Journal of Gastrointestinal & Digestive System
Open Access

Zenker diverticulum; Stag beetle knife; Dysphagia; Systematic review; Meta-analysis

SB: Stag Beetle; ZD: Zenker Diverticulum; SMD: Standard Mean Difference; AE: Adverse Effects

Zenker's Diverticulum (ZD), a pulsion diverticulum emerging in the weakened posterior hypopharyngeal area known as Killian's triangle, is a relatively uncommon condition, affecting 0.01% to 0.11% of the American population, notably prevalent among males in their seventh and eighth decades. Despite the prevalence, the exact pathophysiology of ZD remains partially understood. The primary hypothesis suggests that motor abnormalities in the Upper Esophageal Sphincter (UES) facilitate herniation of the esophageal mucosa through Killian's triangle. ZD can either remain asymptomatic or manifest with various symptoms, such as dysphagia, regurgitation, cough, aspiration, foreign body sensation and weight loss. Symptom development correlates with both UES motor dysfunction and the accumulation of ingested material in the diverticular pouch, contingent on diverticulum size. Consequently, ZD treatment aims to address motor abnormalities through myotomy of UES muscles, potentially involving suspension or resection of the diverticular pouch [1-4].

Treatment options for ZD encompass open surgery, rigid endoscopy and flexible endoscopy, particularly Flexible Endoscopic Septum Division (FESD). In contrast to open surgery and rigid endoscopy, FESD offers advantages by obviating the need for general anesthesia and neck hyperextension. The procedure entails incising the mucosa and muscular fibers of the diverticular septum, achieving a partial myotomy of the cricopharyngeal muscle and creating a passage for clearing ingested materials from the diverticular pouch. Introduced in 1995, FESD has undergone various modifications and employed diverse cutting devices, signifying a substantial evolution in ZD treatment techniques [5].

Zenker's Diverticulum (ZD) is a mucosal outpouching of the cervical esophagus through the Killian triangle. When compared to endoscopic endoscopic procedures, the surgical approach has much higher procedure-related morbidity and hospital stay. Amongst the endoscopic methods, the flexible endoscope method is far less complicated and less invasive than the rigid endoscope method. Several instances of intraluminal therapy of ZD using a flexible endoscope have been published, with many various procedures available: Needle-knife, hook-knife, monopolar forceps, argon plasma coagulation and so on [6].

The Stag Beetle Knife (SB Knife) is a novel scissor-shaped, rotating device with two insulated monopolar blades increasingly used in the endoscopic management of Zenker Diverticulum (ZD). This study aimed to assess the pooled safety, efficacy and feasibility of using SB knife for the management of ZD [7].

Protocol and eligibility criteria

This systematic review, conducted per the Preferred Reporting System for Systematic Reviews and Meta-analyses (PRISMA) guidelines, comprehensively assessed the efficacy of the stag beetle knife in managing Zenker Diverticulum (ZD) through a meta-analysis of studies. Inclusion criteria embraced studies evaluating the stag beetle knife's application in ZD endoscopic management, encompassing various techniques like endoscopic septal division or peroral endoscopic myotomy. Geographical and setting constraints were disregarded, covering both inpatient and outpatient settings, as long as relevant data for analysis were provided. Exclusion criteria excluded case reports and non-English language studies. To ensure efficiency in data collection and avoid redundancy, cases with multiple publications prioritized data extraction from the most recent or comprehensive reports. Additionally, papers on flexible endoscopy for symptomatic ZD patients were included, requiring only the utilization of flexible endoscopic treatment and a follow-up duration exceeding two months, while exclusion criteria comprised comments or review articles, lack of outcome and/or follow-up data, exclusive use of animal models, studies with fewer than 10 patients and the expansion of previously published series. This meticulous approach underscores the commitment to a thorough assessment of the stag beetle knife's efficacy in ZD management [8].

Literature search, study selection and data extraction

Conducting a rigorous literature review, this systematic analysis adhered to the Preferred Reporting System for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Employing comprehensive search strategies, the meta-analysis delved into the efficacy and safety of the stag beetle knife in treating Zenker's Diverticulum (ZD). Database searches, including PubMed, Cochrane and MedLine, were executed from their inception to November 2023. A systematic algorithm was applied to PubMed and EMBASE databases, incorporating specific keywords such as ("Zenker Diverticulum" (Mesh) OR "Zenker Diverticulum" (All Fields) OR "Zenker's Diverticulum" (All Fields) OR "Zenker's Diverticula" (All Fields) OR "Zenker Diverticula" (All Fields) OR "pharyngeal pouch" (All Fields)) AND ("endoscopy" (MeSH Terms) OR "endoscopy" (All Fields) OR "endoscopic" (All Fields)) AND English (lang). The inclusion criteria focused on studies involving human subjects, published in English-language, peer-reviewed journals and examining the stag beetle knife's application in ZD endoscopic management, irrespective of the techniques used [9].

After eliminating duplicates, two independent reviewers (MKB, BPM) meticulously screened titles and abstracts, ensuring alignment with the research question and pre-specified criteria. Full-text retrieval followed and eligibility screening was conducted, resolving discrepancies through co-author consultation. Data extraction from selected studies, performed independently by three reviewers, covered study design, patient demographics, clinical features, symptom evaluation criteria, adverse events, treatment success, follow-up duration and recurrences. The primary clinical outcomes assessed the success rate, adverse events rate and recurrence rate of stag beetle knife treatment in ZD. Subgroup analyses were conducted based on sample size, evaluating mean dysphagia score reduction and the number of sessions required [10].

Quality assessment

Conducting a methodological quality assessment, two reviewers independently evaluated the susceptibility to bias through the MINORS quality score, adapting items to suit the review's scope as detailed in Table 2. Resolution of any divergent quality assessments between these two contributors involved seeking guidance from coauthors. Following this, a team of at least two authors (MKB, BPM) extracted data on study-related outcomes from individual studies onto a standardized form [11].

Statistical analysis

Clinical data from individual studies were analyzed for summary statistics, reporting patient age as median (IQR) or mean (SD) for continuous variables and gender as counts and percentages for categorical data. Meta-analysis, employing the random-effects model, assessed outcomes like clinical success, recurrence rate, adverse events and dysphagia score improvement. Heterogeneity was gauged through Cochran Q, I2 statistics and a 95% prediction interval. Subgroup analysis, based on sample size, utilized the Standard Mean Difference (SMD) with a 95% CI for continuous variables. Metaregression explored covariates, including socio-demographic attributes, methodology and clinical/technical parameters. All analyses were conducted using meta-package software and R programming. Event rates for outcomes in each study were calculated as proportions and the I2 statistic guided the use of a random effect model in cases of substantial heterogeneity (I2>50%) [12].

Search results and population characteristics

A total of 8 studies met the inclusion criteria. They comprised 299 patients (60.5% males), the mean age was 72.75 ± 2.86 years and the mean size of ZD was 2.66 ± 0.52 cm. The mean procedure duration was 23.06 ± 10.00 minutes [13].

Characteristics and quality of included studies

Out of 900 initially identified records, 500 duplicates were removed, leaving 18 eligible studies. Among them, 8 studies met the inclusion criteria for the meta-analysis, encompassing various study designs such as retrospective cohort, retrospective case-control, crosssectional, prospective cohort and prospective case-control, as shown in Figure 1. Notably, three studies were deemed of high quality, with the remaining studies classified as medium quality; no low-quality studies were identified, as shown in Table 2. The distribution of study designs included 4 prospective, 2 retrospective and 2 observational studies. According to the MINORS scale, all studies demonstrated moderate or high quality. The average follow-up period was 22.24 months and the mean size of Zenker Diverticulum (ZD) was 2.66 cm, as shown in Table 1 [14].

 

Figure 1: PRISMA study.

Table 1: Study characteristics table for systematic review.

Table 2: Quality of included studies according to MINORS criteria.

Meta-analysis outcomes

Clinical success was achieved after a mean of 10.98 (2.63-19.32); I2 93% number of sessions and 22.74% patients required more than one treatment session (up to 4) to achieve clinical remission. The pooled clinical success rate, defined as symptomatic remission after the first procedure, was 86% (95% CI: (81-90; I2 0%). The pooled recurrence rate, defined as relapse of symptoms after the first intervention, was 15% (11-20; I2 0%). The pooled prevalence of intraprocedural complications encountered during the procedure was 9% (5-13; I2=29%). The majority were minor bleeding (9.6%), followed by micro perforation (2%), odynophagia (1.3%) and fever (1.05%). Only 1 study reported a case of late-onset bleeding in 3.2% of patients after 1 week. All these adverse events were managed conservatively, including endoscopic management of bleeding, as shown in Tables 3 and 4 [15].

Table 3: Random effect model results of primary outcomes of stage Beetle knife in Zenker Diverticulum (ZD).

Table 4: Random effect model results of secondary outcomes of stage Beetle knife in Zenker Diverticulum (ZD).

On subgroup analysis based on study sample size, a statistically significant subgroup difference was seen (p=0.02) for the mean number of sessions required. For studies with n>25, it was 20.79 (6.36-35.23); I2 93% and for studies with n<25, it was 3.7 (1.21-6.18); I2 65% number of sessions. The decrease in dysphagia score was SMD (95% CI) 1.59 (2.27-0.91; I2 97%), p<0.01, after a mean follow-up of 22.23 ± 11.47 months (Supplementary Figures 2-6) [16].

Validation of meta-analysis results

Sensitivity analysis: To assess whether any one study had a dominant effect on the meta-analysis, we excluded one study at a time and analyzed its effect on the main summary estimate. In this analysis, no single study significantly affected the outcome or the heterogeneity [17].

Heterogeneity: We assessed the dispersion of the calculated rates using the Prediction Interval (PI) and I2 percentage values. The PI gives an idea of the range of the dispersion and I2 tells us what proportion of the dispersion is true vs. chance.

Publication bias: Since the number of studies was less than 10, publication bias cannot be assessed accurately.

In our attempt to investigate the efficiency and safety of endoscopic management of ZD by SB knife, we performed a meta-analysis and systematic review of relative literature articles. The meta-analysis incorporated eight studies encompassing 299 patients undergoing stag beetle knife treatment for Zenker Diverticulum (ZD). These studies provided clinical outcomes, follow-up observations and adverse events from 299 individuals who underwent endoscopic treatment of ZD. Study designs included prospective cohorts, retrospective observational, retrospective analysis, descriptive observational and observational human study. The predominant technique employed across studies varied, with mucomyotomy, modified DISR and single incision, flexible endoscopy, FESD, endoscopic septotomy and CP myotomy. Pooling data from 299 individuals was performed in order to compare and statistically analyze clinical outcomes of treatment with SB knife in individuals with ZD, as well as to identify disease recurrence rate and the degree of post-procedure complications. The pooled clinical success rate was 86%, with a mean of 10.98 sessions required. The recurrence rate stood at 15% and intraprocedural complications were observed in 9% of cases, mainly minor bleeding.

Dysphagia score improvement was notable, with a standardized mean difference of 1.59, showcasing clinical efficacy. While the MINORS scale indicated moderate to high study quality, the diversity in techniques and potential publication bias necessitate cautious interpretation of the overall positive outcomes [18].

Zenker's diverticulum is one of the rare disorders of the esophagus that primarily affects the elderly and is the most common mucosal and sub mucosal out pouching in the upper gastrointestinal tract. This disorder was first documented in the 18th century and since then, its treatment and management have evolved. Since 1917, the concept of endoscopic intervention has been presenting encouraging outcomes to the management of ZD, including various non-surgical interventions. The indication for treatment is mainly based on symptomatology and the associated size of the diverticulum. When small (<2 cm) diverticula are incidentally found, no intervention is usually offered; however, the age population and symptoms may prompt a noninvasive intervention such as local administration of botulinum toxin. Management of larger diverticula usually indicates surgical intervention, as increasing age may be followed by various risk factors, which can lead to adverse events due to high risk. More invasive techniques, such as open surgery, usually lead to a more extended hospitalization as well as other common complications of the procedure, such as injury to the laryngeal nerve, esophageal perforation and extensive bleeding. Endoscopic treatment can be superior in high-risk elderly patients who can undergo a brief procedure without general anaesthesia in an inpatient or outpatient setting and aggressive manipulation of the cervical spine as recent data has been showing encouraging outcomes of endoscopic intervention, various endoscopic techniques have been suggested, including myomectomy using endoscopic carbon dioxide laser, Harmonic scalpel, needle-knife, hook-knife, monopolar forceps, argon plasma coagulation, as well as an insulated scissor style knife, the SB knife.

The complication rate post-treatment was found to be in <10% of the cases. Common complications included mostly minor bleeding, micro-perforation, odynophagia and fever. These findings confirm the existing understanding that myomectomy by SB knife in ZD can be a safe and effective approach in cases of ZD that qualify for an endoscopic intervention. Our subjects included mostly individuals >70 years old with a nearly balanced biological male-to-female ratio, males (60%) and females (40%). The above findings were supported by analyzing the reported improvement of symptoms as per dysphagia score and total number of sessions required for management. Though these data were not compared to other endoscopic techniques, our findings produced statistically significant evidence of an efficient myomectomy technique by SB knife in elderly individuals with ZD.

Assessing differences in clinical outcomes, recurrence rate, costeffective approach and complication rate in different endoscopic techniques would surely give a greater insight into where SB knife procedures compare to other existing endoscopic procedures in ZD. These results underscore the necessity for comprehensive, prospective, and multisite investigations to validate the effectiveness of emerging technologies in Zenker Diverticulum (ZD) treatment and to pinpoint potential recurrence determinants. Meta-regression analyses exploring success and safety reveal that factors such as the cutting device and diverticulum size did not influence the observed outcomes and neither did trial sample magnitude nor the anesthesia approach [19].

The strengths of this review lie in its meticulous literature search, clearly outlined inclusion and exclusion criteria and the meticulous exclusion of redundant studies. Particularly noteworthy is the exclusion of papers utilizing non-rigid devices like harmonic scalpels, preserving a key technique advantage-eliminating the need for neck hyperextension. Additionally, the review boasts a rigorous analysis of study quality. However, the limitations are notable, including a relatively limited number of studies, often constrained sample sizes, the presence of retrospective series and heterogeneity issues impacting generalizability. Variations in success definitions across studies and the potential for marginal publication bias further contribute to the review's limitations.

Incorporating data from eight studies with 299 patients (60.5% males), the meta-analysis yielded robust outcomes. Procedures lasting 23.06 ± 10.00 minutes achieved clinical success in 86% after an average of 10.98 sessions, with 22.74% requiring multiple sessions (up to 4). The recurrence rate stood at 15% and intraprocedural complications occurred in 9%, predominantly minor bleeding (9.6%), micro-perforation (2%), odynophagia (1.3%) and fever (1.05%). Lateonset bleeding occurred in 3.2% after 1 week. Adverse events were conservatively managed. Subgroup analysis by sample size revealed a significant difference in mean sessions (p=0.02). Dysphagia score improvement was notable, with a Standardized Mean Difference (SMD) of 1.59, observed over a mean follow-up of 22.23 ± 11.47 months [20].

In conclusion, this meta-analysis strongly underscores the efficacy of SB knife treatment for Zenker Diverticulum, showcasing not only excellent safety but also a significant improvement in dysphagia. While affirming its effectiveness, the study highlights the need for further research to define optimal patient cohorts and compare its efficacy with alternative management techniques.

The discernible heterogeneity observed in our systematic review is predominantly associated with the limited sample size in the chosen studies. While conducting a Randomized Controlled Trial (RCT) comparing the KB knife treatment to procedures without surgical incisions may raise ethical considerations, there is an imperative need for extensive, forward-looking and collaborative studies to substantiate the ongoing advancements in KB knife treatment. Moreover, it is essential to augment standardization, particularly in terms of symptom assessment, objective scoring and precise definitions of achievement, recurrence and adverse events.

MKB, BPM, AB: Conception and design, Interpretation of the data, drafting of the article, intellectual content and final approval of the manuscript.

Mannat KB: Study search, review and selection, initial write-up, editing.

Mannat KB, PGD, OO, Mehar KB: Data collection and synthesis, editing.

BPM, MKB, SD: Statistical analysis of data and interpretation of results, editing.

SD, BPM, AB: Supervision, Manuscript editing.

All authors: Critical revision of the article for important intellectual content and final approval of the article.

This type of study does not involve active human participants and/or animals, therefore a formal consent, informed consent, institutional review board approval and ethical approval are not applicable and/or not required.

All authors: No conflict of interest.

None.

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