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Flexible endoscopic and surgical management of Zenkers diverticulum

Expert Rev. Gastroenterol. Hepatol. 6(4), 449466 (2012)

Ivana Dzeletovic1, Dale C Ekbom2 and Todd H Baron*3

Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, AZ, USA 2 Division of Otorhinolaryngology, Head and Neck Surgery, Rochester, MN, USA 3 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA *Author for correspondence: Tel.: +1 507 284 2174 Fax: +1 507 255 7612 baron.todd@mayo.edu
1

Zenkers diverticulum is an outpouching of the mucosa through the Killians triangle. The etiology of Zenkers diverticulum is not well understood. It is thought to be due to the incoordination or incomplete relaxation of the cricopharyngeal muscle. Most patients are men who present with symptoms of dysphagia between the seventh and eighth decades of life. The diagnosis is made with a dynamic contrast swallowing study. Treatment options include open surgical diverticulectomy and diverticulopexy with myotomy or myotomy alone using flexible or rigid endoscopes. Rigid endoscopic treatment is currently the preferred initial choice for Zenkers diverticulum of any size. The flexible endoscopic technique is used when there is a high risk of general anesthesia, or neck extension is contraindicated. Some centers use flexible endoscopy as the initial treatment option. Due to a lack of prospective studies, the treatment choice should be tailored to the individual patient and local expertise.
Keywords: cricopharyngeal muscle dysphagia endoscopic staple diverticulostomy flexible endoscopy myotomy needle knife rigid endoscopy Zenkers diverticulum

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Release date: August 27, 2012; Expiration date: August 27, 2013

Learning objectives Upon completion of this activity, participants will be able to:
Assess the clinical presentation of Zenkers diverticulum Distinguish the best imaging modality to diagnose Zenkers diverticulum Evaluate endoscopic treatment for Zenkers diverticulum Evaluate surgical treatment for Zenkers diverticulum

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10.1586/EGH.12.25

2012 Expert Reviews Ltd

ISSN 1747-4124

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Financial & competing interests disclosure

Editor Elisa Manzotti Publisher; Future Science Group, London, UK. Disclosure: Elisa Manzotti has disclosed no relevant financial relationships. CME Author Charles P Vega, MD Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine, CA, USA. Disclosure: Charles P Vega, MD, has disclosed no relevant financial relationships. Authors And CrEdEntiAls Ivana Dzeletovic, MD Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, AZ, USA. Disclosure: Ivana Dzeletovic, MD, has disclosed no relevant financial relationships. Dale C Ekbom, MD Division of Otorhinolaryngology, Head and Neck Surgery, Mayo Clinic, Rochester, Minnesota, MN, USA.

Disclosure: Dale C Ekbom, MD, has disclosed no relevant financial relationships.

Todd H Baron, MD, FASGE Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, MN, USA.

Disclosure: Todd H Baron, MD, has disclosed no relevant financial relationships.

Zenkers diverticulum (ZD) (Figure 1A) , also called cricopharyngeal or pharyngoesophageal diverticulum, is an outpouching of the mucosa through Killians triangle. It was first described as an autopsy finding by Ludlow, a surgeon from Bristol, Great Britain, in 1769 [1]. German pathologist Zenker together with von Ziemssen further characterized this entity in 1877. Zenker explained the pathogenesis of ZD to be due to the forces with the lumen acting against restriction. From that time on, this type of the diverticulum has been called ZD [2]. In the early 1900s, the anatomy of the condition was described by Killian [3], who observed that pharyngeal pouches arise posteriorly in the midline between the thyropharyngeus muscle above and the cricopharyngeal muscle below. ZD is a relatively rare disorder with an annual incidence estimated at 2/100,000 per year in the UK [4] . ZD occurs most often in patients 6575 years of age [5] . The neck of the pseudodiverticulum is located proximal to the upper esophageal sphincter (UES) on the posterior hypopharyngeal wall [6] . The tissue bridge is composed of mucosa, submucosa, connective tissue
Lateral pharyngeal pouch

and muscle between the esophageal lumen and diverticulum. Its pathophysiology is not well known but is thought to result from incoordination between pharyngeal contraction and UES relaxation (e.g., cricopharyngeal dysfunction). Fibrosis of muscle fibers and constant tension over the esophageal wall results in formation of a diverticulum [7] . The mainstay of treatment of symptomatic ZD has been surgery via an open or endoscopic approach under general anesthesia [813] . However, endotherapy using flexible endoscopes has evolved over the last 12 years [1418] . The purpose of this review is to discuss the anatomy and pathophysiology of ZD along with surgical, rigid and flexible endoscopic treatment.
Anatomy & pathophysiology of the pharyngeal swallowing mechanism

The mechanism of swallowing seems effortless to most of us, but it is a complex process that involves the CNS, more than 40 paired muscles and majority of the bones of the head and neck. Humans typically swallow about 600-times a day [19].

KilianJamieson diverticulum Zenkers diverticulum Zenkers diverticulum

Cricopharyngeus muscle (bar)

Figure 1. Images of Zenkers diverticulum, KillianJamieson diverticulum and cricopharyngeal bar. (A) Zenkers diverticulum, (B) Zenkers diverticulum and KillianJamieson diverticulum, and (C) cricopharyngeal bar.

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Figure 2. Double contrast barium swallow esophagram showing Zenkers diverticulum. (A) Anteroposterior view and (B) lateral view.

The inferior pharyngeal constrictor is composed of the thyropharyngeus and the cricopharyngeus (CP). The CP has superior and inferior components, each of which arises bilaterally from the sides of the cricoid lamina; the superior fibers course posteromedially to the median raphe and the inferior fibers loop around the esophageal inlet without a median raphe. Killians triangle is formed posteriorly between these components of the CP and is the site of origin for ZD (FigurE 1B). The CP contributes the zone of maximal UES pressure, which is about 1 cm in length [20] . Resting UES pressure is distinctly asymmetrical; anterioposteriorly (5560 mmHg) and transversely (30 mmHg) [21,22] . The zone of greatest pressure is located immediately above the inferior fibers of the CP.
Pathogenesis of ZD

model would result from elevation of normal UES pressures, including increased resting pressures, cricopharyngeal achalasia, incomplete/delayed relaxation and opening, premature closure and lack of coordination between pharyngeal contractions and UES opening/dysmotility secondary to neurologic injury [2533]. Histological studies established the presence of inflammation and fibrosis, confirming the hypothesis of the poorly compliant cricopharyngeal mechanism [26].
Gastroesophageal reflux disease & ZD

After more than a century of investigation, no consensus exists regarding the exact pathogenesis of ZD. Of the early theories, Zenkers proposal that the pouch is the result of the forces within the lumen acting against a restriction is closest to present understanding of the pathogenesis [2]. Westrin et al. described their neuromuscular dysfunction theory with anatomical weakness of the posterior pharyngeal musculature above the CP and muscular dysfunction of the UES [23]. Age-related changes that may contribute to impaired pharyngeal swallowing include altered coupling between the oral and pharyngeal phase of swallowing, delayed anterior movement of the hyoid bone and a decreased number of cells in Auerbachs plexus [24]. In addition, older people have higher hypopharyngeal wave amplitudes that could result from faulty opening or increased connective tissue in the CP. Pharyngeal mucosal herniation in Westrins
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Gastroesophageal reflux disease (GERD) has been implicated in the development of cricopharyngeal dysfunction and subsequent ZD. The question of the association between GERD and ZD began in 1970 when Smiley et al. reported an increased incidence of hiatal hernia in the patients with ZD [34]. The same year, the group also reported that the increased cricopharyngeal pressure decreased after the repair of hiatal hernia [35]. Four years later Stanciu and Bennett found no significant elevation of cricopharyngeal resting pressure in patients with GERD [36]. The contribution of GERD to cricopharyngeal spasm and subsequent formation of ZD is poorly understood. Two studies have reported significantly increased UES pressures in response to esophageal acid exposure [37,38], whereas one study did not [39]. In two studies, a persistent cricopharyngeal bar was seen significantly more often in patients with GERD than those without (40 vs 12% and 55 vs 20%, respectively) [40,41]. Although a persistent cricopharyngeal bar often indicates cricopharyngeal spasm, it may also indicate impaired muscle compliance (Figure 1C) . Cricopharyngeal specimens taken from patients with ZD demonstrate histological and biochemical abnormalities
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ZD may also coexist with other intraluminal pathologies, including laryngocele [45] , benign tumors of pharynx and esophagus [46] , polymyositis [47] , cervical esophageal webs [48] , carotid body tumors [49] , anterior cervical fusion, upper esophageal stricture, hiatal hernia and GERD [50] . These coexisting pathologies can be additional causes of dysphagia. ZD occurs between the seventh and eighth decades of life and uncommonly before the fourth decade [5] ; it is more common in men [5,51] . The prevalence of ZD is believed to be about 0.11% [52] . It is more frequent in the USA, Canada and Australia compared with Japan and Indonesia [13] . Anatomical differences between geographic areas may contribute to differences in prevalence [53] . A minority of patients have abnormal findings on physical examination. These are usually seen in more advanced cases and include malnutrition, voice changes, neck mass, cervical borborygmi and crepitus. Boyces sign is a soft swelling, usually occurring on the left side of the neck in the lower part of the anterior triangle, which may gurgle on palpation and/or induce coughing may be due to spillage of contents into the larynx [4,44] . Although the history, clinical symptoms and physical exam may suggest the diagnosis of ZD, it is necessary to confirm the diagnosis by esophagography (FigurE 2A & B) . Static images may not demonstrate a diverticulum, if it is small or when imaged in one plane; therefore, dynamic continuous fluoroscopy should be used. A videFigure 3. Transcervical cricopharyngeal myotomy with diverticulectomy. ofluoroscopic swallowing study, commonly (A) Zenkers pouch held with forceps. (B) Right-angled hemostat holding up the performed in conjunction with a speech cricopharyngeus muscle. pathologist, is essential to treatment planconsistent with fibrosis, increased collagen content and fatty ning; it allows identification of additional swallowing abnormalireplacement [26,42,43]. ties such as diffuse pharyngeal weakness, which may predict a poor outcome following myotomy [54] . Complications of ZD include aspiration pneumonia, retention Clinical features & diagnosis of foreign bodies (including medications and capsule endoscopes) Both cricopharyngeal abnormalities and the presence of diverticu- [5557] and food leading to bezoar formation [58] , tracheoesophalum may cause symptoms. A poorly compliant CP may result in geal fistula [59] , vocal cord paralysis, fistula to the prevertebral dysphagia, as may the diverticulum by direct compression of the ligament and cervical osteomyelitis, ulceration and hemorrhage esophagus. Regurgitation of undigested food, halitosis, aspiration [50,60,61,62] . Use of guidewires or overtubes may prevent diverwith or without pneumonia, gurgling in the throat, presence of ticular perforation during blind passage of nasogastric tubes neck lump, hoarseness and malnutrition, all relate primarily to and endoscopes [63] . Squamous cell carcinoma in a ZD was first the presence of the diverticulum and are dependent on its size reported by Pitt in 1896 [64] , with an estimated incidence of [44] . Symptoms may be present for several weeks to several years 0.41.5% [6568] . There should be a high index of suspicion for before diagnosis. development of a cancer within a ZD in the presence of alarm
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symptoms, which include neck pain, hemoptysis or hematemesis, an increase in the severity of dysphagia, regurgitation and malnutrition [65] .
Treatment

Open surgery

ZD can be found incidentally in patients who undergo flexible upper endoscopy because of unrelated symptoms. Treatment should be reserved for symptomatic patients. Strategies to treat ZD reflect changes in understanding its pathogenesis. Until the role of the cricopharyngeal muscle in development of ZD and contribution to dysphagia was recognized, surgery was focused on the diverticulum only; excision, inversion and suspension of the diverticulum were the surgical options. Subsequently, cricopharyngeal myotomy was done alone or in combination with diverticulectomy, diverticulopexy or diverticular inversion. More recently, both rigid and flexible endoscopic cricopharyngeal myotomy have been used. Table 1. Results reported for open surgery.
Study (year) Procedure

As mentioned, early surgeries focused on diverticular excision; however, mediastinal sepsis resulting from stagnant material inside the diverticulum was a limitation of this approach. A two-stage operation was therefore developed; inversion or diverticulopexy of the pouch at initial surgery, allowing it to empty into the esophagus, followed by diverticulectomy a few weeks later [69] . The two-stage approach was later replaced with a single-stage technique [70] ; the same group from the Mayo Clinic subsequently added cricopharyngeal myotomy to the pouch excision [10,71] . Surgical technique has evolved with regard to the suture line closure, such that diverticulectomy is associated with few adverse events. Compared with hand-sewn closure after diverticulum excision, which was complex in the deeper recess of the retropharyngeal space of the neck, application of staple-assisted techniques has led to a more secure pharyngeal closure, shorter operative times, shorter hospital stays and a decreased number of perioperative

Patients Initial Major Perforation Recurrence Median Ref. (n) satisfactory morbidity or leak (%) of symptoms follow-up outcome (%) (%) (%) (months)
20 158 15 12 10 888 12 20 43 100 6 15 87 37 17 9 40 13 34 79 77 Total: 1793 90 95 100 85 100 96 100 100 82 96 100 100 78 93 59 100 92 NA 98 100 99 95 96 (59100) 10 23 0 25 0 8 0 20 7 33 0 40 24 23 6 0 10 27 13 12 4 13 11 (040) 10 7 0 8 0 1 0 5 0 12 0 13 NA 5 14 0 3 23 13 6 4 4 5 (023) 85 20 NA 8 0 4 0 0 0 NA NA 7 3 12 11 0 0 NA 8 0 3 5 3.5 (085) NA 36 NA 16 36 NA 12 12 25 NA NA 40 8 84 43 5 36 NA NA 41 NA 41 36 (584)
[29] [108] [109] [110] [80] [71] [111] [111] [112] [113] [78] [77] [83] [114] [115] [72] [116] [117] [74] [118] [73] [119]

Negus (1950) Hiebert (1976) Orringer (1980) Ellis and Crozier (1981) Payne and King (1983) Konowitz and Biller (1989) Konowitz and Biller (1989) Barthlen et al. (1990) Lerut et al. (1992) Johnson and Weissman (1992) Morton and Bartley (1993) Bonafede et al. (1997) Fraczek et al. (1998) Van Eeden et al. (1999) Busaba et al. (2001) Leporrier et al. (2001) Sydow et al. (2001) Gutschow et al. (2002) Zaninotto et al. (2003) Colombo-Benkmann et al. (2003) Rizzetto et al. (2008) Median (range)

D DpM M and DM DM D DpM DM M and DM D, DM and DpM IM DM M, DM and DpM DM and DpM M, DM and DpM DM DM and DpM M, DM and DpM DM and M D and DM DM, DpM and M

Bertelsen and Aasted (1976) D

M, D, DM and DpM 101

D: Diverticulectomy; DM: Diverticulectomy/myotomy; DpM: Diverticulopexy/myotomy; IM: Invagination/myotomy; M: Myotomy; NA: Data not available.

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severe complications from mediastinitis, the procedure did not become widely accepted [76]. In 1960, Dohlman described a 30-year experience with an endoscopic approach using a modified rigid endoscope (FigurE 4) to expose the septum and electrocautery to divide it (symptomatic recurrence rate was 7%) [11]. Until 1990s, this technique was popular among surgeons [84,85]. In 1990, van Overbeek reported a modification of the Dohlman procedure by using a CO2 laser instead of electrocautery [6]. A few years later two other centers reported their experience (FigurE 5A5C) [86,87]. In 1993, Collard et al. [12] and MartinHirsch et al. [88] from Europe independently described the use of an endoscopic Figure 4. Dohlman diverticuloscope (Karl Storz, CA, USA; Tuttlingen, Germany). stapling device to divide the cricopharynadverse events [72] . A more recent open approach when the sac is geal bar, and subsequently this method became widespread. The exposed through the neck is to use the gastrointestinal anastomosis technique was introduced to the USA by Scher and Richtsmeier in stapler for excision and immediate staple closure. 1996 as an endoscopic staple-assisted esophagodiverticulostomy Diverticulectomy has low but significant adverse events; in addi- [89] . Rigid endoscopic stapling diverticulostomy is performed in tion to mediastinitis, recurrent laryngeal nerve injury, esopha- the operating room under general anesthesia (FigurE 6A6C) . geal stricture, fistula, esophageal perforation, hematoma, wound The patient is placed supine on the operating table with the infection, pneumonia and death may occur [9,10,73,74] . head extended. The surgeon sits behind the patients head. A Because of the initial leak rates and morbidity and mortality bivalved diverticuloscope (FigurE 7) (Karl Storz, CA, USA; Karl following diverticulectomy, diverticulopexy and inversion evolved Storz, Tuttlingen, Germany) is inserted positioning the anterior as techniques to avoid esophagotomy. Diverticulopexy involves blade in the esophageal lumen and the posterior blade in the fixation of the base of the diverticulum superiorly to the prever- diverticulum. A 5-mm telescope is passed through the endotebral fascia or to the pharyngeal musculature in order to prevent scope. After visualization of the septum, the scope is suspended accumulation of debris [75] . The technique has never achieved wide in position (FigurE 8) . recognition because of increased ZD recurrence [76] . Inversion A disposable surgical endostapler (Ethicon Endo-Surgery, OH, involves placement of a purse-string suture around diverticular USA) is inserted through the rigid endoscope to divide the septum neck, inversion of the sac through it and ligation [77,78] . Both between the diverticulum and the esophageal lumen creating a diverticulopexy and inversion with cricopharyngeal myotomy are diverticuloesophagostomy. The anvil is placed in the diverticuprobably only suitable for smaller pouches [8] . lum, and the cartridge in the esophagus. The stapling sutures the Since the important role of the CP became recognized in both posterior esophageal wall to the wall of the diverticulum. The pathogenesis and symptoms of ZD, cricopharyngeal myotomy procedure takes about 20 min, if there is no difficulty exposing alone evolved as a successful treatment option for small-size the diverticulum with the diverticuloscope. diverticula [10,7983]. Staple-assisted diverticulotomy uses a bivalved diverticuloThere are no randomized controlled trials comparing different scope or similar instrument to tent open both the esophageal surgical approaches. However, what can be concluded from the and diverticular lumens. This allows room to maneuver both literature is that patients with small pouches (less than 2 cm) can be an endoscopic stapling device and a telescope (with or without adequately managed with myotomy alone; patients with moderate/ camera) for adequate visualization (FigurE 7) . This technique has large pouches can be managed with combined diverticulopexy and advantages over open surgery, including less morbidity, a shorter cricopharyngeal myotomy and larger pouches (more than 5 cm) operating time, rapid resumption of oral intake, shorter hospital likely warrant excision with cricopharyngeal myotomy (FigurE 3A & stay and quicker recovery [90,91] . B & tABlE 1) . With an average follow-up of 36 months, mean initial The efficacy of rigid endoscopic technique has been proven in satisfactory outcome of open surgery technique was 96%, and multiple studies (tABlE 2). The median initial satisfactory outcome mean morbidity was 11%, with perforation or leak in 5%. was 95% with a 5% recurrence or persistence and a 4% conversion to open surgery. The reported median severe morbidity was 3% with a perforation or leak of 0%, which makes this techRigid endoscopic treatment for ZD The endoscopic approach to treat ZD pouch is almost a century old. nique ideal for poor surgical candidates. Most adverse events are In 1917, Mosher described dividing the common wall between the minor and include sore throat, gingival or mucosal laceration and diverticulum and the esophagus using a rigid endoscope. Because of dental damage.
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Although radiographic evidence of a persistent septum and/or residual pouch is common after rigid endoscopic or surgical treatment, there is no correlation between the size and symptomatic recurrence. Persistent symptoms may be due to other underlying swallowing abnormalities and/or inadequate myotomy, which is the most likely reason. Endoscopic stapling of a recurrent pouch is technically simple [92] . However, one of the disadvantages of stapling is that small diverticula may not allow the device to pass deep enough to perform an adequate myotomy; therefore, a CO2 laser may be a better option to divide the entire septum. In order to overcome the stapler limitations, the traction stitch can be placed with the Endostitch device (US Surgical, Norwalk, CT, USA) to improve staple placement. In addition, some surgeons choose to modify the metal tip of the anvil by machining it down all the way to the distal tip of the stapler to allow for a lower stapler positioning [93] . Because of the physical limitations of the endostapler, a harmonic scalpel (FigurE 9), initially used in laparoscopic surgery

(Ethicon Endo-Surgery, Inc), is another option that has become popular in the treatment of ZD by otorhinolaryngologists with excellent results. The harmonic scalpel uses ultrasonographic energy to coagulate and seal tissue before dividing it [94,95].
Flexible endoscopic treatment for ZD

Many patients with ZD are older adults; because of swallowing difficulties, they are often malnourished and at higher risk for perioperative adverse events, including anesthesia-related events. Endoscopic stapling using a rigid endoscope is not feasible in patients with retrognathia, prominent teeth, severe temporomandibular joint disease and rigid cervical kyphosis that limit neck extension. Anatomic head and neck features that can affect the feasibility of rigid endoscopic treatment and necessitate conversion to an open surgery are seen in about 5% of cases [96] . In 1995, for the first time, two separate studies published the use of a flexible endoscope for treatment of ZD [14,16]. Since then,

Figure 5. Staple-assisted cricopharyngeal myotomy. (A) Endo GIA anastomosis universal stapler. (B) Mid-procedure staple cricopharyngeal septal myotomy and (C) end result.

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Figure 6. Carbon dioxide laser cricopharyngeal myotomy. (A) Cricopharyngeal septum within the Dohlman diverticuloscope (Karl Storz, CA, USA; Tuttlingen, Germany). (B) CO2 laser incision. (C) Cricopharyngeal septum division final result.

several case series have demonstrated both safety and efficacy of this approach (tABlE 3). The procedure is of short duration and is most commonly performed in the endoscopy unit under moderate sedation or monitored anesthesia care without need for neck hyperextension. The goal is the same as for rigid endoscopy; cricopharyngeal myotomy allowing clearance of ingested bolus from the pouch thus preventing recurrence of symptoms (FigurE 10). Cricopharyngeal myotomy ideally reduces the septum to less than 1 cm, decreasing the UES pressure [11,97]. Manometric studies have demonstrated efficacy in reducing UES pressure after flexible endoscopic cricopharyngeal myotomy [16]. The myotomy can be accomplished by using electrocautery. The incision is made beginning from the superior part of the cricopharyngeal bar using a needle knife [14,16,98101]. Alternatively, argon plasma coagulation (APC) can be used for the incision [18,97]. The CO2 laser is probably superior to APC in the rigid endoscopic approach, but it is not the safest choice for the flexible endoscope because of the positioning in relationship to the cricopharyngeal bar. The optimal cutting technique is unknown, since prospective randomized trials are lacking. The technique chosen is based on endoscopist experience and preference.
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A transparent hood (FigurE 11) (MH589; Olympus Optical Co., Ltd., Tokyo, Japan), as is used for endoscopic mucosal resection, attached to the tip of the flexible endoscope [17] or a soft diverticuloscope (ZD overtube, ZDO-22-30; Wilson-Cook, Winston Salem, NC, USA) [102] help improve exposure, endoscopic visualization of the cricopharyngeal septum, stabilize the cautery instrument and provide room between the tip of the endoscope and the cricopharyngeal bar. The placement of nasogastric tube is helpful to maximize endoscopic visualization (exposure) of the cricopharyngeal septum and to protect the anterior esophageal wall during incision. The nasogastric tube tip is cut to create an end hole and is passed over a guidewire [51] . The decision to leave or remove the tube after the procedure is based on endoscopists preference.
Specific techniques

Use of the needle-knife technique may be used with different accessories (cap, hood and overtube), and it is more difficult to master, but it is an attractive approach for patients in whom an excellent view of septum can be obtained. The septum is dissected using blended current, alternating cut and coagulation mode or a
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pure coagulation current starting at the top of the septum in the midline [99,103] . The needle is advanced from the sheath, and the tip is positioned at the top of the septum at its midpoint. An incision is created in a caudal direction, toward the inferior aspect of the diverticulum. The cut can be directed from the inside of the diverticulum toward the posterior esophageal wall or in the opposite direction. Some endoscopists routinely place endoclips at the base of the septal incision to prevent microperforation [100] . The incision must not extend past the inferior border of the diverticulum, because this leads to mediastinal perforation. When using APC probe, one can begin the incision 23 cm below the top of the septum and pull back the endoscope, or begin at the top and extend downward [18] . High-power settings are used (APC 300 Figure 7. Bivalved diverticuloscope (Karl Storz, CA, USA; Tuttlingen, Germany). EEBE Generator at 99 W and EEBE VIO APC at 50 W and APC mode pulsed 1) in with a flexible endoscopic natural orifice transluminal endoscopic a noncontact method [18] . The bilateral forceps technique with the transparent hood to surgery scissors. Bleeding can be controlled with the BELA placed identify the septum can be used for small diverticula. The rationale in a coagulation mode. The advantages of this instrument include is that bilateral endoclips protect two sides of the septum before coaptation of the dissected septum edges and increasing precision dissection. After nasogastric tube placement, one endoclip is placed of dissection when compared to a needle knife; monopolar energy on each side of the cricopharyngeal bar. Needle knife with the leads to muscle contraction and imprecise myotomy. Further studcoagulation current completely dissects between two clips down ies are needed to address the device applicability to ZD in humans. Despite initial recommendations to limit the flexible endoscopic to the bottom of the diverticulum. Recently published technique uses a harmonic scalpel with a soft approach to high-risk older adults and poor operative candidates, diverticuloscope (ZD overtube, ZDO-22-30; Cook Endoscopy, some centers offer it to all symptomatic patients referred for treatWinston-Salem, NC, USA) (FigurE 9) [95]. With the flexible endoscope ment [105] . The relief of dysphagia after the first procedure varies in the esophagus the diverticuloscope is inserted and positioned to from 43100% (median 96%); repeated number of sessions vary allow better exposure of the septum and provide wall protection. A shear-type harmonic scalpel (Ultracision ACE 36 P; Ethicon Endo-Surgery, Cincinnati, OH, USA) is introduced through the soft diverticuloscope next to the endoscope, and the septum is divided. Cervical extension is necessary for easier positioning of the diverticuloscope and for the introduction of the harmonic scalpel. General anesthesia is recommended. A newer forceps technique has been recently described in a pig animal model [104] . A flexible, rotatable bipolar sealing forceps (BELA, Ethicon Endo-Surgery, Cincinnati OH, USA), developed for natural orifice transluminal endoscopic surgery has been used to coapt the septum at the midline using coagulation current (bipolar sort mode, 60W, effect 4; VIO 300D; ERBE, Tubingen, Germany). Fused tissue is Figure 8. Rigid endoscopic cricopharyngeal myotomy operating room set up. cut using the cutting mode of the device or
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contrast to identify fluid collections and free perforation. Bleeding occurs in about 3% (010%) of cases (tABlE 3) . Incidental, intraprocedural bleeding can be treated with electrocautery (using the tip of the needle knife, hot biopsy forceps and APC probe), dilute epinephrine injection or endoclips. Delayed bleeding is uncommon, and it can be managed similarly. Mortality is usually caused by complications that are unrelated to the procedure [51] . The median perforation and leak rates occur in approximately 4% of patients (range 027) with other major morbidities (such as mediastenitis) occurring in 1.5% (range 032%) of patients. The flexible endoscopic approach is a promising treatment modality, especially for high-risk older patients who would benefit from a shorter procedure withFigure 9. Harmonic scalpel (Ethicon Endo-Surgery, Inc., OH, USA). out the need for general anesthesia and extension of the neck. However, most from one to three (tABlE 3) with a median follow-up of 23 months endoscopists in the USA are not trained in endoscopic myotomy (range 038). for ZD. Indeed only a few centers offer endoscopic treatment, Throat pain should be expected. Fever lasting less than 24 h and it remains in the hands of highly experienced therapeutic is common after APC treatment, and it does not require further endoscopists. The learning curve is unknown, and the relatively evaluation [18] . Fever lasting for more than 36 h and elevated low volume of patients may not allow an individual to master white blood cell count without signs of perforation or medias- the techniques. In addition, the approach is not as standardized tinitis should be treated with antibiotics until the fever subsides. as in the rigid approach, and the optimal technique has yet to Uncomplicated cervical emphysema represents microperforation, be identified. The diversity of different options is an indicator is usually asymptomatic and generally resolves in 25 days; anti- that none of them are ideal. A prospective comparative trial of biotics are optional [18,100] . Development of systemic inflammatory the most important variants is needed. Furthermore, additional response syndrome with cervical or mediastinal emphysema should research is necessary to identify the ideal candidates for flexible be further evaluated with the chest computed tomography with oral endoscopic procedures. Table 2. Treatment of Zenkers diverticulum via rigid endoscopy.
Study (year) Patients (n)
6 95 102 74 32 23 31 25 55 28 Total: 494

Initial Recurrence or Major Perforation Converted Median Ref. satisfactory persistence morbidity or leak (%) to open follow-up outcome (%) (%) (%) (%) (months)
100 93 100 97 96 80 87 95 96 90 85 95 (80100) 0 5 0 5 4 7 13 22 4 9 10 5 (022) 0 1 0 3 1 4 0 10 12 4 7 3 (012) 0 0 0 2 4 0 0 10 0 2 4 0 (010) 0 3 4 8 0 16 30 0 0 7 4 4 (030) 5 23 16 NA 12 24 12 61 10 33 NA 16 (561)
[120] [121] [122] [123] [124] [125] [126] [127] [94] [128] [129]

Fremling et al. (1995) Peracchia et al. (1998) Narne et al. (1999) Cook et al. (2000) Jaramillo et al. (2001) Thaler et al. (2001) Counter et al. (2002) Fama et al. (2009) Wasserzug et al. (2010) Peretti et al. (2010) Median (range)
NA: Data not available.

Lscher and Johansen (2000) 23

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Figure 10. Flexible endoscopic cricopharyngeal myotomy using the needle-knife technique. (A) Cricopharyngeal septum exposure via clear hood. (B) Initial cut performed with a needle-knife. (C) Midway through the procedure. (D) Residual septum at the end of the procedure.

Conclusion

Treatment for ZD has progressed, as did the understanding of the underlying pathophysiology. The central role of cricopharyngeal pathology is supported by the studies using combined fluoroscopy and manometry [27] and studies demonstrating cricopharyngeal inflammation and fibrosis all leading to formation of a pulsation diverticulum. Therefore, cricopharyngeal myotomy became an integral part of both endoscopic (rigid or flexible), and open surgical strategies leading to decrease of adverse events and recurrence. Rigid endoscopic treatment is currently the preferred initial choice for ZD of any size, small or large; transcervical approach
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is used if exposure is inadequate or other complications arise or for very large diverticula. There have been no prospective trials comparing different endoscopic options with open surgery; therefore, it is difficult to draw conclusions. One retrospective study compared open surgical approaches versus endoscopic therapy and found shorter operative times and shorter hospital stays in the endoscopic approach [106]. Another retrospective study compared flexible endoscopy with rigid endoscopy and found comparable results [107]. One of the major obstacles to successful endoluminal therapy is judging the extent of cutting to the most inferior part of the septum because of the risk of exposing the mediastinum; if a long residual wall remains then symptoms will likely
459

460

Table 3. Treatment of Zenkers diverticulum via flexible endoscopy.

Review

Study (year)

Patients (n)
Forceps Coagulation NK NK NK None APC NK APC Monopolar forceps NK 100 100 88 78 0 1.5 (032) 0 4 (027) 12 6 6 3 3 11 0 8.5 (035) 32 18 27 0 NA 0 84 3 35 23 100 0 10 5 1 1 1 1 1 NA 1 1 (13) 95 0 17 3 3 43 14 2 NA 18 100 NA 2 Cap Cap Hood Cap Hood/endoclips NK Cap NK Hook knife NK None None Soft Harmonic scalpel 100 diverticuloscope 96 (43100) 2 15 NA 36 16 23 26 NA 13 20 28 NA 23 (038) 96 2 NA NA 13 100 1 0 NA 0 Range: 212 Range: 012 93 1 7 2 38 2 NA NA 3 7 Hood 0 0
[14] [16] [103] [98] [97] [100] [18] [17] [99] [130] [15] [131] [101] [95]

NGT guide

Endoscopic device Incision

Morbidity Perforation Recurrence or Sessions, Median Initial or leak (%) persistence satisfactory (%) median follow-up outcome (%) (%) (n) (months)

Ref.

Mulder et al. (1995)

20

Yes

Ishioka et al. (1995)

42

Variable Variable

Sakai et al. (2001)

10

No

Hashiba et al. (1999)

47

Yes

Mulder (1999)

125

Yes

Costamagna et al. (2007) 28

Yes

Rabenstein et al. (2007)

41

Yes

Dzeletovic, Ekbom & Baron

Christiaens et al. (2007)

21

Yes

Vogelsang et al. (2007)

31

Yes

Tang et al. (2008)

Yes

Case and Baron (2010)

22

Yes

Repici et al. (2010)

32

Yes

Al-Kadi et al. (2010)

18

Yes

Hondo et al. (2011)

No

Median (range)

Total: 449

APC: Argon plasma coagulation; NA: Data not available; NGT: Nasogastric tube; NK: Needle-knife.

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recur. Endoscopic treatment is an appealing option because it is less invasive, has lower complication rate (median morbidity, open surgery vs rigid/flexible endoscopic therapy; 11 vs 3/1.5%, respectively) even though it is sometimes less effective in relieving dysphagia. The flexible endoscopic technique has additional benefits when compared with rigid endoscopy because it does not require general anesthesia or neck extension. In conclusion, ZD can be effectively treated with either endoscopic cricopharyngeal myotomy using rigid or flexible endoscopic technique or open surgery. All modalities have advantages and disadvantages. Future studies will have to demonstrate whether the long-term results between endoscopic rigid or flexible endoscope and surgical modalities are comparable, and if they are, endoscopic treatment would represent a significant step forward.
Expert commentary & five-year view

The prevalence of ZD will likely increase due to the increased aging population. Subsequently, the need for endoscopic therapy will increase in the future, although there will always be a place for open surgical management for those patients who are not candidates for flexible or rigid endoscopic approaches. Endoscopic treatment of ZD with either flexible or rigid endoscopes will almost certainly continue to evolve over the next 5 years because of the potential of further development of new cutting devices (BELA, Harmonic scalpel etc.) that seal the tissue together decreasing morbidity. A randomized, prospective control trial comparing different endoscopic modalities is necessary in order to standardize the technique better and choose the ideal patient population for different endoscopic options. Revision endoscopic or open surgery will remain Key issues

Figure 11. Transparent hood (MH589; Olympus Optical Co., Ltd, Tokyo, Japan).

on the surgical forefront for those patients that have persistent symptoms despite initial surgery.

A typical individual swallows about 600 times a day without significant effort. Zenkers diverticulum occurs in individuals between 60 and 70 years of age. Incidence of gastroesophageal reflux disease among patients with Zenkers diverticulum ranges from 20 to 95%. Flexible endoscopic treatment of Zenkers diverticulum is a short procedure most commonly performed in the endoscopy unit under moderate sedation or monitored anesthesia care without the need for neck hyperextension. The goal is the same as for rigid endoscopy, to divide the cricopharyngeal septum completely achieving a diverticulotomy and thus allowing clearance of ingested bolus from the pouch and preventing recurrence of symptoms. Best candidates for flexible endoscopy are older patients who are poor surgical candidates with head and neck anatomy that make rigid endoscopic access difficult. Rigid endoscopic techniques include use of a stapler, laser or harmonic scalpel to divide the cricopharyngeal muscle allowing for a diverticulotomy. The open surgical technique is a very good option for those patients where endoscopic exposure is impossible. Typically, a cricopharyngeal myotomy and diverticulectomy via the use of a stapler is the best for achieving watertight closure and avoiding fistulae.

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stapling technique. Acta Otolaryngol. Suppl. 543, 235238 (2000).

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Jaramillo MJ, McLay KA, McAteer D. Long-term clinicoradiological assessment of endoscopic stapling of pharyngeal pouch: a series of cases. J. Laryngol. Otol. 115(6), 462466 (2001). Thaler ER, Weber RS, Goldberg AN, Weinstein GS. Feasibility and outcome of endoscopic staple-assisted esophagodiverticulostomy for Zenkers diverticulum. Laryngoscope 111(9), 15061508 (2001). Counter PR, Hilton ML, Baldwin DL. Long-term follow-up of endoscopic stapled diverticulotomy. Ann. R. Coll. Surg. Engl. 84(2), 8992 (2002). Wasserzug O, Zikk D, Raziel A, Cavel O, Fleece D, Szold A. Endoscopically stapled

diverticulostomy for Zenkers diverticulum: results of a multidisciplinary team approach. Surg. Endosc. 24(3), 637641 (2010).
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Peretti G, Piazza C, Del Bon F, Cocco D, De Benedetto L, Mangili S. Endoscopic treatment of Zenkers diverticulum by carbon dioxide laser. Acta Otorhinolaryngol. Ital. 30(1), 14 (2010). Tang SJ, Jazrawi SF, Chen E, Tang L, Myers LL. Flexible endoscopic clip-assisted Zenkers diverticulotomy: the first case series (with videos). Laryngoscope 118(7), 11991205 (2008). Repici A, Pagano N, Romeo F et al. Endoscopic flexible treatment of Zenkers diverticulum: a modification of the needle-knife technique. Endoscopy 42(7), 532535 (2010).

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Flexible endoscopic and surgical management of Zenkers diverticulum

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You are seeing a 70-year-old man with a history of dysphagia and hoarseness. You consider whether he might have Zenkers diverticulum (ZD). Which of the following statements is most consistent with the clinical presentation of ZD?

A B C D

ZD usually occurs between the seventh and eighth decades of life ZD is more common among women ZD usually presents with acute symptoms for days or hours Most patients with ZD have physical findings of the abnormality

2. Which of the following means is the best way to evaluate this patient for ZD?

A B C D

Esophagogastroduodenoscopy Plain radiography of the neck Videofluoroscopic swallowing study CT of the neck

3. The patient is diagnosed with ZD and referred for endoscopic treatment. Which of the following statements regarding endoscopic treatment for ZD is most accurate?

A A large residual pouch after rigid endoscopic treatment indicates a high risk for symptomatic recurrence B The initial satisfactory outcome after rigid endoscopic treatment is 95% C Any fever is a sign of potential mediastinitis after flexible endoscopic treatment and requires immediate medical evaluation
and antibiotics

D Most endoscopists in the United States now prefer flexible endoscopic treatment for ZD
4. The patient fails endoscopic treatment and is referred for open surgery. What should you consider regarding surgery for ZD?

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A B C D

Sutures are similar to staples in securing the pharyngeal closure Diverticulopexy reduces the risk of ZD recurrence compared with other surgical techniques Pouches less than 2 cm can be treated with myotomy alone The initial rate of satisfactory outcome of surgery is less than 50%

Expert Rev. Gastroenterol. Hepatol. 6(4), (2012)