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New methods Clinical endoscopy: Editorial| Volume 91, ISSUE 1, P169-171, January 2020

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Will there be light at the end of this tunnel?

      Abbreviations:

      CP (cricopharyngeal), POEM (per-oral endoscopic myotomy), ZD (Zenker’s diverticulum)
      As techniques and devices continue to evolve, a welcomed shift toward minimally invasive interventions has been universally observed in procedural specialties. The management of Zenker’s diverticula (ZD) in the past 25 years has evolved from open surgical approach, through rigid endoscopic techniques, to finally flexible endoscopic interventions. Less-invasive approaches are more attractive in the treatment of ZD because this condition typically appears in the seventh and eighth decades of life, usually in patients with a high comorbidity burden who are less-than-ideal surgical candidates.
      • Sato H.
      • Takeuchi M.
      • Hashimoto S.
      • et al.
      Esophageal diverticulum: new perspectives in the era of minimally invasive endoscopic treatment.
      Flexible endoscopic procedures have allowed otherwise suboptimal surgical candidates to undergo diverticulectomy. However, high recurrence rates from incomplete septotomy and risk for mediastinitis due to mucosal injury are current major concerns. The approach to and therapeutic management of ZD remain to be standardized, inasmuch as the findings of many smaller studies report a myriad of techniques without convincing evidence of the superiority of a single technique over another. This may seemingly lead to the current practice of selecting the therapeutic approach primarily based on personal expertise, not necessarily on evidence.
      Most of these techniques still have a place in the management of this condition, depending primarily on the patient’s surgical candidacy and also on the size of the diverticulum. Furthermore, major factors deterring the performance of flexible endoscopic techniques are the high recurrence rates (up to 35%) and the subsequent need of repeating the procedure. It has been recognized that reasons for recurrence are the incomplete direct endoscopic visualization of the diverticulum’s apex, leading to fear of perforation, and the high rates of incomplete septotomy with flexible endoscopic approaches.
      More recently, the use of flexible endoscopic procedures is being preferred for frail patients at high surgical risk. Recognized benefits of the flexible endoscopic approach over all others include earlier resumption in oral intake and decreased morbidity, mortality, procedural time, and length of stay, resulting in decreased costs. Since its application was first described in 2016, peroral endoscopic myotomy (POEM) of ZD (Z-POEM) has been proposed as an elegant solution to leave an intact mucosa over an adequate myotomy and then closing the mucosa at the origin of the tunnel, which is a few centimeters away from the myotomy. This makes Z-POEM an attractive technique because it is thought that it will have less risk for mediastinitis and/or morbidity while permitting a generous myotomy to minimize recurrence.
      • Li Q.L.
      • Chen W.F.
      • Zhang X.C.
      • et al.
      Submucosal tunneling endoscopic septum division: a novel technique for treating Zenker's diverticulum.
      However, to date only small case series and case reports had been published, for which evidence supporting the use of Z-POEM (although very promising) is less than ideal.
      In this issue of Gastrointestinal Endoscopy, Yang et al
      • Yang J.
      • Novak S.
      • Ujiki M.
      • et al.
      An international study on the use of peroral endoscopic myotomy in the management of Zenker's diverticulum.
      elegantly present the outcomes of Z-POEM in the treatment of 75 patients with ZD in this international multicenter retrospective cohort study. It is worth noting that the examined population was primarily composed of elderly patients with a high comorbidity burden. Technical and clinical success was achieved in >90% of cases, with 92% of patients achieving a significant decrease in dysphagia score at a median follow-up time of 292 days. The reported adverse events consisted of 1 case of bleeding (managed conservatively) and 4 cases of perforation (1 self-contained perforation that resolved with conservative management, 2 that required cyanoacrylate glue closure, and 1 that required clip closure). There were no cases of mortality in the study.
      Despite the admitted shortcomings of the current study by Yang et al,
      • Yang J.
      • Novak S.
      • Ujiki M.
      • et al.
      An international study on the use of peroral endoscopic myotomy in the management of Zenker's diverticulum.
      including the retrospective design, the lack of intercenter standardization management, and suboptimal follow-up times, the results certainly send a very positive message to the advanced endoscopy community. The authors have done their best to standardize as much as possible in this retrospective design by using the Charlson comorbidity index, grading the severity of adverse events according to the American Society for Gastrointestinal Endoscopy Lexicon, dysphagia scoring system and standardized electrocautery setting. The reported results are promising. Not only do these outcomes show that Z-POEM is a safe and effective procedure, but also we cannot help noticing that the population of patients who have undergone Z-POEM has a significantly elevated comorbidity index. Therefore, it seems almost unfair to compare the outcomes in this patient population with the outcomes in patients with far lower comorbidity indices undergoing open surgical or rigid endoscopic procedures.
      To us, it also raises sobering issues that better outcomes are directly related to the advanced endoscopist’s expertise in POEM. In this specific case, Z-POEM requires an amalgamation of cricopharyngeal (CP) myotomy and POEM skills. Given the novel nature of the procedure, no studies examining learning curves have yet been performed for Z-POEM. CP myotomy typically requires needle-knife expertise, and it is suggested that the endoscopist perform at least 20 cases to get over the learning curve.
      • Baron T.H.
      Endoscopic management of Zenker diverticula.
      By comparison, POEM requires specialized training in this tunneling procedure, with dedicated studies showing that at least 13 procedures are necessary to overcome the learning curve.
      • El Zein M.
      • Kumbhari V.
      • Ngamruengphong S.
      • et al.
      Learning curve for peroral endoscopic myotomy.
      Acknowledging the lack of head-to-head comparison of outcomes between treatment alternatives, one cannot help but wonder which among the treatment options (ie, standard rigid/flexible endoscopic CP myotomy or open surgical techniques) is potentially less effective and associated with worse outcomes. In the meantime, it is our duty to exercise careful consideration in deciding which treatment approach to offer the patient with ZD: one size does not fit all. The outcomes of flexible endoscopic techniques have not been, and are unlikely to be, compared directly with those of rigid endoscopy or open surgery because the flexible endoscopic approach is usually reserved for frail elderly patients with numerous comorbidities that render them very poor high-risk surgical candidates. Furthermore, a very high level of heterogeneity exists between existing studies comparing flexible endoscopic techniques.
      • Ishaq S.
      • Hassan C.
      • Antonello A.
      • et al.
      Flexible endoscopic treatment for Zenker's diverticulum: a systematic review and meta-analysis.
      With the advent of Z-POEM, large prospective studies that standardize the evaluation of outcome measures (including adverse events and symptom scoring systems) will be needed. Additionally, clear definitions of success and studies that are aimed at determining predictors are needed to better elucidate the benefits of POEM in ZD. For the time being, it seems that the application of this novel technique in the management of ZD will depend on the local availability of expertise in the field. In the meantime, we suggest that all cases of ZD in which POEM is considered as a therapeutic option should be referred to high-volume POEM centers.
      In summary, we think that all therapeutic approaches to ZD still have their respective indications and that clinical judgment in individualizing the selection of the optimal procedural approach should be exercised, taking into account clinical factors that determine outcomes. For instance, we hypothesize that several patient-related factors may confer a higher risk of undergoing Z-POEM compared with the other approaches. A patient’s history of therapeutic radiation to the area may prevent the safe creation of a tunnel. Severe stasis or edema in the area could potentially make the procedure more technically challenging or cause delayed complications. Certain jaw abnormalities can effectively reduce the working space and compromise the endoscopist’s ability to maneuver and deploy the necessary hardware appropriately. In such cases, other approaches may be more appropriate. Nevertheless, it is our opinion that in expert hands, Z-POEM can potentially represent a very attractive treatment option, given the balance between safety and efficacy, not only for frail and elderly patients but for any patient afflicted with a ZD.

      Disclosure

      All authors disclosed no financial relationships relevant to this publication.
      Table 1Comparison of Zenker's diverticulum repair techniques: efficacy and morbidity
      ApproachAdverse event rate (%)Mortality (%)Symptom-free (%)

      (follow-up months)
      Open surgical10.50.696.7 (60)
      • Bonavina L.
      • Bona D.
      • Abraham M.
      • et al.
      Long-term results of endosurgical and open surgical approach for Zenker diverticulum.
      Rigid endoscopic
       Stapling7.10.392 (27)
      • Beard K.
      • Swanström L.L.
      Zenker's diverticulum: flexible versus rigid repair.
       Laser9.30.293 (12-36)
      • Beard K.
      • Swanström L.L.
      Zenker's diverticulum: flexible versus rigid repair.
       Electrocautery7.8-18.00.290.6 (10)
      • Beard K.
      • Swanström L.L.
      Zenker's diverticulum: flexible versus rigid repair.
      Flexible endoscopic (non-POEM)11.3082 (12.7)
      • Case D.J.
      • Baron T.H.
      Flexible endoscopic management of Zenker diverticulum: the Mayo Clinic experience.
      Z-POEM00100 (5)
      • Yang J.
      • Novak S.
      • Ujiki M.
      • et al.
      An international study on the use of peroral endoscopic myotomy in the management of Zenker's diverticulum.
      Superscript numbers in the right column are correlated to references in the reference list.
      POEM, peroral endoscopic myotomy; Z, Zenker’s diverticulum.

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