Achalasia is a rare esophageal motility disorder characterized by impaired relaxation of the lower esophageal sphincter (LES) and absence of peristalsis, leading to significant swallowing difficulties and other symptoms. Traditional treatment options, including Heller myotomy (HM) and pneumatic dilation (PD), have been effective but are associated with risks such as perforation and gastroesophageal reflux disease (GERD). Peroral endoscopic myotomy (POEM) has emerged as a minimally invasive alternative, potentially offering several advantages over conventional methods. This systematic review aims to compare the efficacy, safety, and long-term outcomes of POEM versus HM in the treatment of achalasia. We systematically reviewed studies that compared POEM with HM in achalasia patients, focusing on key outcomes such as myotomy length, operative time, treatment success rates, and complication rates. The review included 15 studies comprising four randomized controlled trials, 10 cohort studies, and one case-control study. The results consistently showed that POEM achieved longer myotomy lengths and shorter operative times compared to HM. POEM also demonstrated higher or comparable treatment success rates, with a uniform definition of success based on achieving an Eckardt score of ≤3. However, the complication rates, particularly the incidence of GERD, varied between the two procedures, highlighting the need for careful patient selection and long-term follow-up. POEM offers a promising alternative to HM for the treatment of achalasia, with advantages in terms of reduced invasiveness, shorter operative times, and potentially higher treatment success rates. However, further high-quality research is necessary to fully establish its long-term efficacy and safety compared to conventional treatments.

Two common surgical procedures used to treat esophageal motility disorders are laparoscopic Heller myotomy (LHM) with partial fundoplication and per-oral endoscopic myotomy (POEM). The difference in frequency of follow-up interventions following these procedures is unknown. This study was designed to report differences in post-surgical interventions as one of the major long-term follow-up expectations.

An IRB approved registry was used to identify all patients undergoing surgery with LHM or POEM. Following surgery, patients requiring additional interventions with esophageal non-pneumatic dilation, botox injection, or repeat myotomy, as well as persistent proton pump inhibitor (PPI) use were recorded. Multivariable logistic regression analysis was performed to estimate risk factors associated with return for additional post-operative intervention.

A total of 203 patients were identified, 139 met inclusion criteria (33 LHM and 106 POEM). There was a higher rate of non-pneumatic EGD dilation (33% vs 15%, p = 0.04), repeat myotomy (18% vs 2%, p < 0.01), and higher rate of overall post-operative intervention in LHM than POEM. With POEM, there was a higher rate of post-operative PPI use (63 vs 29%, p < 0.01). There was no difference in time to post-operative intervention for either group, but if intervention were to occur the median time was within the first year. Patients with a change in pre- to post-operative Eckardt score of 4 or greater decreased their chance of having a post-operative intervention.

Our results for both LHM and POEM emphasize the importance of long-term follow-up in patients with an esophageal motility disorder. We have found that patients undergoing LHM are more likely to have a post-operative intervention as well as a higher rate of repeat myotomy than POEM. With both interventions, a greater change in Eckardt score decreased the likelihood of reintervention.

There is limited evidence on the efficacy of peroral endoscopic myotomy (POEM) in patients with esophageal diverticula.

This meta-analysis aimed to assess the efficacy and safety profile of POEM in patients with Zenker (ZD) and epiphrenic diverticula.

With a literature search through August 2020, we identified 12 studies (300 patients) assessing POEM in patients with esophageal diverticula. The primary outcome was treatment success. Results were expressed as pooled rates and 95% confidence intervals.

Pooled rate of technical success was 95.9% (93.4%-98.3%) in ZD patients and 95.1% (88.8%-100%) in patients with epiphrenic diverticula. Pooled rate of treatment success was similar for ZD (90.6%, 87.1%-94.1%) and epiphrenic diverticula (94.2%, 87.3%-100%). Rates of treatment success were maintained at 1 year (90%, 86.4%-97.4%) and 2 years (89.6%, 82.2%-96.9%) in ZD patients. Pooled rate of symptom recurrence was 2.6% (0.9%-4.4%) in ZD patients and 0% in patients with epiphrenic diverticula. Pooled rates of adverse events and severe adverse events were 10.6% (4.6%-16.6%) and 3.5% (0%-7.4%) in ZD and 8.4% (0%-16.8%) and 8.4% (0%-16.8%) in epiphrenic diverticula, respectively.

POEM represents an effective and safe therapy for the treatment of esophageal diverticula.

Achalasia is a rare benign esophageal motor disorder characterized by incomplete relaxation of the lower esophageal sphincter (LES). The treatment of achalasia is not curative, but rather is aimed at reducing LES pressure. In patients who have failed noninvasive therapy, surgery should be considered. Myotomy with partial fundoplication has been considered the first-line treatment for non-advanced achalasia. Recently, peroral endoscopic myotomy (POEM), a technique that employs the principles of submucosal endoscopy to perform the equivalent of a surgical myotomy, has emerged as a promising minimally invasive technique for the management of this condition.

To compare POEM and laparoscopic myotomy and partial fundoplication (LM-PF) regarding their efficacy and outcomes for the treatment of achalasia.

Forty treatment-naive adult patients who had been diagnosed with achalasia based on clinical and manometric criteria (dysphagia score ≥ II and Eckardt score > 3) were randomized to undergo either LM-PF or POEM. The outcome measures were anesthesia time, procedure time, symptom improvement, reflux esophagitis (as determined with the Gastroesophageal Reflux Disease Questionnaire), barium column height at 1 and 5 min (on a barium esophagogram), pressure at the LES, the occurrence of adverse events (AEs), length of stay (LOS), and quality of life (QoL).

There were no statistically significant differences between the LM-PF and POEM groups regarding symptom improvement at 1, 6, and 12 mo of follow-up (P = 0.192, P = 0.242, and P = 0.242, respectively). However, the rates of reflux esophagitis at 1, 6, and 12 mo of follow-up were significantly higher in the POEM group (P = 0.014, P < 0.001, and P = 0.002, respectively). There were also no statistical differences regarding the manometry values, the occurrence of AEs, or LOS. Anesthesia time and procedure time were significantly shorter in the POEM group than in the LM-PF group (185.00 ± 56.89 and 95.70 ± 30.47 min vs 296.75 ± 56.13 and 218.75 ± 50.88 min, respectively; P = 0.001 for both). In the POEM group, there were improvements in all domains of the QoL questionnaire, whereas there were improvements in only three domains in the LM-PF group.

POEM and LM-PF appear to be equally effective in controlling the symptoms of achalasia, shortening LOS, and minimizing AEs. Nevertheless, POEM has the advantage of improving all domains of QoL, and shortening anesthesia and procedure times but with a significantly higher rate of gastroesophageal reflux.

Peroral endoscopic myotomy (POEM) utilizes the principles of natural orifice transluminal surgery to create an operative tunnel within the submucosal space, perform an endoluminal esophagogastromyotomy, and ultimately mitigate the progressive symptoms of achalasia. POEM is an innovative minimally invasive technique increasing in popularity and clinical significance as an effective treatment for achalasia and other disorders of spastic esophageal motility.

A comprehensive literature review was performed regarding the procedure, outcomes, and technical advancements in POEM.

A growing number of studies world-wide have shown that POEM is a safe and effective for all types of achalasia, sigmoid and non-sigmoid type.

POEM continues to gain traction as a highly effective therapeutic modality for achalasia. As natural orifice transluminal surgery advances, further research is necessary to optimize utilization of endoluminal functional imaging, to tailor endoscopic technique, and to address the adverse effect of post-operative reflux and esophagitis.

Achalasia is a debilitating chronic condition of the esophagus. Currently there are no national estimates on the epidemiologic and economic burden of disease. We sought to estimate trends in incidence and prevalence of achalasia by age-sex strata, and to estimate the total direct medical costs attributed to achalasia in the United States.

We conducted a cohort study using two administrative claims databases: IBM MarketScan Commercial Claims and Encounters database (2001-2018; age <65) and a 20% sample of nationwide Medicare enrollment and claims (2007-2015; age ≥65). Point prevalence was calculated on the first day of each calendar year; the incidence rate captured new cases developed in the ensuing year. Utilization rates of healthcare services and procedures were reported. Mean costs per patient were calculated and standardized to the corresponding U.S. Census Bureau population data to derive achalasia-specific total direct medical costs.

The crude prevalence of achalasia per 100,000 persons was 18.0 (95% CI, 17.4, 18.7) in MarketScan and 162.1 (95% CI, 157.6, 166.6) in Medicare. The crude incidence rate per 100,000 person-years was 10.5 (95% CI, 9.9, 11.1) in MarketScan and 26.0 (95% CI, 24.9, 27.2) in Medicare. Incidence and prevalence increased substantially over time in the Medicare cohort, and increased with more advanced age in both cohorts. Utilization of achalasia-specific healthcare was high; national estimates of total direct medical costs exceeded $408 million in 2018.

Achalasia has a higher epidemiologic and economic burden in the US than previously suggested, with diagnosis particularly increasing in older patients.

Peroral endoscopic myotomy (POEM) in patients with achalasia who are status post bariatric surgery may be technically challenging due to postsurgical scarring and altered anatomy. The aim of the study was to assess the efficacy and safety of POEM for achalasia in patients with prior bariatric surgery. A review of prospectively maintained databases at three tertiary referral centers from January 2015 to January 2021 was performed. The primary outcome of interest was clinical success, defined as a post-treatment Eckardt score ≤ 3 or improvement in Eckardt score by ≥ 1 when the baseline score was <3, and improvement of symptoms. Secondary outcomes were adverse event rates and symptom recurrence. Sixteen patients status post Roux-en-Y gastric bypass (n = 14) and sleeve gastrectomy (n = 2) met inclusion criteria. Indications for POEM were achalasia type I (n = 2), type II (n = 9), and type III (n = 5). POEM was performed either by anterior or posterior approach. The pre-POEM mean integrated relaxation pressure was 26.2 ± 7.6 mm Hg. The mean total myotomy length was 10.2 ± 2.7 cm. The mean length of hospitalization was 1.4 ± 0.7 days. Pre- and postprocedure Eckardt scores were 6.1 ± 2.1 and 1.7 ± 1.8, respectively. The overall clinical success rate was 93.8% (15/16) with mean follow-up duration of 15.5 months. One patient had esophageal leak on postprocedure esophagram and managed endoscopically. Dysphagia recurred in two patients, which was successfully managed with pneumatic dilation with or without botulinum toxin injection. POEM appears to be safe and effective in the management of patients with achalasia who have undergone prior bariatric surgery.

Peroral endoscopic myotomy (POEM) has been recommended for achalasia treatment. To prevent the potential of infective risk, antibiotic prophylaxis is usually administered, whereas the additional need of antibiotic therapy after POEM is uncertain. The primary endpoint was to determine whether prophylaxis versus prophylaxis plus short therapy was needed after POEM.

Consecutive patients scheduled for POEM were randomly assigned (1:1) to group A (prophylactic cefazolin 2 g IV) or group B (prophylaxis + cefazolin 2 g IV × 3 followed by oral amoxicillin/clavulanate 3 g/day). Infective risk was assessed by means of host response, namely body temperature and serum levels of white blood cells and C-reactive protein; immune response (the cytokines interleukin [IL]-6, IL-1β, and tumor necrosis factor-α and microbial translocation mediators lipopolysaccharide binding protein and soluble CD14); and blood cultures at time points before (t0) and after (t1, t2) POEM.

After POEM, none of the 124 enrolled patients (54.6 ± 12.6 years old; 64 men) developed any fever (body temperature: t0, 36.56± .49°C; t1, 36.53± .52°C; t2, 36.48± .41°C), without any differences between groups at any time point. Regarding systemic inflammation, no difference was reported between groups in serum levels of C-reactive protein and white blood cells. Considering microbial translocation mediated response, lipopolysaccharide binding protein (group A: t0, 1539 ± 168.6 pg/mL; t1, 1321 ± 149.1 pg/mL; t2, 2492 ± 283.2 pg/mL; group B: t0, 1318 ± 115.9 pg/mL; t1, 1492 ± 163.8 pg/mL; t2, 2600 ± 328.2 pg/mL) and soluble CD14 (group A: t0, 2.16 ± .15 μg/mL; t1, 1.89 ± .15 μg/mL; t2, 2.2 ± .15 μg/mL; group B: t0, 2.1 ± .13 μg/mL; t1, 2 ± .13 μg/mL; t2, 2.5 ± .2 μg/mL) were similar between the 2 groups; the immune response cytokines IL-6, IL-1β, and tumor necrosis factor-α also were similar in the 2 groups. In relation to blood cultures, at t1 the group B bacteremia rate was 3.2% (2/62) and group A was 1.6% (1/62) with no difference (P = .6). All subsequent blood cultures were negative at t2.

According to our study, postprophylactic short-term antimicrobial therapy after POEM is not required because of a very low residual infective risk. (Clinical trial registration number: NCT03587337.).

This study aimed to determine the clinical efficacy of measuring the esophagogastric junction (EGJ) distensibility index (DI) in patients with achalasia before and after peroral endoscopic myotomy (POEM).

Retrospective data were collected from 195 patients who underwent POEM from November 2014 to November 2017 at our clinic. The Eckardt score, high-resolution manometry, and EGJ distensibility were measured before and six months after POEM. Treatment failure was defined as a postprocedure Eckardt score >3 or patients who underwent repeat POEM.

The DI (mm2/mmHg) before and after POEM was 3.42±3.55 and 11.57±6.64, respectively (p<0.01). There was no difference in the DI between achalasia subtypes I, II, and III (11.45±6.24 versus 15.49±11.53 versus 13.27±9.49, p=0.22) or previous treatment history (15.39±10.85 versus 11.10±7.25, p=0.20). The DI was higher in patients with reflux esophagitis after POEM, but the difference was not significant (13.59±7.15 versus 12.54±10.9, p=0.571).

This study showed that EGJ distensibility measurement is useful to assess post-POEM outcomes. These findings suggest that the functional lumen imaging probe may be a useful method for assessing clinical efficacy of POEM in patients with achalasia. However, this is a costly procedure that requires experience.

The purpose of this review is to discuss the efficacy, morbidity and side-effects of innovative management strategies for achalasia that include high-resolution manometry (HRM), pneumatic dilatation, laparoscopic Heller's myotomy (LHM), injection of botulinum toxin into the lower esophageal sphincter and peroral endoscopic myotomy (POEM).

HRM has enabled identification of achalasia subtypes that have important prognostic implications. Pneumatic dilatation 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. Botulinum toxin injection of the lower esophageal sphincter has a waning and short duration of efficacy and is used primarily for patients unsuitable for more definitive invasive procedures. POEM is considered the most effective treatment for type III achalasia but carries a high risk of iatrogenic gastroesophageal reflux disease that might predispose to the development of Barrett's esophagus.

HRM and POEM are two major innovations in the management of achalasia developed over the past decade. There are now three major management options for patients with achalasia, namely pneumatic dilatation, LHM and POEM. Treatment selection should be tailored to the patient's individual esophageal physiology, physical fitness and dominant symptoms.

The main scope of this review article is to introduce readers to the innovative field of third-space endoscopy and offer a closer look at its history, milestones, and procedure spectrum while discussing ongoing and future challenges arising from its increasing adoption worldwide.

Over the past few years, third-space endoscopy has been utilized in various diagnostic and interventional procedures performed throughout the gastrointestinal tract: obliteration of Zenker's diverticulum, myotomy for achalasia, gastroparesis or Hirschsprung's disease, biopsy or removal of subepithelial tumors, stricture management, post-per-oral endoscopic myotomy endoscopic fundoplication, and mediastino-, thoraco-, and peritoneoscopy. Third-space endoscopic interventions have revolutionized the management of esophageal motility disorders, gastroparesis, and gastrointestinal tract subepithelial tumors. Despite the high efficacy and safety of such interventions, some common (e.g., the high level of necessary endoscopic skill) and unique for each procedure (e.g., post-procedure gastroesophageal reflux or poor outcomes in patient subgroups) challenges still remain. Through a dedicated endoscopic training, a rigorous pre-procedure patient evaluation and selection, and the application of modified or new techniques, challenges can be overcome thus establishing existing procedures and paving the way for additional breakthroughs in the field of third-space endoscopy.

Achalasia is a relatively rare primary motor esophageal disorder, characterized by absence of relaxations of the lower esophageal sphincter and of peristalsis along the esophageal body. As a result, patients typically present with dysphagia, regurgitation and occasionally chest pain, pulmonary complication and malnutrition. New diagnostic methodologies and therapeutic techniques have been recently added to the armamentarium for treating achalasia. With the aim to offer clinicians and patients an up-to-date framework for making informed decisions on the management of this disease, the International Society for Diseases of the Esophagus Guidelines proposed and endorsed the Esophageal Achalasia Guidelines (I-GOAL). The guidelines were prepared according the Appraisal of Guidelines for Research and Evaluation (AGREE-REX) tool, accredited for guideline production by NICE UK. A systematic literature search was performed and the quality of evidence and the strength of recommendations were graded according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Given the relative rarity of this disease and the paucity of high-level evidence in the literature, this process was integrated with a three-step process of anonymous voting on each statement (DELPHI). Only statements with an approval rate >80% were accepted in the guidelines. Fifty-one experts from 11 countries and 3 representatives from patient support associations participated to the preparations of the guidelines. These guidelines deal specifically with the following achalasia issues: Diagnostic workup, Definition of the disease, Severity of presentation, Medical treatment, Botulinum Toxin injection, Pneumatic dilatation, POEM, Other endoscopic treatments, Laparoscopic myotomy, Definition of recurrence, Follow up and risk of cancer, Management of end stage achalasia, Treatment options for failure, Achalasia in children, Achalasia secondary to Chagas' disease.

The efficacy of per oral endoscopic myotomy (POEM) in non-achalasia esophageal motility disorders such as esophagogastric junction outflow obstruction (EGJOO), diffuse esophageal spasm (DES), and jackhammer esophagus (JE) has not been well demonstrated. The aim of this international multicenter study was to assess clinical outcomes of POEM in patients with non-achalasia disorders, namely DES, JE, and EGJOO, in a large cohort of patients.

This was a retrospective study at 11 centers. Consecutive patients who underwent POEM for EGJOO, DES, or JE between 1/2014 and 9/2016 were included. Rates of technical success (completion of myotomy), clinical response (symptom improvement/Eckardt score ≤ 3), and adverse events (AEs, severity per ASGE lexicon) were ascertained .

Fifty patients (56 % female; mean age 61.7 years) underwent POEM for EGJOO (n = 15), DES (n = 17), and JE (n = 18). The majority of patients (68 %) were treatment-naïve. Technical success was achieved in all patients with a mean procedural time of 88.4 ± 44.7 min. Mean total myotomy length was 15.1 ± 4.7 cm. Chest pain improved in 88.9 % of EGJOO and 87.0 % of DES/JE ( P  = 0.88). Clinical success was achieved in 93.3 % of EGJOO and in 84.9 % of DES/JE ( P  = 0.41) with a median follow-up of 195 and 272 days, respectively. Mean Eckardt score decreased from 6.2 to 1.0 in EGJOO ( P  < 0.001) and from 6.9 to 1.9 in DES/JE ( P  < 0.001). A total of 9 (18 %) AEs occurred and were rated as mild in 55.6 % and moderate in 44.4 %.

POEM is effective and safe in management of non-achalasia esophageal motility disorders, which include DES, JE, and EGJOO.

Per-oral endoscopic myotomy (POEM) has been rapidly gaining ground as a treatment for achalasia. Although POEM is a safe and effective treatment, a subset of patients has persistent or recurrent symptoms after POEM. This study aimed to examine the efficacy of different retreatments after failed POEM.

POEM was performed on 441 patients with achalasia at 3 tertiary-care hospitals between 2010 and 2015. A review of prospectively collected data was conducted. All patients with achalasia with significant persistent or recurrent symptoms within 3 years after POEM, defined as an Eckardt symptom score >3, were included.

Forty-three of 441 patients (9.8%) had persistent or recurrent symptoms after POEM, of which 34 (8%) received 1 or more retreatments. Retreatment with laparoscopic Heller myotomy and retreatment with POEM showed a modest efficacy of 45% and 63%, respectively, whereas pneumatic dilatation showed a poor efficacy of only 0% to 20%, depending on the size of the balloon. Male patients were more likely to have retreatment failure than female patients (P = .038).

In patients with achalasia with persistent or recurrent symptoms after failed POEM, retreatment with laparoscopic Heller myotomy or retreatment with POEM has a higher efficacy than retreatment with pneumatic dilatations. Failure of retreatment occurred more often in male patients.

Peroral endoscopic myotomy (POEM) is a natural orifice, translumenal endoscopic surgical procedure that achieves endoscopic myotomy by conducting a submucosal tunnel as an operating space. It is conventionally performed in achalasia. Recently, several centers worldwide have reported the feasibility of this procedure not only in early achalasia but also in other particular patient cohorts. Possible indications for POEM include previously failed Heller myotomy, pneumatic balloon dilatation or POEM, sigmoid achalasia, pediatric patients, spastic esophagus disorders, Zenker's diverticulum and gastroparesis. However, its application in large numbers of special patient groups awaits knowledge of the long-term outcome and greater experience with POEM.

Several uncontrolled studies comparing peroral endoscopic myotomy (POEM) and Heller myotomy have demonstrated equivalent short-term efficacy and safety. However, no data exists rergarding the cost of POEM and how it compares to that of robotic Heller myotomy (RHM). The primary aim of this study was to compare the inpatient charges incurred in patients who underwent POEM or RHM for the treatment of achalasia.

A retrospective single center review was conducted among 52 consecutive POEM patients (2012-2014) and 52 consecutive RHM patients (2009-2014). All RHM procedures included a Toupet fundoplication and were performed via a transabdominal approach. All POEM procedures were performed by a gastroenterologist in the endoscopy unit. Clinical response was defined by improvement of symptoms and decrease in Eckardt stage to ≤I. All procedural and facility charges were obtained from review of the hospital finance records.

There was no difference between POEM and RHM with regards to age, gender, symptom duration, achalasia subtype, manometry findings, or Eckardt symptom stage. There was no significant difference in the rate of adverse events (19.2% vs 9.6%, P = 0.26) or the length of stay (1.9 vs. 2.3, P = 0.18) between both groups. Clinical response rate of patients in the POEM groups was similar to that in the RHM group (94.3% vs. 88.5%, P = 0.48). POEM incurred significantly less total charges compared to LHM ($14481 vs. $17782, P = 0.02).

POEM when performed in an endoscopy unit was similar in efficacy and safety to RHM. However, POEM was associated with significant cost savings ($3301/procedure).

The Chicago classification (CC) is most valued for its systematic approach to esophageal disorders and great impact in unifying practice for esophageal manometric studies. In view of the ever-growing wealth of knowledge and experience gained by the expanding use of high-resolution manometry (HRM) in various clinical scenarios, the CC is regularly updated. Its clinical impact and ability to predict clinical outcome, both in adults and pediatrics, will be further promoted by recognizing its current limitations, incorporating new metrics in its diagnostic algorithms and adjusting the HRM protocols based on the clinical question posed. Herein, we discuss the current limitations of the CC and highlight some areas of improvement for the future.