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ACHALASIA

Achalasia is a rare motility disorder of the esophagus and is defined by three elements: the reduction or absence of the primary peristaltic waves in the distal two thirds of the esophagus, incomplete or no relaxation of the lower esophageal sphincter (LES) during swallowing, and increased resting LES tone. There is degeneration of the esophageal muscle and the nerves that control the muscles. The cause of primary or idiopathic achalasia is unknown. Secondary achalasia is caused by diseases that cause esophageal motor abnormalities (e.g., Chagas disease, esophageal cancer, Fabry disease, amyloidosis). Men and women are affected with equal frequency, with no racial predilection, and achalasia is usually diagnosed in individuals between the ages of 30 and 60 years. Symptoms of achalasia include dysphagia, heartburn, difficulty belching, chest pain, regurgitation of undigested food and liquid, and weight loss (Vaezi et al., 2020a; Tefas et al., 2018; National Organization for Rare Disorders [NORD®], 2017). 

Achalasia is defined by aperistalsis and abnormal LES relaxation (integrated relaxation pressure [IRP] >15 mm Hg). The disorder is characterized manometrically by insufficient relaxation of LES and loss of esophageal peristalsis; radiographically by aperistalsis, esophageal dilation, with minimal LES opening, “bird-beak" appearance, poor emptying of barium; and endoscopically by dilated esophagus with retained saliva, liquid, and undigested food particles in the absence of mucosal stricturing or tumor. 

The three types of achalasia based on the Chicago Classification of patterns of esophageal pressurization on high-resolution manometry (HRM) (Chicago Classification v3.0) include the following: 

• Type I (classic achalasia) – Incomplete LES relaxation, aperistalsis, and absence of esophageal pressurization. Swallowing results in no significant change in esophageal pressurization and has 100% failed peristalsis with a distal contractile integral (DCI, an index of the strength of distal esophageal contraction) <100 mm Hg. 
  
  
• Type II – Incomplete LES relaxation, aperistalsis, and panesophageal pressurization in at least 20% of swallows. Swallowing results in simultaneous pressurization that spans the entire length of the esophagus. Type II achalasia has 100% failed peristalsis and panesophageal pressurization with ≥20 percent of swallows. 
  
  
• Type III (spastic achalasia) – Incomplete LES relaxation and premature contractions (distal latency [DL] <4.5 seconds) in at least 20% of swallows. Swallowing results in abnormal, lumen-obliterating contractions or spasms. Type III achalasia has no normal peristalsis and premature (spastic) contractions with DCI >450 mm Hg/sec/cm with ≥20 percent of swallows (Schlottmann et al., 2017).
  

The Eckardt symptom score is used to quantify the severity and frequency of symptoms. It attributes points (0 to 3 points) for four symptoms of the disease (dysphagia, regurgitation, chest pain, and weight loss), ranging from 0 to 12. Scores of 0–1 correspond to clinical stage 0; 2–3, to stage I; 4–6, to stage II; and >6 to stage III (Laurino-Neto et al., 2018).

Eckardt Score for Symptomatic Evaluation in Achalasia

The primary treatment objective for achalasia is to relieve obstruction in the distal esophagus by decreasing the resting pressure in the LES to a level at which the sphincter no longer impedes the passage of undigested food and liquid. Established treatment options include pharmacotherapy (e.g., injection of botulinum toxin into the esophagus, use of oral nitrates) or mechanical disruption of the muscle fibers of the LES by surgical interventions (i.e., endoscopic balloon dilation, surgical LHM with or without fundoplication) to reduce the incidence of gastroesophageal reflux disease (GERD). LHM is the treatment of choice and has an 85% to 90% effect in treating the condition. When an individual has dysphagia following surgical myotomy, the first suspicion is incomplete myotomy (FernandezAnanin et al., 2018; Tefas et al., 2018).

PERORAL ENDOSCOPIC MYOTOMY (POEM) OR ESOPHAGEAL PERORAL ENDOSCOPIC MYOTOMY (E-POEM)

POEM is a minimally invasive intervention that aims to treat achalasia. It is regarded as the endoscopic equivalent of Heller myotomy (HM). The POEM technique involves guiding an endoscope through the esophagus, making an incision in the mucosa, creating a submucosal tunnel for access to the lower esophagus and gastroesophageal junction, and cutting the muscle fibers in the lower esophagus and proximal stomach. Internal incisions are closed with clips after myotomy is complete. The proposed advantage of POEM is that it can deliver a longer myotomy than pneumatic dilation (PD) or the Heller procedure. The length of myotomy from the esophageal to the gastric side can be adjusted on a case-by-case basis while achieving functional durability of traditional surgical myotomy. A longer myotomy may be more effective in controlling symptoms. POEM includes no antireflux procedure and can therefore result in GERD. POEM is a proposed treatment. Reasonable treatment options following a failed surgical myotomy include PD or redo myotomy using either the same or an alternative myotomy technique (POEM or LHM) (Khashab et al., 2021; Inoue et al., 2018). 

POEM is a complex procedure, demanding skilled hands to avoid serious complications. Endoscopists should be able to recognize structures beyond mucosa, including vasculature nerves and the anatomy of the mediastinum. POEM should be performed in highly specialized centers by experienced endoscopists or surgeons (Ahmed and Othman, 2019).

The American College of Gastroenterology (ACG), in its clinical guideline on diagnosis and management of achalasia (Vaezi et al., 2013), identified POEM as experimental. It stated that "Randomized prospective comparison trials with standard laparoscopic myotomy and/or PD [pneumatic dilation] are needed and POEM should only be performed in the context of clinical trials with the understanding that other effective well-studied alternatives are available."

Von Renteln et al. (2013) stated that pilot studies have indicated that POEM might be a safe and effective treatment for achalasia. These investigators performed a prospective, international, multicenter study to determine the outcomes of 70 individuals who underwent POEM at five centers in Europe and North America. Three months after POEM, 97% of individuals were in symptom remission (95% confidence interval [CI], 89%–99%); symptom scores were reduced from 7 to 1 (P<0.001) and LES pressures were reduced from 28 to 9 mm Hg (P<0.001).  The percentage of individuals in symptom remission at 6 and 12 months was 89% and 82%, respectively. The authors concluded that POEM was found to be an effective treatment for achalasia after a mean follow-up period of 10 months. The main drawbacks of this study were the lack of a control group and the short-term follow-up.

In a prospective trial, Verlaan et al. (2013) evaluated the effect of POEM on esophagogastric function. Individuals were greater than 17 years of age with achalasia and an Eckardt score of greater than or equal to 3. Before and 3 months after POEM, 10 consecutive individuals underwent esophageal manometry, timed barium esophagograms, and endoscopic functional lumen imaging probe (EndoFLIP) as well as an esophagogastroduodenoscopy (EGD). Main outcome measures were Eckardt symptom score, LES resting pressure, centimeters of barium stasis, esophagogastric junction (EGJ) distensibility, and reflux esophagitis. Compared with scores before POEM, individual symptom scores were significantly reduced (1, interquartile range [IQR, 0– 1] vs 8 [IQR 4–8]; P=0.005). LES pressure decreased significantly (6.0 mm Hg [IQR, 2.6–7.4] vs 19.0 mm Hg [IQR 13.0–28.0]; P=0.008). Esophageal emptying increased significantly, and a 5-minute barium column measured 2.3 cm (IQR, 0–3.2 cm) versus 10.1 cm (IQR, 5.7–10.8 cm; P=0.005). EGJ distensibility increased significantly (6.7 mm²/mm Hg [IQR, 3.8–16.6] versus 1.0 mm²/mm Hg [IQR, 0.4–2.3]; P=0.02) at 50 mL. In six of 10 individuals, reflux esophagitis was seen. Of these individuals, three reported reflux symptoms. The authors concluded that POEM improves esophagogastric function and suggested favorable long-term results based on Eckardt score, esophageal manometry, esophageal emptying, and EGJ distensibility.  Moreover, they stated that long-term follow-up of larger series will determine whether the high rate of reflux esophagitis affects the clinical application of POEM. The main drawbacks of this study were the small number of individuals and the short-term follow-up.

Onimaru et al. (2013) evaluated the safety and effectiveness of POEM for surgical myotomy failure as a rescue second-line treatment, and discussed the treatment options adapted in achalasia recurrence. A total of 315 consecutive individuals with achalasia received POEM from September 2008 to December 2012 in the authors' hospital. Eleven (3.5%) individuals, who had persistent or recurrent achalasia and had received surgical myotomy as a first-line treatment from other hospitals, were included in this study. Individual background, barium swallow studies, EGD, manometry, and symptom scores were prospectively evaluated. In principle, all individuals in whom surgical myotomy failed received pneumatic balloon dilatation (PBD) as the first-line "rescue" treatment, and only if PBD failed were individuals considered for rescue POEM. The PBD alone was effective in one individual, and in the remaining 10 individuals, rescue POEM was performed successfully without complications. Three months after rescue POEM, significant reduction in LES resting pressures (22.1 ± 6.6 mm Hg vs 10.9 ± 4.5 mm Hg; P<0.01) and Eckardt symptom scores (6.5 ± 1.3 vs 1.1 ± 1.3; P<0.001) were observed. The authors concluded that short-term results of POEM for failed surgical myotomy were excellent; long-term results are awaited.

Yang and Wagh (2013) stated that achalasia is a motility disorder of the esophagus, characterized by a peristalsis of the esophageal body and incomplete relaxation of the LES. Treatment of achalasia is currently aimed at decreasing the resting pressure in the LES. POEM is an emerging novel endoscopic procedure for the treatment of achalasia with initial data suggesting an acceptable safety profile, excellent short-term symptom resolution, low incidence of postprocedural GERD, and improvement in manometric outcomes. The authors concluded that further prospective randomized trials are needed to evaluate the long-term effectiveness of this promising technique compared to other treatment modalities for achalasia. 

Friedel et al. (2013) stated that the volume of POEMs performed worldwide has grown exponentially. In fact, surgeons who have performed HM have embraced POEM as the preferred intervention for achalasia. However, the authors stated that the niche of POEM remains to be defined and long-term results are awaited.

Pescarus et al. (2014) stated that POEM is a new minimally invasive endoscopic treatment for achalasia. Since the first modern human cases were published in 2008, around 2000 cases have been performed worldwide. This technique requires advanced endoscopic skills and a learning curve of at least 20 cases. POEM is highly successful, with over 90% improvement in dysphagia while offering individuals the advantage of low-impact endoscopic access. The main long-term complication is GERD, with an estimated incidence of 35%, similar to the incidence of GERD postlaparoscopic HM with fundoplication. The authors concluded that although POEM represents a paradigm shift in the treatment of achalasia, more long-term data are needed to further define its role in the treatment algorithm of this rare disease.

Bredenoord et al. (2014) noted that treatment of achalasia is complicated by symptom recurrence and a significant risk for severe complications. Endoscopic myotomy was developed in the search for a highly effective treatment with lower risks. Since its introduction in 2010, several centers have adopted the technique and published excellent short-term results of open label series. These researchers stated that randomized trials with long-term end-point comparing POEM with the established treatments such as balloon dilation and surgical myotomy are now warranted, before POEM can be regarded as the routine clinical care for achalasia individuals.

Schlottmann et al. (2018) compared the outcome of POEM and LHM for the treatment of esophageal achalasia. These researchers performed a systematic Medline literature search of articles on LHM and POEM for the treatment of achalasia. The main outcomes measured were improvement of dysphagia and posttreatment GERD. Linear regression was used to model the effect of each procedure on the different outcomes. Fifty-three studies reported data on LHM (5834 individuals), and 21 articles examined POEM (1958 individuals). Mean follow-up was significantly longer for studies of LHM (41.5 vs 16.2 months; P<0.0001). Predicted probabilities for improvement in dysphagia at 12 months were 93.5% for POEM and 91.0% for LHM (P=0.01), and at 24 months were 92.7% for POEM and 90.0% for LHM (P=0.01). Individuals undergoing POEM were more likely to develop GERD symptoms (odds ratio [OR], 1.69; 95% CI, 1.33–2.14; P<0.0001), GERD evidenced by erosive esophagitis (OR, 9.31; 95% CI, 4.71–18.85; P<0.0001), and GERD evidenced by pH monitoring (OR, 4.30; 95% CI, 2.96–6.27; P<0.0001). On average, length of hospital stay was 1.03 days longer after POEM (P=0.04). The authors concluded that short-term results showed that POEM is more effective than LHM in relieving dysphagia, but it is associated with a very high incidence of pathologic reflux. The clinical sequalae of the increase in pathologic reflux are currently unclear, but it is possible that longer term outcomes associated with POEM may demonstrate GERD complications such as stricture and/or Barrett esophagus. These researchers stated that longer follow-up studies and randomized trials comparing POEM with LHM are needed to establish the role of this new technique in the treatment algorithm of achalasia.

The authors stated that this study had several drawbacks. Because of the rarity of achalasia, few controlled trials were available for analysis and most of the studies reviewed by these investigators were retrospective or cohort studies, subject to selection bias and reporting bias. In addition, POEM studies have significantly shorter follow-up as compared with LHM studies, which may influence the results. As noted previously, POEM is also a newer technology, and the extent to which outcomes change as operators exit their learning curves is unclear. Heterogeneity in reporting outcomes among studies may have also affected the results and limited the categorization of outcomes into simple dichotomous variables that could be easily quantified. LHM studies in general evaluated their primary outcomes by the improvement in the swallowing status; POEM studies, on the other hand, most commonly assessed outcomes using the Eckardt score, a more precise evaluation as it considers not only the improvement in dysphagia, but also the effect of the procedure on regurgitation, retrosternal pain, and weight loss.

In a systematic review and meta-analysis, Awaiz et al. (2017) compared the safety and effectiveness of LHM and POEM for the treatment of achalasia. These investigators carried out a search of PubMed, Cochrane database, Medline, Embase, Science Citation Index, and Current Contents for English-language articles comparing LHM and POEM between 2007 and 2016. Variables analyzed included prior endoscopic treatment, prior medical treatment, prior HM, operative time, overall complications rate, postoperative GERD, length of hospital stay, postoperative pain score, and long-term GERD. Seven trials consisting of 483 individuals (LHM, 250; POEM, 233) were analyzed. Preoperative variables (e.g., prior endoscopic treatment [OR, 1.32; 95% CI, 0.23–4.61; P=0.96], prior medical treatment [weighted mean difference (WMD), 1.22; 95% CI, 0.52–2.88; P=0.65], and prior HM (WMD, 0.47; 95% CI, 0.13–1.67; P=0.25) were comparable. Operative time was 26.28 minutes, nonsignificantly longer for LHM (WMD, 26.28; 95% CI, −11.20 to 63.70; P=0.17). There was a comparable overall complication rate (OR, 1.25; 95% CI, 0.56–2.77; P=0.59), postoperative GERD rate (OR, 1.27; 95% CI, 0.70–2.30; P=0.44), length of hospital stay (WMD, 0.30; 95% CI, −0.24 to 0.85; P=0.28), postoperative pain score (WMD, −0.26; 95% CI, −1.58 to 1.06; P=0.70), and long-term GERD (WMD, 1.06; 95% CI, 0.27–4.1; P=0.08) for both procedures. There was a significantly higher short-term clinical treatment failure rate for LHM (OR, 9.82; 95% CI, 2.06–46.80; P<0.01). The authors concluded that POEM compared favorably to LHM for achalasia treatment in short-term perioperative outcomes. However, there was a significantly higher clinical treatment failure rate for LHM on short-term postoperative follow-up. They stated that currently, long-term postoperative follow-up data for POEM beyond 1 year are unavailable in all the comparative trials and therefore meaningful comparison with LHM is impossible. In the future, several issues need to be addressed to determine the clinical outcomes, safety, and effectiveness of these two methods for achalasia treatment. These include the following: 

• standardized definition of failure rate;
• standardized method of detecting recurrence of achalasia (e.g., timed barium swallow [TBS], HRM, functional lumen imaging probe [FLIP], and 24-hour pH monitoring); and
• long-term postprocedural data collection using disease-specific–validated instruments to gauge the effectiveness and durability of POEM.
  

These researchers stated that until all the above-mentioned issues are rigorously addressed in a well-designed randomized controlled trial (RCT) comparing POEM with LHM, the routine use of POEM should proceed with caution.

Crespin et al. (2017) performed a systematic review of the literature to evaluate the safety and effectiveness of POEM for the treatment of achalasia. The systematic review was conducted following the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Evidence-based medicine reviews, Cochrane Central Register of Controlled Trials, Medline, including in-process and nonindexed citations, were searched for POEM studies using the keywords esophageal achalasia, POEM, endoscopy, natural orifice surgery, laparoscopic Heller myotomy (LHM), and related terms. Eckardt score, LES pressure, and reported complications were the main outcomes. Two authors reviewed the search results independently. A third reviewer resolved all disagreements. Data abstraction was pilot-tested and approved by all authors. Data were examined for clinical, methodological, and statistical heterogeneity with the aim of determining whether evidence synthesis using meta-analysis was possible. The search strategy retrieved 2894 citations. After removing duplicates and applying the exclusion criteria, 54 studies were selected for full-text review, of which 19 studies were considered eligible for further analysis. There were 10 retrospective and nine prospective studies, including 1299 POEM procedures. No randomized control trial (RCT) was identified. Overall, the pre- and post-POEM Eckardt scores and LES pressure were significantly different. The most frequently reported complications were mucosal perforation, subcutaneous emphysema, pneumoperitoneum, pneumothorax, pneumomediastinum, pleural effusion, and pneumonia. The median follow-up was 13 months (range, of 3–24). The authors concluded that POEM is a safe and effective alternative for the treatment of achalasia. However, only short-term follow-up data compared with LHM are available. These investigators stated that RCTs and long-term follow-up studies are needed to establish the safety and effectiveness of POEM in the treatment of individuals with achalasia.

Hernández Mondragón et al. (2017) noted that POEM is an excellent endoscopic treatment for achalasia. Clinical and manometric parameters are used for evaluation and follow-up.  However, clinical success does not guarantee high QOL scores, generating doubts about their direct relationship.  These researchers evaluated quality of life (QOL) scores before and after POEM to evaluate differences among achalasia subtypes and find which factors related to low QOL scores. Achalasia-confirmed individuals undergoing POEM between February 2012 and November 2016, and completing at least 1 year of follow-up, were included. Assessment before and at 1, 6, 12, 24, 36 and 48 months after POEM employed manometry, barium series, Eckardt score, and the AE-18 health-related QOL scale.  Demographic, clinical, and procedure characteristics were documented, with comparisons between subgroups. Multiple logistic regression analysis was done; 65 of 88 individuals were included (38 women and 27 men; median age of 47 years, IQR 20 – 81), and 50 (76.9 %) completed 4 years of follow-up. Eckardt score improved (median preprocedure 10 vs postprocedure 2; P= 0.002) and this persisted.  There was initial improvement in median IRP (29.4  mm Hg [16 –55] vs 10.3  mm Hg [3 t–18]; P= 0.000) and median QOL scores (40 vs 68  at 1 month;  P= 0.002); however, IRP increased and QOL scores decreased. Men with confirmed type III achalasia had low QOL scores. The authors concluded that all individuals had significant clinical improvement after POEM, with medium- to long-term persistence. These investigators noted that although QOL and IRP initially improved, they deteriorated in the long term; male sex and type III achalasia appeared to be associated with low QOL scores.

With the development of endoscopic interventions and inspired by the success of POEM for the treatment of achalasia, Liu et al. (2017) investigated an old method of direct POEM without a submucosal tunnel for the treatment of achalasia. The authors called it open-POEM (O-POEM).  In this study, clinical success was achieved in the individual after O-POEM.  A reduction of LES pressure, Eckardt score, and a timed barium esophagogram were observed during follow-up. There were no severe complications and no recurrences during 2 months of follow-up. The authors concluded that O-POEM is a feasible and effective endoscopic treatment modality for achalasia. However, long-term outcomes of O-POEM require further follow-up.

Banks and Sweis (2017) stated that achalasia is a rare esophageal motility disorder predominantly causing dysphagia and regurgitation of food and fluids. Diagnosis is made typically after a combination of tests including endoscopy, barium swallow, and esophageal manometry.  The advent of HRM has led to the Chicago Classification that divided achalasia into three types. This classification improved the understanding of presentation and prognosis, and might also help tailor therapy. Botulinum toxin has been shown to have good but short-term efficacy. The predominant treatments include PBD and LHM, both of which have similar and durable outcomes, although the success of both reduces with time; POEM has been shown to be as effective, safe and durable as earlier treatments for achalasia; however, RCTs are lacking.  The authors noted that indications for POEM are expanding to other hyper-contractile motility disorders of the esophagus.

Nabi et al. (2017) stated that POEM has emerged as an efficacious treatment modality for the management of achalasia cardia (AC) and nonachalasia spastic esophageal motility disorders. Initial results are encouraging. These investigators analyzed the safety and effectiveness of POEM in a large cohort of individuals with AC. The data from individuals who underwent POEM (January 2013–June 2016) was prospectively collected and analyzed. Clinical success was defined as Eckardt score less than or equal to  3 after POEM procedure. Objective parameters including HRM and TBS were analyzed and compared before and after the procedure. GER was analyzed using 24-hour pH impedance study and esophagogastroduodenoscopy. A total of 408 individuals (mean age, 40 years; range, 4 –77 years) underwent POEM during the specified period. POEM could be successfully completed in 396 (97 %) individuals. Clinical success rates at 1, 2 and 3 years were 94 %, 91 % and 90 %, respectively. Mean Eckardt score was 7.07 ± 1.6 prior to POEM and 1.27 ± 1.06 after POEM (P= 0.001) at 1 year. Significant improvement in esophageal emptying on TBE (>50 %) was documented in 93.8 % individuals who completed 1-year follow up. Preprocedure and postprocedure mean LES pressure was 45 ± 16.5  mm Hg and 15.6 ± 6.1  mm Hg, respectively (P = 0.001). Technical and clinical success were comparable in naïve versus prior treated cases (97.3 % vs 96.8 %; P = 0.795) (95.7 % vs 92.6 %; P = 0.275). GERD was documented in 28.3 % of individuals with 24-hour pH-impedance study; erosive esophagitis was seen in 18.5 % of individuals who underwent POEM. The authors concluded that POEM is safe, effective, and durable for treatment of AC. The incidence of GERD did not appear to be higher than with LHM. However, randomized comparisons are needed; whether POEM should be offered as a first-line treatment to all individuals with AC is a matter of debate. Moreover, they stated that long-term follow-up studies and randomized comparison with established modalities such as PBD and LHM will provide conclusive information.

Schlottmann and Patti (2018) noted that esophageal achalasia is a rare disorder characterized by a failure of the LES to relax during swallowing, combined with aperistalsis of the esophageal body. Treatment is not curative, but aims to eliminate the outflow resistance caused by the nonrelaxing LES. Current evidence suggests that both LHM and POEM are very effective in the relief of symptoms in individuals with achalasia. Specifically, for type III achalasia, POEM may achieve higher success rates. However, POEM is associated with a very high incidence of pathologic reflux, with the risk of exchanging one disease (achalasia) with another (gastroesophageal reflux).

Kroch and Grimm (2018) stated that POEM was introduced in 2008 for the treatment of esophageal achalasia. It is performed endoscopically, which allows transection of the muscular fibers of the distal esophagus and of the LES. The procedure is therefore similar to a LHM without a fundoplication. Short-term studies have shown that POEM is very effective in relieving dysphagia and regurgitation, but concerns have been raised about the incidence of post-POEM GER. The authors concluded that prospective and randomized trials are needed to determine the role of this new procedure in the treatment algorithm of esophageal achalasia.

Repici et al. (2018) stated that POEM represents a less-invasive alternative to conventional LHM for individuals with achalasia. However, it cannot be excluded that the lack of fundoplication after POEM may result in a higher incidence of reflux disease, as compared with LHM.  The researchers conducted a systematic review of prospective studies reporting the incidence of reflux disease developed after POEM and LHM. A literature search with electronic databases was performed (up to February 2017) to identify full articles on the incidence of GER symptoms and endoscopic monitoring and pH monitoring findings after POEM and LHM (with fundoplication). Proportions and rates were pooled by means of random or fixed-effects models, according to the level of heterogeneity between studies. After the selection criteria were applied, 17 and 28 studies, including 1542 and 2581 participants who underwent POEM and LHM, respectively, were included. The pooled rate of postprocedural symptoms was 19.0% (95% CI,15.7%–22.8%) after POEM and 8.8% (95 % CI, 5.3%–14.1%) after LHM, respectively. The pooled rate estimate of abnormal acid exposure at pH monitoring was 39.0% (95% CI, 24.5%–55.8%) after POEM and 16.8% (95 % CI, 10.2%–26.4%) after LHM, respectively. The rate of esophagitis after POEM was 29.4% (95% CI, 18.5%–43.3%) after POEM and 7.6% (95% CI, 4.1%–13.7%) after LHM. At meta-regression, heterogeneity was explained partly by the POEM approach and study population. The authors concluded that the incidence of reflux disease appeared to be significantly more frequent after POEM than after LHM with fundoplication. Monitoring pH and ensuring appropriate treatment after POEM should be considered in order to prevent long-term reflux-related adverse events (AEs).

Cho and Kim (2018) noted that POEM is an endoluminal procedure that involves dissection of esophageal muscle fibers followed by submucosal tunneling. Inoue et al. first attempted to use POEM for the treatment of achalasia in humans (2010). Expanded indications of POEM include classic indications such as type I, type II, type III achalasia, failed prior treatments, including botulinum toxin injection, endoscopic balloon dilation, LHM, and hypertensive motor disorders such as diffuse esophageal spasm and jackhammer esophagus. Contraindications include prior radiation therapy to the esophagus and prior extensive esophageal mucosal resection/ablation involving the POEM field. Most of the complications are minor and self-limited and can be managed conservatively. As POEM emerged as the main treatment for achalasia, various adaptations to tunnel endoscopic surgery have been attempted. Tunnel endoscopic surgery includes POEM, peroral endoscopic tumor resection, and gastric peroral endoscopic pyloromyotomy. The authors concluded that POEM is a safe and effective option for treating type I, type II, type III achalasia, and even for specific cases such as achalasia with failed prior treatments, botulinum toxin injection, endoscopic balloon dilation, LHM, and hypertensive motor disorders. However, they stated that large-scale studies and long-term outcomes are needed; OEM has expanded the scope of adaptation to tunnel endoscopic surgeries such as POEM and G-POEM, which also require larger scale studies with long-term outcomes.

van Lennep et al. (2018) stated that achalasia is a rare esophageal motility disorder. Much of the literature is based on the adult population. In adults, guidance of therapeutic approach by manometric findings has led to improvement in individual outcome. Promising results have been achieved with novel therapies such as POEM. The authors review the novel diagnostic and therapeutic tools for achalasia management and in what way they will relate to the future management of pediatric achalasia. These investigators performed a PubMed and Embase search of English literature on achalasia using the keywords children, achalasia, pneumatic dilation, myotomy, and POEM. Cohort studies of fewer than 10 cases and studies describing individuals greater than or equal to 20 years were excluded. Data regarding individual characteristics, treatment outcome, and AEs were extracted and presented descriptively, or pooled when possible. The authors concluded that available data reported that PD and LHM are effective in children, with certain studies suggesting lower success rates in PD; POEM is increasingly used in the pediatric setting with promising short-term results; moreover, GERD may occur postachalasia intervention due to disruption of the LES and therefore requires diligent follow-up, especially in children treated with POEM.

Yeung et al. (2018) noted that experience of POEM for treatment of achalasia in pediatric population is limited with varying techniques in different centers. The accurate extent of submucosal tunneling into the gastric cardia and the adequacy of myotomy are the important determining factors to success of POEM. Most studies in the pediatric population have described using submucosal dye injection for assessing the adequacy of myotomy; however, this is a rather crude and inaccurate method. These investigators described the first case of pediatric achalasia managed with POEM incorporated with novel combined techniques using EndoFLIP and double endoscope. EGJ was identified with a gastroscope. Before POEM, EndoFLIP showed EGJ distensibility index of 1.7 mm²/mm Hg. Submucosal tunnel was created from the mucosal entry site at midesophagus down and approximately 3 cm beyond the EGJ. Anterior myotomy cutting the circular muscle layer while preserving the longitudinal muscle was performed for 8 cm. Double-endoscope technique was used to confirm the adequacy of myotomy by inserting a smaller endoscope through nostril into stomach and observing the transillumination of the first endoscope at the end of the submucosal tunnel. After POEM, repeat EndoFLIP measurements revealed increased distensibility index to 6.0 mm²/mm Hg. Endoscopic examination at the end of the procedure showed widely patent EGJ. Eckardt symptoms score improved from 9 to 0. At 7 months after POEM, esophagoscopy showed widely open EGJ with no esophagitis, and high-resolution esophageal manometry (HREM) revealed normalized LES pressure and resting tone. The authors concluded that they introduced the intraoperative use of the EndoFLIP system that allowed real-time assessment of EGJ distensibility and immediate treatment effect evaluation. Incorporation of double-endoscope POEM was also first described in these pediatric individuals for ensuring complete gastric myotomy. They stated that from their experiences, POEM for achalasia in pediatric population appeared to have encouraging results similar to adult individuals.

POEM FOR THE TREATMENT OF TYPE III ACHALASIA
In an update of the clinical practice from the American Gastroenterological Association (AGA) on the use of POEM in achalasia, Kahrilas et al. (2017) described a place for POEM among the currently available robust treatments for achalasia. The recommendations outlined were based on expert opinion and on relevant publications from PubMed and Embase. The clinical practice updates committee of the AGA proposed the following recommendations: (1) in determining the need for achalasia therapy, individual-specific parameters (Chicago Classification subtype, comorbidities, early vs late disease, primary or secondary causes) should be considered along with published efficacy data; (2) given the complexity of this procedure, POEM should be performed by experienced physicians in high-volume centers because an estimated 20 to 40 procedures are needed to achieve competence; (3) if the expertise is available, POEM should be considered as primary therapy for type III achalasia; (4) if the expertise is available, POEM should be considered as treatment option comparable with LHM for any of the achalasia syndromes; (5) post-POEM individuals should be considered high-risk to develop reflux esophagitis and advised of the management considerations (potential indefinite proton pump inhibitor (PPI) therapy and/or surveillance endoscopy) before undergoing the procedure.

In a review on current treatment of achalasia, von Rahden (2019) stated that advantages of POEM are the possibility to perform a long-myotomy (of the entire length of the esophagus if necessary) and the relatively free choice of the localization of the myotomy (anterior/posterior POEM). The disadvantage is the increased postoperative GERD following POEM; however, this sequela is managed with PPI therapy in most cases, or a laparoscopic fundoplication, if necessary. Preliminary results of two prospective, randomized trials showed the superiority of POEM over endoscopic PD, as well as the noninferiority to LHM, but increased postoperative GERD. The author uses a tailored approach, with preference of POEM for achalasia type III and type II with chest pain and LHM + Dor procedure for sigmoid achalasia and other associated morphological changes.

Zaninotto et al. (2019) evaluated the efficacy, morbidity, and side effects of innovative management strategies for achalasia that include HRM, pneumatic dilatation, LHM, injection of botulinum toxin (BTX) into the LES and POEM. HRM has enabled identification of achalasia subtypes that have important prognostic implications. DP is a commonly used and cost-effective method of treating achalasia but has shown poor longevity of symptom relief compared with other modalities and carries a risk of esophageal perforation. LHM is often the preferred, most effective treatment modality; however, new studies may show that outcomes are equivalent or even inferior to POEM; BTX injection of the LES has a waning and short duration of efficacy and is used primarily for individuals unsuitable for more definitive invasive procedures. POEM is considered the most effective treatment for type III achalasia but carries a high risk of iatrogenic GERD that might predispose to the development of Barrett esophagus. The authors concluded that HRM and POEM are two major innovations in the management of achalasia developed over the past 10 years. There are now three major management options for individuals with achalasia: PD, LHM, and POEM.

Werner et al. (2019) noted that PD and LHM are established treatments for idiopathic achalasia. POEM is a less-invasive therapy with promising early study results. In a randomized, multicenter study, these researchers compared POEM with LHM plus Dor fundoplication in individuals with symptomatic achalasia. The primary endpoint was clinical success, defined as an Eckardt symptom score of 3 or less (range, 0–12, with higher scores indicating more severe symptoms of achalasia) without the use of additional treatments, at the 2-year follow-up; a noninferiority margin of −12.5 percentage points was used in the primary analysis. Secondary endpoints included AEs, esophageal function, Gastrointestinal Quality of Life Index score (range, 0–144, with higher scores indicating better function), and GER. A total of 221 individuals were randomly assigned to undergo either POEM (112 individuals) or LHM plus Dor fundoplication (109 individuals). Clinical success at the 2-year follow-up was observed in 83.0% of individuals in the POEM group and 81.7% of individuals in the LHM group (difference, 1.4 percentage points; 95% CI, −8.7 to 11.4; P=0.007 for noninferiority). Serious AEs occurred in 2.7% of individuals in the POEM group and 7.3% of individuals in the LHM group. Improvement in esophageal function from baseline to 24 months, as assessed by measurement of the IRP of the LES, did not differ significantly between the treatment groups (difference, −0.75 mm Hg; 95% CI, −2.26 to 0.76), nor did improvement in the score on the Gastrointestinal Quality of Life Index (difference, 0.14 points; 95% CI, −4.01 to 4.28). At 3 months, 57% of individuals in the POEM group and 20% of individuals in the LHM group had reflux esophagitis, as assessed by endoscopy; at 24 months, the corresponding percentages were 44% and 29%. The authors concluded that POEM was noninferior to LHM plus Dor fundoplication in controlling symptoms of achalasia at 2 years; however, GER was more common among individuals who underwent POEM than among those who underwent LHM .

Werner et al. stated that this study had several drawbacks. Fewer than 50% of the eligible individuals participated in the trial, mainly because of a lack of individual consent to undergo randomization. The surgeons were more experienced in performing LHM plus Dor fundoplication than the endoscopists were in performing POEM. These researchers did not analyze treatment effects on postoperative pain or on the use of pain medications; in general, the findings at the 2-year follow-up in this study suggested that there was no between-group difference in improvements in individual-reported QOL. Individuals and trial personnel were aware of the treatment-group assignments because blinding was not possible. This factor was a potential source of bias given that the primary endpoint was based on individuals' reports of symptoms; however, objective assessment by manometry corroborated the primary finding.

Vaezi et al. (2020) stated that achalasia is an esophageal motility disorder characterized by aberrant peristalsis and insufficient relaxation of the LES. Individuals most commonly present with dysphagia to solids and liquids, regurgitation, and occasional chest pain with or without weight loss. HRM has identified three subtypes of achalasia distinguished by pressurization and contraction patterns. Endoscopic findings of retained saliva with puckering of the gastroesophageal junction or esophagram findings of a dilated esophagus with bird beaking are important diagnostic clues. In an ACG guideline, the authors used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) process to provide clinical guidance on how best to diagnose and treat individuals with achalasia. The guideline states that "POEM or PD result in comparable symptomatic improvement in individuals with types I or II achalasia – Low GRADE quality; and 'conditional' recommendation."

In a systematic review and network meta-analysis, Facciorusso et al. (2021) examined the comparative efficacy of different strategies for management of achalasia. These researchers identified six RCTs in adults with achalasia that compared the efficacy of PD (n=260), LHM (n=309), and POEM (n=176). Primary efficacy outcome was 1-year treatment success (individual-reported improvement in symptoms based on validated scores); secondary efficacy outcomes were 2-year treatment success and physiologic improvement; safety outcomes were risk of GERD, severe erosive esophagitis, and procedure-related serious AEs. These investigators performed pair-wise and network meta-analysis for all treatments, and used GRADE criteria to appraise quality of evidence. Low-quality evidence, based primarily on direct evidence, supports the use of POEM (RR [risk ratio], 1.29; 95% CI, 0.99–1.69), and LHM (RR, 1.18 [0.96–1.44]) over PD for treatment success at 1 year; no significant difference was observed between LHM and POEM (RR 1.09 [0.86–1.39]). The incidence of severe esophagitis after POEM, LHM, and PD was 5.3%, 3.7%, and 1.5%, respectively. Procedure-related serious AE rate after POEM, LHM, and PD was 1.4%, 6.7%, and 4.2%, respectively.  The authors concluded that POEM and LHM have comparable efficacy, and may increase treatment success as compared to PD with low confidence in estimates. POEM may have a lower rate of serious AEs compared to LHM and PD, but higher rate of GERD. Moreover, these researchers stated that future prospective studies comparing long-term safety and efficacy of POEM, LHM, and PD, particularly across specific achalasia subtypes, are needed.

Facciorusso et al. noted that this study had several drawbacks. The studies had a short duration of follow-up, and the primary outcome of this network meta-analysis was focused on short-term (1-year) success. Limited postintervention follow-up prevented the ability to understand long-term comparative efficacy between interventions, which is critical for a chronic disease. There was also a paucity of direct head-to-head comparative trials, in particular comparing POEM to the other treatments. Further, performance and detection bias related to the nonblinded design of included trials introduced significant risk of bias. Performance and detection bias were not easily avoidable in RCTs testing new devices or techniques in surgery or endoscopy, given the nature of the intervention under study, and this represented a limitation in particular when considering subjective outcomes such as improvement of symptoms in individuals with achalasia. Assessment of vital physiologic outcomes by blinded readers could overcome limitations related to blinding in these trials; however, these outcomes were infrequently and/or inconsistently reported in trials data, which limited ability to compare posttreatment physiologic efficacy. Similarly, treatment-related AEs were poorly reported and a thorough assessment of risk–benefit profile could not be performed. Finally, inherent to network meta-analyses is risk of misinterpretation due to conceptual heterogeneity, related to differences in subjects, interventions, cointerventions/background treatment, and outcome assessment, which may limit comparability of trials; these could not be adequately accounted for with study-level synthesis, and individual participant-level pooled analyses will be needed.

Cappell et al. (2020) reviewed clinical presentation, diagnosis, and therapy for achalasia, focusing on recent developments in HREM for diagnosis and POEM for therapy. These researchers carried out a systematic review of achalasia using computerized literature search via PubMed and Ovid of articles published since 2005 with keywords ("achalasia") AND ("high resolution" or "HREM" or "peroral endoscopic myotomy" or "POEM").  Two authors independently performed literature searches and incorporated articles into this review by consensus according to prospectively determined criteria. Achalasia is an uncommon esophageal motility disorder, usually manifested by dysphagia to solids and liquids, and sometimes manifested by chest pain, regurgitation, and weight loss.  Symptoms often suggest more common disorders, such as GERD, thus often delaying diagnosis. Achalasia is a predominantly idiopathic chronic disease. Diagnosis is typically suggested by barium swallow showing esophageal dilation; absent distal esophageal peristalsis; smoothly tapered narrowing ("bird's beak") at EGJ; and delayed passage of contrast into stomach. Diagnostic findings at HREM include distal esophageal aperistalsis and IRP (trough LES pressure during 4 s) of greater than 15 mm Hg.  Achalasia is classified by HREM into type 1 (classic), type 2 (compartmentalized high pressure in esophageal body), and type 3 (spastic).  This classification impacts therapeutic decisions. Esophagogastroduodenoscopy is required before therapy to assess esophagus and EGJ and to exclude distal esophageal malignancy. POEM is a revolutionizing achalasia therapy. POEM creates a myotomy via interventional endoscopy.  Numerous studies demonstrated that POEM produces comparable, if not superior, results compared to standard LHM, as determined by LES pressure, dysphagia frequency, Eckardt score, hospital length of stay (LOS), therapy durability, and incidence of GERD. Other therapies, including botulinum toxin (BTX) injection and PD, have moderately less efficacy and much less durability than POEM. The authors concluded that this comprehensive review suggested that POEM is equivalent or perhaps superior to LHM for achalasia in terms of cost efficiency, hospital LOS, and relief of dysphagia, with comparable side effects. The data are, however, not conclusive due to sparse long-term follow-up and lack of randomized comparative clinical trials; and POEM therapy is currently limited by a shortage of trained endoscopists.

Martins et al. (2020) noted that achalasia is a neurodegenerative motility esophageal disorder characterized by failure of LES relaxation. The conventional therapeutic option for achalasia has been LHM. However, in 2010, Inoue et al. described POEM, a minimally invasive procedure, as an alternative therapy. To date, some studies with small sample sizes have compared outcomes of LHM versus POEM. These researchers carried out a systematic review and meta-analysis to better evaluate the safety and efficacy of these two procedures. Individualized search strategies were developed from inception through April 2019 in accordance with PRISMA guidelines. Variables analyzed included operative time, overall AE rate, postprocedure GERD, hospital LOS, postprocedure pain score, and Eckardt score reduction. Twelve cohort trials were selected, consisting of 893 individuals (359 in the POEM group and 534 in LHM). No randomized clinical trials were available. There was no difference in operative time (mean difference [MD], −10.26; 95% CI, −5.6 to 8.2); P<0.001) or postoperative gastroesophageal reflux (risk difference [RD], −0.00; 95% CI, −0.09 to 0.09; I2, 0%). There was decreased hospital LOS for POEM (MD, −0.6; 95% CI, −1.11 to −0.09; P=0.02), and an increased mean reduction in Eckardt score in POEM individuals (MD, −0.257; 95% CI, −0.512 to −0.002; P=0.048), with similar rates of AEs. The authors concluded that POEM demonstrated similar results compared to LHM with regards to improvement of dysphagia, postprocedure reflux, and surgical time, with the benefit of shorter hospital LOS; thus, POEM could be considered an option for individuals with achalasia. Moreover, these researchers pointed out several limitations due to heterogeneity among the studies. Only one study had a follow-up period of greater than 12 months, making it impossible to evaluate long-term outcomes. These investigators stated that randomized trials comparing methods are not available yet in the literature, which reduces the level of evidence from this review.

In a systematic review and meta-analysis, Tan et al. (2021) examined the safety and efficacy of POEM in achalasia individuals with failed previous intervention. These investigators searched the Medline, Embase, Cochrane, and PubMed databases using the queries "achalasia", "peroral endoscopic myotomy" and related terms in March 2019. Data on technical and clinical success, AEs, Eckardt score, and LES pressure were collected. The pooled event rates, MDs, and RRs were calculated. Fifteen studies with 2276 achalasia individuals were included. Overall, the pooled technical success, clinical success, and AE rate of rescue POEM were 98.0% (95% CI, 96.6%–98.8%), 90.8% (95% CI, 88.8%–92.4%) and 10.3% (95% CI, 6.6%–15.8%), respectively. Seven studies compared the clinical outcomes of POEM between previous failed treatment and the treatment-naïve individuals. The RR for technical success, clinical success, and AEs were 1.00 (95% CI, 0.98–1.01), 0.98 (95% CI, 0.92–1.04), and 1.17 (95% CI, 0.78–1.76), respectively. Overall, there was significant reduction in the pre- and post-Eckardt score (MD, 5.77; P<0.001) and LES pressure (MD, 18.3 mm Hg; P<0.001) for achalasia individuals with failed previous intervention after POEM. The authors concluded that POEM appeared to be a safe, effective, and feasible treatment for individuals who had undergone previous failed intervention. It had similar outcomes in previously treated and treatment-naïve achalasia individuals. These researchers stated that POEM may be an attractive option for the treatment of individuals with this difficult condition; however, further studies with a long-term follow-up to determine the durability of rescue POEM are still needed.

The authors noted several drawbacks. First, only retrospective and prospective studies were included. No RCTs were found. Second, owing to the paucity of data in the included studies, the safety and efficacy of POEM for individuals with previous surgical or endoscopic interventions separately could not be evaluated. Third, some studies included pediatric individuals with achalasia and some individuals with other esophageal dysmotility disorders. However, these individuals accounted for a small percentage and the outcomes were unchanged after removing these studies. Fourth, these investigators were unable to examine the QOL in individuals with prior treatments after POEM due to the limited number of studies reporting these findings. Last, long-term (>2 years) differences between the individuals with and without prior intervention should be interpreted carefully as only two studies reported these outcomes.

Dirks et al. (2021) examined the literature comparing POEM with HM and PD for the treatment of achalasia. These researchers carried out a systematic review of comparative studies between POEM and HM or PD. A priori outcomes pertained to efficacy, perioperative metrics, and safety. Internal validity of observational studies and RCTs was judged using the Newcastle Ottawa Scale and the Cochrane Risk of Bias 2.0 tool, respectively. From 1379 unique literature citations, these investigators included 28 studies comparing POEM and HM (n=21) or PD (n=8), with only one RCT addressing each. Aside from two 4-year observational studies, POEM follow-up averaged less than or equal to 2 years. While POEM had similar efficacy to HM, POEM treated dysphagia better than PD both in an RCT (treatment "success" RR, 1.71; 95% CI, 1.34–2.17; 126 individuals) and in observational studies (Eckardt score MD, −0.43, 95% CI, −0.71 to −0.16; five studies; I2 21%; 405 individuals). POEM needed re-intervention less than PD in an RCT (RR, 0.19; 95% CI, 0.08–0.47; 126 individuals) and HM in an observational study (RR, 0.33; 95% CI, 0.16–0.68; 98 individuals). Although 6 to 12 months individual-reported reflux was worse than PD in three observational studies (RR, 2.67; 95% CI, 1.02–7.00; I2 0%; 164 individuals), postintervention reflux was inconsistently measured and not statistically different in measures greater than or equal to 1 year. POEM had similar safety outcomes to both HM and PD, including treatment-related serious AEs. The authors concluded that POEM has similar outcomes to HM and greater efficacy than PD; however, reflux remains a critical outcome with unknown long-term clinical significance due to insufficient data and inconsistent reporting.

Zhong et al. (2021) stated that POEM is a novel minimally invasive intervention in treating achalasia in adults. Presently, POEM was also reported to be effective for achalasia in children. These researchers examined the clinical outcomes of POEM for pediatric achalasia. They carried out a systematic literature search in PubMed, Embase, and Cochrane databases, which covered the period from January 2009 to June 2020. Selecting studies and collecting data was carried out independently by two reviewers according to predefined criteria. The statistical analysis was conducted using Comprehensive Meta-Analysis software version 2 and Review Manager 5.3. Eleven studies with 389 children were identified in the final analysis. Pooled technical success of POEM treatment achalasia was achieved in 385 children (97.4%; 95% CI, 94.7%–98.7%), and the pooled clinical success was achieved in 348 children (92.4 %; 95% CI, 89.0%–94.8%). After POEM, the Eckardt score was significantly decreased by 6.76 points (95% CI, 6.18–7.34; P<0.00001), and the LES pressure was significantly reduced by 19.38 mm Hg (95% CI, 17.54–21.22; P<0.00001). The pooled major AEs rate related to POEM was 12.8% (95% CI, 4.5%–31.5 %) and the GER rate was 17.8% (95% CI, 14.2%–22.0%). The authors concluded that the current study demonstrated that POEM was a safe and effective technique for treating achalasia in children. Moreover, they stated that further randomized comparative studies of POEM and other therapeutic methods are needed to determine the most effective treatment modality for achalasia in children.

Furthermore, the current version of UpToDate review on “Overview of the treatment of achalasia" (Spechler, 2021) states that “POEM is an effective submucosal endoscopic technique for performing myotomy of the LES and more proximal esophageal muscle. In addition, good results for POEM have been reported in individuals with achalasia conditions that often do not respond well to conventional therapies such as type III (spastic) achalasia and "end stage" achalasia (markedly dilated, sigmoid esophagus), and in individuals who have failed prior endoscopic and surgical achalasia treatments. The role of POEM in the treatment of achalasia continues to evolve, although there is a consensus that POEM is the procedure of choice for the treatment of type III achalasia. It has been suggested that individuals undergoing POEM should be counseled regarding the increased risk of postprocedure reflux compared with other treatments."

For adults who have achalasia who receive POEM, the evidence includes systematic reviews of primarily observational studies, four RCTs, and nonrandomized comparative studies. Relevant outcomes are symptoms, functional outcomes, health status measures, resource utilization, and treatment-related morbidity. Compared with PD or LHM, findings from RCTs demonstrated that POEM had a similar or greater treatment success rate based on the Eckardt score and similar or fewer overall AE rates. However, POEM had significantly higher rates of endoscopically confirmed reflux esophagitis and more daily PPI use at 24 months. An important conduct limitation of the RCTs is that blinded assessment of outcomes was not used. Given that the primary outcome was based on subjective individual report of symptoms, this is a potential source of bias. Additionally, a potential relevance limitation is that the RCTs did not include any United States sites. The comparative observational studies have primarily reported similar outcomes for POEM and for LHM in symptom relief, as assessed by the Eckardt score. Some studies have shown a shorter hospital LOS and less postoperative pain with POEM. However, potential imbalances in individual characteristics in these nonrandomized studies might have biased the treatment comparisons. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome for types I and II esophageal achalasia.

For pediatric individuals who have achalasia who receive POEM, the evidence includes several nonrandomized studies and three systematic reviews. Relevant outcomes are symptoms, functional outcomes, health status measures, resource utilization, and treatment-related morbidity. The studies reported treatment success for POEM based on decreases in Eckardt scores and LES pressure. No RCTs have been reported. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

The most recent systematic reviews and meta-analyses provide evidence that pediatric individuals treated with POEM do not have the same Eckardt score or LES pressure decreases that are seen in the adult population (Dimopoulou et al., 2024; Pu et al., 2024). However, there have been some recent lower quality design studies that do in fact demonstrate similar effectiveness, possibly indicating an improvement in technique as the procedure becomes more widely utilized in the research setting (Bi et al., 2023; Luvsandagva et al., 2024). Importantly, recent clinical professional guidelines (1) exclude pediatric individuals (Khashab et al., 2020); (2) do not mention pediatric individuals (Yang et al., 2024; Kahrilas et al., 2017); (3) provide low quality, conditional recommendation (Zaninotto et al., 2018); or (4) extrapolate the adult data (Kohn et al., 2021) despite the meaningful difference in effectiveness described above.

Gastric peroral endoscopic myotomy (G-POEM) or peroral pyloromyotmy (POP)

For adults who have gastroparesis who receive gastric POEM (G-POEM), also known as peroral pyloromyotomy, the evidence includes two meta-analyses, one RCT, and several nonrandomized studies. Relevant outcomes are symptoms, functional outcomes, health status measures, resource utilization, and treatment-related morbidity. The studies generally reported treatment success for G-POEM based on a decrease in Gastroparesis Cardinal Symptom Index (GCSI) score and ranged from 60.7% at 1 year to 75% at 3 years in the meta-analyses. One RCT comparing G-POEM to sham was identified that found greater rates of treatment success and gastric retention at 6 months follow-up in the G-POEM group. Both the RCT and the largest observational study found the greatest treatment effect in individuals who had a diabetic etiology for gastroparesis. The evidence is insufficient to determine that the technology results in an improvement in the net health outcome.

Although there has been robust growth in G-POEM research in recent years, as evidenced by several recent systematic reviews and meta-analyses, the effectiveness of G-POEM remains slightly higher than 50% (Dolan et al., 2025; Shargo et al., 2025; Mandarino et al., 2024; Stojilkovic et al., 2023; Aziz et al., 2023; Khashab et al., 2023; Camilleri et al., 2022). In light of this, careful individual selection of those most likely to benefit from G-POEM undergo the procedure. As noted by Mandarino et al. (2024) in one recent systematic review and meta-analysis: " One of the critical issues with G‐POEM is identifying individuals with refractory GP [gastroparesis] who could benefit from the procedure…However, at present, the outcome predictors of myotomy appear to be inconsistent and somewhat contradictory. For example, factors such as predominant nausea or a high 4‐h PGR [percent gastric retention] have been identified as both a success factor and a failure factor. These conflicting results make it challenging to establish clear guidelines for predicting outcomes. Currently, the evidence remains weak, and unfortunately, the implications for clinical practice are merely suggestive at this time. This highlights the need for further research to better define the predictors of success for G‐POEM and to standardize criteria for individual selection."

Similarly, in the AGA 2023 clinical practice update, the authors write, “Future directions include studies to better understand which individuals might benefit the most from G-POEM, as well as how and which ancillary tests might be used to help prognosticate postprocedural success." The authors, however, also note, “Even if the durable clinical success of G-POEM is in the 50%–60% range, this represents a huge clinical benefit to individuals with refractory gastroparesis, which is a disease associated with substantial morbidity, poor QOL, and a paucity of safe and effective treatments" (Khashab et al., 2023).

Diverticular peroral endoscopic myotomy (D-POEM) 

Esophageal diverticula are rare outpouchings of the esophagus that can cause dysphagia, regurgitation, chest pain, and aspiration pneumonia as they progress. Interventional treatment should be considered for symptomatic cases. Surgical resection of the diverticulum has traditionally been considered to be the only curative option. The D-POEM technique is unique in that, through the creation of submucosal tunneling, the cricopharyngeus muscle or the diverticular septum can be methodically exposed, allowing for careful complete septotomy under direct endoscopic visualization. The D-POEM technique for the treatment of esophageal diverticula has only been reported in limited case reports (Yang et al., 2019).

Studies in the peer-reviewed literature investigating D-POEM are primarily in the form of small prospective studies with individual populations ranging from 11 to 25 with follow-up of 12 months. Further well-designed studies with large individual populations are needed to assess the efficacy and safety of D-POEM (Wessels et al., 2023; Khashab 2021; Orlandini et al., 2020; Yang et al., 2019; Maydeo et al., 2019). There is insufficient evidence in the published peer-reviewed literature to support the safety and efficacy of D-POEM for the treatment of esophageal diverticula or any other indication. 

Zenker peroral endoscopic myotomy (Z-POEM) 

A Zenker diverticulum (ZD), or pharyngeal pouch, is an outpouching that occurs at the junction of the lower part of the throat and the upper portion of the esophagus. The pouch forms because the muscle that divides the throat from the esophagus, the cricopharyngeal (CP) muscle, fails to relax during swallowing. Symptoms of ZD include dysphagia, regurgitation, and associated complications. Symptomatic ZD is more prominent in male individuals (ratio 1:5) and typically seen in middle-aged adults and older adults in their seventh or eighth decade of life. The occurrence of ZD shows geographical variation and has been described more frequently in Northern Europe, North America, and Australia than in Southern Europe, Japan, or Indonesia (Ishaq et al., 2018). The available treatment modalities include open surgery, rigid endoscopy, and flexible endoscopy. Z-POEM, also known as submucosal tunneling endoscopic septum division (STESD), is a modified POEM technique. This technique eliminates direct dissection of the CP septum and, instead, involves dissecting a submucosal tunnel around the septum to achieve a complete myotomy. The procedure is indicated for treating small (< 2 cm) ZD because the small pocket may disappear after the myotomy is performed (Brewer Gutierrez et al., 2019). 

Studies in the peer-reviewed literature investigating Z-POEM are primarily in the form of retrospective studies. Large, well-designed, RCTs showing long-term safety and efficacy are lacking (Kahaleh et al., 2022; Budnicka et al., 2021; Yang et al., 2020; Ishaq et al., 2018). Swei et al. (2023) conducted a prospective study that compared Z‑POEM with standard flexible endoscopic septotomy (FES) for ZD. Individuals were included in the study if they were aged 18 years or older with a history of dysphagia and/or regurgitation, evidence of ZD, and had an endoscopic myotomy. The comparator group included individuals who had undergone FES. The primary outcome compared the technical and clinical success of endoscopic ZD therapy between the two groups. The secondary outcome was assessment of AEs in either group. Thirteen individuals underwent Z-POEM and 15 individuals underwent traditional FES. The mean procedure time was similar between groups and technical success was seen in 100% of individuals. There was one AE in the FES group (dehydration resulting in near syncope). Overall clinical success was seen in 92.8% of individuals and was not significantly different between groups by either Eckardt score or dysphagia score (Z-POEM, 13/13, 100% vs FES; 13/15, 86.7%; P=0.18). One-year follow-up data were available for 25 individuals, (n=12/Z-POEM, n=13/FES). The two groups did not significantly differ in terms of postprocedure Eckardt score (P=0.34), or dysphagia score (P=0.24). The median 2-year Eckardt score and dysphagia score for nine Z-POEM individuals was 1 and 0, respectively. None of the individuals who had 2-year data required additional therapy following Z-POEM. Author-noted limitations included the small number of individuals, the single-center design, and the comparison of Z-POEM to retrospective FES data. Additionally, it was noted that recruitment was impacted by the COVID-19 pandemic and all procedures (Z-POEM and FES) were performed by a single endoscopist. Lastly, follow-up data were collected by a phone call if not available from clinical encounters, which may have introduced reporting bias. The authors concluded that Z-POEM appears to be safe and comparable to FES when performed by an experienced endoscopist. Larger, longer term studies are needed to compare the two techniques. No health disparities were identified by the investigators. There is insufficient evidence in the published peer-reviewed literature to support the safety and efficacy of Z-POEM for the treatment of dysphagia or any other indication.