Submucosal Injection-Guided Septotomy for Zenker's Diverticulum: Finding the Middle Ground

Abstract

Flexible endoscopic treatment has transformed the management of Zenker's diverticulum. Yet the optimal technique remains uncertain. Zenker's diverticulum is structural in appearance but functional in origin; the pouch is a consequence of disordered cricopharyngeal relaxation rather than the disorder itself. Impaired cricopharyngeal relaxation limits upper esophageal sphincter opening, generating elevated hypopharyngeal pressure that drives mucosal and submucosal herniation through Killian's triangle. The diverticulum is therefore the visible manifestation of the disease, but the therapeutic target is the dysfunctional cricopharyngeus. Persistent cricopharyngeal dysfunction and the consequent diverticulum can lead to dysphagia, regurgitation, cough, aspiration, and weight loss. Open surgery and rigid endoscopic septotomy remain appropriate in selected patients; however, flexible endoscopic therapy has become the preferred first-line approach for symptomatic Zenker's diverticulum, supported by favorable clinical success and safety profiles, its feasibility in patients with cervical spine disease or limited neck mobility, and its suitability for the older, medically complex population in whom Zenker's diverticulum commonly occurs [1-3].

The field has therefore moved beyond the simple question of whether the septum can be divided endoscopically, toward how to divide it completely, efficiently, safely, and reproducibly, without leaving residual septum or mucosal flap that can sustain symptoms. Conventional flexible endoscopic septotomy (FES) remains an accessible, efficient, and effective option, but its limitations are recognized: incomplete myotomy, limited visualization of the distal septal margin, bleeding, perforation, and recurrence [1]. Zenker's peroral endoscopic myotomy (Z-POEM) and peroral endoscopic septotomy (POES) were developed to address these shortcomings by bringing the principles of third-space endoscopy to the cricopharyngeal septum, enabling complete exposure and more precise myotomy. However, this precision comes at a cost: the need for third-space expertise and the potential for a residual redundant mucosal flap after myotomy, particularly in larger diverticula [4, 5].

In this issue of Digestive Endoscopy, Azzolini, Dell'Anna, and colleagues introduce submucosal injection-guided septotomy (SING), a hybrid technique designed to preserve the practicality of FES while incorporating principles from submucosal endoscopy [6]. The procedure begins with the placement of a nasogastric tube in the esophageal lumen as an orienting landmark. The proximal two-thirds of the septum is then divided using a conventional full-thickness septotomy. In the distal third, bilateral submucosal injection delineates the cricopharyngeal muscle by creating contrast between the stained submucosa and muscle fibers. Selective myotomy is then extended through the septal muscle to the transition with the thinner esophageal muscle layer, without a submucosal tunnel. The mucosal defect is subsequently closed with clips.

The authors report outcomes in 102 treatment-naive patients treated at three Italian tertiary centers between 2019 and 2024 [6]. The cohort reflects the population encountered in Zenker's diverticulum practice: older patients, predominantly male, with a median age of 74 years, median baseline Kothari-Haber Symptom Score (KHSS) of 4, and median diverticular depth of 30 mm. 78 patients (76.5%) had large diverticula, a subgroup in which complete septal division and prevention of residual mucosal flap may be particularly important. Technical success was achieved in all cases, and 3-month clinical success, defined as a KHSS less than 2, was 98.2%. Median procedure time was 30 min, and median hospital stay was 1 day. Adverse events occurred in 3.1% of patients, including two intraprocedural bleeds and one diverticuloscope-related perforation; all were managed endoscopically, without surgical intervention. During a median follow-up of 15 months, recurrence occurred in 7% of patients. Estimated recurrence-free probabilities were 93.5% at 6 months and 92.0% at both 12 and 24 months. In the context of FES recurrence rates of 11%–32%, these durability data suggest that the distal submucosal dissection step contributes to a more complete myotomy [1, 4].

These results are impressive, although they should be interpreted as hypothesis-generating rather than definitive. Comparative literature suggests that endoscopic submucosal tunneling techniques may achieve higher clinical success than FES, without clear differences in technical success, adverse events, procedure time, or length of stay in pooled observational data [4]. A multicenter comparison of Z-POEM, flexible septotomy, and rigid septotomy reported high success across modalities but did not establish a universal best approach [7]. Similarly, a contemporary UK multicenter series found that Z-POEM, flexible diverticulotomy, and rigid diverticulotomy can all be effective, although outcomes varied across centers and techniques [8]. SING enters this landscape as a technical variation that proposes a middle path: preserve the familiarity and efficiency of FES for the proximal septum, and reserve third-space endoscopy precision for the distal margin where it matters most.

This approach has potential advantages. Conceptually, SING tailors each phase of treatment to the method best suited for that part of the septum. The proximal septum can be divided efficiently using conventional FES, where formal third-space dissection may add time without clear technical benefit. As the dissection approaches the distal septal margin, however, the value of submucosal endoscopy becomes apparent. Bilateral injection improves visualization of the cricopharyngeal muscle, helps define the transition to the thinner esophageal muscle layer, and permits a more controlled distal myotomy while preserving the ability to close the mucosal defect. In this way, SING attempts to capture the efficiency of FES and the precision of third-space endoscopy, while avoiding unnecessary tunneling. The technique may also lower the barrier to adoption for operators who perform advanced flexible septotomy but do not routinely work in the submucosal space. SING may be particularly attractive in larger diverticula, where residual septum and redundant mucosa can contribute to persistent or recurrent symptoms, and where complete distal septal division is especially important. Reassuringly, in the study, clinical success was similar in large and small diverticula, at 97.4% and 100%, respectively, suggesting that SING may be applicable beyond small, technically straightforward pouches.

The study also offers a useful caution regarding equipment. Diverticuloscope-assisted SING and conventional SING achieved similar clinical success, but all adverse events occurred in the diverticuloscope-assisted group, including the only perforation. Recurrence was also numerically higher with diverticuloscope assistance. These findings are intriguing but not definitive, because diverticuloscope use was confined to a single center and may reflect center-specific practice rather than an effect of the device itself. The appropriate conclusion is therefore not that diverticuloscopes should be abandoned, but that their use should be individualized. In selected cases, a diverticuloscope may improve stability and exposure; in others, it may add trauma, reduce maneuverability, and introduce an additional step that may offer little advantage over nasogastric-tube guidance in this hybrid approach. Prospective evaluation is needed to determine whether diverticuloscope assistance improves outcomes, adds risk, or simply reflects operator preference and case selection.

Despite the elegant design and technical merit of SING, several limitations deserve emphasis. The analysis was retrospective, although the data were prospectively collected; there was no concurrent comparator group; and all procedures were performed by expert operators involved in developing and standardizing the technique. As with many early reports in third-space endoscopy, excellent outcomes may reflect the operators as much as the operation. Follow-up was meaningful but still incomplete for a condition in which recurrence may emerge late, and the number of patients evaluable at 24 months was limited. Subgroup analyses by diverticulum size and diverticuloscope use are clinically interesting but underpowered. Although symptom assessment with the Kothari-Haber Symptom Score is a strength, the absence of broader swallowing-specific or quality-of-life instruments limits assessment of patient-centered benefit. Finally, SING requires precise orientation, controlled full-thickness septotomy, selective distal myotomy, and reliable closure. It is simpler than full tunneling, but it is not simple.

The appropriate place for SING in current practice is as an addition to the therapeutic toolbox rather than a new standard. FES remains appropriate for many patients because it is efficient, widely available, and supported by guideline recommendations. Z-POEM and POES remain attractive when controlled submucosal exposure is prioritized, particularly in recurrent, fibrotic, or anatomically complex cases [7]. SING may occupy a pragmatic space between these approaches: patients with moderate-sized or large Zenker's diverticula in whom the endoscopist seeks greater distal precision than conventional FES, but without the added complexity of a full submucosal tunnel. It may also be useful when residual septum or redundant mucosa is a particular concern. However, if SING consistently delivers the distal precision of third-space endoscopy without its added complexity, a reasonable question is whether it should become the default flexible endoscopic approach rather than a middle-ground option—a question only comparative, prospective data can answer.

The next step should be comparative evidence. Prospective studies should compare SING with FES and Z-POEM/POES using standardized symptom scores, patient-reported outcomes, objective radiographic or endoscopic assessment of recurrence, procedure time, cost, hospital stay, and standardized adverse-event reporting. These studies should also report learning curves and outcomes outside the originating centers. The most useful future algorithm will likely not crown a single technique, but rather individualize treatment: matching diverticulum size, septal anatomy, prior therapy, patient frailty, and local expertise to the approach that best balances safety, efficiency, and durable symptom relief, while minimizing the residual septum or mucosal flap that can drive recurrence.

SING is valuable not because it is revolutionary, but because it is disciplined. It recognizes that the critical step in Zenker's diverticulum therapy is not simply cutting the septum, but cutting enough, stopping safely, and avoiding residual anatomy that can perpetuate symptoms. By using submucosal injection to clarify the distal septum while avoiding a full tunnel, SING offers a plausible balance of precision and pragmatism. The current study is an important contribution, but its message should be measured: in expert hands, SING appears safe, efficient, and effective; in the broader community, its role should be defined by careful training, transparent outcomes, and comparative trials. For now, it deserves a place in the Zenker's toolbox, not as the final word, but as a well-reasoned step toward more tailored endoscopic therapy.

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The author declares no conflicts of interest.

This article is linked with Azzolini et al. To view this article, visit https://doi.org/10.1111/den.70156.

The author has nothing to report.