Current status of endoscopic treatment for esophageal diverticulum based on diverticular peroral endoscopic myotomy

Abstract

Esophageal diverticulum can be broadly classified into three main types: Pharyngoesophageal diverticulum located near the upper esophageal sphincter (including Zenker’s diverticulum, Killian-Jamieson diverticulum, and Laimer’s diverticulum); Mid-esophageal diverticulum, and epiphrenic diverticulum located just above the lower esophageal sphincter. Most asymptomatic esophageal diverticulum are incidentally detected during routine imaging studies, such as barium swallow, computed tomography scans, or esophagogastroduodenoscopy. For these patients, regular follow-up is typically sufficient. However, a small subset may experience persistent symptoms such as dysphagia and acid reflux. Patients with symptomatic diverticulum should be assessed for the potential need for surgical intervention to prevent serious complications, including aspiration pneumonia and malnutrition. The treatment options for symptomatic esophageal diverticulum encompass both endoscopic and surgical approaches. Due to the technical complexity and significant risks associated with surgical intervention, endoscopic treatment has gained increasing preference, achieving remarkable results with the advancements in endoscopic instruments and techniques. Given the anatomical location and pathophysiological differences among esophageal diverticulum, a personalized endoscopic strategy is essential to achieve optimal results. This review provides an overview of the characteristics of esophageal diverticulum and offers a comprehensive discussion of diverticular peroral endoscopic myotomy and its related variations as the primary endoscopic treatment strategy.

Key Words: Diverticular peroral endoscopic myotomy; Esophageal diverticulum; Peroral endoscopic septotomy; Salvage peroral endoscopic myotomy; Zenker’s diverticulum; Killian-Jamieson diverticulum; Mid-esophageal diverticulum; Epiphrenic diverticulum

Core Tip: Since submucosal tunneling endoscopic septum division was introduced for the endoscopic treatment of Zenker’s diverticulum, it has been proven to offer superior safety and clinical success rates. The treatment of esophageal diverticulum based on Zenker’s peroral endoscopic myotomy and its various technical modifications is collectively referred to as diverticular peroral endoscopic myotomy; however, the nomenclature and abbreviations for these techniques have not yet been fully standardized. This review will summarize the characteristics of esophageal diverticulum and key aspects of the diverticular peroral endoscopic myotomy procedure.

INTRODUCTION

Twenty years ago, the introduction of flexible endoscopic septum division (FESD) revolutionized the treatment of Zenker’s diverticulum (ZD)[1,2]. Since then, a variety of cutting tools have been employed in FESD, including needles, hooks, stag-beetle knives, hybrid or dual knives, insulated-tip knives, coagulation forceps, hot biopsy forceps, and argon plasma coagulation[3]. To aid in dissection, devices like diverticuloscopes are commonly used, enabling precise delineation of the diverticulum’s extent and minimizing the risk of damaging surrounding tissues[4]. FESD has become a widely adopted approach for patients with ZD and Killian-Jamieson diverticulum (KJD), though its use is less common for mid-esophageal diverticulum and epiphrenic diverticulum. However, FESD carries a relatively high risk of recurrence and complications due to the inability to fully sever the diaphragmatic portion[5,6], and in the case of KJD surgery, there is an increased risk of damaging the recurrent laryngeal nerve. The advent of diverticular peroral endoscopic myotomy (D-POEM) offers a more promising future than FESD by providing better exposure of the diaphragm muscle and enabling complete myotomy, thereby reducing the risk of treatment failure and symptom recurrence[7]. D-POEM is a general term for endoscopic treatments of diverticulum based on the tunneling. D-POEM requires complete separation of the diaphragm to prevent increased submucosal fibrosis during recurrence, which would complicate future surgeries. While FESD can be used to relieve symptoms in cases requiring repeat surgery. Depending on the anatomical characteristics and location of the diverticulum, different surgical approaches have evolved from this technique.

ZD

Esophageal diverticulum develop through two primary mechanisms: Pulsion and traction. Pulsion occurs when increased intraluminal pressure causes the herniation of the mucosal and submucosal layers, resulting in a false diverticulum. In contrast, traction, often due to chronic inflammation, pulls the entire esophageal wall, including all layers, leading to the formation of a true diverticulum. ZD, resulting from pulsion, contains only mucosa and submucosa, and is classified as a false diverticulum. Ludlow first described it in 1767[8] and later named after the German pathologist Friedrich Albert von Zenker in 1877[9]. ZD is the most common type of esophageal diverticulum, with an incidence of approximately 0.01% to 0.11% in the population[10-12]. ZD and KJD together account for 70% of all esophageal diverticulum (Laimer’s diverticulum is negligible due to its rarity). ZD occurs at a physiological weak point known as “Killian’s triangle”, located at the junction of the hypopharynx and esophagus. This area consists of the cricopharyngeus muscle, the inferior pharyngeal constrictor muscle, and some muscle fibers of the cervical esophagus. Under normal conditions, these muscle fibers coordinate with the upper esophageal sphincter (UES) to facilitate swallowing. The formation of ZD may result from increased oropharyngeal pressure and impaired relaxation of the cricopharyngeus muscle during swallowing. These factors lead to incomplete relaxation of the UES, causing the esophageal mucosa to herniate through the relatively weak posterior wall of the pharyngoesophageal junction[13-15]. Early studies on UES function have confirmed its role as a critical barrier against gastric acid reflux[16]. The two factors mentioned above may be the primary causes of dysphagia and gastroesophageal reflux becoming the main symptoms. Although malignant transformation of ZD is exceedingly rare, the risk ranges from 0.3% to 7%[17,18]. Advanced age, larger diverticulum size, and longer disease duration are risk factors for malignancy in ZD, likely due to chronic irritation and inflammation caused by the prolonged accumulation of food and liquids[19-21].

The general principle for ZD management is to intervene only in symptomatic cases[22]. Surgical procedures, refined through long-term practice, achieve treatment success rates of approximately 80% to 100% by removing the diverticulum or correcting anatomical abnormalities[23]. However, postoperative complications can occur in up to 11% of cases, and the recurrence rate remains close to 10%[24]. In 2016, Li et al[25] first used the submucosal tunneling endoscopic septum division technique to treat ZD, later known as Zenker’s peroral endoscopic myotomy (Z-POEM). The Z-POEM technique involves submucosal injection and mucosal incision 3 cm proximal to the diverticulum septum, followed by dissection of the submucosal fibers to create a tunnel between the esophagus and the diverticulum side of the septum. The septum is then divided, completing the myotomy, and the tunnel entry is finally closed. Z-POEM pioneered the tunneling approach for treating ZD. In contrast, the subsequent peroral endoscopic septotomy (POES) for ZD (ZD-POES, also referred to as Z-POES or simply POES) simplifies the procedure by initiating the tunneling directly at the septum, simplifying the procedure and broadening its range of indications[26-28]. Mavrogenis G and colleagues proposed replacing the creation of tunneling with a submucosal cushion formed by injecting a mixture of hydroxyethyl starch and indigo carmine[29,30]. This led to the development of the single tunnel technique (ST Z-POEM) and the tunnel-free technique (TF Z-POEM)[29,30]. Subsequently, they conducted a single-center retrospective study comparing Z-POEM (more accurately referred to as POES), ST Z-POEM, and TF Z-POEM techniques. The results demonstrated that, while maintaining safety, the modified techniques significantly reduced operative time[31]. Estevinho et al[32] described TF Z-POEM as “readily” peroral endoscopic septotomy (R-POES) and conducted a retrospective analysis of four cases. R-POES simplified the procedure, significantly reducing the operative time (mean duration: 9 ± 5 minutes) and avoiding potential mucosal injury associated with submucosal tunneling[32]. A 2025 meta-analysis showed that Z-POEM has a higher clinical success rate compared to FESD, while the technical success rate, operative time, adverse events, and symptom recurrence rates are similar[33]. Cartoon illustration of the D-POEM technique for ZD (Figure 1).

Figure 1 Schematic diagram. A: Zenker’s peroral endoscopic myotomy (Z-POEM) first, submucosal injection and mucosal incision are performed 1 cm-2 cm proximal to the septum, followed by the creation of a submucosal tunnel toward the septum. Then, two short tunnels are created by carefully dissecting the submucosal fibers on both sides of the esophagus, fully exposing the septum. Finally, septotomy is performed, followed by the closure of the mucosal incision; B: Peroral endoscopic septotomy (POES) submucosal injection and mucosal incision are performed to the top of the septum; C: Tunnel-free technique Z-POEM based on POES, submucosal cushions are created by injection on both sides of the septum, replacing mechanical dissection. For single tunnel technique (Z-POEM), a submucosal tunnel is created on the diverticulum side, while a submucosal cushion is chosen on the esophageal side. Z-POEM: Zenker’s peroral endoscopic myotomy; POES: Peroral endoscopic septotomy; TF: Tunnel-free.

KJD

In 1983, Ekberg and Nylander[34] first described the KJD as an anterolateral pharyngoesophageal pouch and classified it as a false diverticulum. KJD is named in honor of Gustav Killian and James Jamieson for their significant contributions to the anatomy of the cervical esophagus. KJD arises from a prominent anatomical weak spot, located beneath the transverse fibers of the cricopharyngeus muscle and laterally to the longitudinal fibers of the cervical esophagus, forming an inverted triangle. KJD is more commonly found on the left side, possibly due to the thinner muscular layer on that side. Right-sided and bilateral cases of KJD have also been reported, but they are rare[35]. Additionally, concurrent occurrences of ZD and KJD in the same patient have been reported. However, current studies have not established a definitive correlation between the occurrence of the two[36].

Compared to ZD, a smaller proportion of patients with KJD are symptomatic, with dysphagia being the primary complaint and gastroesophageal reflux rarely reported. The average age at onset for KJD is 58 years, compared to 70 years for ZD[37,38]. Additionally, imaging studies have shown that the incidence of KJD is about a quarter of that of ZD. In general, KJD is smaller than ZD, with an average size of approximately 1.4 cm, compared to 2.5 cm for ZD[39]. To date, there have been no reports of malignant transformation associated with KJD.

KJD presents greater therapeutic challenges than ZD, due to its extension into the upper mediastinum and its close proximity to the recurrent laryngeal nerve. Thus, accurately differentiating between these two types of diverticulum is essential to prevent recurrent laryngeal nerve injury during surgery. A barium swallow is generally useful for delineating the relationship between the diverticulum’s opening and the cricopharyngeal muscle, while a computed tomography scan can provide additional diagnostic clarity. During cervical ultrasound, the anatomical location of KJD can easily lead to misdiagnosis as a thyroid nodule. Two case reports have suggested that dynamic ultrasound performed during soda ingestion can effectively differentiate KJD from thyroid nodules[40,41]. Nonetheless, ultrasound practitioners should exercise caution to avoid unnecessary thyroid biopsies[42]. Historically, open surgical resection has been the treatment of choice for KJD. Given the anatomical similarity between KJD and ZD, FESD is also applicable to KJD[43-45]. However, due to the need to avoid recurrent laryngeal nerve injury, a full-length myotomy comparable to that achieved in open surgery is not feasible, leading to a relatively higher recurrence rate[46]. Z-POEM and Z-POES have also been adapted for use in KJD, and are thus referred to as KJD-POEM or KJD-POES[47,48]. Assefa et al[49] collectively referred to these endoscopic approaches as KJD-POEM. Among the cases, all 8 FESD and 5 KJD-POES procedures achieved both clinical and technical success. Some patients were initially diagnosed with ZD based on barium esophagography, only to be found intraoperatively to have KJD[50,51]. Modayil et al[6] compared FESD with endoscopic tunneling diverticulotomy (including KJD-POEM and KJD-POES, favoring the latter), and noted one case in the FESD group with persistent dysphagia. Some studies suggest that under standard endoscopic orientation, ZD typically appears at the 6:00 position, while the more commonly left-sided KJD is seen at the 9:00 to 10:00 position[52]. Palisade vessels have also been noted to act as a landmark for the UES during endoscopy, helping to distinguish ZD from KJD[53]. Endoscopic findings, when combined with the gold-standard barium swallow, may enhance diagnostic accuracy in the future[54].

LAIMER’S DIVERTICULUM

Laimer’s diverticulum is the rarest form of pharyngoesophageal diverticulum, with only five cases documented in the literature to date[55-59]. Laimer’s diverticulum is anatomically adjacent to both ZD and KJD, arising from the area between the cricopharyngeus muscle and the longitudinal muscle of the esophagus, known as the Laimer-Haeckerman triangle. Unlike ZD and KJD, Laimer’s diverticulum is a true diverticulum, involving all layers of the esophageal wall. Treatment typically involves open surgery through the neck, and currently, no endoscopic treatments have been reported for this condition. Due to its rarity and the diagnostic and therapeutic challenges it presents, further research and clinical experience are needed to improve our understanding and management of this type of diverticulum.

MID-ESOPHAGEAL DIVERTICULUM

The mid-esophageal diverticulum, also referred to as Rokitansky’s diverticulum, typically occurs as a protrusion in the mid-esophagus. Its diameter is usually less than 2 centimeters. The traditional view suggests that its formation is due to chronic inflammation and fibrosis, leading to scar contracture or tumor infiltration, which results in a true diverticulum that includes all layers of the esophageal wall. Mid-esophageal traction diverticulum are most commonly located on the right side, owing to the close anatomical relationship between the esophagus and the subcarinal lymph nodes in this region[60]. However, recent studies suggest that the formation of the mid-esophageal diverticulum may also be associated with increased intraluminal pressure caused by esophageal motility disorders (EMD)[22,61]. A relatively small mid-esophageal diverticulum was successfully treated with FESD in 2004, resulting in favorable long-term outcomes[62]. Salvage peroral endoscopic myotomy (S-POEM) was first applied to a patient with significant submucosal fibrosis due to prior treatments, with a second submucosal tunnel created on the opposite side for treatment[63]. Subsequently, it was also applied to a patient with a mid-esophageal diverticulum. Although high-resolution manometry (HRM) did not show primary motor dysfunction, S-POEM was performed on the opposite side of the diverticulum, improving the patient’s symptoms[64]. In 2016, two cases of giant mid-esophageal diverticulum were reported, where patients successfully resolved their dysphagia through D-POEM treatment, demonstrating the efficacy of D-POEM in managing mid-esophageal diverticulum[65]. D-POEM avoids the postoperative complications associated with open surgery, such as tracheoesophageal fistula, pneumothorax, and empyema. In 2024, Wang et al[66] reported a case of a patient with an enlarging thoracic mid-esophageal diverticulum compressing the heart. The team employed endoscopic submucosal dissection (ESD) combined with metal clip closure to prevent further esophageal dilation and cardiac compression that could potentially be caused by D-POEM. Simple mucosal dissection is typically sufficient for pseudodiverticula, whereas for true diverticulum, part of the muscularis propria must also be dissected[67]. The ESD combined with metal clip closure approach represents a novel attempt tailored to a specific patient. However, further research and validation are needed to assess its applicability to the broader diverticulum patient population.

EPIPHRENIC DIVERTICULUM

Epiphrenic diverticulum refers to a false diverticulum located within 10 cm of the distal esophagus, near the lower esophageal sphincter (LES), with the most common site being 4 cm to 8 cm above the gastroesophageal junction[68-70]. The majority of the epiphrenic diverticulum are located on the right side of the esophagus. This may be attributed to the adjacent left-sided mediastinal structures restricting diverticulum formation on that side[71,72]. Epiphrenic diverticulum is associated with an increased risk of malignancy, estimated at approximately 0.6%[17]. Therefore, regular follow-up for these patients is crucial. Esophagram, upper gastrointestinal endoscopy, and esophageal HRM are standard diagnostic procedures. Over 75% of patients with epiphrenic diverticulum have underlying EMD[73]. Achalasia is the most commonly associated EMD, followed by hypertensive LES, ‘nutcracker’ esophagus, and diffuse esophageal spasm. The onset of symptoms in patients with epiphrenic diverticulum is more likely related to the size of the diverticulum rather than underlying EMD.

The treatment of epiphrenic diverticulum can be based on D-POEM technique[7,74,75]. In cases of EMD, the endoscopic treatment of epiphrenic diverticulum differs from that of other types of diverticulum. LES myotomy can effectively address the underlying motility disorder at its pathological origin. The current debate centers around whether to combine standard D-POEM. One approach is standard POEM (POEM-S or S-POEM)[76-80], which involves reducing LES pressure without septotomy and has been shown to be effective in relieving symptoms (Figure 2). An alternative is to combine D-POEM with LES myotomy (POEM + S or E-POEM): Septotomy is technically straightforward and can be performed within the same tunnel, while preserving the intact diverticulum and septum may increase the risk of recurrence[81-83]. In the POEM-S technique, the diverticulum is typically avoided, and standard POEM is performed only on the opposite side. In POEM + S, the submucosal tunnel is extended along the same side as the diverticulum, followed by LES myotomy (extending at least 2 cm beyond the gastroesophageal junction) and septotomy. A 2024 multicenter study comparing POEM + S and POEM-S for the treatment of epiphrenic diverticulum found no significant differences in clinical success rates (POEM + S: 89.6% vs POEM-S: 89.2%, P = 1) and adverse event rates (POEM + S: 4.2% vs POEM-S: 8.1%, P = 0.6)[84]. Due to the close relationship between esophageal diverticulum and EMD, and the fact that HRM cannot be applied in some cases, endoscopic treatment for epiphrenic diverticulum without accompanying EMD is still primarily based on POEM + S. Even when preoperative HRM does not clearly confirm the presence of motility disorders, Nabi et al[85] still perform LES myotomy as part of the procedure. A retrospective study by Noh et al[86], which applied the endoscopic functional luminal imaging probe (EndoFLIP) based on HRM, demonstrated the value of EndoFLIP and the indications for POEM + S in epiphrenic diverticulum without accompanying EMD. Current evidence suggests that approximately 17% to 40% of patients experience symptomatic reflux after POEM[87]. Due to the implementation of LES myotomy, both POEM + S and POEM-S increase the risk of postoperative reflux esophagitis. Although reflux esophagitis is common, most cases of gastroesophageal reflux are asymptomatic[79,84-86].

Figure 2 The choice of myotomy. A: When a diverticulum is located at the right side (2:00-5:00 position), a posterior myotomy should be performed at the 6:00-8:00 position; B: Conversely, if the diverticulum is situated on the left side (7:00-10:00 position), an anterior myotomy is recommended at the 1:00-2:00 position. For standard peroral endoscopic myotomy, Zenker’s peroral endoscopic myotomy or peroral endoscopic septotomy can be used as the foundation as appropriate, and lower esophageal sphincter myotomy is performed within the same tunnel (at least 2 cm beyond the gastroesophageal junction).

CONCLUSION

Compared with traditional surgical procedures, endoscopic treatment of esophageal diverticulum, as a minimally invasive approach, has gained increasing popularity due to its reduced trauma, faster recovery, and lower risk of complications. During the FESD era, treatment focused primarily on the mechanical separation of the septum using various instruments. However, in the current era of D-POEM technology, the focus is more on achieving complete division of the septum muscles within the tunnel, representing a more minimally invasive approach. Given the close connection between the epiphrenic diverticulum and motility disorders, the emergence of S-POEM and S + POEM represents a physiological, mechanism-based treatment approach. We performed a PubMed literature search for studies on the treatment of esophageal diverticulum using D-POEM, covering publications up to March 2025. The primary search term was “D-POEM”, and studies were included if they covered at least two of the three types of esophageal diverticulum. Additional relevant references cited in the selected articles were also reviewed for inclusion. The initial search yielded 20 articles, of which 6 met the inclusion criteria after excluding unrelated studies (Table 1)[7,74,83,88-90]. Only one case of technical failure was reported. By the end of the follow-up period, clinical success was achieved in at least 85% of patients. Emphysema and mucosal injury were the most frequently reported adverse events, noted in half of the included studies. These findings suggest that D-POEM is technically feasible and yields favorable clinical outcomes. However, further studies are required to confirm its safety and optimize long-term outcomes. D-POEM and its variations offer broader applicability and improved safety over FESD in treating all three types of esophageal diverticulum. Nonetheless, additional research is needed to refine treatment strategies, systematically evaluate associated risks, and develop more effective therapeutic approaches.

Table 1 The initial search yielded 20 articles, of which 6 met the inclusion criteria after excluding unrelated studies[7,74,83,88-90].

No.	Publication year	Researchers	Study type	Diverticulum type	Type of poem	Technical/clinical success rate and follow-up duration	Adverse events
1	2019	Yang et al[7]	Multicenter and retrospective	7 ZD, 1 MED, 3 ED	D-POEM	90.9%/100% (patients who successfully underwent POEM) (12 months)	None
2	2019	Maydeo et al[74]	Prospective	20 ZD, 5 ED	D-POEM	100%/86% (12 months)	None
3	2020	Basile et al[83]	Retrospective	7 MED and ED	POEM + S (all diverticulum are associated with EMD)	100%/85.71% (12 months)	None
4	2021	Zeng et al[88]	Retrospective	2 ZD, 5 MED, 3 ED	D-POEM (POEM + S performed for ED with achalasia)	100%/90% (11.0 months) (IQR: 10.25-17.25 months)	Emphysema (n = 1, 10%)
5	2022	Samanta et al[89]	Retrospective	3ZD, 2ED	POEM (POEM + S for ED, larger diverticulum underwent POES)	100%/100% (9.33 months) (range: 3.27-11 months)	Emphysema (n = 1, 20%); mucosal injury (n = 1, 20%)
6	2024	Ren et al[90]	Multicenter and prospective	12 ZD, 12 MED, 10 ED	D-POEM (POEM + S performed for diverticulum with coexistent achalasia)	100%/88.2% (25 months) (range: 3-68 months)	Emphysema (n = 5, 14.7%); mucosal injury (n = 1, 2.9%)

ZD: Zenker’s diverticulum; ED: Epiphrenic diverticulum; MED: Mid-esophageal diverticulum; D-POEM: Diverticular peroral endoscopic myotomy; EMD: Esophageal motility disorders; POES: Peroral endoscopic septotomy; IQR: Interquartile range.