World J Surg (2011) 35:14471453 DOI 10.

1007/s00268-011-1065-z

Therapeutic Strategies for Epiphrenic Diverticula: Systematic Review

Giovanni Zaninotto Giuseppe Portale Mario Costantini Lisa Zanatta Renato Salvador Alberto Ruol

Published online: 4 May 2011 te Internationale de Chirurgie 2011 Socie

Abstract Most patients with epiphrenic diverticula are asymptomatic. When dysphagia or regurgitation is limited and respiratory complaints are absent, these patients usually can live with the diverticulum left in place. Fewer than one-third of the diverticula produce symptoms severe enough to seek medical attention or to warrant surgery. The purpose of this systematic review was to analyze the therapeutic strategies for epiphrenic diverticulafrom a nonsurgical alternative such as endoscopic dilatation for symptomatic patients unt for surgery, to the traditional approach of surgical resection (left thoracotomy), and nally to the minimally invasive techniques (thoracoscopy, laparoscopy) used more recently. Whatever treatment and approach are used for the patient with epiphrenic diverticula, a tailored protocol always involves detailed study of the esophageal morphology and function.

Introduction Epiphrenic diverticula are out-pouchings of the esophageal lumen originating in the distal third of the esophagus, close to the diaphragm. They have historically been considered

G. Zaninotto (&) ` Operativa Complessa General Surgery, Santi Giovanni e Unita Paolo Hospital, ULSS 12, Castello 6777, 30100 Venice, Italy e-mail: giovanni.zaninotto@unipd.it G. Portale ` Operativa Complessa General Surgery, ULSS 15, Unita Cittadella, Italy M. Costantini L. Zanatta R. Salvador A. Ruol Department of Surgical and Gastroenterological Sciences, University of Padova School of Medicine, Padova, Italy

pulsion diverticula because of the high intraluminal pressure in a short segment of the esophagus (with or without chronic inammatory processes starting from the mediastinal lymph nodes and due to granulomatous disease such as tuberculosis) [1, 2]. This anatomic and pathogenetic dichotomous classication of esophageal body diverticula (mid-thoracic traction versus epiphrenic pulsion diverticula) was challenged by Jordan and Kinner in 1999, who said that small diverticula can originate anywhere in the distal half of the esophagus. They also noted that and when the diverticula enlarge and approach the diaphragm, they acquire the status of epiphrenic diverticula [3]. Radiological studies (contrast esophagography) have shown that epiphrenic diverticula have a prevalence of around 0.015% in the United States and up to 0.77% in Japan and 2.0% in Europe [46]. The true prevalence of epiphrenic diverticula remains unknown, however. Trastek and Payne estimated the ratio of epiphrenic to Zenkers diverticula at 1:5; and because the annual incidence of Zenkers diverticula is generally assumed to be less than 1:100,000 the estimated incidence of epiphrenic diverticula would be approximately 1:500,000 annually. This gure gives us an idea of the rarity of diverticula of the thoracic esophagus [7]. Stationary perfusion manometry reveals motor abnormalities in 75% to 90% of patients with epiphrenic diverticula [8], the most common of which are achalasia and diffuse esophageal spasm (DES). Esophageal motor disorders are not always demonstrated by ordinary means (i.e., stationary esophageal manometry), however. Using 24-hour ambulatory manometry, Nehra and coworkers reported a 30% diagnostic yield [9]. The most consistent nding with ambulatory manometry was a high percentage of simultaneous, high-amplitude, persistent esophageal

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body contractions during mealswhich stationary manometry (with the ten 5-ml wet swallows that are normally used to elicit peristalsis during esophageal manometry) were unable to pinpoint. The clinical questions to address when dealing with epiphrenic diverticula of the thoracic esophagus are the following: (1) Do they always require treatment? (2) What is the best approach? Open, minimally invasive, or combined? Transthoracic, transabdominal, or combined? The aim of this article was to review the literature to nd evidence to support decisions on these issues. The disease is so rare that only cohort studies or case series with a low level of evidence (2? to 3) have been published. Therefore, the grade of recommendation they reect is low.

the diverticulum enlarges, the reason being that it eventually acts as a reservoir [11]. They also pointed out the difference between a signicantly dilated esophagus (capable of accommodating the contents of the diverticulum as it spills over into the esophageal lumen) and a minimally dilated esophagus, which carries a higher risk of aspiration. Although a linear correlation between diverticular symptoms and size cannot be demonstrated, it is common to nd that small, mid-esophageal diverticula are mildly or not at all symptomatic and rarely require surgery, whereas large diverticula are often associated with food retention and regurgitation, prompting the need for diverticulectomy. Risk of complications

Do epiphrenic diverticula always require treatment? One of the most intriguing questions regarding epiphrenic diverticula is if all epiphrenic diverticula require treatment. The natural history of epiphrenic diverticula is not clear, and whether to operate has long been (and still is) a matter of debate. The decision is often based on the physicians and patients personal preferences. Orringer has said: A masterful inactivity in asymptomatic or mildly disturbing diverticula is a good practice even if, in this time of minimally-invasive surgery and stapling devices, an esophageal diverticulectomy may represent a tempting trophy for a hyperactive surgeon [10]. The presence of a diverticulum cannot, per se, be considered an indication for surgery. The surgeon should weigh the surgery-related risks against the potential benets, carefully assessing the patients symptoms and the risk of complications related to the presence of the diverticulum. Symptoms The proportion of diverticula symptomatic enough to warrant surgery is highly variable, ranging from 0% to 40% [1114]. In general, severe dysphagia, regurgitation, and contrast retention on esophagography, with the implicit or explicit risk of aspiration pneumonia, make surgery recommendable. We have reported a series of 41 patients with epiphrenic diverticula, one-third of whom were severely symptomatic. One patient suffered spontaneous rupture of the diverticulum and required emergency surgical repair [15]. Thomas et al. published a review in 1956 that also mentioned a large series of 121 diverticula patients, with 97 (80%) asymptomatic [16]. The diverticulums size is not strictly related to the severity of a patients symptoms, so it should not be considered a reliable guide to treatment [17, 18]. Altorki et al. suggested that symptoms can, paradoxically, diminish as

The most severe complications related to a diverticulum in the thoracic esophagus are perforation or rupture of the diverticulum in the mediastinum and (less frequently) progression to carcinoma within the diverticulum [11, 19]. Aside from anecdotal reports from Altorki et al. (who strongly advocated surgery for all epiphrenic diverticula) of a high rate of aspiration (9/20 patients) and even a case of tracheoesophageal stula, the natural history of a mildly symptomatic or even asymptomatic diverticulum is difcult to predict [11, 2023]. It has been estimated that fewer than 10% of patients develop symptoms or complications of their diverticula (Table 1) [3, 9, 1113, 15, 24]. On the other hand, in cases of epiphrenic diverticula that are moderately to severely symptomatic, the disease usually tends to progress, sometimes even to the point of making surgery not feasible, as reported by DeMeesters group (one patient died of aspiration pneumonia before surgery could be undertaken) [11]. In our experience, we had one case of rupture of the diverticulum and one patient whose symptoms worsened (over a period of 7 years) sufciently to prompt a request for surgical repair. We have never encountered esophageal carcinoma arising within a diverticulum. Surgical risk Another important aspect to bear in mind when evaluating a patient with an epiphrenic diverticulum is the risk related to surgical treatment. The overall mortality rate for surgery for epiphrenic diverticula is nearly 5% (even higher than after esophagectomy for benign diseases), and the morbidity rate is nearly 20% [25]. Table 2 shows the mortality and morbidity rates for more than 200 patients operated on because of epiphrenic diverticula. As expected, the most common complication following diverticulectomy was suture leakage [3, 9, 1115, 24, 2630]. Overall, in our experience, asymptomatic patients with small, incidentally diagnosed diverticula and mildly

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World J Surg (2011) 35:14471453 Table 1 Natural history of epiphrenic diverticula Study No. of patients Clinical condition Diam (cm) F-up (years) Evolution Stable Altorki [11] Benacci [12] Castrucci [13] Jordan [3] Nehra [9] Klaus [24] Zaninotto [15] All authors 3 42 16 6b 3c 5 16e 91abce
b a

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Progressing 1 MI (),1 asp pn () 0 7 0 2 ref surgery 1 asp pn ()d 0 0 2 surgery 2 (2.8%) 12 (92.3%)

3 symptomatic 35 asympt/mild 7 sympt ref surgery 13 asymptomatic 5 asymptomaticb 1 symptomatic 4 asympt/mild 14 asympt/mild 2 symptomatic 71 asympt/mild 13 symptomatic
b

C3.5 C1.5 B2 4

7 5 5.3 6 3.8

1 (liquid diet) 35 0 13 1 asympt, 2 mild 0 2 asympt, 2 mild 14 asympt/mild 0 69 (97.2%) 1 (7.7%)

Follow-up data are expressed as the median F/U follow-up, pts patients, sympt symptomatic, asympt asymptomatic, MI myocardial infarction, () died, asp pn aspiration pneumonia, ref surg referred to surgery
a b c d e

Three patients lost to follow-up One patient lost to follow-up This series also included two patients who refused surgery and were lost to follow-up One patient died while awaiting surgery This study also included three symptomatic patients who underwent pneumatic dilation and had symptom relief

Table 2 Morbidity and mortality following surgery for esophageal diverticula

Study Streitz [14] Altorki [11] Benacci [12] Castrucci [13] Jordan [3] Rosati [26] Nehra [9] Klaus [24] Del Genio [27] Tedesco [28] Fernando [29] Zaninotto [15] Melman [30]

Level of evidence 2? 2? 2? 2? 2? 3 2? 3 3 3 3 3 3

No. of pts 13 17 33 27 19 11 18 11 13 7 20 22 13 224

Mortality 0 1 (5.9%) 3 (9.0%) 2 (7.0%) 0 0 1 (5.5%) 0 1 (7.7%) 0 1 (5.0%) 0 0 9 (4.0%)

Leaks 1 (7.7%) 0 6 (18.0%) 2 (7.0%) 1 (5.3%) 1 (9.0%) 1 (5.5%) 1 (9.0%) 3 (23.0%) 1 (14.3%) 4 (20.0%) 6 (27.2%) 1 (7.7%) 28 (12.5%)

Morbidity 1 (7.7%) 0 11 (33.0%) 3 (11.0%) 1 (5.3%) 1 (9.0%) 2 (11.0%) 2 (18.0%) 4 (31.0%) 1 (14.3%) 9 (45.0%) 4 (18.0%) 2 (15.4%) 41 (18.3%)

Data are expressed as the number

All authors

symptomatic patients with medium-sized pouches have been managed conservatively with no specic therapy apart from proton pump inhibitors or H2-blockers in patients with symptoms related to reux or gastritis. The nonsurgical alternative of endoscopic pneumatic dilation has proved valuable in symptomatic patients who had an underlying motility disorder (achalasia or hypertensive lower esophageal sphincter) but were unt for or unwilling to undergo surgery. Each of these patients beneted from

this treatment and were symptom-free at a minimum of 2 years of follow-up [15]. If we compare the surgical complications with the fate of unoperated patients, at least in the medium term, surgery is justied only when the patient is suffering from severe, incapacitating symptoms (e.g., dysphagia, regurgitation, aspiration) and/or in the case of existing or impending complications. Patients with minimal or no symptoms should be managed conservatively.

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What is the best approach? Transthoracic, transabdominal, combined? Open, minimally invasive, combined? When surgical management of epiphrenic diverticulum is indicated, treatment should focus on the underlying motor disorder and the pouch. Treating the underlying motor disorder An abnormal lower esophageal sphincter (LES) (hypertensive or nonrelaxing) and/or abnormal peristalsis in the lower part of the esophagus, with simultaneous contractions, are common ndings. These motor abnormalities create a high-pressure segment that contributes to protrusion of the esophageal wall. The functional disorder may be treated by myotomy. It should start in line with the neck of the diverticulum and on the opposite side to the diverticulum to avoid interfering with subsequent pouch resection and muscle closure. Most surgeons extend the myotomy onto the gastric wall. The importance of myotomy as a fundamental part of treatment for epiphrenic diverticula was clearly illustrated in a series of 21 patients published by the Mayo Clinic: Patients treated with diverticulectomy alone suffered from higher leakage and recurrence rates (24% and 19%, respectively) than those who underwent diverticulectomy with myotomy (0% for both leakage and recurrence rates) [31]. Tables 3 and 4 show outcomes after diverticulectomy alone and diverticulectomy plus myotomy [3, 9, 1115, 24, 2628, 30]. When the two alternatives are compared, the rate of leakage from the diverticulectomy suture line and the prevalence of persistent/recurrent symptoms and/or recurrent diverticulum are higher without myotomy. Several authors nonetheless recommend selective use of myotomy [3, 13, 14]. In fact, because the rationale for myotomy is to reduce endoluminal esophageal pressure, its use is questionable in cases where hypotonic motility patterns of the esophageal body and LES are detected by manometry.

When myotomy is performed, partial fundoplication is recommended to avoid the risk of subsequent gastroesophageal reux (GER). Data in the medical literature on the prevalence of GER after surgery with or without fundoplication for epiphrenic diverticula are scarce, but GER occurs in more than 50% of achalasia patients when myotomy is performed without adding an antireux procedure [32]. Because the motor disorder associated with epiphrenic diverticula is often characterized by abnormal peristalsis of the esophageal body, partial fundoplication is usually preferred (Dor, Toupet, or Belsey-Mark IV) to avoid excessive outow resistance [33]. Treatment of the pouch Small diverticula usually do not require specic treatment because they tend to shrink after myotomy. For large diverticula, the treatment should include diverticulectomy. For many years, diverticulectomy was performed via a transthoracic route, usually through a left thoracotomy, which allowed resection of the diverticulum and myotomy. This approach, however, was associated with high morbidity and mortality rates (up to 20% and 10%, respectively) [1214]. Minimal access surgery has become popular for treating a number of benign esophageal diseases. The rst minimally invasive approach used to treat epiphrenic diverticula was thoracoscopica logical evolution of the traditional thoracotomy route. The rst report came from the Milan group, which treated eight patients. The operation was completed thoracoscopically in six, and there was one leak [34]. A Dutch team reported on their experience with ve patients operated on using this method, with no deaths and one leak [35]. Few authors used a transabdominal approach before the advent of minimally invasive techniques, but matters changed when the opportunity arose to treat epiphrenic diverticula laparoscopically. The advantages of the transabdominal approach are more evident when the epiphrenic diverticulum is associated with hiatal hernia or achalasia

Table 3 Results after diverticulectomy alone for esophageal diverticula Study Streitz [14] Benacci [12] Castrucci [13] Jordan [3] Klaus [24] All authors No. of patients 3 7 5 6 1 22 Mortality (no.) 0 0 1 (20.0%) 0 0 1 (4.5%) Leaks (no.) 1 (33.3%) 0 1 (20.0%) 1 (16.7%) 1 (100%) 4 (18.2%) Persistent/recurrent symptoms (no.) 0 1 (14.3%) 0 1 (16.7%) 2 (9.2%) Recurrent diverticulum (no.) 0 0 0 0

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World J Surg (2011) 35:14471453 Table 4 Results following diverticulectomy and myotomy for esophageal diverticula Study Streitz [14] Altorki [11] Benacci [12] Castrucci [13] Jordan [3] Rosati [26] Nehra [9] Klaus [24] Del Genio [27] Tedesco [28] Zaninotto [15] Melman [30] All authors
a b c

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No. of pts 13 14 22 12 9 11 13 5 13 7 15c 13 147

Mortality (no.) 0 0 3 (13.6%) 1 (8.3%) 0 0 1 (7.7%) 0 1 (7.7%) 1 (5.0%) 0 0 7 (4.7%)

Leaks (no.) 0 0 6 (27.2%) 1 (8.3%) 0 1 (9.0%) 1 (7.7%) 0 3 (23.0%) 1 (14.3%) 4 (26.7%) 1 (7.7%) 18 (12.2%)

Persistent/recurrent symptomsa (no.) 0 1 (7.1%) 3 (13.6%) 1 (9.0%) 0 0 0 0 4 (26.7%) 2 (15.3%) 11 (8.5%)a

Recurrent diverticulumb (no.) 0 0 0 1 (11.1%) 1 (9.0%) 0 2 (13.3%) 0 2 (1.8%)b

Data were available on persistent/recurrent symptoms for 129 patients Data were available on recurrent diverticulum for 110 patients This series also included seven patients who did not have a myotomy

because it affords a better view of the hiatus for reapproximating the crura in cases of hernia. More importantly, there is a better view of the esophagogastric junction when performing myotomy and partial fundoplication. Introduction of an endostapler capable of transecting the neck of the diverticulum while remaining parallel to the esophageal axis has contributed to more widespread use of the laparoscopic approach. The feasibility of using the transabdominal route may be limited, even when a laparoscopic technique is adopted, by the distance of the diverticulum from the hiatus, the diverticulums size, or severe inammation and adhesions between the wall of the diverticulum and the mediastinal pleura. Dissecting the upper part of the diverticulum becomes more difcult, especially where there are adhesions to the pleura, with the likelihood of pleural tearing. Transabdominal (be it open or laparoscopic) approximation of the muscle layers may be challenging when the diverticulum is large and its neck is high in the mediastinum, although there are reports of laparoscopic resection of diverticula as large as 7 to 10 cm [24, 36]. Another problem to consider when choosing the approach is the size of the diverticulum neck. When it is very wide, it may take two or more rings of the endostapler to cut it, in which case points where suture lines cross over become a potential site of leakage. Although the laparoscopic approach to epiphrenic diverticula seems more popular, it is worth mentioning that the largest reported series contained only 13 patients (Table 5) [15, 24, 2630, 37].

The above-mentioned disadvantages of the technique warrant a tailored, combined approach. The thoracotomy approach should be considered when planning to treat large diverticula so a TA stapler can be used, inserted via a thoracotomy or a mini-thoracotomy if the diverticulum is dissected thoracoscopically. The TA stapler has a longer jaw than the endostapler and thus enables the use of just one cartridge to suture the diverticulum neck, avoiding any weak points being created where suture lines cross over. Myotomy, approximation of the crura, and partial fundoplication can then be accomplished via a laparoscopic route after thoracotomy or thoracoscopy for the dissection and resection of a large diverticulum.

Conclusions A tailored approach is warranted for epiphrenic diverticula requiring surgery. In the case of small diverticula, the pouch can be left in place and the treatment focused on the underlying motor disorder, with myotomy and partial fundoplication. Medium-size diverticula can be resected using a stapler, and myotomy can be performed on the side contralateral to the diverticulum. Using the laparoscopic approach in such cases affords the best view of the esophagogastric junction and an adequate view of the lower mediastinum. With a combined approach to large diverticula, laparoscopic myotomy and fundoplication may be implemented after transthoracic (open or minimally invasive) resection of the diverticulum.

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1452 Table 5 Laparoscopic treatment of epiphrenic diverticula: results Studya Rosati [26] Klaus [24] Fraiji [37] Del Genio [27] Tedesco [28] Fernando [29] Zaninotto [15]c Melman [30] All authors No. of patients 11 10 5 13 7 10 17 13 96
b

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Type of surgery DMF 4 DM 1 D 3 Div included in fundo 2 Div inverted ? myotomy DMF DMF DMF DMF 14 DMF 3 DF DMF

Mortality (no.) 0 0 0 1 (7.7%) 0 1 (10.0%) 0 0 2 (2.1%)

Leaks (no.) 1 (9.0%) 1 (10.0%) 1 (20.0%) 3 (23.0%) 1 (14.3%) 2 (20.0%) 4 (23.5%) 1 (7.7%) 16 (16.7%)

F/U (months) 36 26 9 58 6 48 13

Good/excellent outcome (%) 100 100 100 100 82 85

F/U follow-up, D diverticulectomy alone, DM diverticulectomy ? myotomy, DF diverticulectomy ? fundoplication, DMF diverticulectomy ? myotomy ? fundoplication, Div diverticulectomy, fundo fundoplication
a b

All references offered level 3 evidence

This series also included 10 patients operated via video-assisted thoracic surgery (VATS) (n = 7), combined VATS/laparoscopy (n = 2) and thoracotomy (n = 1). Specic data for the 10 laparoscopic patients were available only for mortality and leakage rates, not for follow-up and outcome This series also included ve patients who did not undergo laparoscopic surgery

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