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FRONTIERS IN ENDOSCOPY, SERIES #71

Endoscopic Treatment of Symptomatic Zenker’s Diverticula

Endoscopic Treatment of Symptomatic Zenker’s Diverticula

Introduction

Originally described by Ludlow in 1767,1 and then with a case series collected by Zenker et al. in 1877,2 after whom the entity was named, a Zenker’s diverticulum (ZD) is a pharyngeal pouch in which the mucosa extends through Killian’s triangle, the oblique inferior pharyngeal constrictor muscle and the transverse cricopharyngeal muscle, usually occurring in older patients.3 A pathological combination of increased intraluminal pressure in the oropharynx, inadequate relaxation of the cricopharyngeus, and incomplete upper esophageal sphincter (UES) relaxation is thought to lead to this outpouching of the dorsal pharyngoesophageal wall.4 Our understanding of and treatments for this entity have evolved substantially over nearly 200 years. Endoscopic techniques were described as early as 1917 by Mosher with cricomyotomy.5 This was followed by the use of a rigid transoral endoscope by Dohlman and Mattson in 1960.6 Collard et al. first described the use of an endoscopic stapling device for Zenker’s repair in 1993,7 and since then, surgical and flexible endoscopic methods for ZD repair have become the mainstay in treatment of this entity. This article will review modern treatments for ZD, with an emphasis on endoscopic approaches.

Zenker’s repair in 1993,7 and since then, surgical and flexible endoscopic methods for ZD repair have become the mainstay in treatment of this entity. This article will review modern treatments for ZD, with an emphasis on endoscopic approaches.

ZD Repair: Surgical Techniques

Surgical approaches for repair of ZD include Dolman’s procedure, division of the septum between the esophagus and the diverticulum pouch, cricopharyngeal myotomy alone or in combination with either suspension, inversion, or excision of the pouch.1 The open surgical technique is accomplished under general or selective spinal anesthesia with transcervical access. Exposure of the ZD is made by dividing the platysma, retracting the sternocleidomastoid and carotid sheath laterally and thyroid gland medially. Myotomy is first performed on the cricopharyngeus followed by a variety of procedures—removal of the diverticulum (diverticulectomy), the diverticulum is retracted and suspended (diverticulopexy), or the diverticulum is inverted into the esophageal lumen and oversewn (diverticulum invagination).8,9 Minimally invasive options have largely replaced open surgical techniques with endoscopic therapies as the mainstay of treatment of ZD repair.

ZD Repair: Endoscopic Techniques

Endoscopic repair methods include surgical-type options e.g., stapling, harmonic scalpel, in addition to cap-assisted or flexible endoscopic techniques: carbon dioxide laser diverticulostomy with argon plasma anticoagulation, needle and hook knife, bipolar forceps, endoscopic scissoring, and submucosal septum division among others.10

When performing the endoscopic myotomy, the technical goal is to achieve an endoscopic muscular dissection (EMD) of the cricopharyngeus sufficient to improve symptoms, while avoiding perforation (or treating it endoscopically if it develops).

A key to proficiency and durable outcomes of endoscopic methods is an understanding of the anatomic landmarks of the oropharynx and esophageal introitus. Additionally, knowledge of the layers beneath the mucosa – submucosa, cricopharyngeus muscle, buccopharyngeal fascia, retropharyngeal space, alar fascia, and the danger space just above the prevertebral fascia – will allow for a more complete resection of the cricopharyngeus which decreases recurrence rates (Figure 1).

Regarding which technique is the most commonly performed, one study examined over 600 flexible endoscopic ZD repairs and found the most common instrument reported for the myotomy was needle knife (59.6%) followed by argon plasma coagulation (25.7%). Forceps coagulation, hook knife, among other methods comprised the remaining 14.7%.11 Although there is sufficient evidence to consider endoscopic myotomy as a safe and effective method of ZD repair, there is currently no consensus on which technique or instrument is superior in regard to outcomes, and several different methods may be equally viable.12

In order to enhance the view of the operative field and reduce collateral injury to tissue surrounding the myotomy site, endoscopic accessories are often used in combination with the needle-knife technique. A nasogastric (NG), orogastric (OG) tube, or even biliary guidewire by itself can be placed in order to identify the true lumen of the esophagus and protect the anterior esophageal wall from thermal or mechanical injury during ZD repair. These objects also help the endoscopist to have a very clear reference point for the esophageal lumen when performing the myotomy. Clear mucosectomy caps, which are utilized broadly in endoscopic procedures to depress mucosal folds and improve visualization, have been described in ZD repair to enhance the view of the septum and diverticulum. Another accessory used to enhance the endoscopist’s view and protect the diverticular walls from injury is the “soft diverticuloscope”. This is a specially crafted overtube which goes over the endoscope and has two flaps which straddle the diverticular septum, providing stability during the procedure while avoiding the risk of trauma from a rigid endoscope.5,13,14,15

Flexible Endoscopic Myotomy Techniques Hook Knife Technique

The Hook knife (Olympus endotherapy, Tokyo, Japan) has a 5mm rotatable, hook-shaped knife tip that allows for variable dissection orientations with the ability to pull tissue prior to cutting it. After visualization of the diverticulum and septum, the myotomy technique with the Hook knife is as follows: The hook is locked in the 12 o’clock position, and then the incision is performed from the superior aspect of the bridge moving inferiorly, allowing the hook to pull the muscle fibers prior to cutting them. Through-the-scope (TTS) endoscopic clips are placed on either side of the inferior portion of the myotomy site for prophylaxis against bleeding and micro-perforation.16

Stag Beetle Knife (SB Knife) Technique

The Stag beetle knife (SB knife, Sumitomo Bakelite, Tokyo, Japan) is a scissor-like instrument developed for ESD and often used for myotomy in ZD repair. The Stag beetle (SB) knife junior has a similar design and rotational mechanism with slightly smaller dimensions (3.5mm x 4.5mm). The instrument is electrically insulated in a manner which allows the current to be focused on the electrodes at the edges of the blade, and the curved upward knife tips also serve to prevent inadvertent tissue damage and reduce perforation risk.17 The myotomy incision is initiated at the center of the diverticulum septum, and can progress both across the septum and deeper through the muscle fibers and the knife is rotated circumferentially, simultaneously cutting and coagulating, to perform the submucosal dissection and myotomy in the desired tissue plane while avoiding deeper tissue injury. One advantage of this knife is its ability to also function as a hemostatic device.18 (Figure 2)

Needle-knife Technique

The needle-knife is the most commonly used instrument for ZD repair, owing to the low cost and widespread availability of this device. (Figure 3) The tip of the instrument is placed at the center of the septum where either coagulation, blended, or alternating current is used depending on the preference of the operator. The incision is often made craniocaudally, exposing the transverse cricopharyngeus muscles. Care should be taken to avoid a myotomy which exceeds 10mm from the inferior portion of the diverticulum, as this is associated with a higher risk of perforation. If intra-procedural bleeding develops, argon plasma coagulation (APC) is often then applied to ensure hemostasis.5,19,20

Outcomes: Endoscopy vs. Surgery in ZD Repair

Albers et al. performed a meta-analysis of 11 retrospective cohort studies comparing outcomes in endoscopic vs. surgical repair of ZD. Endoscopic treatment was found to be superior to surgical repair in regard to reduced operative time, shorter length of hospitalization, and faster time to diet introduction. Surgical repair was found to be superior with regard to the risk of recurrence of symptoms compared to those treated endoscopically.21

Antonello et al. described a series of 25 patients who underwent flexible endoscopic repair for ZD. This study compared two treatment groups. The first group had experienced symptom recurrence after having surgical and/or endoscopic stapling previously vs. a treatment naïve group. The methods of myotomy used included needle knife (n=6), hook knife (n=9), and SB knife (n=15). After a mean follow-up of 17 months, no significant difference was found between the two groups with regards to symptom improvement, complications, or adverse events.22

Leong et al. performed a meta-analysis of 15 retrospective studies of patients who underwent endoscopic stapling for ZD repair. Of the 585 patients, 540 (92.3%) were successfully stapled. By the first post-op day, 92% of those who underwent stapling were able to resume oral intake, 87% were discharged on post-op day 2, and greater than 90% had greatly improved symptoms.23

Mittal et al. performed a retrospective, multicenter study examining 161 patients who underwent endoscopic myotomy for ZD. No significant difference was found in technical or clinical success (defined by patients experiencing improvement and/or resolution of their symptoms) between various knives utilized in the cohort. Clinical success was the highest among patients whose repairs were performed via hook knife (n= 43, 96.7%) followed by needle knife (n= 33, 76.6%), and then insulated (IT) tip knife (n=33, 47.1%).24

Brueckner et al. described a case series of 46 patients who underwent ZD repair with only the Hook knife technique with a similar success rate of 95%. This study reported a higher recurrence rate of 30%.25 Similarly, Christiaens et al. also published a series of 21 patients receiving ZD repair strictly with Hook knife myotomy; their reported recurrence rate was lower at 9.5%.26

Repici et al. also reported a series of 32 patients who underwent ZD repair using the hook-knife ESD technique. After a mean follow-up of 23.87 months, the authors reported an overall success rate 90.6%, with four patients reporting ongoing dysphagia. Of these four, three were found to have a residual Zenker’s bridge and achieved clinical success with a second treatment of the same endoscopic technique. The last patient declined further treatment due to advanced age.27

Jain et al. reviewed the outcomes from 23 original studies including 997 patients who underwent flexible endoscopic diverticulotomy (FED) for ZD. The follow-up between the studies varied widely from 7 to 43 months. The authors found the composite technical success rate of the procedures to be 99.4% with a clinical success rate of 87.9%. The composite rate for symptom recurrence after long-term follow-up was 13.6%, but 61.8% of these patients experienced symptom relief after repeat endoscopic intervention. The authors also reported differences in clinical outcomes between FED with diverticuloscope (FEDD) vs. FED with cap (FEDC). Technical outcomes in both groups were near 100%. The clinical success rates, defined by symptom improvement and/or resolution, differed significantly. Clinical success rates in the FEDC group were higher (86.8% vs 75.4%), and the FEDC group had nearly half the risk of symptom recurrence vs. the FEDD group (9.5 vs 16.5%).28

Vogelsang et al. described long-term outcomes in a series of 31 patients who underwent myotomy with the needle-knife technique for ZD. Of the 31 patients, four had previously underwent ZD repair unsuccessfully via argon beam coagulation (mean number of treatments=2.8). All of the patients had initial symptomatic relief, with 10 requiring repeat treatment due to recurrence of symptoms after a mean of 5.3 months. After a mean follow-up 26 months, 84% experienced long-term symptom relief to varying degrees, with 61% experiencing relief of symptoms after a single treatment.29

Adverse Events

Perbtani et al. published a retrospective analysis of adverse events in the 678 total patients from the 19 published case series from 1995 to 2015 who underwent flexible endoscopic ZD repair. Of the 678 patients, adverse events were reported in 80 (11.8%). These were, in descending order of frequency, micro-perforations (7.7%), infection (1.8%), bleeding (1.3%), macro-perforations (0.6%), and death (0.1%).5 However, reported rates of adverse events vary. Leong et al.’s metaanalysis of 15 retrospective case series of a total of 585 patients who underwent endoscopic stapling, demonstrated an overall perforation rate of 4.8%, and a mortality rate of 0.2%.17

Regarding adverse events with specific endoscopic knife utilization, Rouquette et al. reported an overall adverse event rate of 8.3% (2/24 with mild intra-procedural bleeding) in 24 patients treated with hook-knife myotomy. No perforations or post-procedural bleeding complications were reported.10 Adverse events reported in patients treated with the needle -knife technique for EMD vary substantially. Costamagna et al. reported an adverse event rate of 32% in those undergoing cap-assisted needle-knife myotomy, with 18% (5/28 patients) having perforations which were managed conservatively. Conversely, in the same study, 11 patients underwent diverticuloscopeassisted needle-knife myotomy with zero reported complications.8 In a series of 31 patients who underwent needle-knife myotomy, Vogelsang et al. described a minor complication rate (e.g., subcutaneous or mediastinal emphysema) of 23% and no major complications.23

In Rouquette et al.’s case series of 24 patients with ZD repair performed strictly with the Hook knife technique, the authors reported an overall adverse event rate of 8.3% (2/24) due to intraprocedural bleeding. There were no perforations or post-procedural events reported. Fever and/ or mild pain was reported in 37.5% of patients, which was managed conservatively.10 Repici et al. reported a series of 32 patients who also underwent ZD repair with hook-knife myotomy. The adverse event rate was reported at 6.25% (2/32), with one patient having intra-procedural bleeding treated successfully with APC, and one with cervical emphysema managed without additional procedures but via medical management (nasogastric tube, total parenteral nutrition, intravenous proton pump inhibitor, and antibiotics). 21

Crawley et al. recently published a metaanalysis examining adverse events in rigid vs. flexible endoscopic ZD repair in 2019 examining a total of 115 studies. The authors found bleeding (20% vs. 4%) and recurrence of symptoms (4% vs. 0%) to be significantly higher in flexible vs. rigid endoscopy techniques. Of note, the flexible endoscopic studies were more likely to report bleeding as an adverse event. Adverse events associated with rigid endoscopy were dental injury (1%) and vocal fold palsy (0.3%). Differences in rates of mortality, infection and perforation were not found to be statistically significant between the two groups.30

Conclusion

Endoscopic treatment of ZD appears to be safe and effective. There are currently no randomized controlled trials comparing outcomes among patients who have undergone endoscopic vs. surgical ZD repair. Although there are several studies comparing short-term outcomes between endoscopic and surgical techniques ZD, long-term outcome data is still lacking. Among the various flexible endoscopic techniques available, there is insufficient data to conclude that one method is superior to another. Nevertheless, the data that is available is sufficient to conclude that flexible endoscopic ZD repair should be considered first-line due to its minimally-invasive nature, effectiveness, and acceptable safety profile in a predominately elderly patient population.

References

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