment CT scanning vs conventional radiology in determining
composition,dissolvability and fragmentability of gallbladder stones(GBS).Journal of Hepatology 9
: S211(Abstract)
2.Pauletzki J, Althanus R, Holl J, Sackmann M, Paumgartner G 1996 Gallbladder emptying and
gallstone formation : aprospective study on gallstone recurrence. Gastroenterology 111: 765-771
3.Rege R V,Pyrstowsky J B 1998 Inflammation and thickened mucus layer in mice with cholesterol
gallstones.Journal of Surgical research 74: 81-85.
4.Swidsinski A,Khilkin M,Pahlig H,Swidsinski S,Priem F 1998 Time dependent changes in the
concentration and type of bacterial sequences found in cholesterol gallstones. Hepatology 27:
662-665
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Journal of Gastroenterology 94: 3502-3506
6.Attili A F, Capocaccia L, Carulli N, Festi D et al 1997 Factors associated with gallstone disease in
the MICOL experience.I.Hepatology 26 ; 809-818.
7.Miquel J F, Covarrubias C,Villaroel L et al 1998 Genetic epidemiology of cholesterol cholelithiasis
among Chilean Hispanics, Amerindians and Maoris.Gastroenterology 115: 937-946
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8.Lammert F, Wang D Q, Paigen B,Carey M C 1999 Phenotypic characterization of lith genes that
determine susceptibility to cholesterol cholelithiasis in inbred mice: integrated activities of hepatic
lipid regulatory enzymes. Journal of Lipid research 40: 2080-2090
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pigment & cholesterol stones.Gastroenterology 97 :1479-1484.
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pigment and cholesterol stones.Gastroenterology 113:930-937.
11.Chen Q,Amaral J,Bincani P 1999 Excess membrane cholesterol alters human gallbladder muscle
contractility and membrane fluidity.Gastroenterology 116:678-685.
12.Hendel H W,Hojgaard L,Andersen T et al 1998 Fasting gallbladder volume and lithogenicity in
relation to glucose tolerance,total and intra-abdominal fat masses in obese non-diabetic
subjects.International Journal of Obesity and Related Metabolic Disorders 22: 294-302
13.Johnston S M, Murray K P, Martin S A et al 1997 Iron deficiency enhances cholesterol gallstone
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th
476
th
In the last few decades, mainly eighties and early nineties, many diagnostic and
therapeutic modalities for biliary calculus disease were tried. Some of these like laparoscopic
cholecystectomy have stood the test of time and have been further refined. Some others
have fallen aside or have limited usefulness. We will briefly consider some of these in this
article and their present status. These advances include the diagnostic tools like the
Ultrasound, CT scan, MRI -
ultrasonography. On the therapeutic side oral bile acid therapy, extracorporeal shock wave
lithotripsy, percutaneous transhepatic contact dissolution, percutaneous gallstone extraction,
laparoscopic
approach,
open
mini-cholecystectomy,
and
endoscopic-laparoscopic-
percutaneous approaches to the CBD are some of the recent modalities tried. Management
of CBD stone is also fiercely debated. Since the diagnostic aspect, laparoscopic
management, role of endoscopy and open cholecystectomy is being separately discussed,
this article will mainly address the issues of dissolution of gall stones, ESWL, and the
management of CBD stones. One latest advance at the experimental level is the advent of
transgastric endoscopic surgery. We will briefly cover its progress, the present status and
future possibilities.
Dissolution of gall stones - Bile Acid Therapy
Gall Stone disease has been seen in 10-15% of population in surveys from the
industrialized countriesxxxiv. In mildly symptomatic disease, at least in a subset of patients,
surgical treatment could be replaced by other methods. Surgery is associated with 0.3- 0.5%
incidence of bile duct injuries and about 20% of patients continue to suffer from pain for
which the original surgery was donexxxv. Preserving the gall bladder and dissolving the gall
stone could be considered as most physiological form of treatment.
First dissolution of gall stones in man using chenodeoxycholic acid (CDCA) was
reported by Danzinger et al in 1972xxxvi. Makino et al used Ursodeoxy cholic acid (UDCA) in
1975xxxvii. Since then these have been extensively studied. While both these are naturally
occurring bile acids in humans, UDCA is present only in traces. It can be manufactured from
CDCA both in liver and the intestine. UDCA is now considered to be the better bile acid of
the two as it is more effective and has lesser side effects. CDCA causes diarrhoea in 40%
and hypertransaminasaemia in 15%. These effects are dose related and may lead to
noncompliance in significant number of patients. UDCA on the other hand has no such side
477
478
Recurrence of stones is considerable (39-47% over 5 years) and is the main reason for
limited use of this technology, which is also costly. Although no deaths have been reported
due to ESWL, pancreatitis, liver haematoma and biliary colics are not uncommon. ESWL is
now used only for CBD stones resistant to endoscopic extraction and rarely for gall stonexli.
Management of CBD stones
Management of CBD stones is currently intensely debated between the surgeons,
laparoscopic surgeons and the endoscopists. Appropriate treatment is governed by the
patients condition, and the expertise available. It also depends on the stage at which the
stones are detected in the CBDxlii.
Diagnosis of CBD stone. Based on history the detection of CBD stone is 7%, 16%, 20%,
45% and 100% for cholecystitis, biliary colic, pancreatitis, jaundice and cholangitis. In 1000
consecutive patients with intraoperative cholangiography Tranter et al demonstrated an
incidence of 14.2% for CBD stonesxliii.
Amongst the diagnostic modalities LFT, abdominal ultrasound, MRCP with MRI,
CECT ERCP and endoscopic ultrasound have been investigated extensively. ERCP has a
procedure related mortality of 1% and a morbidity of about 15%. Only 40% of all ERCP for
CBD stone will be found positive and hence a selective approach may be of benefit in
reducing this morbidity and mortality. Endosonography, MRCP and Helical CT are equally
efficient in detecting CBD stone in the range of 95-98%. Endosonography may be better for
stones smaller than 5mm but is operator dependent. However all these are expensive and
may add to the treatment costs.
Preoperative Endoscopic Therapy. Preoperative ERCP may be unnecessary in 60% of
the patient besides carrying significant morbidity and some mortalityxliv. It should therefore be
done in cases of high suspicion of CBD stones. Advantage of preoperative ERCP is that
cases of failure may be dealt at the time of operation. In cases of unfit elderly patients EPT
alone could be done with gall bladder left in situ.
To reduce the morbidity of sphincterotomy, balloon dilatation was tried. Recent
studies have shown it to be associated with higher rates of pancreatitis and this procedure is
therefore not recommended at present.
Laparoscopic CBD Exploration. Laparoscopically, CBD stones can be detected with
peroperative cholangiography or by laparoscopic ultrasound with equal efficacy. CBD can be
explored transcystic or by choledochotomy. The choledochotomy can be closed primarily,
over an antegrade stent or with T Tube. Retained stones can be removed percutaneously
479
xlvi
operation should preferably be dealt with laparoscopic or open exploration depending on the
expertise. Sometimes stones in a thin CBD may be left as the risk may be higher of causing
CBD stricture. Smaller stones may be able to pass on their own.
Open CBD Exploration and Choledochoenterostomy. Open CBD exploration is time
tested method and should be undertaken whenever required. It should be undertaken if
there are multiple stones with dilated CBD requiring choledochoduodenostomy, impacted
stone at ampulla, large stones, laparoscopic expertise is not available or it fails.
Algorithm for management of CBD stones
Cholelithiasis with suspected choledocholithiasis
LFT
US
Stone
Negative
MRCP (95-100%)
Stone
No Stone
ERCP + EPT
Lap CCx
No IOC
Successful
Fit
Lap CCx
Unsuccessful
Retained Stone
Unfit
ES + Stone Extraction
Observe
480
Expertise
Primary Closure
(Stented)
Bilioenteric anas
T tube
No stone
Remove T tube
Remove T tube
Retained Stone
Remove via T tube/ES
481
482
Open cholecystectomy has been employed for over 100 years and is a safe and
effective method for treating symptomatic gallstones, ones that are causing significant
symptoms. At surgery, direct visualization and palpation of the gallbladder, bile duct, cystic
duct, and blood vessels allow safe and accurate dissection and removal of the gallbladder.
Intra-operative cholangiography has been variably used as an adjunct to this operation.
Laparoscopic cholecystectomy is now the standard treatment for symptomatic
gallstones. Soon after the introduction in 1987 of laparoscopic cholecystectomy, it was
considered the method of choice for treatment of gallstone disease (1). Initially it was also
thought that it might confer economic advantages over open surgery. At that time, little
information
was
available
concerning
mini-laparotomy
or
small-incision,
open
cholecystectomy. Later single blind, randomized controlled trials have indicated that
convalescence differences between laparoscopic and small-incision surgery are small (7).
No significant differences were observed between mini-laparotomy and laparoscopic
cholecystectomy in terms of patients' opinion of general well being, abdominal pain, and
scarring one year after surgery. Health-care costs are lower after mini-laparotomy
cholecystectomy than after laparoscopic cholecystectomy.
Conversion of laparoscopic cholecystectomy to open cholecystectomy is performed
in 5.3 to 10.6 % cases (5). Open cholecystectomy therefore should be performed in
approximately 10% cases if the reasons for conversion can be diagnosed preoperatively.
The reasons for conversion were liability to identify anatomical structures correctly
secondary to severe inflammation or dense adhesions, hemorrhage, bile duct injury,
choledocholithiasis and gallbladder cancer. Out of all these conditions choledocholithiasis
and a thickened gallbladder wall were the most predictive of conversions (4).
Laparoscopic cholecystectomy is converted to open in a simple gall bladder, it is
most commonly due to injuries. The incidence of bile duct injury is higher than for open
cholecystectomy. The results of four multicenters study of laparoscopic cholecystectomy
show a morbidity rate of 3.0% and a mortality rate of 0.05%. Injuries to the common bile duct
or to an accessory bile duct occurred in 0.43% of cases and were recognized and treated
intraoperatively in 31.3% (5).
483
several
options
are
available.
Endoscopic
retrograde
surgeons
consider
empyema
relative
484
contraindication
to
laparoscopic
cholecystectomy, because of the increased risk of common duct injury or potential spillage of
infected bile.
Gangrenous Cholecystitis has high chances of bile spillage during manipulation of the
gallbladder, therefore the presence of gangrenous cholecystitis precludes removal of the
gallbladder laparoscopically. If not suspected preoperatively, gangrenous cholecystitis will be
apparent after introduction of the laparoscope and visualization of the gallbladder. In this
instance, safety concerns necessitate open cholecystectomy.
Patients with a medical illness considered to be a contraindication to general anesthesia
are not eligible for laparoscopic cholecystectomy. If open cholecystectomy is contraindicated
because of a severe underlying medical illness such as cardiac or pulmonary disease,
laparoscopic surgery is also contraindicated. Patients who are at high risk for complications
associated with anesthesia should be considered for alternative therapy for symptomatic
cholelithiasis, such as lithotripsy or dissolution therapy.
Because hemostasis is difficult to obtain through the laparoscope, coagulopathy is a
contraindication to laparoscopic surgery. Patients with thrombocytopenia, deficiency of
clotting factors or a prolonged bleeding time should undergo open cholecystectomy.
Patients with cirrhosis and portal hypertension are at increased risk for bleeding during
both open and laparoscopic cholecystectomy. Tributaries of the portal vein are dilated and
under high pressure in the liver bed and porta hepatis. Open cholecystectomy, which allows
direct access for control of hemostasis, is more appropriate in patients with portal
hypertension because profuse and intractable bleeding may be encountered in this situation.
Advocates of open cholecystectomy by mini incision still exist, particularly in European
countries. As per the proponents open, small incision cholecystectomy for all patients is
compatible with short hospital stay, evidence-based gall bladder surgery, and training of
surgical residents (7). In India away from the urban and mostly semi urban towns, open
cholecystectomy still is the most performed procedure.
Bibliography
1. Cushieri A, Dubois F, Mouiel J et al. The European experience with laparoscopic
cholecystectomy. Am J Surg 1991;161:385-387.
2. MacFadyen BV Jr, Vecchio R, Ricardo AE. Bile duct injury after laparoscopic cholecystectomy.
The United States experience. Surg Endosc 1998;12:315-321.
3. Way LW, Stewart L et al. Causes and prevention of laparoscopic bile duct analysis of 252 cases
from a human factors and cognitive psychology perspective. Ann Surg 2003;237:460-469.
4. Ishizaki Y, Miwa K, et al. Conversion of elective laparoscopic to open cholecystectomy between
1993 and 2004. Br J Surg 2006;93:987-991.
485
486
487
surgeon must make a cut that exposes the area of the body to be operated on. Until a few
years ago, opening up the body was the only way a surgeon could perform the procedure.
Now, laparoscopy eliminates the need for a large cut. Instead, the surgeon uses a
laparoscope, a thin telescope-like instrument that provides interior views of the body.
MAIN WORRY WITH LAPAROSCOPIC CHOLECYSTECTOMY
The wide-spread use of laparoscopic cholecystectomy is associated with an
increased risk of intra-operative injury involving the bile ducts, bowel, and vascular structures
as compared to open cholecystectomy. Since surgeons are reluctant to publish their own
complications rate, and since the complications of laparoscopic cholecystectomy are treated
in tertiary centers, the precise magnitude of the problem remains obscure. Large populationbased studies have, however, allowed an accurate estimate the magnitude of the increased
risks following laparoscopic cholecystectomy.
Misidentification of anatomy appears to be the most common cause of laparoscopic
bile duct injury. The most common scenario, initially described by surgeons at Duke
University as the "classic" Injury, occurred in 63% of their patients. The "classic" injury
occurs due to mistaking the common bile duct for the cystic duct. The Common Bile Duct
then is clipped and divided. Further retraction of the gallbladder then leads to a second
higher injury with division of the common hepatic duct as it approaches the bifurcation. This
second ductal injury is often described in the operative note as being a 'second cystic duct"
or "an accessory duct." This injury is particularly devastating as complete transection of the
biliary tree virtually removes any possibility of non-operative management by either
endoscopic or transhepatic technique and mandates the need for surgical reconstruction of
the biliary tree to establish biliary-enteric drainage.
Other less common mechanisms of injury include a "tenting injury" in which the
common bile duct is pulled laterally at the time of occlusion of the cystic duct and caught in
the clip, thermal injuries due to injudicious use of cautery or laser, excessive application of
clips to control bleeding in the area of the triangle of Calot. and. finally, injuries to an
aberrant or low-inserting right hepatic duct. Regardless of the nature of the injury, the
majority of. biliary injuries are not recognized during the initial laparoscopic cholecystectomy.
Delay in recognition of biliary injuries invariably results in infection and significantly reduces
the chance for optimal outcome after reconstruction.
The SAGES guidelines require the surgeons to adhere the the following steps:
1. The surgeon must clearly identify the cystic duct at its junction with the gallbladder
488
2. The surgeon should retract the gallbladder infundibulum laterally rather than in
cephalad direction
3. The surgeon should Meticulously dissect the cystic duct and cystic artery.
4. The surgeon should limit the use of all energy sources near the Common Bile Duct
and recognize that they can cause occult injury.
5. The surgeon should use operative cholangiography liberally to discover surgically
important anomalies, clarify difficult anatomy and to detect common bile duct stones.
6. The surgeon should not hesitate to convert to an open operation for technical
difficulties, anatomic uncertainties, or anatomic anomalies, especially in cases of
acute cholecystitis
7. The surgeon need to see all structures clearly before dividing any ductal structures
LATERAL RETRACTION OF THE INFUNDIBULUM
In 1991 Hunter proposed a 5 step approach to prevent the high rate of biliary injury in the
United States. Hunter noted that Bile duct injuries with
laparoscopic cholecystectomy appeared to be more common in
the U.S. (0.5 to 2.7%) than in Europe (0.33%) . He observed that
American teaching stressed cephalic (towards the Right
shoulder) traction on the infundibulum of the gallbladder, tenting
the CBD and risking its mis-identification. The cystic duct
emerges at acute angle to the CBD and this angle actually narrows when the fundus is
retracted towards the shoulder. From the perspective of the telescope, the distal Common
Bile Duct appears continuous with the cystic duct and can easily be mistakenly identified as
a long cystic duct. European instruction stresses the lateral retraction. Such retraction places
the cystic duct at right angles to the CBD, reducing the likelihood of misidentification.
GANESHA SIGN
No clip should be placed on, and no incision should be made in, any structure until the
transition between cystic duct and gallbladder infundibulum is clearly
visualized. This is known as the Ganesha sign
amongst Indian laparoscopic surgeons. It is not
adequate to see the cystic duct '"entering" the
gallbladder" as this may belie a tented
Common
Bile
Duct
coursing
behind the
gallbladder, drawn up by chronic inflammation. Safe dissection absolutely requires that the
cystic duct must be seen widening into the gallbladder before one can certify accurate
489
anatomic identification. In the case of the absent, or short, wide-mouthed cystic duct
identified during this step, the surgeon must consider conversion to open cholecystectomy or
develop the skills to laparoscopically suture the cystic duct stump without impinging on the
lumen of the Common Bile Duct .
490
Jaundice (Icterus) : Jaundice is yellowish tint or discoloration of body tissues including skin
as well as deep tissues.
Carotenemia also produces yellowish discoloration but importantly it does not produce
Scleral Icterus; the reason for which becomes clear as we proceed in our discussion.
The symptomatology & signs that appear in the due course of jaundice which progresses
from mild to severe and from acute to chronically progressive disease state can be easily
explained & understood by going into the details of physiology & pathophysiology of biliary
metabolism.
Normal Secretion of Bile: 600-1200 ml/day
Bilirubin Yellowish Red- pigment (C33H36O6N4)) produced 300 mg/day
COMPOSITION OF BILE
Liver Bile
G. B. Bile
Water
97.5 gm/dL
92 gm/dL
Bile Salts
1.1 gm/dL
6 gm/dL
Bilirubin
0.04 gm/dL
0.3 gm/dL
Cholestrol
0.1 gm/dL
Fatty Acids
0.12 gm/dL
Lecithin
0.04 gm/dL
0.3 gm/dL
145 m Eq/L
130 m Eq/L
5 m Eq/L
12 m Eq/L
Ca
5 m Eq/L
23 m Eq/L
CL-
100 mEq/L
25 m Eq/L
HCO3-
28 mEq/L
10 m Eq/L
Na
+
491
Total Bilirubin
Generally Indirect Fraction is calculated as:Total Bilirubin Direct Bilirubin Fraction = Indirect Bilirubin Fraction
Normal Bilirubin Concentration in plasma is 0.2 1.0 mg% and clinically icterus
begins to appear when plasma concentration becomes 2-3 times the normal values. Scleral
icterus becomes evident at 2.5mg% & cutaneous/mucous membrane icterus at 6.0 mg%.
The clinical journey of birth of jaundice begins with the death of Red Blood Cells - the
poor cell which nourished our tissues through out its life; along with other heme containing
cells.
Let us now summarize the clinical signs of Jaundice so that we can understand their
basis while we go through the journey of senescent RBCs & destruction of other heme
containing proteins.
The patient of jaundice may be
-
asymptomatic
Pruritus
Malaise
492
Mailaise
Anorexia
Dark Urine
Amenorrhea
Vascular Spiders
Palmar Erythema
Ascites
Gynecomastia
Weight Loss
Fetor Hepaticus
Asterixis
Bleeding tendencies
Vitamin deficiency
Weight Loss
493
Let us now take a look at the formation of bile and how the obstructive state
leads to the signs above.
Marrow
days)
deformable
Rheological
becomes
with
leads
this
Destruction
less
Maturing
altered
to
of
15-20%
Erythroid Cells.
their
early
labeled
of
(80-85%
source
fraction
Liver
of
Turnover
bilirubin)
heme
&
of
heme
products P450
etc.
Globins/Proteins
Hemoglobin/Hemeproteins
Heme (Tetra pyrole ring)
Straight Chain
Heme oxygenase
Biliverdin
Biliverdin reductase
Bilirubin
The older less deformable RBCs get ruptured in the splenic capillaries as they are now not
able to negotiate the smaller diameter capillaries as compared to their own diameter.
Rupture of RBC membrane releases Hemoglobin
This hemoglobin is spontaneously phagocytosed by tissue macrophages
(The Reticuloendothelial system Kupffers cells of liver)
494
Heme
Globin Re-used
Transferrin + Fe++
Biliverdin
Bilirubin
Loosely complexes reversibly with plasma albumin which acts as carrier protein to take
bilirubin to liver for further metabolism to water soluble form
(In chronic long standing conjugated hyperbilirubinaemia this reversible form partly becomes
irreversible to form Delta fraction.)
This binding to plasma albumin is important in infants predisposed to Kernicterus (affecting
lipid rich Basal ganglia controlling motor activity)
Sulfonamides displace this bilirubin from albumin binding sites by competitive action & leads
to aggravation of disease state.
495
Once this Albumin Bilirubin complex reaches hepatocytes there is carrier mediated uptake
at sinusoidal membrane.
Albumin Bilurubin
Albumin Back
to Plasma
Bilirubin
Glucuronic acid
10% to other
Products
Uridine
Di-phosphate
Glucuronyl
Transferase
10% Bilirubin
Sulphate
Glucuronic Acid
Bilirubin
Diglucuronide (80%)
Hepatic Ducts
Gall Bladder
Cystic Duct
CBD
Duodenum
496
Once into the gut, Conjugated Bilirubin diglucuronide and monoglucuronide is acted upon by
bacterial -Glucuronidase enzyme.
Bilirubin Mono & Di-Glucuronide in Gut
-Glucuronidase
20% is re-absorbed
in ileum & colon
Liver
Excreted by Kidneys
This Stercobilin imports yellow
color to stool.
Gut
Urobilin
Here it becomes clear that in cases of complete obstruction no conjugated bilirubin reaches
gut & consequently no urobilinogen & stercobilin So no yellow color to stools Clay
colored stools.
Obstructive Jaundice : Also known as Conjugated Hyperbilirubinemia
As we can infer from the flow diagram conjugated hyperbilirubinemia may occur due to
(i)
(ii)
497
The end result of both these being conjugated bilirubin diffusing back into blood capillaries
with consequent raised plasma bilirubin levels.
As we have seen that bile also contains bile salts & bile acids and in cases of
50%
Diffusion
Gut
The Enterohepatic
Circulation
(About 18 such
cycles daily)
Bile
50%
Active Transport
Portal Blood
Liver
The Bile Salts thus diffusing back to plasma gets deposited into skin where it leads to mast
cell degranulation on consequent itching Pruritus - & therefore this pruritus is effect of
bile salts & not bilirubin as commonly perceived.
Conjugated bilirubin diffusing back to plasma is still soluble & therefore easily excreted by
kidneys producing high colored urine. Unconjugated bilirubin is not filtered at kidneys.
This forms important feature which helps us to easily detect type of Jaundice by examining
urine for
1. In complete obstruction no Urobilinogen in Urine.
2. Urine test positive for conjugated bilirubin but negative for free unconjugated bilirubin.
The stasis of bile into the ducts partial or complete leads to inflammation leading to pain
perceived by patient or the tenderness we elicit.
The hollow viscus when tries to clear the obstruction, produces colic against the
background constant pain. Since the patient perceives some degree of pain or there is
tenderness when patient is examined the biliary colic is not true colic as there is no
symptom free interval as per definition of colicky pain.
498
Bilirubin has affinity for Elastin, which being rich in sclera & skin accounts for
scleral and cutaneous icterus. Carotene has no such affinity for elastin &
therefore does not stain sclera.
499
Gynecomastia
Vascular Spiders
Palmar Erythema
Cirrhosis,
Facial
telangiectesia
Dupuytrens Contracture
Liver is the site of synthesis of Ceruloplasmin- the Copper binding protein & in chronic
obstruction with attendant liver damage Ceruloplasmin synthesis is hampered with
subsequent copper deposition at iris Kayser Fleischers Ring.
Advanced obstructive damage leads to inability to metabolise urea. This hyper ceramic
state cause hepato-cerebral syndrome with tumor known as asterixis. And also at such
advanced disease state there is musty odor of breath & urine imported due to
mercaptans, is known as Fetor Hepaticus.
Occult blood loss with weight loss are features in obstruction due to ampullary
carcinoma along with intermittent jaundice. The jaundice clearing when a part of tumor
500
sloughs out. Blood loss is from fragile neo-vasculature of tumor which at some time also
erodes areas having normal vasculature.
-
In obstruction of biliary tract levels of bilirubin tend to plateau at 30-40 mg% (510-680
mol/L) because bile salts leaking back to plasma along with conjugated bilirubin tend to
enhance glomerular filteration of bilirubin diglucuronide. This is not the case with
hepatocellular disease where only conjugated bilirubin leaks to plasma but bile salts are
excreted into gut & consequently higher bilirubin levels are seen in hepatocellular
disease & this high level may also be indicative of acute renal failure i.e.a patient who
suddenly shows acute rise of plasma bilirubin.
Biliary obstruction is associated with depression of RES & this leads to decreased
endotoxin clearance with spillover leading to systemic endotoxemia)
Sepsis Syndrome
Charcots triad
Cholangitis
Alteration of host defence
- Fever
- Right Upper Quadrant pain
- Jaundice
are characteristic of cholangitis.
501
Bile contains bile salts & mainly the phospholipid lecithin which are extremely important for
emulsification.
These have water soluble & fat soluble ends. Fat soluble portions dissolve in surface layer of
fat globule with polar portions projecting outwards & soluble in surrounding fluids; this greatly
decreases the interfacial tension of fat. When tension is low, this non-miscible fluid on
agitation can be broken into many smaller particles far more easily. Each time diameter of fat
globules decrease by factor of 2 total surface area increases by 2.
The lipases are water soluble compounds & can attack fat globules only on their surfaces.
Role of Bile Salts in accelerating Fat digestion Formation of Micelles
End-product of fat digestion are
1) Free Fatty Acids
2) 2- Monoglycerides
Tri Glycerides
(Emulsified Fat)
Lipase
From
pancreas
FFA +
2- Monoglycerides
As this is reversible reaction digestion of fats to continue needs quick removal of F.F.A. & 2Monoglycerides; so that unidirectional character remains maintained.
Bile salts when in high concentration have propensity to form
micelles small
502
It is evident that when bile is not able to reach gut, there is improper digestion & absorption
of fat & fat soluble vitamins (A, D, E, K). Fat is lost in stools leading to foul smelling sticky
stools (Steatorrhea)
Vitamin A & E deficiency causes coarse skin with vision problem as Vitamin A
(Retinol) is important for Rhodopsin (Dark Vision) & also iodopsin (Color vision).
503
504
(b) In certain situations with isolated born metastasis surgical treatment is considered
along with appropriate local treatment to the metastatic site with a potentially curative
intent
Comments: Dr Harit Chaturvedi
Question: What are the requirements for patients being considered for breast
conservation surgery?
In oncology practice, our objective is to get rid of the cancer and as far as possible it should
not adversely affect any body function or image. Therefore when a lady is diagnosed with
breast cancer a serious consideration is given to the possibility of breast conservation. We
must remember while considering this option, that, all those who undergo breast
conservation surgery (BCS) must be followed with breast irradiation compared with about
25% of the patients with similar tumors who undergo modified radical mastectomy.
Availability of radiation facility should always be borne in mind in our social context.
The contradictions for BCS are:
1. Multicentric tumor; however, if there are two invasive foci, nearby, so that the outer
limit of these is not more than 5 cm away then this may still be considered for breast
conservation surgery with caution.
2. Tumor size more than 5 cm is not a desirable situation. However, if the patient is
keen, then neoadjuvant chemotherapy should be advised for tumor down-staging. In
a large breast the option of BCS may still be rarely considered, though judiciously.
3. History of previous radiation in this area is also a limiting factor for the option of
BCS. Since these patients must be followed by radiation therapy to the breast. The
cumulative dose may not give the desired cosmetic outcome.
4. Extensive intra-ductal carcinoma or persistent positive margins on repeated
surgeries or a picture of malignant appearing diffuse micro calcification in large area
are also not suitable for breast conservative surgery.
5.
Pregnancy in I & II trimester with breast cancer may not be suitable for breast
conservative surgery since these patients would need radiation which would not be
possible during the period of pregnancy. Since radiation is often advised after
completion of chemotherapy it is possible as a reasonable option for patients in third
trimester.
505
7. Multiple benign tumors along with malignancy may pose a difficult situation to rule
out malignancy in these lumps.
8. Young patients with high suspicion of genetic breast cancer or those proven with
genetic etiology are unfavorable candidates, because of the high risk of subsequent
new cancers in the same breast.
We should remember that axillary status is no way influences the decision for BCS, neither
does the location of the primary tumor. A centrally placed lesion, where nipple areola would
be sacrificed, may still suitable for BCS, even though the nipple areola is sacrificed.
In BCS the tumor size, breast size, tumor breast ratios are carefully assessed keeping in
mind, tumor control & conservative outcome fro tumor. We must achieve at least 1 cm gross
all around clearance from the tumor (preferred is 2cm.). For desirable cosmetic result, as
much skin as possible should be preserved. The cavity should not be drained. As far as
possible the axilla should be separated. If it is unavoidable then a mini Latssimus Dorsi
muscle flap would give a good cosmetic outcome. Tomours in medial half and upper half
generally provide better outcomes.
Question: What are the recommendations for axillary dissection? When not to do
axillary dissection.
Axillary dissection is performed for the purpose of pathological staging, treatment decisions,
prognostication and also for the purpose of locoregional control. However, the morbidity of
axillary dissection in terms of seroma formation, pain in the shoulder, numbness in upper
arm and lymphoedema are significant enough to push us in the quest for avoiding axillary
dissection.
We know that the possibility of lymph node metastasis increases as the tumour size
increases or the grade of the tumour is higher. When a patient of invasive breast cancer is
undergoing primary surgery with a clinically palpable ipsilateral axillary node or the tumour
size is more than 4cms or if she is not suitable for sentinel lymph node sampling for other
reasons then she must undergo axillary dissection upto level II. This may be enough for
staging and decision making. A minimum of ten lymph nodes must be removed, sampled
and reported by the surgeon-pathologist team for completion of requirement. However in the
presence of gross disease level III clearance should always be performed.
When we have a smaller primary and the axillary nodes are not palpable then sentinel lymph
node biopsy must be considered. This should be considered only when the surgical team is
well trained with more than 50 cases and less than 5% false negative rate. Preferably, both,
the dye and the radioguided selection of nodes should be done for more accurate
506
localization. Frozen section evaluation should be avoided. If and when required a second
stage axillary dissection should be performed. The patient should fully understand the
procedure and the consequences thereof. Patients who have had neo-adjuvant
chemotherapy should always undergo complete axillary dissection.
It is understood that axillary dissection and axillary irradiation have almost equal outcome on
locoregional control, but axillary dissection is imperative to help further decision making and
prognostication. Patients with negative sentinel nodes should be kept under follow-up.
Patients with Ductal or Lobular carcinoma-in-situ without any invasive component are ones
where axillary dissection is not required.
507
508
509
510
511
What are the roles of staging laparotomy/Diagnostic Lap for staging of Hodgkins
Disease?
At one time, staging laparotomy was considered a useful tool in the staging
evaluation of Hodgkins Lymphoma. However, with advances in imaging modalities
the role of laparotomy has progressively diminished. Current generation CT scan and
MRI scanners can detect lymph node enlargement with a high sensitivity. In addition,
functional imaging with gallium and now PET Scanning can identify presence of
active disease.
In addition, a more aggressive use of chemotherapy in the management of Hodgkins
lymphoma has also reduced the role of staging laparotomy. The current dictum is to
consider staging laparotomy only when its results will alter the treatment plan. For
patients who have been planned for chemotherapy, there is no role of staging
laparotomy.
Comments: Dr Kishore Singh
What is the significance of pathological classification of Hodgkins Lymphoma with
reference to clinical presentation, management and prognosis?
The criteria for diagnosis of Hodgkins Lymphoma include both the presence of
Reed-Sternberg Cells and/or Hodgkins cells in the characteristic background of
normal lymphocytes, plasma cells and eosinophils. FNAC can be suggestive but is
not adequate for the diagnosis of Hodgkins Lymphoma. Open biopsy is required to
establish diagnosis unequivocally and to determine subtype. WHO Classify
Hodgkins Lymphoma into following sub types:
512
Frequency
ICD O*
65
9663/3
Lymphocyte Rich
9651/3
Mixed Cellularity
12
9652/3
9653/3
9659/3
12
9650/3
Lymphocyte Depleted
rd
Hodgkins
Lymphoma
patients
generally
present
with
Nodular
Mixed Cellularity
Lymphocyte Rich
Sclerosing
Age
Depleted
Older Age & pediatric
adults
Percentage of
Lymphocyte
Old
60% - 70%
25%
5% - 10%
Rare <1%
Developed
Emerging
No geographical predilection
Under-developed
disease (U.S.)
Geographical
513
area
Sex
Lymph
Node
Areas
Equal M: F
>M
M: F 3:1
Equal M: F
Abdominal involvement
Central
clavicular
common,
(high
and
diffuse
or
cervical,
mandibular,
sub
mediastinal
lymphadenopathy
epitrochlear,
(Supra
inguinal, femoral)
Not common
Common
Not common
Common
at
Localized
Advanced
Localized
Advanced
Pathognomonic
Collagen
Inflammatory
features
lacunar
background, malignant
diaphragmatic)
B-symptoms
Stage
presentation
bands,
cells
(RS
variant)
Reedcells
pleomorphic
sparse
and
cells,
number
of
normal lymphocytes
Natural history
Orderly
pattern
of
spreads
Orderly
pattern
spread
of
Miscellaneous
BNLI
Sub
Commonest in India
classification NS - I
May
be
with HIV
Pathology review
History & physical examination (B symptom and search for advanced disease)
Laboratory tests
CBC with ESR
Serum creatinine, alkaline phosphatase, lactate dehydrogense, bilirubin, AST
& albumin
Fertility counseling & sperm banking if appropriate
514
associated
TEST
Bone
PRESENTATION / CONDITION
marrow
biopsy
and
symptoms
or
aspiration
ENT Examination
HIV antibody
STAGING
Ann Arbor Staging System with Cotswolds modification
I
II
III
lymphoid tissue in the oropharynx and the spleen both count as nodal sites in this
system.
IV Reserved for extra nodal disease, which for all practical purposes is
disease of bone marrow, lung, bone or liver. Extra nodal disease d\at any site other
than those four should prompt questioning of diagnosis or a search for HIV infection
RISK ASSESMENT
It is useful for subdividing patients for purpose of planning treatment and interpretating clinical trails.
Approximately 40% have limited and 60% have advanced diseas
Limited stage
Clinical stage I & II without risk factors (Bulk <10cm & no B symptoms)
Intermediate stage
Advanced stage
PROGNOSIS
Two factors dominate the prognosis: age and stage.
Age - Elderly (60 to 75 years) forms about 5% of group but have only 50% likelihood
of being cured that of younger patient. This may be attributed to inability to tolerate
515
full dose therapy, co morbid conditions, low bone marrow reserve & intrinsic
resistance in the disease as it presents in older patients.
Stage It is the other dominant prognostic factor. A limited stage presentation
associated with cure rates in excess of 90%, in compared to this advanced disease
has only about 70% chance of cure.
Additional prognostic factors This includes histological subtypes, performance
status, gender, number of nodal sites, symptoms such as Pruritus & numerous
laboratory tests. All of these have been found significant in univariate analysis.
In early stage disease with good chances of control, utility of prognostic factor
is limited. On the other hand late stage disease has clear utility of these for therapy
planning.
The International Prognostic Factor Project on Advanced Hodgkins Lymphoma has
identified seven factors with approximately equal impact on probability of cure and
survival for advanced Hodgkins
Lymphoma.
International Prognostic Factors of Importance in Advanced Hodgkins
Lymphoma
Gender
Male
Age
>45years
Stage
IV
Hb
<10gm%
WBC
>15000/mm
Lymphocyte Count
Five-year
differential
Serum Albumin
<4gm%
freedom from
progression varied from almost 80% for patient with only zero or one adverse factor
to less than 50% for those with 4 or more adverse factors.
No of factors
Frequency encountered
0-1
29
79
2-7
71
60
0-2
58
74
516
3-7
42
55
0-3
81
70
4-7
19
47
Bulk
IA, IIA
Any
Treatment
Low
stage
with
Low
symptoms
Any stage
ABVD X 2 + IFRT
Bulky*
ABVD X 6 + IFRT
PRIMARY TREATMENT
Limited stage Hodgkins Lymphoma is defined on the basis of stage,
symptom state plus an assessment of tumor mass. Patients with B symptoms are
excluded because even with IB or IIB they still require extended CT, either due to
upstaging at laprarotomy (40% - 50%) or to eventual relapse (25%). Similarly bulky
disease indicates multimodality therapy. Once stage, bulk and symptoms have been
taken into account, treatment strategies appropriate for this group can be relied on
regardless of site of presentation (above or below the diaphragm) or histological
subtype.
One of the most controversial areas of Hodgkins Lymphoma management
until recently was the role of staging laprarotomy. Recent trial using optimum patient
selection and superior chemotherapy, however have proved enough information to
517
settle the issue. Using the data from literature two strategies for the management of
stage IA & IIA non-bulky disease can be compared:
Three trials have reported results of using brief ABVD & RT for limited stage IA & IIA
non-bulky Hodgkins Lymphoma in adult patients.
Brief ABVD followed by RT for limited stage Hodgkins Lymphoma
ELIGIBLE STAGES
MILAN
VANCOUVER
GHSG
IA, IIA*
IA, IIA
Number of patients
Median follow up (mo)
114
38
4
RT field
or Extended
Disease free survival
204
22
42
Months of ABVD
Overall survival
170
Involved
Extended
94
96
96
100
97
100
Extended
99
98
98
These data make it clear that brief CT with ABVD followed by RT is highly effective
at eradicating limited stage disease. Combined with its other advantage over
laparotomy-based approach. In addition reduce cycles of chemotherapy results in
elimination of substantial risk of infertility, premature menopause or leukemia and
hold to minimum concerns about cardiopulmonary toxicity. The efficacy of such an
approach makes it the best currently available therapy. Relative substitution of brief
CT for laparotomy however eliminates importance of factors such as ESR, number of
site of disease, gender, age when staging laparotomy and RT are used.
Special cases:
Two situations deserve individualized approaches.
518
bulky
IA
Nodular
Sclerosing
Hodgkins
Lymphoma
of
anterior
To be done after 4 cycles and after the last cycle of CT or CT-RT by physical
examination, laboratory analysis and same initially abnormal imaging tests.
Patients with incomplete radiological radiological response should be
evaluated for active disease by biopsy or at least by repeat radiological
testing. If available PET scan may identify partial responders at high risk for
early relapse.
519
Follow up
History and physical examination every 3 months for 1 year, every 6 months
for 3 years, then once a year.
Schedule of ABVD
2
ABVD
Dose (mg/m )
Route
Days
Doxorubicin
25
IV
1,15
Bleomycin
10
IV
1,15
Vinblastin
IV
1,15
Dacarbazine
375
IV
1,15
DIAGNOSIS
STAGING
LIMITED STGE
ADVANCED STAGE
520
FEATURES
II
Involvement of two or more lymph node regions on the same side of the
diaphragm
III
IV
No symptom
Fever (>38 C), drenching sweats, weight loss (>10% body weight over 6
months)
For stages I-III
E
Cotswolds modifications
(i)
521
(ii)
(iii)
(iv)
(v)
Concept of staging
Modern staging incorporates pathology decipher by immunologic and molecular
tumor markers. It helps in dividing particular type of lymphoma into different groups
with different prognosis or treatment requirements. Workup for stage begins with
history and detailed physical examination and is complete after a spectrum of
possible investigation directed at determining optimal management has been
performed. The pattern of Hodgkins disease is prototype for anatomic staging
classification.
Technique for detecting clinically impalpable lymphadenopathy has advanced
over past 25 years from plain radiography through whole lung tomography to
lymphography & CT scan. MRI & gallium scan may contribute under some
circumstances. PET is gaining popularity & relevance. CT guided biopsy may obviate
the need of open surgery. Bone marrow aspirate and biopsy may now reveal
involvement immunologically (MAb) at the level of 1 cell in 1000 or molecularly
(PCR) at the level of 1 cell in 100,000.
Anatomic staging is a powerful predictor of prognosis (independent of
histology) for last 20 years. Cooperation of several large centers and groups lead to
formulation of the International Prognostic Index (IPI). Therefore it is appropriate to
retain anatomic stage as an integral part of the information required for selection of
therapy in the 21st century.
522
The ex
tent of disease
The decision and chances of success will be greatly influenced by whether it is made
at the initial presentation or later in the course of the illness when earlier strategies
have failed.
Broadly NHL divided into following categories:
Szary syndrome
Primary cutaneous anaplastic large cell lymphoma
Anaplastic large cell lymphoma
Peripheral T cell lymphoma, unspecified
Angioimunoblastic T-cell lymphoma
Extranodal NK/T cell lymphoma, nasal type
Enteropathy type T-cell lymphoma
Hepatosplenic Tcell lymphoma
Subcutaneous panniculitis like Tcell lymphoma
Blastic NK cell lymphoma
CHARACTERISTICS & THERAPY OF SPECIFIC LYMPHOMAS
To provide optimal care, a patient with NHL shouldnt be approached as
belonging to a broad category (e.g. low grade or aggressive) but rather as having a
specific type of lymphoma, the clinical characteristics of patients with different
lymphoma vary considerably, the appropriate management can also vary widely.
Excellent care for a patient with lymphoma requires an accurate and specific
diagnosis.
MAKING THE DIAGNOSIS
Confirmation of disease rests entirely on biopsy of a lymph node or an
affected extranodal site. Usually the largest or most rapidly enlarging node is
chosen, because it is thought most likely to reveal the most aggressive histology and
it will provide the most tissue. While excision biopsy is preferred, trucut needle
biopsy under computed tomography (CT) or ultrasonic guidance in the hands of
expert radiologist may sometime provide enough tissue to avoid open surgery, either
in chest or abdomen. Fine needle aspiration for cytology only, should be used only
when biopsy is impossible or when confirmation of previously established lymphoma
is required. It does not allow morphological distinction between different types of
lymphoma and may be misleading. Repeat biopsy may be performed as
circumstances dictate, but it is always wise to perform a repeat biopsy if the patient
was rendered disease free by initial therapy. Repeat biopsy may reveal same or
altered lymphoma pathology, it may reveal another diagnosis.
525
Selected patients with bulky tumors systemic therapy (CVP) as for advanced
stages may also be used. Site of involvement and other general factors may
dictate the choice.
Stage III & IV: majority of patients fall under this category.
Has long natural history characterized by spontaneous regression in 15% 20% of cases and varies from case to case.
Treatment modalities:
Either chemotherapy (CT) or radiotherapy (RT) both are equally effective.
526
At 4 year only 20% - 25% remain disease free with either regimen.
For grade II follicular lymphoma, combination CT &/or maintenance CT has
high CR & prolong RFS but no difference in long term OS.
Rationale of combined RT & CT Although RT provides excellent local
control, systemic extranodal site of relapse are common. CT is given to take
care of distant disease. Combination of both is likely to produce beneficial result
in terms of improved RFS or OS. Some of the combinations are CVP + TBI or
CVP + TLI, CHOPBleo + IFRT
Rituximab (Mabthera Roche) in combination with CT should be considered
(licensed for use in refractory & relapsed follicular lymphoma) 4 injections
weekly, RR 50% - 60% with few CR.
Consolidation
Survival benefit with interferon maintenance therapy but this has to be
balanced against toxicity.
Rituximab prolongs RFS.
527
present
with
bulky
adenopathy,
majority
asymptomatic.
Sensitive
to
528
Extra Nodal MZL: Account for 5% of all NHL, 25% of them have bone
marrow/peripheral blood involvement, otherwise remain localized, when MZL
involves extranodal sites they are called mucosa associated lymphatic tissue (MALT)
lymphoma, usual sites are GIT, lung, lacrimal gland, salivary gland, thyroid. They
less often involve the orbit, skin, conjunctiva, breast, bladder, kidney, thymus or any
other epithelial tissue. The MALT lymphomas are subdivided into the gastric versus
non gastric. Gastric MALT lymphomas account for majority of extranodal MZL,
usually have history of Helicobactor gastritis. Present with early stage of disease (I &
II), B symptoms are uncommon. Treatment with antibiotics may resolve about 2/3 rd
cases of localized involvement, otherwise RT will yield CR. Stage I or II H. Pylori
negative could be treated with empiric course of antibiotics and re-evaluation at 3
months with endoscopy. Alternatively may be treated with RT. When disseminated
behave & treated like any other low-grade lymphoma. Non-gastric MALT
lymphoma often require surgery to make diagnosis, with no further treatment if
complete removal. Incompletely resected tumor can be treated appropriately with RT
or adjuvant chemotherapy with Chlorambucil. Patients with widespread disease can
be
offered
combination
or CHOP for
transformation to DLBCL.
Splenic MZL: Closely related to other MZL. forms 2% of lymphomas, median age 65
years, 90% are stage IV (frequent bone marrow involvement), presents with massive
splenomegaly (with hypersplenism) and without lymphadenopathy. Splenectomy as
initial treatment often required establishing diagnosis and relieving symptoms of
hypersplenism. This may results in prolonged remission. Advanced cases managed
like any other low-grade lymphoma with Chlorambucil & Prednisolone, keeping
Combination CT + Rituximab for transformation. Usually run an indolent course, 70%
survive at 10 years.
MANTLE CELL LYMPHOMA
About 7% of all NHL, 3/4th are males, median age 63 years, 70% are stage IV, B
symptoms occur in 1/3rd. Typical presentation have diffuse adenopathy and spleen,
liver, bone marrow & peripheral blood in 25% (marked lymphocytosis in 1/4 th).
Mantle cell lymphoma is more aggressive in its course. Median survival 3 4 years,
very few long survival, very difficult to achieve CR. CHOP + Rituximab associated
529
with best remission rates. Hyper CVAD + Rituximab have much higher CR rates.
High dose CT +stem cell rescue may achieve long-term survival in some cases.
Allogenic bone marrow transplant in fit young patient may be considered. For
palliation Rituximab might be important.
DIFFUSE LARGE B CELL LYMPHOMA (DLBCL)
This is characterized by diffuse proliferation of transformed large B cells.
Commonest of all lymphomas. Account for 1/3rd of cases. Median age 64 years, both
nodal & extra nodal types are seen. B symptoms seen in 30% and elevated LDH in
50%. Natural course involve progression into liver, lung, kidney (highly aggressive
nature), may lead to compression of vessels, nerves, airways and destruction of
bones. Bone marrow infiltration has strong correlation with CNS spread, so also
other risk factors like PNS, testicle & high LDH.
Multidisciplinary management is advocated in most situations (potentially
curable). Everything argues in favour of urgent initiation of therapy with curative
intent. The establishment of diagnosis and work up should be completed in one
week & therapies begin. The best chance of cure is with first line of treatment. Only a
minority of relapsing patient may be salvaged & even fewer refractory so.
Early stage:
<20% are truly localized disease.
Non bulky I & IE or limited II or IIE respond well to RT alone (45 to 50 Gy), but
associated with poor 30% long term survival. It is now rarely the therapy of
choice.
Chemotherapy alone also produced disappointed results.
Combination of both CT & RT not only results in reduction in amount of
chemotherapy to half but also produced significantly better outcome. No doubt
it is (CHOP + IFRT) now the preferred treatment.
Five-year result of combined modality Vs CT alone are 75% & 64% respectively
for PFS and 82% & 72% respectively for OS.
530
531
Finally most recent data showed that CHOP + Rituximab was clearly superior to
CHOP in elderly patients.
At present time CHOP is no longer the first choice of therapy. The definitive
standard regimen is not yet known but will certainly is a combination of
Rituximab and dose intense CHOP like regimen.
CNS Prophylaxis: Involvement is common in patients with bone marrow, testicular,
sinus, epidural or orbital involvement. In such situation it is reasonable to examine
CSF and may be prophylactic administration of intrathecal therapy. Overt disease
should be treated with intrathecal chemotherapy and if the systemic disease is
controlled, encephalic irradiation should be considered.
Patients with persistent image abnormalities but otherwise complete response:
Whether it is residual disease or slowly resolving fibrotic reaction is an important
issue. Dramatic reduction after first four cycles but little change thereafter is often
reality CR. But biopsy only can give definitive answer. Use of gallium or PET scan to
differentiate residual disease from fibrosis in mass detected on CT scan is found
beneficial.
Response evaluation: By imaging after 2 to 4 cycles and after last cycle of
chemotherapy or CT+RT. An initial pathological bone marrow biopsy or spinal tap
should be repeated at the end of treatment. Consider for early salvage regimen in
partial responders.
Follow up:
Physical examination every 3 months for 2 years, 6 months for 3 more years &
then yearly.
Blood count, LDH at 3, 6, 12, & 24 months & then only as needed.
Minimal adequate radiological examination at 6, 12 & 24 months after end of
treatment, by
Failure: Any of the salvage regimens combined with Rituximab (R-) DHAP, (R-)
ESHAP, (R-) EPOCH, and (R-) ICE etc. may be adequate. Autologus bone marrow
532
transplant in young, fit patient, who have sensitive disease. For palliation low dose IF
RT or iceberg radiation may be used.
Aggressive lymphoma in older patients: (R-) CHOP for 8 cycles is clearly superior to
CHOP alone. Aggressive approach will be inappropriate because of frailty. Age
alone should not be the criteria to withhold potentially curable therapy.
DIFFUSE LARGE B CELL LYMPHOMA
Extensive
stage
III or IV, any mass>10cm
CHOP + rituximab X 3 or 4
& IF RT
II
CHOP + rituximab X 4
Restage
CR
CR
Follow
rituximab X 2
PR
CHOP + rituximab X 2
Follow
CHOP +
Restage
CR
Restage
Follow*
DRUG
DOSE (mg/m )
ROUT OF ADMINISTRATION
Cyclophosphamide
750
IV
Doxorubicin
50
IV
Vincristine
IV
533
Prednisolone
PO
15
Rituximab
375
IV
534
vascular system from the aortic arch to the toes in less than 30 seconds is a clinical
reality. With MDCT, vessels over a metre long can be imaged in a single acquisition,
with a contrast resolution that distinguishes the lumen of the artery from opacified veins,
calcification, plaque and thrombus. It can be used in evaluating peripheral vascular
atherosclerotic steno-occlusive disease embolic phenomenon, congenital abnormalities,
popliteal entrapinent syndrome, traumatic and iatrogenic injuries, inflammatory condition
and aneurysms, as well as assessing the patency and integrity of bypass grafts.
What is the best investigation to visualize incompetent perforators.
Duplex Doppler sonography is the most useful diagnostic modality in the work up of
chronic venous insufficiency. Incompetent perforators are identified as dilated (> 3 mm)
veins coursing between the deep and superficial veins, showing flow from deep to
superficial compartment i.e. opposite to the normal direction and flow. It is also possible
to mark the position of the incompetent perforators preoperatively with Doppler
scanning.
What are the causes, recent advances in investigative techniques and present day
interventional modalities for a patient with diabetic foot.
A diabetic foot has 3 main components which reflect its etiology
a) neuropathic component b) ischaemic component
c) infective component.
The pattern of atherosclerotic occlusive disease in diabetes tends to involve the crural
arteries (i.e., the anterior tibial, posterior tibial and peroneal arteries). Arteries in the
foot, specially the dorsalis pedis are often spared.
revascularization is essential for salvaging the limb and/or to expedite healing of the
ulcers. Duplex-Doppler study acts as a screening modality. An angiography is required
to evaluate the exact site and extent of the involved segments and to see the run-off
vessels so that the mode of revascularization may be planned. An MRA/CTA can give as
accurate assessment of the vascular involvement and MRA has the advantage of using
a non-iodinated contrast medium which is well tolerated by diabetic patients who may
have renal impairment.
The goals of arterial reconstruction are to restore maximal perfusion to the foot and,
ideally, to restore a palpable foot pulse. Possible approaches include endovascular
techniques (angioplasty and stenting), bypass grafting (with autogenous or prosthetic
grafts), and some combination of the two. Ultimately, the choice of procedure in any
given case is based on the individual patients anatomy, the comorbid conditions
present, and the results of the preoperative assessment, with the aim being to provide
the most durable procedure with the least risk. As a rule, arterial bypass grafting is
required for restoration of the foot pulse. Proximal bypass to either the popliteal artery or
the tibial and peroneal arteries may restore foot pulses, and preference should be given
to these vessels if they are in continuity with the foot. Often, however, because of the
presence of more distal obstructive disease, bypass grafting to the popliteal or even the
tibial artery will not restore the foot pulse. In such cases, restoration of pulsatile flow to
the foot may be accomplished with autogenous vein bypass grafts to the paramalleolar
or inframalleolar arteries (e.g., the dorsalis pedis).
The other important aspect of the diabetic foot which needs radiologic imaging is the
detection of osteomyelitis; Imaging modalities available are :
1. Radiographs
2. Scintigraphy Bone scan
-
Gallium scan
Polyclonal antibodies.
3. CT
4. MRI
Plain radiographs are the first imaging study. However, radiographic changes may not
be seen for 1-2 weeks after onset of acute osteomyelitis and often it may not be easy to
distinguish osteomyelitis from neuropathic arthropathy specially in the tarsal and tarsometatarsal region. MRI is the most sensitive and specific modality for detection of
osteomyelitis and wherever available it should be done as the second line investigation
after plain radiographs. It can give the exact site and extent of involvement of bone and
soft tissues. These days PET CT is being evaluated in the assessment of osteomyelitis
with favorable results.
Comments: Dr Kumud Rai
What are the indications for endovascular intervention for lower limb ischemia?
What are the recent advances in endovascular interventional techniques?
Endovascular intervention is generally reserved for advanced ischemic symptoms like
tissue loss (gangrene/non-healing ulcers) or persistent rest-pain. It is also indicated in
severe intermittent claudication with a short claudication distance. The long-term results
of interventions in larger vessels (like iliac arteries) are much better than that of smaller
vessels, and therefore the threshold for intervention is lower in aorto-iliac disease is
lower (i.e. intervention may be done with moderate symptoms) compared to smaller
(crural) arteries where it is only done only when limb is threatened with tissue loss.
Recent advances in endovascular intervention include:
1. Sub-intimal angioplasty
2. Drug-eluting stents
3. Covered stents
4. Laser recanalization (enjoying resurgence in some centers) / atherectomy
5. Cryoplasty
3. IIb. Severe intermittent claudication interfering with lifestyle. The maximum walking
distance is usually less than 200 meters in such instances.
What is the status of stripping for varicose veins of the lower limbs? Is flush
ligation of SF or SP sufficient, or is it mandatory to add stripping. If stripping is
required then till what level and why?
The addition of stripping to flush ligation considerably reduces the recurrence rates of
varicose veins; this has been demonstrated in several randomized clinical trials*. This is
at the cost of local tissue bruising, and an increased rate of injury to accompanying
nerves (resulting in dysthesia/paresthesia). The inversion technique has been
employed to decrease the chances of nerve injury. Stripping is not mandatory for the
short saphenous vein. It is strongly recommended for GSV incompetence. If utilized, it
should be done only till just below the knee because
1. The chances of injury to saphenous nerve are much higher if stripping is done till the
ankle.
2. Perforators of leg arise from posterior arch vein (rather than the main GSV), so little
would be gained by stripping the vein to ankle as these perforators would not be
avulsed.
* Having said this, these trials were conducted in the era when good color Doppler
(Duplex scans) were not available. In modern practice, a good color Doppler machine
(operated by an experienced sinologist) can localize all perforators, and these can be
marked on the skin pre-operatively. Stripping of saphenous vein can thus be dispensed
with. This ensures low recurrence rates, and practically eliminates chances of nerve
injury.
Comments: Dr Rajiv Parakh
What are the indications of sympathectomy in lower limb ischaemia? Why is
lumbar sympathectomy pre-and post ganglionic?
Lumbar Sympathectomy in Lower Limb Ischemia indications:
1. Causalgia
2. Vasospastic disorders complicated by digital ulceration
3. Frost bite
4. Buergers Disease
5. Claudication pain
6. Diabetic neuropathy
7. Non-reconstructible atherosclerotic occlusion with rest pain or gangrene to
enable amputation stump healing
Anatomic Considerations:
The sympathetic nervous system consists of afferent and efferent fibers that form a
reflux arc. At segmental levels, efferent fibers exit from preganglionic neurons in
paravertebral ganglia via white rami communicantes. A small percentage of preganglionic efferent fibers either bypass the para-vertebral ganglia to synapse in more
peripherally located intermediate ganglia or cross-over to innervate contra-lateral regions
via conventional pathways. Characteristically, preganglionic fibers that supply a specific
somatic region either synapse with multiple postganglionic fibers in paravertebral ganglia
or more peripherally in intermediate ganglia. Complete sympathetic denervation of an
extremity requires division of preganglionic fibers along their segmental origin and
resection of their corresponding relay ganglia and inter-communicating fibers.
Sympathetic outflow to the lower extremities originates in spinal cord segments from T10
to L3. Variations in the number and location of sympathetic ganglia are most common in
the lumbar region, with most occurring at L1, L4 and L5 level. Commonly three ganglia
are found, with the fusion of the L1 and L2 ganglia most commonly accounting for the
reduced number. Cross-over fibers occur in 15% of patients, with most leaving via the
fourth and fifth lumbar ganglia. For most indications, L2 and L3 ganglionectomy is
sufficient, but also removing L4 is advised to reduce the possibility of collateral
reinnervation. High Bilateral ganglionectomies, including L1 ganglion, may result in
ejaculatory disturbances and is usually not warranted. Impotence is more likely to be
produce by extensive dissection of the distal aorta, particularly around the origin of the
left common iliac artery. Nerve fibers serving ejaculation stem mainly from L1 and
occasionally from L2. This disturbance of ejaculation may occur after resection of L2
when it is fused with L1.
high ligation and stripping of the greater saphenous vein with avulsion of branch
varicosities is concomitantly performed in the majority of patients undergoing SEPS. The
clinical and hemodynamic improvements attributable to SEPS thus are difficult to
ascertain. As with open perforator ligation, clinical and hemodynamic results are better in
patients with primary valvular incompetence (PVI) than in those with the postthrombotic
(PT) syndrome. Until prospective, randomized, multicenter clinical trials are carried out
to answer lingering questions regarding the efficacy of SEPS, the procedure is
recommended in patients with advanced CVI secondary to PVI of superficial and
perforating veins, with or without deep venous incompetence.
The vessels are blocked and limit the free flow of blood. Oxygen supply, then,
does not meet the exercising muscles' demands.
The result of these actions is leg pain during exercise, which is relieved only by rest. Leg
pain occurs in one leg in 40% and in both legs in 60% of patients. The most frequently
affected artery in intermittent claudication is the popliteal artery.
Intermittent claudication is usually described as a cramping, tightness or fatigue in the
calves, thighs or buttocks, occurring primarily with walking, and relieved upon resting. Its
onset is fairly predictable as it develops at the same distance traveled. With progression
of the underlying disease, symptoms begin at shorter and shorter distances walked and
ultimately, will even occur at rest.
Risk factors for the development of peripheral vascular disease (PVD) and intermittent
claudication (IC) are similar to those for coronary heart disease. Smoking, however,
probably plays a larger role in PVD than does cholesterol, although both are important
risk factors. Smokers have at least a four times greater risk of developing PVD than
nonsmokers, and smoking cessation strongly reduces the progression of disease.
Hypertension increases the risk three times compared to non-hypertensives probably by
gradually damaging the endothelium. Diabetes increases the risk by three times over the
normal population by causing disease of the smaller arteries of the legs. Unfortunately,
because of the decreased pain sensation found in many diabetics, the disease may not
be recognized until ulceration appears. Hypercholesterolemia plays a significant role in
the early development and progression of the atherosclerotic plaque.
The presence of genetic factors like hyperhomocysteinemia, Protein C & S deficiency,
Anti-thrombin-III deficiency, Factor V Leiden mutation, antiphospholipid antibodies play a
contributory role to the development of early thrombosis and claudication.
Diagnosis of Intermittent Claudication
The presence of classical symptoms of intermittent claudication with absent and
diminished pulses point towards a vascular pathology. These findings are confirmed
non-invasive diagnostic modalities.
1. Ankle Brachial Index : The simplest of these tests is the Ankle Brachial Index
(ABI) which is a ratio of the systolic blood pressure measured simultaneously in the
leg and arm. An ABI ratio less than 0.9 implies significant arterial obstruction while a
ratio of 0.5 or less implies critical obstruction. Occasionally, the ABI ratio can be
normal even with significantly obstructed arteries, mostly in diabetics due to medial
calcification.
2. TcPO2 measurements: This is a relatively easy test to demonstrate arterial
insufficiency in distal vessels by measuring observing the oxygen uptake by tissues.
This is more accurate especially in diabetics where ankle brachial index gives false
high values.
3. Duplex doppler : Duplex studies provide an accurate non-invasive ultrasound
picture of the leg arteries along with a relative estimate of the severity of any arterial
of the biochemical effects of cilostazol are known (clot inhibition, blood vessel
dilatation, triglyceride lowering, reducing cellular energy production), the exact
mechanism for reducing claudication is not clear. Studies have shown that 12 weeks
of cilostazol use reduces claudication severity and increases walking distance by as
much as 40% when compared to a placebo.
Revascularization
While many patients with intermittent claudication receive enough symptomatic benefit
from risk factor reduction and a combination of medicines, a significant percentage of
patients will remain functionally limited. Patients with severe claudication or disabling
claudication (claudication distance > 400 metres) and patients with non-healing ulcers
will not improve unless revascularisation of distal limb is done.
1) Angioplasty : Diagnostic angiography may reveal certain lesions like stenosis less
than 3 cms point occlusion, which are highly amenable to endovascular procedures
like balloon angioplasty and stenting. Angioplasty is a therapeutic intervention taken
at the time of angiography and requires the use of balloons and stents. These are
minimally invasive procedure and patient can usually be discharged next day. Use of
drug coated and/or biodegradable stents will greatly improves long-term patency of
stents making them the procedure of choice.
2) Surgery: Diagnostic peripheral angiography is mandatory before any surgical
intervention is carried out. The surgical intervention depends upon the site and
extent of lesion with equal stress given to distal run off. Presence of collaterals /
Corkscrew collaterals should not be considered as a contraindication of surgery, a
very common false perception among physicians. Femoro popliteal bypass or
Femoro distal bypasses are the common surgical interventions undertaken. These
bypasses used either vein (LSV) or synthetic material like ePTFE or Dacron for
reconstruction. Patient with good distal run off do better than patient with poor run
off. Control of diabetes, hypertension, cholesterol and strictly no smoking give better
results.
3) Stem cell therapy may be beneficial in the years to come.
4) Lumbar sympathectomy has no role in the management of claudication.
What are the various ways that vesical neck dysfunction can be evaluated?
Aetiology:
-
Diagnosis:
Uroflowmetry
RGU
Normal
Stricture urethra
Treatment
So-called classical urodynamic findings in DM are elevated PVR, impaired bladder sensation,
increased cystometric capacity and decreased bladder contractility. These together constitutes
Diabetic Cystopathy. It is most common in patients who have associated peripheral
neuropathy.
Second commonly found problem on CMG is a compliant, large capacity bladder with areflexia
and impaired sensation of bladder filling.
Prostate contains an enzyme called as 5 alpha reductase which converts testosterone into DHT.
This DHT is responsible for growth of prostate. Inhibitors of enzymes 5 Alpha reductase will stop
conversion of testosterone into DHT. Lack of DHT causes decrease in size of prostate due to
apoptosis of prostate cells.
Drugs:
-
Finasteride 5 mg OD
Dutastride 0.5 mg OD
Prerequisite:
S. PSA should be normal as they low S. PSA also and can mark cancer of prostate.
Duration of Treatment: 9-12 months
Indication: Prostate 30-60 gms size
II.
Known as alpha-blockers. Nowadays selective alpha-blockers are available and they have less
side effects.
Non-selective alpha-blockers Prazosin & Terazosin
Selective alpha blockers Alfuzosin 10 mg OD and Tamsulosin 0.4 mg HS
Side effects:
-
Postural hypotension
Retrograde ejaculation
Comments: Dr PN Dogra
Components of Urodynamics in bladder outlet obstruction (BOO)
1. Uroflowmetry: It is the non-invasive determination of characteristics of urine flow .The
voided volume, average flow rate (Qave) and maximal flow rate (Q max) are recorded.1
The voided volume should be more than 150 ml .The typical obstructed flow pattern is a
plateau shaped curve with a prolonged flow time, sustained low flow rate and increased
time to Qmax.It is insufficient to diagnose BOO as it cannot distinguish true obstruction
from poor detrusor contractibility.2 However, we can differentiate between stricture
urethra and BOO on the basis of the curve.
2. Pressure flow micturition study: This study can differentiate between patients with a
low Qmax secondary to obstruction and those whose low Qmax is due to poor
contractibility. It can also identify patients with high pressure obstruction and normal flow
rates.3The International Continence Society (ICS) provisional nomogram should be used
to give a continuous grading of obstruction by calculating BOOI (bladder outlet
obstruction index)
a. B00I = Pdet.Qmax - 2Qmax, (Pdet.Qmax = detusor pressure at maximal flow
rate)
The patient is considered obstructed if BOOI is > 40, unobstructed if BOOI <20, and
equivocal if BOOI is between 20 and 40.4
3. Videourodynamics: The simultaneous fluoroscopic screening of the bladder outlet
during voiding and while pressure pressure-flow data are being recorded, helps to
identify the site of obstruction as being at either the bladder neck, the prostatic urethra or
the distal sphincter mechanism in these patients. e.g. young men with lower urinary tract
symptoms 5, identification of dyssynergia of proximal and distal sphincter mechanisms in
neurogenic patients, women with BOO.6
4. Sphincter
Electromyography:
It
checks
whether
there
is
coordination
or
discoordination between external sphincter and the bladder, thus demonstrating the
neurogenic cause of BOO. e.g. Detrusor- sphincter dyssynergia in suprasacral spinal
cord lesions: shown as failure of sphincter to relax or stay completely relaxed during
micturition.7
5. Micturitional Urethral pressure profilometry (MUPP): During voiding, bladder
pressure and urethral pressure are same. If an obstruction exists in the urethra, the
intraurethral pressure distal to the obstruction is low while the pressures in the urethra
proximal to the obstruction and in bladder are high. Thus, when a significant pressure
drop is seen on catheter withdrawl, this corresponds to the site of obstruction. 1, 8MUPP
has been used to diagnose BOO, and seems to correlate well with pressure flow study.
9
ambulatory patients and the ability to localize the site of obstruction10, it is difficult to
perform, suffers from distortion artifact, and location of pressure transducer is inexact.
References
1. Webster GD, Guralnick ML. The neurourologic evaluation. In Walsh PC(ed): Campbells
Urology, eighth edition, 2002, Philadelphia, pp: 900-930.
2. Neilson KK , Nording J , Hald T . Critical review of the diagnosis of prostatic obstruction.
Neurourol Urodyn 1994; 13:201-217.
3. Abrams P. Bladder outlet obstruction index, bladder contractibility index and bladder voiding
efficiency: three simple indices to define bladder-voiding function. BJU Int 1999; 84:14-15.
4. Gerstenberg TC, Anderson JT, Klarskov P. High flow infravesical obstruction in men:
Symptomatology, urodynamics and the results of surgery. J Urol 1982; 127:943-946.
5. Nitti VW, Tu LM, Gitlin J. Diagnosing bladder outlet obstruction in women. J Urol 1999;
161:1535-1540.
6. Webster GD, Older RA. Video urodynamics. Urology 1980a; 16:106-114.
7. Abrams P, Blaivas JG, Stanton SL, Anderson JT. The standardization of terminology of lower
urinary tract function. Scand J Urol Nephrol.1998; 114:5-19.
8. Schafer W. The contribution of the bladder outlet to the relation between pressure and flow rate
during micturition. In Hinman F Jr(ed): Benign prostatic hypertrophy. New York, SpringerVerlag, 1983:pp 470 496.
9. DuBeau CE, Sullivan MP, Cravalho E. Coorelation between micturitional Urethral pressure
profile and pressure- flow criteria in bladder outlet obstruction. J Urol 1995; 154:498-503.
10. Sullivan MP, Comiter CV, Yalla SV.Micturitional urethral pressure profilometry. Urol Clin North
Am 1996; 23:263-278.
1,3
Early incontinence
is usually urge symptomatic, either because of irritative symptoms such as fossa healing and
associated UTI or detrusor instability caused by long-lasting benign hyperplasia of prostate.1
Symptomatic treatment should include time limited anticholinergic selective drugs such as
toltoredine or darifenacin , as well as anti inflammatory regimens such as diclofenac.
Further evaluation : Incontinence that persists longer than 6 months , requires complete
investigations , including ascending urethrogram , cystourethroscopy , and urodynamic
evaluation.1 There are several causes of incontinence
3,4
detrusor instability (20%) , mixed incontinence (30%) , residual adenoma (5%) , bladder neck
contracture (5%) , and urethral stricture(5%).
Late management: Depending on endoscopic and urodynamic findings, conservative treatment
with pelvic floor exercises combined with TRUS biofeedback and electrostimulation might be
indicated. Promising experiences with duloxetine ( 40 mg 1 bd) must be balanced against the
side effects , which cause patients to discontinue use. Since periurethral injection therapy was
not very successful, an artificial sphincter might be indicated for a few patients whose
incontinence causes more severe bother and affects the patients quality of life.4, 5,6 Recently,
higher success rates (67% dry, 92 % improvement) were reported with inflatable paraurethral
balloons.2 Sling procedures to compress the urethra have also been used to treat sphincter
dysfunction. 7 Occasionally, refractory cases of postprostatectomy incontinence may necessitate
urinary diversion to resolve debilitating incontinence.
References
1. Zwergel U . Benign Prostatahyperplasie BPH Syndrome. Operative and interventionelle
Therapieoptionen.Urologe A 2001;40:319-329.
2. Hubner WA , Sshlarp OM. Treatment of incontinence after prostatectomy using a new minimally
invasive device: adjustable continence therapy. BJU Int 2005; 96:587-594.
3. Theodorou C , Moutzouris S , Floratos D , Plastiras D , Katsifotis C , Mertziotis N . Incontinence
after surgery for benign prostatic hypertrophy: the case for complex approach and treatment. Eur
Urol 1998; 33; 370-375.
4. Wasson JH , Reda DJ , Bruskewitz RC , Ellison J , Kelly N , Henderson WG for the Veterans
affairs cooperative study group on transurethral resection of the prostate . N Engl J Med 1995;
322: 75-9.
5. Imamoglu MA, Tuygun C, Bakirtas H, Yigitbasi O, Kiper A. The comparison of artificial urinary
sphincter implantation and endourethral macroplastique injection for the treatment of
postprostatectomy incontinence. Eur Urol. 2005 Feb; 47(2): 209-13.
6. Kuznetsov DD,Kim HL, Patel RV, Steinberg GD,Bales GT. Comparison of artificial urinary
sphincter and collagen for the treatment of postprostatectomy incontinence. Urology. 2000 Oct 1;
56(4): 600-3
7. Petrou SP. Treatment of postprostatectomy incontinence: is the bulbourethral sling a viable
alternative to the artificial urinary sphincter? Curr Urol Rep. 2002 Oct;3(5):360-4.
1, 2
can be delivered as - end firing, side firing and interstitial .The various techniques used
are:
(a) Holmium laser prostatectomy (HoLEP): Laser is used as a knife through a
cystoscope, stabilizing the fibre with a ureteral catheter. The laser effectively
mimics the surgeons index finger during an open prostatectomy, making the
Holmium Laser Enucleation of the prostate (HoLEP) its endoscopic equivalent.
A 100 watt Versapulse Holmium laser with a 550 micro meter end firing fiber is
commonly used.
morbidity.
3,4
complete volitional voiding, again at low pressure. For this purpose the bladder and urethra
work as an integrated unit along with the autonomic and somatic nerves, spinal cord and
supraspinal central nervous system.
Neural Control of Lower Urinary Tract
Peripheral Nervous System
The lower urinary tract is innervated by parasympathetic, sympathetic and somatic nerves.
Pelvic parasympathetic nerves, which arise from sacral segments of spinal cord, cause voiding
of urine by contracting detrusor and relaxing urethral sphincter. The lumbar sympathetic nerves
help in storage of urine by contracting the sphincter and relaxing detrusor. The preganglionic
noradrenergic fibers arise in the thoracic segments and reach bladder and urethra via
sympathetic chain and hypogastric nerves. The somatic (pudendal) nerves contract the striated
sphincter.
The afferent fibers from bladder and urethra travel thorough pelvic nerves. The afferent fibers
are myelinated (A delta) and unmyelinated (C fibers). Some of these afferents monitor the
bladder volume and tension and help in complete bladder evacuation, while others are silent
under normal circumstances. These become active only during abnormal conditions like bladder
inflammation and lead to bladder pain and detrusor instability.
Reflex Circuitry Controlling Micturition
Multiple reflex pathways in brain and spinal cord coordinate activity between bladder and
urethra. Some of these reflexes facilitate storage of urine while others coordinate voiding.
Storage Phase
The low pressure storage of urine in the bladder is primarily due to the properties of detrusor
muscle. In addition, bladder distention may increase sympathetic outflow to bladder (bladder to
sympathetic reflex), causing bladder relaxation. The bladder distention also causes increase
activity of pudendal motor fibers, facilitating continence (bladder to sphincter/ guard reflex).
Voiding Phase
The storage phase of bladder can be switched to voiding phase involuntarily (reflex voiding) or
voluntarily. In case of reflex voiding (seen in infants and certain neurological conditions), once
the bladder volume reaches a critical level, the increasing afferent signals cause
parasympathetic discharge and suppression of sympathetic and somatic signals. The process of
voiding consists of an initial relaxation of sphincter followed by sustained bladder contraction.
The urethra to bladder reflexes help in complete bladder emptying.
Spinal and Supraspinal Pathways
Afferent impulses from perineum (somatobladder reflex) and pelvic organs (viscerobladder
reflex) may modulate both urine storage as well as voiding. The main facilitatory center for
voluntary control of voiding is located in pons (Barringtons nucleus) and is under inhibitory
control of right side of cerebrum.
Receptors in LUT
The nerves supplying the bladder and urethra bring about their action through various receptors.
These receptors can also be modulated by systemically and locally administered drugs, which
permit treatment of various abnormalities of micturition.
Cholinergic muscarinic receptors
Of various receptor subtypes, M1, M2 and M3 are found in human bladder. Blockage of these
receptors by antagonists such as oxybutynin and tolterodine, is widely used to suppress bladder
contractions in cases of urinary incontinence.
Beta adrenergic receptors
Stimulation of beta2 and beta3 receptors found in human bladder leads to relaxation of detrusor
muscle. However, there is no established clinical use of this fact.
Alpha adrenergic receptors
Under normal circumstances, alpha1 adrenergic receptors are predominantly found in bladder
neck and urethra, where they cause increased bladder tone and continence. Based on this
feature, alpha1 antagonists are used for treatment of bladder outlet obstruction due to BPH
while alpha1 agonists are used for treating incontinence. Since blockage of alpha1 receptors
may cause postural hypotension, more selective alpha1A antagonists are being used with an
intention of reducing postural hypotension.
outflow or below it. After the period of spinal shock, reflex detrusor activity returns to varying
degree. Tone also returns to both striated and smooth sphincters. The effectiveness of reflex
micturition depends on the extent of detrusor sphincter dyssynergia. Those with relatively low
outlet obstruction may empty bladder adequately by stimulating certain dermatomes and initiate
reflex micturition periodically. In those individuals where either the detrusor does not contract
adequately or there is significant detrusor sphincter dyssynergia, effective bladder emptying
requires additional form of therapy.
Sacral Spinal Cord Injury
Detrusor areflexia becomes evident in these patients after the period of spinal shock is over.
Both smooth and striated sphincters show persistent tonicity. While the storage of urine is at low
pressure, reflex micturion is not established and clean intermittent catheterization may be
required to periodically empty the bladder.
Urinary bladder should have normal capacity and compliance with no episodes of
intermittent high pressure contractions. In case there is no evidence of detrusor
instability, it should be corrected by medical and surgical means.
There should be some form of bladder sensation so that patient can time CIC correctly.
The upper limb should be functional and patient should be able to balance in upright
position.
The patient should be motivated with adequate family and community support.
Technique of CIC
For adult male patients, a No. 14 or No. 16 Fr red rubber catheter is generally used. In patients
with impaired fine motor skills, stiffer plastic catheters may be easier to insert. A notable
advantage of the red rubber catheter is its longevity. It can be reused indefinitely and boiled or
microwaved
for
sterilization.
For
female
patients,
disposable
plastic
catheters
are
What are the other benign causes of obstructive jaundiced other than calculus?